Connection Failure: Differences in White Matter Microstructure Are Associated with 5-HTTLPR but Not with Risk Seeking for Losses.

S/S carriers of 5-HTTLPR have been found to be more risk seeking for losses compared to L/L carriers. This finding may be the result of reduced top-down control from the frontal cortex due to altered signal pathways involving the amygdala and ventral striatum. The serotonergic system is known to be involved in neurodevelopment and neuroplasticity. Therefore, the aim of this study was to investigate whether structural differences in white matter can explain the differences in risk-seeking behaviour. Lower structural connectivity in S/S compared to L/L carriers and a negative relationship between risk seeking for losses and connectivity were assumed. Diffusion-weighted imaging was used to compute diffusion parameters for the frontostriatal and uncinate tract in 175 genotyped individuals. The results showed no significant relationship between diffusion parameters and risk seeking for losses. Furthermore, we did not find significant differences in diffusion parameters of the S/S vs. L/L group. There were only group differences in the frontostriatal tract showing stronger structural connectivity in the S/L group, which is also reflected in the whole brain approach. Therefore, the data do not support the hypothesis that the association between 5-HTTLPR and risk seeking for losses is related to differences in white matter pathways implicated in decision-making.

Factors influencing adherence to clinical practice guidelines in patients with suspected chronic coronary syndrome: a qualitative interview study in the ambulatory care sector in Germany.

BACKGROUND: Chronic coronary syndrome (CCS) is a potentially progressive clinical presentation of coronary artery disease (CAD). Clinical practice guidelines (CPGs) are available for prevention, diagnosis, and treatment. Embedded in the "ENLIGHT-KHK" healthcare project, a qualitative study was conducted to identify factors that influence guideline adherence from the perspective of general practitioners (GPs) and cardiologists (CA) in the ambulatory care sector in Germany. METHODS: GPs and CAs were surveyed via telephone using an interview guide. The respondents were first asked about their individual approach to caring for patients with suspected CCS. Subsequently, the accordance of their approach with guideline recommendations was addressed. Finally, potential measures for assisting with guideline adherence were discussed. The semi-structured interviews were transcribed verbatim and analysed using a qualitative content analysis in accordance with Kuckartz and Rädiker. Factors influencing adherence to CPGs were categorised by assessing whether they (i) inhibited or facilitated guideline adherence, (ii) played a role in patients at risk of CCS or with suspected or known CCS, (iii) were mentioned in implicit or explicit thematic reference to CPGs, and (iv) were declared a practical problem. RESULTS: Based on interviews with ten GPs and five CAs, 35 potential influencing factors were identified. These emerged at four levels: patients, healthcare providers, CPGs, and the healthcare system. The most commonly cited barrier to guideline adherence among the respondents was structural aspects at the system level, including reachability of providers and services, waiting times, reimbursement through statutory health insurance (SHI) providers, and contract offers. There was a strong emphasis on interdependencies between factors acting at different levels. For instance, poor reachability of providers and services at the system level may result in inexpedience of guideline recommendations at the CPG level. Likewise, poor reachability of providers and services at the system level may be aggravated or alleviated by factors such as diagnostic preferences at the patient level or collaborations at the provider level. CONCLUSIONS: To assist with adherence to CPGs regarding CCS, promoting measures may be needed that account for interdependencies between barriers and facilitators at various healthcare levels. Respective measures should consider medically justified deviations from guideline recommendations in individual cases. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00015638; Universal Trial Number (UTN): U1111-1227-8055.

A time-driven activity-based costing approach of magnetic resonance-guided high-intensity focused ultrasound for cancer-induced bone pain.

OBJECTIVE: To determine resource consumption and total costs for providing magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) treatment to a patient with cancer-induced bone pain (CIBP). METHODS: We conducted a time-driven activity-based costing (TD-ABC) of MR-HIFU treatments for CIBP from a hospital perspective. A European care-pathway (including a macro-, meso-, and micro-level) was designed to incorporate the care-delivery value chain. Time estimates were obtained from medical records and from prospective direct observations. To calculate the capacity cost rate, data from the controlling department of a German university hospital were allocated to the modules of the care pathway. Best- and worst-case scenarios were calculated by applying lower and upper bounds of time measurements. RESULTS: The macro-level care pathway consisted of eight modules (i.e., outpatient consultations, pretreatment imaging, preparation, optimization, sonication, post-treatment, recovery, and anesthesia). The total cost of an MR-HIFU treatment amounted to €5147 per patient. Best- and worst-case scenarios yielded a total cost of €4092 and to €5876. According to cost categories, costs due to equipment accounted for 41% of total costs, followed by costs with personnel (32%), overhead (16%) and materials (11%). CONCLUSION: MR-HIFU is an emerging noninvasive treatment for alleviating CIBP, with increasing evidence on treatment efficacy. This costing study can support MR-HIFU reimbursement negotiations and facilitate the adoption of MR-HIFU as first-line treatment for CIBP. The present TD-ABC model creates the opportunity of benchmarking the provision of MR-HIFU to bone tumor.Key pointsMagnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) is an emerging noninvasive treatment modality for alleviating cancer-induced bone pain (CIBP).From a hospital perspective, the total cost of MR-HIFU amounted to €5147 per treatment.This time-driven activity-based costing model creates the opportunity of benchmarking the provision of MR-HIFU to bone tumor.

Cost-Effectiveness of Targeted Genetic Testing for Breast and Ovarian Cancer: A Systematic Review.

BACKGROUND: Targeted genetic testing is a tool to identify women at increased risk of gynaecological cancer. OBJECTIVE: This systematic review evaluates the results and quality of cost-effectiveness modeling studies that assessed targeted genetic-based screen-and-treat strategies to prevent breast and ovarian cancer. METHODS: Using MEDLINE and databases of the Centre for Reviews and Dissemination, we searched for health economic modeling evaluations of targeted genetic-based screen-and-treat strategies to prevent inheritable breast and ovarian cancer (until August 2020). The incremental cost-effectiveness ratios (ICERs) were compared. Methodological variations were addressed by evaluating the model conceptualizations, the modeling techniques, parameter estimation and uncertainty, and transparency and validation of the models. Additionally, the reporting quality of each study was assessed. RESULTS: Eighteen studies met our inclusion criteria. From a payer perspective, the ICERs of (1) BRCA screening for high-risk women without cancer ranged from dominating the no test strategy to an ICER of $21 700/quality-adjusted life years (QALY). In studies that evaluated (2) BRCA cascade screening (ie, screening of women with cancer plus their unaffected relatives) compared with no test, the ICERs were between $6500/QALY and $50 200/QALY. Compared with BRCA alone, (3) multigene testing in women without cancer had an ICER of $51 800/QALY (one study), while for (4) multigene-cascade screening the ICERs were $15 600/QALY, $56.500/QALY, and $69 600/QALY for women in the United Kingdom, Norway, and the United States, respectively (2 studies). More recently published studies showed a higher methodological and reporting quality. CONCLUSIONS: Targeted BRCA or multiple gene screening is likely to be cost-effective. Methodological variations could be decreased by the development of a reference model, which may serve as a tool for validation of present and future cost-effectiveness models.

Cost-effectiveness of group-based exercise to prevent falls in elderly community-dwelling people.

BACKGROUND: Clinical studies indicate that strength-balance training for active fall prevention can prevent fractures in older people. The present modelling study evaluates the cost-effectiveness of fall prevention exercise (FPE) provided to independently living older people compared to no intervention in Germany. METHOD: We designed a Markov model to evaluate the cost-effectiveness of a group-based FPE-program provided to independently living people ≥75 years from the perspective of the German statutory health insurance (SHI). Input data was obtained from public databases, clinical trials and official statistics. The incremental cost-effectiveness ratio (ICER) was presented as costs per avoided hip fracture. Additionally, we performed deterministic and probabilistic sensitivity analyses and, estimated monetary consequences for the SHI in a budget impact analysis (BIA). RESULTS: For women, the costs per hip fracture avoided amounted to €52,864 (men: €169,805). Results of deterministic and probabilistic sensitivity analyses confirmed the robustness of the results. According to the BIA, for the reimbursement of FPE additional costs of €3.0 million (women) and €7.8 million (men) are expected for the SHI. CONCLUSIONS: Group-based FPE appears to be no cost-effective option to prevent fall-related hip fractures in independently living elderly. To allow a more comprehensive statement on the cost effectiveness of FPE fracture types other than hip should be increasingly evaluated in clinical trials.

Methodological issues in economic evaluations of disease prevention and health promotion: an overview of systematic and scoping reviews.

BACKGROUND: We aimed to provide a comprehensive overview of methodological challenges in economic evaluations of disease prevention and health promotion (DPHP)-measures. METHODS: We conducted an overview of reviews searching MEDLINE, EMBASE, NHS Economic Evaluation Database, Database of Promoting Health Effectiveness Reviews, Cochrane Database of Systematic Reviews (CDSR) and Database of Promoting Health Effectiveness Reviews (DOPHER) (from their inception to October 2021). We included both systematic and scoping reviews of economic evaluations in DPHP addressing following methodological aspects: (i) attribution of effects, (ii) outcomes, (iii) inter-sectoral (accruing to non-health sectors of society) costs and consequences and (iv) equity. Data were extracted according to the associated sub-criteria of the four methodological aspects including study design economic evaluation (e.g. model-based), type/scope of the outcomes (e.g. outcomes beyond health), perspective, cost categories related to non-health sectors of society, and consideration of equity (method of inclusion). Two reviewers independently screened all citations, full-text articles, and extracted data. A narrative synthesis without a meta-analysis or other statistical synthesis methods was conducted. RESULTS: The reviewing process resulted in ten systematic and one scoping review summarizing 494 health economic evaluations. A lifelong time horizon was adopted in about 23% of DPHP evaluations, while 64% of trial-based evaluations had a time horizon up to 2 years. Preference-based outcomes (36%) and non-health outcomes (8%) were only applied in a minority of studies. Although the inclusion of inter-sectoral costs (i.e. costs accruing to non-health sectors of society) has increased in recent years, these were often neglected (between 6 and 23% depending on the cost category). Consideration to equity was barely given in economic evaluations, and only addressed in six of the eleven reviews. CONCLUSIONS: Economic evaluations of DPHP measures give only little attention to the specific methodological challenges related to this area. For future economic DPHP evaluations a tool with structured guidance should be developed. This overview of reviews was not registered and a published protocol does not exist.

Acute tryptophan loading decreases functional connectivity between the default mode network and emotion-related brain regions.

It has been shown that the functional architecture of the default mode network (DMN) can be affected by serotonergic challenges and these effects may provide insights on the neurobiological bases of depressive symptomatology. To deepen our understanding of this possible interplay, we used a double-blind, randomized, cross-over design, with a control condition and two interventions to decrease (tryptophan depletion) and increase (tryptophan loading) brain serotonin synthesis. Resting-state fMRI from 85 healthy subjects was acquired for all conditions 3 hr after the ingestion of an amino acid mixture containing different amounts of tryptophan, the dietary precursor of serotonin. The DMN was derived for each participant and session. Permutation testing was performed to detect connectivity changes within the DMN as well as between the DMN and other brain regions elicited by the interventions. We found that tryptophan loading increased tryptophan plasma levels and decreased DMN connectivity with visual cortices and several brain regions involved in emotion and affect regulation (i.e., putamen, subcallosal cortex, thalamus, and frontal cortex). Tryptophan depletion significantly reduced tryptophan levels but did not affect brain connectivity. Subjective ratings of mood, anxiety, sleepiness, and impulsive choice were not strongly affected by any intervention. Our data indicate that connectivity between the DMN and emotion-related brain regions might be modulated by changes in the serotonergic system. These results suggest that functional changes in the brain associated with different brain serotonin levels may be relevant to understand the neural bases of depressive symptoms.

Dynamic changes in white matter microstructure in anorexia nervosa: findings from a longitudinal study.

BACKGROUND: Gray matter (GM) 'pseudoatrophy' is well-documented in patients with anorexia nervosa (AN), but changes in white matter (WM) are less well understood. Here we investigated the dynamics of microstructural WM brain changes in AN patients during short-term weight restoration in a combined longitudinal and cross-sectional study design. METHODS: Diffusion-weighted images were acquired in young AN patients before (acAN-Tp1, n = 56) and after (acAN-Tp2, n = 44) short-term weight restoration as well as in age-matched healthy controls (HC, n = 60). Images were processed using Tract-Based-Spatial-Statistics to compare fractional anisotropy (FA) across groups and timepoints. RESULTS: In the cross-sectional comparison, FA was significantly reduced in the callosal body in acAN-Tp1 compared with HC, while no differences were found between acAN-Tp2 and HC. In the longitudinal arm, FA increased with weight gain in acAN-Tp2 relative to acAN-Tp1 in large parts of the callosal body and the fornix, while it decreased in the right corticospinal tract. CONCLUSIONS: Our findings reveal that dynamic, bidirectional changes in WM microstructure in young underweight patients with AN can be reversed with brief weight restoration therapy. These results parallel those previously observed in GM and suggest that alterations in WM in non-chronic AN are also state-dependent and rapidly reversible with successful intervention.

Thermal comfort in environments with different vertical air temperature gradients.

The use of displacement ventilation for cooling environments is limited by the vertical temperature gradient. Current standards recommend a temperature difference of up to 3 K/m between the head and the feet. This paper reviews the scientific literature on the effect of vertical temperature gradients on thermal comfort and compares this to the results of our own experiments. Early experiments have demonstrated a high sensitivity of dissatisfied test subjects to changes in the temperature gradient between head and foot level. Recent studies have indicated that temperature gradients of 4-5 K/m are likely to be acceptable, and the mean room temperature may have a greater sensitivity on the percentage of dissatisfied (PD). In new experiments, test subjects have evaluated the thermal comfort of different vertical air temperature gradients in a modular test chamber, the Aachen comfort cube (ACCu), where they have assessed vertical temperature gradients of ΔT/Δy = 1, 4.5, 6, 8, and 12 K/m at a constant mean room temperature of 23°C. The results of the different temperature gradients are in contrast to ANSI/ASHRAE Standard 55 (Thermal Environmental Conditions for Human Occupancy, Atlanta GA, American Society of Heating, Refrigerating and Air Conditioning Engineers, 2013) as the PD increases almost constantly with higher vertical air temperature gradients. The PD for the overall sensation increases by approximately 7% between gradients of 1 and 8 K/m. The evaluation of our own tests has revealed that vertical temperature gradients of up to 8 K/m or higher are likely to be acceptable for test subjects.

Cost-effectiveness-analysis of ultrasound guidance for central venous catheterization compared with landmark method: a decision-analytic model.

BACKGROUND: Ultrasound guidance for central venous catheterization is a commonly used alternative to the conventional landmark method. Because from the German perspective, the cost-effectiveness of ultrasound guidance is unclear, this study examined the cost-effectiveness of ultrasound guidance versus the landmark method for adults undergoing a central venous catheterization. METHODS: A decision-tree based model was built to estimate the costs of averted catheter-related complications. Clinical data (e.g. arterial puncture, failed attempts) were obtained from a Cochrane review and a randomized controlled trial, whilst information about cost parameters were taken from a German hospital of maximum care. The analysis was conducted from the perspective of the German Statutory Health Insurance. Results were presented as incremental cost-effectiveness ratios. To assess the parameter uncertainty, several sensitivity analyses were performed (deterministic, probabilistic and with regard to the model structure). RESULTS: Our analysis revealed that ultrasound guidance resulted in fewer complications per person (0.04 versus 0.17 for the landmark method) and was less expensive (€51 versus €230 for the landmark method). Results were robust to changes in the model parameters and in the model structure. Whilst our model population reflected approximately 49% of adults undergoing a central venous catheterization cannulation per year, structural sensitivity analyses (e.g. extending the study cohort to patients at higher baseline risk of complications, pediatric patients, or using real-time/indirect catheterization) indicated the cost-effectiveness of ultrasound guidance for a broader spectrum of patients. The results should be interpreted by considering the assumptions (e.g. target population) and approximations (e.g. cost parameters) underpinning the model. CONCLUSIONS: Ultrasound guidance for central venous catheterization averts more catheter-related complications and may save the resources of the German Statutory Health Insurance compared with landmark method.

Knowledge-based iterative reconstructions for imaging of coronary artery stents: first in-vitro experience and comparison of different radiation dose levels and kernel settings.

BACKGROUND: Advanced knowledge-based iterative model reconstructions (IMR) became recently available for routine computed tomography (CT). Using more realistic physical models it promises improved image quality and potential radiation dose reductions, both possibly beneficial for non-invasive assessment of coronary stents. PURPOSE: To evaluate the influence of different IMR settings at different radiation doses on stent lumen visualization in comparison to filtered back projection (FBP) and first-generation (hybrid) iterative reconstruction (HIR). MATERIAL AND METHODS: Ten coronary stents in a coronary phantom were examined at four different dose settings (120 kV/125 mAs, 120 kV/75 mAs, 100 kV/125 mAs, 100 kV/75 mAs). Images were reconstructed with stent-specific FBP and HIR kernels and with IMR using CardiacRoutine (CR) and CardiacSharp (CS) settings at three different iteration levels. Image quality was evaluated using established parameters: image noise; in-stent attenuation difference; and visible lumen diameter. RESULTS: Image noise was significantly lower in IMR than in corresponding HIR and FBP images. At lower radiation doses, image noise increased significantly except with IMR CR3 and IMR CS3. Visible lumen diameters were significantly larger with IMR CS than with FBP, HIR, and IMR CR. IMR CR showed the smallest attenuation difference, while attenuation was artificially decreased extensively with IMR CS. FBP and HIR showed moderately increased in-stent attenuations. No relevant influence of used radiation doses on visible lumen diameters or attenuation differences was found. CONCLUSION: IMR CR reduces image noise significantly while offering comparable stent-specific image quality in comparison to FBP and HIR and therefore potentially facilitates stent lumen delineation. Utilization of IMR CS for stent evaluation seems unfavorable due to artificial image alterations.

No association of goal-directed and habitual control with alcohol consumption in young adults.

Alcohol dependence is a mental disorder that has been associated with an imbalance in behavioral control favoring model-free habitual over model-based goal-directed strategies. It is as yet unknown, however, whether such an imbalance reflects a predisposing vulnerability or results as a consequence of repeated and/or excessive alcohol exposure. We, therefore, examined the association of alcohol consumption with model-based goal-directed and model-free habitual control in 188 18-year-old social drinkers in a two-step sequential decision-making task while undergoing functional magnetic resonance imaging before prolonged alcohol misuse could have led to severe neurobiological adaptations. Behaviorally, participants showed a mixture of model-free and model-based decision-making as observed previously. Measures of impulsivity were positively related to alcohol consumption. In contrast, neither model-free nor model-based decision weights nor the trade-off between them were associated with alcohol consumption. There were also no significant associations between alcohol consumption and neural correlates of model-free or model-based decision quantities in either ventral striatum or ventromedial prefrontal cortex. Exploratory whole-brain functional magnetic resonance imaging analyses with a lenient threshold revealed early onset of drinking to be associated with an enhanced representation of model-free reward prediction errors in the posterior putamen. These results suggest that an imbalance between model-based goal-directed and model-free habitual control might rather not be a trait marker of alcohol intake per se.

[Checklist for the Development and Assessment of Cost-of-Illness Studies]. / Checkliste zur Erstellung und Bewertung von Krankheitskostenstudien.

BACKGROUND: Cost-of-illness (CoI) studies are important instruments for estimating the socioeconomic burden of specified diseases. CoI studies provide important information about the cost structure of a disease, the resulting research need, approaches to improve aspects of care and, monetary consequences from different perspectives. This information can be useful for healthcare research and health policy. Due to heterogeneity of available Cost-of-Illness studies, the working group 'Health Economics' of the German Network for Healthcare Research (DNVF) in accordance with the German Society for Health Economics (DGGÖ) developed an instrument for the planning, conduct and assessment of CoI studies. METHODS: The checklist was developed based on a systematic literature search of published national and international checklists as well as guidelines and recommendations for development and assessment of CoI studies and health economic evaluations. Structure and subject matter of the generic checklist was designed, approved and, finally, examined in a pretest by the working group. RESULTS: Based on the results of the literature search (n=2 454), 58 articles were used for the identification of relevant criteria for the checklist. With respect to the results of the pretest, 6 dimensions were included in the checklist: (i) general aspects, (ii) identification of resources, (iii) description and quantification of resource consumption, (iv) valuation of resources (v) analysis and presentation of results and (vi) discussion and conclusion. In total, the 6 dimensions were operationalized through 37 items. CONCLUSION: This checklist is an initial approach to improve transparency and understanding of CoI studies in terms of the extent, structure and development of the socioeconomic burden of diseases. The checklist supports the comparability of different studies and facilitates study conception.

Atrial electrogram quality in single-pass defibrillator leads with floating atrial bipole in patients with permanent atrial fibrillation and cardiac resynchronization therapy.

Many patients receiving cardiac resynchronization therapy (CRT) suffer from permanent atrial fibrillation (AF). Knowledge of the atrial rhythm is important to direct pharmacological or interventional treatment as well as maintaining AV-synchronous biventricular pacing if sinus rhythm can be restored. A single pass single-coil defibrillator lead with a floating atrial bipole has been shown to obtain reliable information about the atrial rhythm but has never been employed in a CRT-system. The purpose of this study was to assess the feasibility of implanting a single coil right ventricular ICD lead with a floating atrial bipole and the signal quality of atrial electrograms (AEGM) in CRT-defibrillator recipients with permanent AF. METHODS AND RESULTS: Seventeen patients (16 males, mean age 73 ±â€¯6 years, mean EF 25 ±â€¯5%) with permanent AF and an indication for CRT-defibrillator placement were implanted with a designated CRT-D system comprising a single pass defibrillator lead with a atrial floating bipole. They were followed-up for 103 ±â€¯22 days using remote monitoring for AEGM transmission. All patients had at last one AEGM suitable for atrial rhythm diagnosis and of 100 AEGM 99% were suitable for visual atrial rhythm assessment. Four patients were discharged in sinus rhythm and one reverted to AF during follow-up. CONCLUSION: Atrial electrograms retrieved from a single-pass defibrillator lead with a floating atrial bipole can be reliably used for atrial rhythm diagnosis in CRT recipients with permanent AF. Hence, a single pass ventricular defibrillator lead with a floating bipole can be considered in this population.

Patient education in osteoporosis prevention: a systematic review focusing on methodological quality of randomised controlled trials.

This review summarizes evidence regarding the effects of patient education in osteoporosis prevention and treatment. The included studies reveal mixed results on a variety of endpoints. Methodological improvem ent of future RCTs (e.g. with regard to randomization and duration of follow-up) might yield more conclusive evidence on the effects of patient education in osteoporosis INTRODUCTION: This review aims to evaluate the effects of patient education on osteoporosis prevention and treatment results. METHODS: Multiple databases including PubMed and Embase were searched until February 2016. Randomised controlled trials (RCTs) were eligible if they included adults diagnosed with or at risk of osteoporosis and assessed patient education interventions (group- or individual-based). Outcomes regarding osteoporosis management including initiation of and adherence to pharmacological therapy, physical activity, calcium and vitamin D intake, changes in smoking behaviour, fractures, quality of life (QoL) and osteoporosis knowledge were evaluated. The Cochrane collaboration's tool for assessing the risk of bias was used to assess the internal validity of included trials. RESULTS: Fifteen articles (13 different studies) published between 2001 and 2013 were included (group-based education = 7, individual-based education = 5, both = 1). The general risk of bias was considered as moderate to high. The effects on 'bone mineral density (BMD) testing and/or pharmacological therapy' (composite endpoint), 'calcium intake' and 'vitamin D intake' as well as 'osteoporosis knowledge' were statistically significant in favour of the intervention in ≥50% of the studies analysing these outcomes. Differences between the intervention and the control group regarding 'pharmacological therapy', 'medication adherence', 'physical activity', 'fractures' and 'QoL' were found to be statistically significant in <50% of the trials. CONCLUSIONS: This review indicates that it is still unclear whether patient education is beneficial and whether it has a significant and clinically relevant impact on osteoporosis management results. Educational programmes for osteoporosis require further investigation within the context of well-conducted RCTs.

Economic evaluation of chronic lymphocytic leukemia from a hospital management perspective.

OBJECTIVES: Treatment of chronic lymphocytic leukemia (CLL) is currently undergoing dramatic changes. We analyzed economic risks in hospitalized patients with CLL from a management perspective. METHODS: One hundred and twelve patients with CLL hospitalized in 2013 and 2014 at the University Hospital of Cologne were analyzed. To assess profit margins (PMs) per case, diagnosis-related group (DRG) reimbursement data were merged with an internal cost accounting scheme depending on age, prognostic factors, and DRG key performance indicators. RESULTS: In 112 patients, 284 cases coded by 19 different DRG with strongly fluctuating cost revenue ratios were found with an overall negative PM of €137 147. The DRG R61H was identified as the one most commonly coded (174 cases, 61.3%) with a deficit per case of €814. Subanalysis demonstrated that the payments were not cost covering due to excessive length of stay and staff costs. Significant differences in PM per case concerning age, length of stay and number of operation and procedure key (OPS) codes (P < 0.05) were found. CONCLUSION: In our research-driven tertiary care hospital, inpatient treatment of patients with CLL is not cost covering. This analysis demonstrates the need for novel care/reimbursement structures in CLL. From a hospital management perspective, cost revenue controlling is crucial to avoid major economic risks.

In vivo analysis of coracoid and subacromial shoulder impingement mechanism during clinical examination.

BACKGROUND: Understanding the mechanisms of shoulder impingement created by clinical tests is crucial to accurately evaluate the condition. The objective of this study was to relate mechanisms of subacromial and coracoid impingement occurring in positions of the shoulder during clinical examination, in quantitative and qualitative terms. METHODS: A 1.0T open magnetic resonance imaging system was used in 18 female and 19 male subjects, to determine the distances between the humeral head and the acromion or coracoid, and contact with the rotator cuff (RC). Measurements were taken with the shoulder in neutral, "Hawkins", "Neer", and 90° abduction/15° internal rotation (horizontal impingement test) positions. Additionally, impingement was classified based on the grade of RC contact with the acromion or coracoid. RESULTS: In the Hawkins position, distance between the supraspinatus and the coracoid was closest (14.5 ± 4.5 mm), while the coracohumeral distance (CHD) narrowed (p < 0.001). In the horizontal impingement test position, the minimum distance between the subscapularis and coracoid was found, whereas the CHD increased (27.4 ± 5.7 mm). In the Neer and Hawkins positions, the space between the greater tuberosity and acromion was significantly narrowed, which was also the case in the horizontal impingement test position compared to neutral position (p < 0.001). CONCLUSION: Shoulder movements of forward flexion and internal rotation (Hawkins test) and abduction and internal rotation (horizontal impingement test) can lead to different coracoid impingement mechanisms during clinical examination. The Hawkins, Neer, and horizontal impingement tests lead to comparable narrowed acromiohumeral distances and subacromial contact of the RC. LEVEL OF EVIDENCE: Therapeutic level III.

Preserved white matter microstructure in young patients with anorexia nervosa?

A massive but reversible reduction of cortical thickness and subcortical gray matter (GM) volumes in Anorexia Nervosa (AN) has been recently reported. However, the literature on alterations in white matter (WM) volume and microstructure changes in both acutely underweight AN (acAN) and after recovery (recAN) is sparse and results are inconclusive. Here, T1-weighted and diffusion-weighted MRI data in a sizable sample of young and medication-free acAN (n = 35), recAN (n = 32), and age-matched female healthy controls (HC, n = 62) were obtained. For analysis, a well-validated global probabilistic tractography reconstruction algorithm including rigorous motion correction implemented in FreeSurfer: TRACULA (TRActs Constrained by UnderLying Anatomy) were used. Additionally, a clustering algorithm and a multivariate pattern classification technique to WM metrics to predict group membership were applied. No group differences in either WM volume or WM microstructure were detected with standard analysis procedures either in acAN or recAN relative to HC after controlling for the number of performed statistical tests. These findings were not affected by age, IQ, or psychiatric symptoms. While cluster analysis was unsuccessful at discriminating between groups, multivariate pattern classification showed some ability to separate acAN from HC (but not recAN from HC). However, these results were not compatible with a straightforward hypothesis of impaired WM microstructure. The current findings suggest that WM integrity is largely preserved in non-chronic AN. This finding stands in contrast to findings in GM, but may help to explain the relatively intact cognitive performance of young patients with AN and provide the basis for the fast recovery of GM structures. Hum Brain Mapp 37:4069-4083, 2016. © 2016 Wiley Periodicals, Inc.

Limitations of N-Terminal Pro-B-Type Natriuretic Peptide in the Diagnosis of Heart Disease among Cancer Patients Who Present with Cardiac or Pulmonary Symptoms.

OBJECTIVES: Recognizing heart disease is relevant to oncologists because cancer patients are at an increased risk of cardiac mortality due to shared risk factors and the adverse effects of cancer therapy. This study assessed the extent to which the measurement of N-terminal pro-B-type natriuretic peptide (NT-proBNP) aids in the diagnosis of heart disease in addition to a history of coronary artery disease and the presence of atrial fibrillation (composite test). The NT- proBNP cutoff value was 100 pg/ml. METHODS: A series of 583 consecutive cancer patients (68.4 ± 11.0 years) who were referred because of cardiac or pulmonary symptoms prospectively underwent a diagnostic work-up. Heart disease was diagnosed if at least one of the following conditions was present: (a) history of coronary artery disease, (b) atrial fibrillation, (c) impaired left ventricular systolic function, (d) significant valvular disease, (e) pulmonary hypertension, or (f) left ventricular hypertrophy. RESULTS: Except for (a), all 6 conditions were associated with NT-proBNP >100 pg/ml. The sensitivity/specificity values of the composite test were 0.92/0.50 for any heart disease. Several extracardiac covariates were associated with NT-proBNP >100 pg/ml, which contributed to the low test specificity. CONCLUSIONS: The low specificity of NT-proBNP limits its value for the diagnosis of heart disease in cancer patients.

A hybrid approach identifies metabolic signatures of high-producers for chinese hamster ovary clone selection and process optimization.

In-depth characterization of high-producer cell lines and bioprocesses is vital to ensure robust and consistent production of recombinant therapeutic proteins in high quantity and quality for clinical applications. This requires applying appropriate methods during bioprocess development to enable meaningful characterization of CHO clones and processes. Here, we present a novel hybrid approach for supporting comprehensive characterization of metabolic clone performance. The approach combines metabolite profiling with multivariate data analysis and fluxomics to enable a data-driven mechanistic analysis of key metabolic traits associated with desired cell phenotypes. We applied the methodology to quantify and compare metabolic performance in a set of 10 recombinant CHO-K1 producer clones and a host cell line. The comprehensive characterization enabled us to derive an extended set of clone performance criteria that not only captured growth and product formation, but also incorporated information on intracellular clone physiology and on metabolic changes during the process. These criteria served to establish a quantitative clone ranking and allowed us to identify metabolic differences between high-producing CHO-K1 clones yielding comparably high product titers. Through multivariate data analysis of the combined metabolite and flux data we uncovered common metabolic traits characteristic of high-producer clones in the screening setup. This included high intracellular rates of glutamine synthesis, low cysteine uptake, reduced excretion of aspartate and glutamate, and low intracellular degradation rates of branched-chain amino acids and of histidine. Finally, the above approach was integrated into a workflow that enables standardized high-content selection of CHO producer clones in a high-throughput fashion. In conclusion, the combination of quantitative metabolite profiling, multivariate data analysis, and mechanistic network model simulations can identify metabolic traits characteristic of high-performance clones and enables informed decisions on which clones provide a good match for a particular process platform. The proposed approach also provides a mechanistic link between observed clone phenotype, process setup, and feeding regimes, and thereby offers concrete starting points for subsequent process optimization. Biotechnol. Bioeng. 2016;113: 2005-2019. © 2016 Wiley Periodicals, Inc.