Cost Estimates for Human Immunodeficiency Virus (HIV) Care and Patient Characteristics for Health Resource Use From Linkage of Claims Data With the Swiss HIV Cohort Study.

BACKGROUND: Comprehensive and representative data on resource use are critical for health policy decision making but often lacking for human immunodeficiency virus (HIV) infection. Privacy-preserving probabilistic record linkage of claim and cohort study data may overcome these limitations. METHODS: Encrypted dates of birth, sex, study center, and antiretroviral therapy (ART) from the Swiss HIV Cohort Study (SHCS) records for 2012 and 2013 were linked by privacy-preserving probabilistic record linkage with claim data from the largest health insurer covering 15% of the Swiss residential population. We modeled predictors for mean annual costs adjusting for censoring and grouped patients by cluster analysis into 3 risk groups for resource use. RESULTS: The matched subsample of 1196 patients from 9326 SHCS and 2355 claim records was representative for all SHCS patients receiving ART. The corrected mean (standard error) total costs in 2012 and 2013 were $30462 ($582) and $30965 ($629) and mainly accrued in ambulatory care for ART (70% of mean costs). The low-risk group for resource use had mean (standard error) annual costs of $26772 ($536) and $26132 ($589) in 2012 and 2013. In the moderate- and high-risk groups, annual costs for 2012 and 2013 were higher by $3526 (95% confidence interval, $1907-$5144) (13%) and $4327 ($2662-$5992) (17%) and $14026 ($8763-$19289) (52%) and $13567 ($8844-$18288) (52%), respectively. CONCLUSIONS: In a representative subsample of patients from linkage of SHCS and claim data, ART was the major cost factor, but patient profiling enabled identification of factors related to higher resource use.

Effect of E-Bike Versus Bike Commuting on Cardiorespiratory Fitness in Overweight Adults: A 4-Week Randomized Pilot Study.

OBJECTIVE: To assess if active commuting with an electrically assisted bicycle (e-bike) during a 4-week period can induce increases in cardiorespiratory fitness measured as peak oxygen uptake (V[Combining Dot Above]O2peak) in untrained, overweight individuals, and if these changes are comparable with those induced by a conventional bicycle. DESIGN: Four-week randomized pilot study. SETTING: Controlled laboratory. PARTICIPANTS: Thirty-two volunteers (28 men) participated. Seventeen {median age 37 years [interquartile range (IQR) 34, 45], median body mass index [BMI] 29 kg/m [IQR 27, 31]} were randomized to the E-Bike group and 15 [median age 43 years (IQR 38, 45), median BMI 28 kg/m (IQR 26, 29)] to the Bike group. INTERVENTIONS: Participants in both groups were instructed to use the bicycle allocated to them (e-bike or conventional bicycle) for an active commute to work in the Basel (Switzerland) area at a self-chosen speed on at least 3 days per week during the 4-week intervention period. MAIN OUTCOME MEASURES: V[Combining Dot Above]O2peak was assessed before and after the intervention in an all-out exercise test on a bicycle ergometer. RESULTS: V[Combining Dot Above]O2peak increased by an average of 3.6 mL/(kg·min) [SD 3.6 mL/(kg·min)] in the E-Bike group and by 2.2 mL/(kg·min) [SD 3.5 mL/(kg·min)] in the Bike group, with an adjusted difference between the 2 groups of 1.4 mL/(kg·min) [95% confidence interval, -1.4-4.1; P = 0.327]. CONCLUSIONS: E-bikes may have the potential to improve cardiorespiratory fitness similar to conventional bicycles despite the available power assist, as they enable higher biking speeds and greater elevation gain.

High prevalence of physical inactivity among patients from the Swiss HIV Cohort Study.

Physical activity (PA) can improve cardiorespiratory status, strength, body composition and quality of life for patients infected with HIV. Evidence from HIV-uninfected populations also shows that PA is associated with a lower risk of mortality, primarily death due to cardiovascular causes. There is, however, a lack of data on how physically active HIV-infected patients are. In this study, we assessed levels of self-reported PA over time in patients enrolled in the Swiss HIV Cohort Study, a large multicentre prospective observational cohort study. We included a total of 10,540 patients who completed at least one report of PA between December 2009 and November 2014 during routine clinical follow-up (scheduled every 6 months). In the first year after December 2009 there was a higher rate of non-response so these data are of a lesser reliability. Over the next four years, the percentage of patients reporting no free-time PA at all declined from 49% to 44%. In contrast, in two "Sport Switzerland" surveys of the general population in 2008 and 2014, the percentage of individuals reporting no sports activities at all was considerably lower and relatively stable over time (27% in 2008; 26% in 2014). In our analysis, the percentage of patients reporting sedentary activity at work increased from 23% to 26% over the four years. Subgroup findings suggest differences between women and men and between patients classified by their age, stage of infection and CD4 cell count. Integrating PA counselling into the routine care of HIV-infected patients and promoting PA among this population has the potential to improve the general state of health and quality of life for HIV-infected patients and reduce their risk of cardiovascular disease.

Colon Perfusion Patterns During Colorectal Resection Using Visible Light Spectroscopy.

BACKGROUND: The impact of blood supply to the anastomosis on development of anastomotic leakage is still a matter of debate. Considering that bowel perfusion may be affected by manipulation during surgery, perfusion assessment of the anastomosis alone may be of limited value. We propose perfusion assessment at different time points during surgery to explore the dynamics of bowel perfusion during colorectal resection and its impact on outcome. METHODS: In this prospective cohort study, patients undergoing elective colorectal resection were eligible. Colon perfusion was evaluated using visible light spectroscopy. Main outcome was the difference in colon perfusion, quantified by measuring tissue oxygen saturation (StO2) in the colonic serosa, before and after anastomosis during surgery. RESULTS: We included 58 patients between July 2013 and November 2015. Colon perfusion increased by an average of 5.9% StO2 during surgery (95% confidence interval 3.1, 8.8; P < 0.001). The number of patients with abnormal perfusion (defined as StO2 < 65%) decreased from 50% at the beginning to 24% by the end of surgery. Six patients (10%) developed anastomotic leaks (AL), of which five patients had abnormal perfusion at the beginning of surgery, whereas four patients had normal StO2 at the anastomosis. CONCLUSION: Colon perfusion significantly increased during colorectal surgery. Considering that one quarter of patients had suboptimal anastomotic perfusion without developing AL, impaired blood flow at the anastomosis alone does not seem to be critical. Further investigations including more patients are necessary to evaluate the impact of perioperative parameters on colon perfusion, anastomotic healing and surgical outcome.

Effects of bright and blue light on acoustic reaction time and maximum handgrip strength in male athletes: a randomized controlled trial.

PURPOSE: To assess which type of evening light exposure has the greatest effect on reaction time and maximum handgrip strength. These were pre-specified secondary outcomes in a trial which primarily investigated the influence of light on cycling performance. METHODS: Seventy-four male athletes were allocated at random to either bright light (BRIGHT), monochromatic blue light (BLUE), or a control condition (CONTROL). Light exposure lasted for 60 min and started 17 h after the individual midpoint of sleep. Reaction time, handgrip strength, and melatonin levels were measured before and after the light exposure. We used analysis of covariance to compare the groups with respect to the investigated outcomes. RESULTS: Two participants had to be excluded retrospectively. The remaining 72 participants had a median age of 23 years. The adjusted difference in reaction time was -1 ms [95% confidence interval (CI) -8, 6] for participants in BRIGHT and 2 ms (95% CI -5, 9) for participants in BLUE, both relative to participants in CONTROL. The adjusted difference in handgrip strength was 0.9 kg (95% CI -1.5, 3.3) for participants in BRIGHT and -0.3 kg (95% CI -2.7, 2.0) for participants in BLUE, both relative to participants in CONTROL. After the light exposure, 17% of participants in BRIGHT, 22% in BLUE, and 29% in CONTROL showed melatonin concentrations of 2 pg/ml or higher. CONCLUSIONS: The results suggest that bright light might reduce melatonin levels but neither bright nor blue light exposure in the evening seem to improve reaction time or handgrip strength in athletes.

Surgery for ischemic colitis: outcome and risk factors for in-hospital mortality.

PURPOSE: Surgery for ischemic colitis is associated with high perioperative morbidity and mortality, but the risk factors for mortality and major surgical complications are unclear. METHODS: In this retrospective single institution cohort study of all patients undergoing colorectal surgery for histologically proven ischemic colitis between 2004 and 2010, we evaluated surgical outcomes and risk factors for in-hospital mortality and major surgical complications. RESULTS: For the 100 patients included in the study, in-hospital mortality was 54 %; major surgical complications, defined as anastomotic leakage or rectal stump and stoma complications, occurred in 16 %. In the multivariable analysis, hospital death was more likely in patients with right-sided (odds ratio [OR] 3.8; 95 % confidence interval [CI] 1.2, 12; P = 0.022) or pan-colonic ischemia (OR 11; 95 % CI 2.8, 39; P < 0.001), both relative to left-sided ischemia. Decreased preoperative pH level (OR 2.5 per 0.1 decrease; 95 % CI 1.5, 4.1; P < 0.001) and prior cardiac or aortic surgery (OR 2.4; 95 % CI 0.82, 6.8; P = 0.109) were further important risk factors for in-hospital mortality. Major postoperative surgical complications were more likely in patients with ischemic alterations at the resection margin of the histological specimen (OR 3.7; 95 % CI 1.2, 11; P = 0.022). CONCLUSIONS: Colonic resection for ischemic colitis is associated with high in-hospital mortality, especially in patients with right-sided or pan-colonic ischemia. In patients developing acidosis, early laparotomy is essential. Since resection margins' affection seems to be underestimated upon surgery, resections should be performed wide enough within healthy tissue.

Personality traits and virtual reality performance.

BACKGROUND: Surgeons' personalities have been described as different from those of the general population, but this was based on small descriptive studies limited by the choice of evaluation instrument. Furthermore, although the importance of the human factor in team performance has been recognized, the effect of personality traits on technical performance is unknown. This study aimed to compare surgical residents' personality traits with those of the general population and to evaluate whether an association exists between their personality traits and technical performance using a virtual reality (VR) laparoscopy simulator. METHODS: In this study, 95 participants (54 residents with basic, 29 with intermediate laparoscopic experience, and 12 students) underwent personality assessment using the NEO-Five Factor Inventory and performed five VR tasks of the Lap Mentor™ basic tasks module. The residents' personality traits were compared with those of the general population, and the association between VR performance and personality traits was investigated. RESULTS: Surgical residents showed personality traits different from those of the general population, demonstrating lower neuroticism, higher extraversion and conscientiousness, and male residents showed greater openness. In the multivariable analysis, adjusted for gender and surgical experience, none of the personality traits was found to be an independent predictor of technical performance. CONCLUSIONS: Surgical residents present distinct personality traits that differ from those of the general population. These traits were not found to be associated with technical performance in a virtual environment. The traits may, however, play an important role in team performance, which in turn is highly relevant for optimal surgical performance.

Impact of an intensive 2-day endovascular training course on technical performance of trainees.

BACKGROUND: The objective of this study was to evaluate the effect of a 2-day international endovascular training course on the performance of trainees as compared with a control group, assessed in a bench model-based task using an objective structured evaluation protocol. METHODS: A total of 50 trainees, 28 course participants of 2 consecutive identical courses and a control group of 22 participants with a similar level of experience without course attendance, underwent baseline and final assessment (simulated arterial access task). The evaluation form consisted of a global assessment (GA), task-specific checklist percentage score (CL), and global rating scale percentage score (GR), with both percentage scores ranging from 0% (worst performance) to 100% (best performance). RESULTS: Course participants were more likely to pass the GA at final testing than the control group (odds ratio=59; 95% confidence interval [CI] 9.5-656; P<0.001). The estimated difference in percentage score at final testing between course participants and the control group was 26% (95% CI 18-34; P<0.001) for the CL and 29% (95% CI 19-40; P<0.001) for the GR. CONCLUSIONS: A 2-day structured endovascular training course significantly improves endovascular performance in a simulated environment. These results are important for the design of endovascular training curricula with the ultimate goal of contributing to patient safety.

Improved detection of microbial ureteral stent colonisation by sonication.

PURPOSE: The diagnosis of microbial ureteral stent colonisation (MUSC) is difficult, since routine diagnostic techniques do not accurately detect microorganisms embedded in biofilms. New methods may improve diagnostic yield and understanding the pathophysiology of MUSC. The aim of the present study was to evaluate the potential of sonication in the detection of MUSC and to identify risk factors for device colonisation. METHODS: Four hundred and eight polyurethane ureteral stents of 300 consecutive patients were prospectively evaluated. Conventional urine culture (CUC) was obtained prior to stent placement and device removal. Sonication was performed to dislodge adherent microorganisms. Data of patient sex and age, indwelling time and indication for stent placement were recorded. RESULTS: Sonicate-fluid culture detected MUSC in 36%. Ureteral stents inserted during urinary tract infection (UTI) were more frequently colonised (59%) compared to those placed in sterile urine (26%; P<0.001). Female sex (P<0.001) and continuous stenting (P<0.005) were significant risk factors for MUSC; a similar trend was observed in patients older than 50 years (P=0.16). MUSC and indwelling time were positively correlated (P<0.005). MUSC was accompanied by positive CUC in 36%. Most commonly isolated microorganisms were Coagulase-negative staphylococci (18.3%), Enterococci (17.9%) and Enterobacteriaceae (16.9%). CONCLUSIONS: Sonication is a promising approach in the diagnosis of MUSC. Significant risk factors for MUSC are UTI at the time of stent insertion, female sex, continuous stenting and indwelling time. CUC is a poor predictor of MUSC. The clinical relevance of MUSC needs further evaluation to classify isolated microorganism properly as contaminants or pathogens.

Transient ischemic attack versus transient ischemic attack mimics: frequency, clinical characteristics and outcome.

BACKGROUND: There is insufficient evidence regarding which clinical features are best suited to distinguish between transient ischemic attack (TIA) and disorders mimicking TIA (TIA mimics). METHODS: We compared the frequency, clinical characteristics and outcome of patients with TIA and TIA mimics in a prospective, single-center emergency department cohort over 2 years. RESULTS: Of 303 patients, 248 (81.8%) had a TIA and 55 (18.2%) had TIA mimics. Epileptic seizures (26/55; 43.7%) and migraine attacks (13/55; 23.6%) were the most common TIA mimics. In patients presenting with unilateral paresis, TIA mimics were less likely than in patients without unilateral paresis [odds ratio (OR) 0.35, 95% confidence interval (CI) 0.17-0.68]. Memory loss (OR 9.17, 95% CI 2.89-32.50), headache (OR 3.71, 95% CI 1.07-12.78) and blurred vision (OR 2.48, 95% CI 0.90-6.59) increased the odds of TIA mimics. Once these clinical features were taken into account, neither aphasia, dysarthria, sensory loss, blood pressure values nor the duration of symptoms were found to improve explanation of the underlying status. At 3 months, stroke, recurrent TIA and myocardial infarction were absent in patients with TIA mimics but occurred in 13 (5.2%), 20 (8.1%) and 3 (1.2%) TIA patients, respectively. CONCLUSIONS: About 1 in every 5 patients with suspected TIA had a TIA mimic. Paresis suggested TIA, while other clinical variables used in risk assessment scores after TIA were not shown to distinguish between the two entities. Patients with TIA mimics had a better short-term prognosis.

Video gaming in children improves performance on a virtual reality trainer but does not yet make a laparoscopic surgeon.

BACKGROUND: In children, video game experience improves spatial performance, a predictor of surgical performance. This study aims at comparing laparoscopic virtual reality (VR) task performance of children with different levels of experience in video games and residents. PARTICIPANTS AND METHODS: A total of 32 children (8.4 to 12.1 years), 20 residents, and 14 board-certified surgeons (total n = 66) performed several VR and 2 conventional tasks (cube/spatial and pegboard/fine motor). Performance between the groups was compared (primary outcome). VR performance was correlated with conventional task performance (secondary outcome). RESULTS: Lowest VR performance was found in children with low video game experience, followed by those with high video game experience, residents, and board-certified surgeons. VR performance correlated well with the spatial test and moderately with the fine motor test. CONCLUSIONS: The use of computer games can be considered not only as pure entertainment but may also contribute to the development of skills relevant for adequate performance in VR laparoscopic tasks. Spatial skills are relevant for VR laparoscopic task performance.

Targeted quantitative analysis of Streptococcus pyogenes virulence factors by multiple reaction monitoring.

In many studies, particularly in the field of systems biology, it is essential that identical protein sets are precisely quantified in multiple samples such as those representing differentially perturbed cell states. The high degree of reproducibility required for such experiments has not been achieved by classical mass spectrometry-based proteomics methods. In this study we describe the implementation of a targeted quantitative approach by which predetermined protein sets are first identified and subsequently quantified at high sensitivity reliably in multiple samples. This approach consists of three steps. First, the proteome is extensively mapped out by multidimensional fractionation and tandem mass spectrometry, and the data generated are assembled in the PeptideAtlas database. Second, based on this proteome map, peptides uniquely identifying the proteins of interest, proteotypic peptides, are selected, and multiple reaction monitoring (MRM) transitions are established and validated by MS2 spectrum acquisition. This process of peptide selection, transition selection, and validation is supported by a suite of software tools, TIQAM (Targeted Identification for Quantitative Analysis by MRM), described in this study. Third, the selected target protein set is quantified in multiple samples by MRM. Applying this approach we were able to reliably quantify low abundance virulence factors from cultures of the human pathogen Streptococcus pyogenes exposed to increasing amounts of plasma. The resulting quantitative protein patterns enabled us to clearly define the subset of virulence proteins that is regulated upon plasma exposure.

Regularized estimation of large-scale gene association networks using graphical Gaussian models.

BACKGROUND: Graphical Gaussian models are popular tools for the estimation of (undirected) gene association networks from microarray data. A key issue when the number of variables greatly exceeds the number of samples is the estimation of the matrix of partial correlations. Since the (Moore-Penrose) inverse of the sample covariance matrix leads to poor estimates in this scenario, standard methods are inappropriate and adequate regularization techniques are needed. Popular approaches include biased estimates of the covariance matrix and high-dimensional regression schemes, such as the Lasso and Partial Least Squares. RESULTS: In this article, we investigate a general framework for combining regularized regression methods with the estimation of Graphical Gaussian models. This framework includes various existing methods as well as two new approaches based on ridge regression and adaptive lasso, respectively. These methods are extensively compared both qualitatively and quantitatively within a simulation study and through an application to six diverse real data sets. In addition, all proposed algorithms are implemented in the R package "parcor", available from the R repository CRAN. CONCLUSION: In our simulation studies, the investigated non-sparse regression methods, i.e. Ridge Regression and Partial Least Squares, exhibit rather conservative behavior when combined with (local) false discovery rate multiple testing in order to decide whether or not an edge is present in the network. For networks with higher densities, the difference in performance of the methods decreases. For sparse networks, we confirm the Lasso's well known tendency towards selecting too many edges, whereas the two-stage adaptive Lasso is an interesting alternative that provides sparser solutions. In our simulations, both sparse and non-sparse methods are able to reconstruct networks with cluster structures. On six real data sets, we also clearly distinguish the results obtained using the non-sparse methods and those obtained using the sparse methods where specification of the regularization parameter automatically means model selection. In five out of six data sets, Partial Least Squares selects very dense networks. Furthermore, for data that violate the assumption of uncorrelated observations (due to replications), the Lasso and the adaptive Lasso yield very complex structures, indicating that they might not be suited under these conditions. The shrinkage approach is more stable than the regression based approaches when using subsampling.

The role of CRP and Pentraxin 3 in the prediction of systemic inflammatory response syndrome and death in acute pancreatitis.

Pentraxin 3 (PTX3) is an acute phase protein. Our goal was to assess PTX3 as a predictor of systemic inflammatory response syndrome (SIRS), death and disease severity in acute pancreatitis (AP) in comparison to C-reactive protein (CRP) and the APACHE II score. From April 2011 to January 2015, 142 patients with AP were included in this single center post hoc analysis of prospectively collected data at the University Hospital Basel, Switzerland. Disease severity was rated by the revised Atlanta criteria (rAC). Inflammatory response was measured by the SIRS criteria. PTX3, CRP and APACHE II score were measured. Patients median PTX3 plasma concentrations in AP were higher in moderate (3.311 ng/ml) and severe (3.091 ng/ml) than in mild disease (2.461 ng/ml). Overall, 59 occurrences of SIRS or death were observed. In the prediction of SIRS or death, PTX3 was inferior to CRP and APACHE II, with modest predictive discriminatory ability of all three markers and AUC of 0.54, 0.69 and 0.69, respectively. Upon combination of CRP with PTX3, AUC was 0.7. PTX3 seems to be inferior to CRP and APACHE II in the prediction of SIRS or death in AP and does not seem to improve the predictive value of CRP upon combination of both parameters.

Exercise, Arterial Crosstalk-Modulation, and Inflammation in an Aging Population: The ExAMIN AGE Study.

Background: Age is a key determinant for the development of cardiovascular disease and higher age coincides with an increased prevalence of obesity and physical inactivity. The study examines the influence of physical activity on aging processes of physiological systems focusing on the mechanisms of vascular aging. Methods/Design: The study consists of two parts. The cross-sectional approach aims at examining the association of physical fitness and cardiovascular risk with large and small artery function in healthy older active (HOA, n = 40) and sedentary (HOS, n = 40) persons as well as older sedentary individuals with increased cardiovascular risk (OSR, n = 80) aged 50-80 years. In the interventional approach, the OSR group is randomized into a 12-week walking-based high intensity interval training (HIIT) group or a control condition, aiming at examining the effects of HIIT on arterial function in diseased older adults. Active lifestyle is defined as >9 metabolic equivalent of task (MET) per week and sedentary as ≤3 MET/week. Inclusion criteria for OSR are overweight or obesity (body mass index ≥30 kg/m2) plus at least one additional cardiovascular risk factor. The primary outcome is arterial stiffness as determined by aortic pulse wave velocity (PWV). The secondary outcomes are retinal arterial and venous diameters. Further cardiovascular assessments include peripheral PWV, central haemodynamics, retinal endothelial function, carotid intima media thickness, cardiac strain and diastolic function as well as autonomic function and inflammation. Physical fitness is measured by a treadmill-based spiroergometry to determine peak oxygen uptake. Discussion: The aim of the study is to demonstrate the importance of and need for specific physical activity programs for seniors to achieve healthier aging as a long-term goal. Vascular function defines disease- and age-related end organ damage and represents the potential to contain health at older age. This research will identify cardiovascular biomarkers that best resemble underlying cardiovascular risk in age and disease. The integrated approach will help define new recommendations for treatment guidance of exercise therapy in an aging population. ClinicalTrials. gov: NCT02796976; registered 02 June 2016 (retrospectively registered).

Retinal Vessel Diameters and Physical Activity in Patients With Mild to Moderate Rheumatic Disease Without Cardiovascular Comorbidities.

Objectives: Low-grade systemic inflammation is responsible for atherosclerotic lesions in patients with rheumatic diseases. Vascular dysfunction is a precursor of atherosclerosis and can be improved by physical activity (PA). Our aim was to asses micro- and macrovascular function as well as PA and cardiorespiratory fitness (CRF) in patients with rheumatic diseases in the absence of cardiovascular (CV) comorbidities compared to controls. Methods: Fifty-one patients without CV comorbidities were compared to 35 controls. Retinal microvascular diameters were assessed using a Retinal Vessel Analyzer. Arterial stiffness (AST) was measured by applanation tonometry. CRF was assessed as peak oxygen consumption and PA was assessed with a questionnaire. Results: Retinal venular diameters were significantly wider in patients [median 221 µm (interquartile range (IQR) 211, 231)] compared to controls [median 215 µm (IQR 196, 223); p = 0.01]. One hour increase of PA per week led to a venular constriction of -0.56 µm (95%CI -1.09, -0.03; p = 0.04). In our patients with low disease activity (median DAS28 1.9; median BASDAI 2.8), no differences in AST were evident compared to controls. The association of PA and CRF with AST was not independent of blood pressure. Conclusions: Patients with rheumatic disease and mild-to-moderate disease activity show an impairment of the retinal microvasculature but not of large artery stiffness. Retinal vessel analysis seems to be a sensitive biomarker to unmask vascular impairments even in the absence of classic CV risk factors. PA may have the potential to counteract the development of small artery disease at early stages of rheumatic disease.

Cortisol Outperforms Novel Cardiovascular, Inflammatory, and Neurohumoral Biomarkers in the Prediction of Outcome in Acute Pancreatitis.

OBJECTIVES: The aims of this study were to assess whether copeptin, pro-atrial natriuretic peptide, proadrenomedullin, and cortisol are associated with disease severity in patients with acute pancreatitis (AP) and to compare their ability in predicting organ failure or death. METHODS: From April 2011 to January 2015, 142 patients with AP were included in this prospective single-center study and observed for 4 days. Disease severity was rated by the Atlanta 1992 and 2012 criteria and organ failure by the modified Marshall score. The aforementioned laboratory markers, C-reactive protein, and procalcitonin were measured. RESULTS: Patients with moderate to severe AP showed significantly higher plasma concentrations of all biomarkers than did those with mild AP. Overall, 30 organ failures or deaths occurred. All biomarkers except cortisol had only modest discriminatory ability, with areas under the receiver operating characteristic curve (AUCs) between 0.44 and 0.66. Cortisol showed an AUC of 0.78 compared with the Acute Physiology and Chronic Health Evaluation II score with an AUC of 0.75. CONCLUSIONS: Cortisol was the best predictor of organ failure or death. All biomarkers were associated with disease severity to a similar degree as C-reactive protein, the criterion-standard marker in AP. Further studies are warranted to define their clinical role.

Living with an imperfect cell wall: compensation of femAB inactivation in Staphylococcus aureus.

BACKGROUND: Synthesis of the Staphylococcus aureus peptidoglycan pentaglycine interpeptide bridge is catalyzed by the nonribosomal peptidyl transferases FemX, FemA and FemB. Inactivation of the femAB operon reduces the interpeptide to a monoglycine, leading to a poorly crosslinked peptidoglycan. femAB mutants show a reduced growth rate and are hypersusceptible to virtually all antibiotics, including methicillin, making FemAB a potential target to restore beta-lactam susceptibility in methicillin-resistant S. aureus (MRSA). Cis-complementation with wild type femAB only restores synthesis of the pentaglycine interpeptide and methicillin resistance, but the growth rate remains low. This study characterizes the adaptations that ensured survival of the cells after femAB inactivation. RESULTS: In addition to slow growth, the cis-complemented femAB mutant showed temperature sensitivity and a higher methicillin resistance than the wild type. Transcriptional profiling paired with reporter metabolite analysis revealed multiple changes in the global transcriptome. A number of transporters for sugars, glycerol, and glycine betaine, some of which could serve as osmoprotectants, were upregulated. Striking differences were found in the transcription of several genes involved in nitrogen metabolism and the arginine-deiminase pathway, an alternative for ATP production. In addition, microarray data indicated enhanced expression of virulence factors that correlated with premature expression of the global regulators sae, sarA, and agr. CONCLUSION: Survival under conditions preventing normal cell wall formation triggered complex adaptations that incurred a fitness cost, showing the remarkable flexibility of S. aureus to circumvent cell wall damage. Potential FemAB inhibitors would have to be used in combination with other antibiotics to prevent selection of resistant survivors.

Mobile Exergaming for Health-Effects of a serious game application for smartphones on physical activity and exercise adherence in type 2 diabetes mellitus-study protocol for a randomized controlled trial.

BACKGROUND: Exergaming is a novel approach to increase motivation for regular physical activity (PA) among sedentary individuals such as patients with type 2 diabetes mellitus (T2DM). Because existing exergames do not offer fitness-level adjusted, individualized workouts and are normally stationary (TV bound), thus not enabling PA anywhere and at any time, we developed a smartphone-based, game-like software application (MOBIGAME) specifically designed for middle-aged T2DM patients to induce a healthier, more active lifestyle as part of successful T2DM treatment and management. In a randomized controlled trial we aim to examine whether our smartphone-based game application can lead to increases in daily PA in T2DM patients that are persistent in the mid to long term and whether these increases are greater than those in a control group. METHODS: This study is designed as a randomized controlled trial. We plan to recruit a total of 42 T2DM patients [45-70 years, body mass index (BMI) ≥25 kg/m2, low daily PA, regular smartphone use]. The experimental intervention (duration 24 weeks) includes individualized multidimensional home-based exercise and daily PA promotion administered through MOBIGAME. The control intervention consists of a one-time standard lifestyle counseling including the promotion of baseline activities. The primary outcome is daily PA measured as steps per day. Secondary outcome is exercise adherence measured via the usage data from the participants' smartphones (experimental intervention) and as self-recorded exercise log entries (control intervention). We will test the hypothesis that there will be differences between the experimental and control group with respect to post-interventional daily PA (as well as all other outcomes) using analysis of covariance. For each analysis, an estimate (with 95% confidence interval) of the difference in outcome between both groups will be reported. DISCUSSION: This research will investigate the effectiveness of a novel smartphone-based, game-like software application to be used as a way to promote regular daily PA among inactive T2DM patients. The results of this trial may have important implications for future PA-promoting interventions and provide relevant information for the general transferability of such applications to be used as part of the treatment in other chronic diseases. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02657018 . Registered on 11 January 2016. Last status update on 3 May 2016. Kofam.ch, SNCTP-number:SNCTP000001652. Registered on 21 January 2016.

Prime Time Light Exposures Do Not Seem to Improve Maximal Physical Performance in Male Elite Athletes, but Enhance End-Spurt Performance.

Many sports competitions take place during television prime time, a time of the day when many athletes have already exceeded their time of peak performance. We assessed the effect of different light exposure modalities on physical performance and melatonin levels in athletes during prime time. Seventy-two young, male elite athletes with a median (interquartile range) age of 23 (21; 29) years and maximum oxygen uptake (VO2max) of 63 (58; 66) ml/kg/min were randomly assigned to three different light exposure groups: bright light (BRIGHT), blue monochromatic light (BLUE), and control light (CONTROL). Each light exposure lasted 60 min and was scheduled to start 17 h after each individual's midpoint of sleep (median time: 9:17 pm). Immediately after light exposure, a 12-min time trial was performed on a bicycle ergometer. The test supervisor and participants were blinded to the light condition each participant was exposed to. The median received light intensities and peak wavelengths (photopic lx/nm) measured at eye level were 1319/545 in BRIGHT, 203/469 in BLUE, and 115/545 in CONTROL. In a multivariate analysis adjusted for individual VO2max, total work performed in 12 min did not significantly differ between the three groups. The amount of exposure to non-image forming light was positively associated with the performance gain during the time trial, defined as the ratio of the work performed in the first and last minute of the time trial, and with stronger melatonin suppression. Specifically, a tenfold increase in the exposure to melanopic light was associated with a performance gain of 8.0% (95% confidence interval: 2.6, 13.3; P = 0.004) and a melatonin decrease of -0.9 pg/ml (95% confidence interval: -1.5, -0.3; P = 0.006). Exposure to bright or blue light did not significantly improve maximum cycling performance in a 12-min all-out time trial. However, it is noteworthy that the estimated difference of 4.1 kJ between BRIGHT and CONTROL might represent an important performance advantage justifying further studies. In conclusion, we report novel evidence that evening light exposure, which strongly impacts the human circadian timing system, enables elite athletes to better maintain performance across a 12-min cycling time trial.