Regional respiratory time constants during lung recruitment in high-frequency oscillatory ventilated preterm infants

To assess the regional respiratory time constants of lung volume changes during stepwise lung recruitment before and after surfactant treatment in high-frequency oscillatory ventilated preterm infants. A stepwise oxygenation-guided recruitment procedure was performed before and after surfactant treatment in high-frequency oscillatory ventilated preterm infants. Electrical impedance tomography was used to continuously record changes in lung volume during the recruitment maneuver. Time constants were determined for all incremental and decremental pressure steps, using one-phase exponential decay curve fitting. Data were analyzed for the whole cross section of the chest and the ventral and dorsal lung regions separately. Before surfactant treatment, the time constants of the incremental pressure steps were significantly longer (median 27.3 s) than those in the decremental steps (16.1 s). Regional analysis showed only small differences between the ventral and dorsal lung regions. Following surfactant treatment, the time constants during decremental pressure steps almost tripled to 44.3 s. Furthermore, the time constants became significantly (p <0.01) longer in the dorsal (61.2 s) than into the ventral (40.3 s) lung region. Lung volume stabilization during stepwise oxygenation-guided lung recruitment in high-frequency oscillatory ventilated preterm infants with respiratory distress syndrome is usually completed within 5 min and is dependent on the position of ventilation on the pressure volume curve, the surfactant status, and the region of interest of the lun

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

Hospital-level associations with 30-day patient mortality after cardiac surgery: a tutorial on the application and interpretation of marginal and multilevel logistic regression

Background: Marginal and multilevel logistic regression methods can estimate associations between hospital-level factors and patient-level 30-day mortality outcomes after cardiac surgery. However, it is not widely understood how the interpretation of hospital-level effects differs between these methods. Methods. The Australasian Society of Cardiac and Thoracic Surgeons (ASCTS) registry provided data on 32,354 patients undergoing cardiac surgery in 18 hospitals from 2001 to 2009. The logistic regression methods related 30-day mortality after surgery to hospital characteristics with concurrent adjustment for patient characteristics. Results: Hospital-level mortality rates varied from 1.0% to 4.1% of patients. Ordinary, marginal and multilevel regression methods differed with regard to point estimates and conclusions on statistical significance for hospital-level risk factors; ordinary logistic regression giving inappropriately narrow confidence intervals. The median odds ratio, MOR, from the multilevel model was 1.2 whereas ORs for most patient-level characteristics were of greater magnitude suggesting that unexplained between-hospital variation was not as relevant as patient-level characteristics for understanding mortality rates. For hospital-level characteristics in the multilevel model, 80% interval ORs, IOR-80%, supplemented the usual ORs from the logistic regression. The IOR-80% was (0.8 to 1.8) for academic affiliation and (0.6 to 1.3) for the median annual number of cardiac surgery procedures. The width of these intervals reflected the unexplained variation between hospitals in mortality rates; the inclusion of one in each interval suggested an inability to add meaningfully to explaining variation in mortality rates. Conclusions: Marginal and multilevel models take different approaches to account for correlation between patients within hospitals and they lead to different interpretations for hospital-level odds ratios. © 2012 Sanagou et al; licensee BioMed Central Ltd

High frequency oscillatory ventilation and prone positioning in a porcine model of lavage-induced acute lung injury

BACKGROUND: This animal study was conducted to assess the combined effects of high frequency oscillatory ventilation (HFOV) and prone positioning on pulmonary gas exchange and hemodynamics. METHODS: Saline lung lavage was performed in 14 healthy pigs (54 ± 3.1 kg, mean ± SD) until the arterial oxygen partial pressure (PaO(2)) decreased to 55 ± 7 mmHg. The animals were ventilated in the pressure controlled mode (PCV) with a positive endexpiratory pressure (PEEP) of 5 cmH(2)O and a tidal volume (V(T)) of 6 ml/kg body weight. After a stabilisation period of 60 minutes, the animals were randomly assigned to 2 groups. Group 1: HFOV in supine position; group 2: HFOV in prone position. After evaluation of prone positioning in group 2, the mean airway pressure (P(mean)) was increased by 3 cmH(2)O from 16 to 34 cmH(2)O every 20 minutes in both groups accompanied by measurements of respiratory and hemodynamic variables. Finally all animals were ventilated supine with PCV, PEEP = 5 cm H(2)O, V(T )= 6 ml/kg. RESULTS: Combination of HFOV with prone positioning improves oxygenation and results in normalisation of cardiac output and considerable reduction of pulmonary shunt fraction at a significant (p < 0.05) lower P(mean )than HFOV and supine positioning. CONCLUSION: If ventilator induced lung injury is ameliorated by a lower P(mean), a combined treatment approach using HFOV and prone positioning might result in further lung protection

Accounting for the mortality benefit of drug-eluting stents in percutaneous coronary intervention: a comparison of methods in a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Drug-eluting stents (DES) reduce rates of restenosis compared with bare metal stents (BMS). A number of observational studies have also found lower rates of mortality and non-fatal myocardial infarction with DES compared with BMS, findings not observed in randomized clinical trials. In order to explore reasons for this discrepancy, we compared outcomes after percutaneous coronary intervention (PCI) with DES or BMS by multiple statistical methods.</p> <p>Methods</p> <p>We compared short-term rates of all-cause mortality and myocardial infarction for patients undergoing PCI with DES or BMS using propensity-score adjustment, propensity-score matching, and a stent-era comparison in a large, integrated health system between 1998 and 2007. For the propensity-score adjustment and stent era comparisons, we used multivariable logistic regression to assess the association of stent type with outcomes. We used McNemar's Chi-square test to compare outcomes for propensity-score matching.</p> <p>Results</p> <p>Between 1998 and 2007, 35,438 PCIs with stenting were performed among health plan members (53.9% DES and 46.1% BMS). After propensity-score adjustment, DES was associated with significantly lower rates of death at 30 days (OR 0.49, 95% CI 0.39 - 0.63, <it>P </it>< 0.001) and one year (OR 0.58, 95% CI 0.49 - 0.68, <it>P </it>< 0.001), and a lower rate of myocardial infarction at one year (OR 0.72, 95% CI 0.59 - 0.87, <it>P </it>< 0.001). Thirty day and one year mortality were also lower with DES after propensity-score matching. However, a stent era comparison, which eliminates potential confounding by indication, showed no difference in death or myocardial infarction for DES and BMS, similar to results from randomized trials.</p> <p>Conclusions</p> <p>Although propensity-score methods suggested a mortality benefit with DES, consistent with prior observational studies, a stent era comparison failed to support this conclusion. Unobserved factors influencing stent selection in observational studies likely account for the observed mortality benefit of DES not seen in randomized clinical trials.</p

Association between two distinct executive tasks in schizophrenia: a functional transcranial Doppler sonography study

BACKGROUND: Schizophrenia is a severe mental disorder involving impairments in executive functioning, which are important cognitive processes that can be assessed by planning tasks such as the Stockings of Cambridge (SOC), and tasks of rule learning/abstraction such as the Wisconsin Card Sorting Test (WCST). We undertook this study to investigate the association between performance during separate phases of SOC and WCST, including mean cerebral blood flow velocity (MFV) measurements in chronic schizophrenia. METHODS: Functional transcranial Doppler sonography (fTCD) was used to assess bilateral MFV changes in the middle (MCA) and anterior (ACA) cerebral arteries. Twenty-two patients with chronic schizophrenia and 20 healthy subjects with similar sociodemographic characteristics performed SOC and WCST during fTCD measurements of the MCA and the ACA. The SOC was varied in terms of easy and difficult problems, and also in terms of separate phases, namely mental planning and movement execution. The WCST performance was assessed separately for maintaining set and set shifting. This allowed us to examine the impact of problem difficulty and the impact of separate phases of a planning task on distinct intervals of WCST. Simultaneous registration of MFV was carried out to investigate the linkage of brain perfusion during the tasks. RESULTS: In patients, slowing of movement execution during easy problems (SOC) was associated with slowing during maintaining set (WCST) (P < 0.01). In healthy subjects, faster planning and movement execution during predominantly difficult problems were associated with increased performance of WCST during set shifting (P < 0.01). In the MCA, patients showed a significant and positive correlation of MFV between movement execution and WCST (P < 0.01). CONCLUSION: The results of this study demonstrate performance and brain perfusion abnormalities in the association pattern of two different tasks of executive functioning in schizophrenia, and they support the notion that executive functions have a pathological functional correlate predominantly in the lateral hemispheres of the brain. This study also underpins the scientific potential of fTCD in assessing brain perfusion in patients with schizophrenia

Acute Effects of Sex Steroid Hormones on Susceptibility to Cardiac Arrhythmias: A Simulation Study

Acute effects of sex steroid hormones likely contribute to the observation that post-pubescent males have shorter QT intervals than females. However, the specific role for hormones in modulating cardiac electrophysiological parameters and arrhythmia vulnerability is unclear. Here we use a computational modeling approach to incorporate experimentally measured effects of physiological concentrations of testosterone, estrogen and progesterone on cardiac ion channel targets. We then study the hormone effects on ventricular cell and tissue dynamics comprised of Faber-Rudy computational models. The “female” model predicts changes in action potential duration (APD) at different stages of the menstrual cycle that are consistent with clinically observed QT interval fluctuations. The “male” model predicts shortening of APD and QT interval at physiological testosterone concentrations. The model suggests increased susceptibility to drug-induced arrhythmia when estradiol levels are high, while testosterone and progesterone are apparently protective. Simulations predict the effects of sex steroid hormones on clinically observed QT intervals and reveal mechanisms of estrogen-mediated susceptibility to prolongation of QT interval. The simulations also indicate that acute effects of estrogen are not alone sufficient to cause arrhythmia triggers and explain the increased risk of females to Torsades de Pointes. Our results suggest that acute effects of sex steroid hormones on cardiac ion channels are sufficient to account for some aspects of gender specific susceptibility to long-QT linked arrhythmias

Comparative Phylogeography in a Specific and Obligate Pollination Antagonism

In specific and obligate interactions the nature and abundance of a given species can have important effects on the survival and population dynamics of associated organisms. In a phylogeographic framework, we therefore expect that the fates of organisms interacting specifically are also tightly interrelated. Here we investigate such a scenario by analyzing the genetic structures of species interacting in an obligate plant-insect pollination lure-and-trap antagonism, involving Arum maculatum (Araceae) and its specific psychodid (Diptera) visitors Psychoda phalaenoides and Psycha grisescens. Because the interaction is asymmetric (i.e., only the plant depends on the insect), we expect the genetic structure of the plant to be related with the historical pollinator availability, yielding incongruent phylogeographic patterns between the interacting organisms

Longitudinal study of adolescent tobacco use and tobacco control policies in India

Abstract Background This project will use a multilevel longitudinal cohort study design to assess whether changes in Community Tobacco Environmental (CTE) factors, measured as community compliance with tobacco control policies and community density of tobacco vendors and tobacco advertisements, are associated with adolescent tobacco use in urban India. India’s tobacco control policies regulate secondhand smoke exposure, access to tobacco products and exposure to tobacco marketing. Research data about the association between community level compliance with tobacco control policies and youth tobacco use are largely unavailable, and are needed to inform policy enforcement, implementation and development. Methods The geographic scope will include Mumbai and Kolkata, India. The study protocol calls for an annual comprehensive longitudinal population-based tobacco use risk and protective factors survey in a cohort of 1820 adolescents ages 12–14 years (and their parent) from baseline (Wave 1) to 36-month follow-up (Wave 4). Geographic Information Systems data collection will be used to map tobacco vendors, tobacco advertisements, availability of e-cigarettes, COTPA defined public places, and compliance with tobacco sale, point-of-sale and smoke-free laws. Finally, we will estimate the longitudinal associations between CTE factors and adolescent tobacco use, and assess whether the associations are moderated by family level factors, and mediated by individual level factors. Discussion India experiences a high burden of disease and mortality from tobacco use. To address this burden, significant long-term prevention and control activities need to include the joint impact of policy, community and family factors on adolescent tobacco use onset. The findings from this study can be used to guide the development and implementation of future tobacco control policy designed to minimize adolescent tobacco use.https://deepblue.lib.umich.edu/bitstream/2027.42/144539/1/12889_2018_Article_5727.pd

Disagreement in primary study selection between systematic reviews on negative pressure wound therapy

<p>Abstract</p> <p>Background</p> <p>Primary study selection between systematic reviews is inconsistent, and reviews on the same topic may reach different conclusions. Our main objective was to compare systematic reviews on negative pressure wound therapy (NPWT) regarding their agreement in primary study selection.</p> <p>Methods</p> <p>This retrospective analysis was conducted within the framework of a systematic review (a full review and a subsequent rapid report) on NPWT prepared by the Institute for Quality and Efficiency in Health Care (IQWiG).</p> <p>For the IQWiG review and rapid report, 4 bibliographic databases (MEDLINE, EMBASE, The Cochrane Library, and CINAHL) were searched to identify systematic reviews and primary studies on NPWT versus conventional wound therapy in patients with acute or chronic wounds. All databases were searched from inception to December 2006.</p> <p>For the present analysis, reviews on NPWT were classified as eligible systematic reviews if multiple sources were systematically searched and the search strategy was documented. To ensure comparability between reviews, only reviews published in or after December 2004 and only studies published before June 2004 were considered.</p> <p>Eligible reviews were compared in respect of the methodology applied and the selection of primary studies.</p> <p>Results</p> <p>A total of 5 systematic reviews (including the IQWiG review) and 16 primary studies were analysed. The reviews included between 4 and 13 primary studies published before June 2004. Two reviews considered only randomised controlled trials (RCTs). Three reviews considered both RCTs and non-RCTs. The overall agreement in study selection between reviews was 96% for RCTs (24 of 25 options) and 57% for non-RCTs (12 of 21 options). Due to considerable disagreement in the citation and selection of non-RCTs, we contacted the review authors for clarification (this was not initially planned); all authors or institutions responded. According to published information and the additional information provided, most differences between reviews arose from variations in inclusion criteria or inter-author study classification, as well as from different reporting styles (citation or non-citation) for excluded studies.</p> <p>Conclusion</p> <p>The citation and selection of primary studies differ between systematic reviews on NPWT, particularly with regard to non-RCTs. Uniform methodological and reporting standards need to be applied to ensure comparability between reviews as well as the validity of their conclusions.</p