Increasing respiratory dead space improves sleep disordered breathing and hypoxemia in patients with chronic mountain sickness

Background: Chronic mountain sickness (CMS), which is characterised by hypoxemia, erythrocytosis and pulmonary hypertension, is a major public health problem in high-altitude dwellers. The only existing treatment is descent to low altitude, an option that for social reasons almost never exists. Sleep disordered breathing may represent an underlying mechanism. We recently found that in mountaineers increasing the respiratory dead space markedly improves sleep disordered breathing. The aim of the present study was to assess the effects of this procedure on sleep disordered breathing in patients with CMS. Methods: In 10 male Bolivian high-altitude dwellers (mean ± SD age, 59 ± 9 y) suffering from CMS (haemoglobin >20 g/L) full night sleep recordings (Embletta, RespMed) were obtained in La Paz (3600 m). In random order, one night was spent with a 500 ml increase in dead space through a custom designed full face mask and the other night without it. Exclusion criteria were: secondary erythrocytosis, smoking, drug intake, acute infection, cardio- pulmonary or neurologic disease and travelling to low altitude in the preceding 6 months. Results: The major new finding was that added dead space dramatically improved sleep disordered breathing in patients suffering from CMS. The apnea/hypopnea index decreased by >50% (from 34.5 ± 25.0 to 16.8 ± 14.9, P = 0.003), the oxygen desaturation index decreased from 46.2 ± 23.0 to 27.2 ± 20.0 (P = 0.0004) and hypopnea index from 28.8 ± 20.9 to 16.3 ± 14.0 (P = 0.01), whereas nocturnal oxygen saturation increased from 79.8 ± 3.6 to 80.9 ± 3.0% (P = 0.009). The procedure was easily accepted and well tolerated. Conclusion: Here, we show for the very first time that an increase in respiratory dead space through a fitted mask dramatically improves nocturnal breathing in high-altitude dwellers suffering from CMS. We speculate that when used in the long-term, this procedure will improve erythrocytosis and pulmonary hypertension and offer an inexpensive and easily implementable treatment for this major public health problem.

Investigation of field and diffusion time dependence of the diffusion-weighted signal at ultrahigh magnetic fields.

Over the last decade, there has been a significant increase in the number of high-magnetic-field MRI magnets. However, the exact effect of a high magnetic field strength (B0 ) on diffusion-weighted MR signals is not yet fully understood. The goal of this study was to investigate the influence of different high magnetic field strengths (9.4 T and 14.1 T) and diffusion times (9, 11, 13, 15, 17 and 24 ms) on the diffusion-weighted signal in rat brain white matter. At a short diffusion time (9 ms), fractional anisotropy values were found to be lower at 14.1 T than at 9.4 T, but this difference disappeared at longer diffusion times. A simple two-pool model was used to explain these findings. The model describes the white matter as a first hindered compartment (often associated with the extra-axonal space), characterized by a faster orthogonal diffusion and a lower fractional anisotropy, and a second restricted compartment (often associated with the intra-axonal space), characterized by a slower orthogonal diffusion (i.e. orthogonal to the axon direction) and a higher fractional anisotropy. Apparent T2 relaxation time measurements of the hindered and restricted pools were performed. The shortening of the pseudo-T2 value from the restricted compartment with B0 is likely to be more pronounced than the apparent T2 changes in the hindered compartment. This study suggests that the observed differences in diffusion tensor imaging parameters between the two magnetic field strengths at short diffusion time may be related to differences in the apparent T2 values between the pools. Copyright © 2013 John Wiley & Sons, Ltd.

Influence of socioeconomic factors on delays, management and boutcome amongst patients with acute myocardial infarction undergoing primary percutaneous coronary intervention

Background¦The outcome after primary percutaneous coronary intervention (pPCI) for STElevation¦Myocardial Infarction (STEMI) is strongly affected by time delays. In thepresent study, we sought to identify the impact of specific socioeconomic factors on time delays, subsequent STEMI management and outcomes in STEMI patients from a well-defined region of the French part of Switzerland.¦Method¦A total of 402 consecutive patients undergoing pPCI for STEMI in a large tertiary hospital were retrospectively studied. Symptom-to-first-medical-contact time was analyzed for the following socioeconomic factors: level of education, gender, origin and marital status. Main exclusion criteria were: time delay beyond 12 hours, previous treatment by fibrinolysis or patients immediately referred for CABG.¦Therefore, 352 patients were finally included.¦Results¦At one year, there was no difference in mortality amongst the different socioeconomic groups. Furthermore, there was no difference in management characteristics between them. Symptom-to-first-medical-contact time was significantly higher for patients with a low level of education, Swiss citizens and non-married patients with median differences of 40 minutes, 48 minutes, and 60 minutes, respectively (p<0.05).¦Nevertheless, no difference was found regarding in-hospital management and clinical outcome.¦Conclusion¦This study demonstrates that symptom-to-first-medical-contact time is higher amongst people with a lower educational level, Swiss-citizens, and non-married people. Because of the low mortality rate in general, these differences in time delays did not affect clinical outcomes. Still, primary prevention measures should particularly focus on these vulnerable populations.

Physicians' attitudes towards prevention: importance of intervention-specific barriers and physicians' health habits.

BACKGROUND: Several studies have explored physicians' attitudes towards prevention and barriers to the delivery of preventive health interventions. However, the relative importance of these previously identified barriers, both in general terms and in the context of a number of specific preventive interventions, has not been identified. Certain barriers may only pertain to a subset of preventive interventions. OBJECTIVES: We aimed to determine the relative importance of identified barriers to preventive interventions and to explore the association between physicians' characteristics and their attitudes towards prevention. METHODS: We conducted a cross-sectional survey of 496 of the 686 (72.3% response rate) generalist physicians from three Swiss cantons through a questionnaire asking physicians to rate the general importance of eight preventive health strategies and the relative importance of seven commonly cited barriers in relation to each specific preventive health strategy. RESULTS: The proportion of physicians rating each preventive intervention as being important varied from 76% for colorectal cancer screening to 100% for blood pressure control. Lack of time and lack of patient interest were generally considered to be important barriers by 41% and 44% of physicians, respectively, but the importance of these two barriers tended to be specifically higher for counselling-based interventions. Lack of training was most notably a barrier to counselling about alcohol and nutrition. Four characteristics of physicians predicted negative attitudes toward alcohol and smoking counselling: consumption of more than three alcoholic drinks per day [odds ratio (OR) = 8.4], sedentary lifestyle (OR = 3.4), lack of national certification (OR = 2.2) and lack of awareness of their own blood pressure (OR = 2.0). CONCLUSIONS: The relative importance of specific barriers varies across preventive interventions. This points to a need for tailored practice interventions targeting the specific barriers that impede a given preventive service. The negative influence of physicians' own health behaviours indicates a need for associated population-based interventions that reduce the prevalence of high-risk behaviours in the population as a whole.

Spin-labeling coronary MR angiography with steady-state free precession and radial k-space sampling: initial results in healthy volunteers.

The purpose of this study was to prospectively compare free-breathing navigator-gated cardiac-triggered three-dimensional steady-state free precession (SSFP) spin-labeling coronary magnetic resonance (MR) angiography performed by using Cartesian k-space sampling with that performed by using radial k-space sampling. A new dedicated placement of the two-dimensional selective labeling pulse and an individually adjusted labeling delay time approved by the institutional review board were used. In 14 volunteers (eight men, six women; mean age, 28.8 years) who gave informed consent, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), vessel sharpness, vessel length, and subjective image quality were investigated. Differences between groups were analyzed with nonparametric tests (Wilcoxon, Pearson chi2). Radial imaging, as compared with Cartesian imaging, resulted in a significant reduction in the severity of motion artifacts, as well as an increase in SNR (26.9 vs 12.0, P < .05) in the coronary arteries and CNR (23.1 vs 8.8, P < .05) between the coronary arteries and the myocardium. A tendency toward improved vessel sharpness and vessel length was also found with radial imaging. Radial SSFP imaging is a promising technique for spin-labeling coronary MR angiography.

Improving appropriateness of antibiotic therapy: randomized trial of an intervention to foster reassessment of prescription after 3 days.

OBJECTIVES: Reassessment of ongoing antibiotic therapy is an important step towards appropriate use of antibiotics. This study was conducted to evaluate the impact of a short questionnaire designed to encourage reassessment of intravenous antibiotic therapy after 3 days. PATIENTS AND METHODS: Patients hospitalized on the surgical and medical wards of a university hospital and treated with an intravenous antibiotic for 3-4 days were randomly allocated to either an intervention or control group. The intervention consisted of mailing to the physician in charge of the patient a three-item questionnaire referring to possible adaptation of the antibiotic therapy. The primary outcome was the time elapsed from randomization until a first modification of the initial intravenous antibiotic therapy. It was compared within both groups using Cox proportional-hazard modelling. RESULTS: One hundred and twenty-six eligible patients were randomized in the intervention group and 125 in the control group. Time to modification of intravenous antibiotic therapy was 14% shorter in the intervention group (adjusted hazard ratio for modification 1.28, 95% CI 0.99-1.67, P = 0.06). It was significantly shorter in the intervention group compared with a similar group of 151 patients observed during a 2 month period preceding the study (adjusted hazard ratio 1.17, 95% CI 1.03-1.32, P = 0.02). CONCLUSION: The results suggest that a short questionnaire, easily adaptable to automatization, has the potential to foster reassessment of antibiotic therapy.

Matrix-assisted laser desorption ionization time-of-flight mass spectrometry and PCR-based rapid diagnosis of Staphylococcus aureus bacteraemia.

Effective empirical treatment is of paramount importance to improve the outcome of patients with Staphylococcus aureus bacteraemia. We aimed to evaluate a PCR-based rapid diagnosis of methicillin resistance (GeneXpert MRSA) after early detection of S. aureus bacteraemia using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Patients with a first episode of S. aureus bacteraemia identified using MALDI-TOF MS were randomized in a prospective interventional open study between October 2010 and August 2012. In the control group, antibiotic susceptibility testing was performed after MALDI-TOF MS identification on blood culture pellets. In the intervention group, a GeneXpert MRSA was performed after S. aureus identification. The primary outcome was the performance of GeneXpert MRSA directly on blood cultures. We then assessed the impact of early diagnosis of methicillin resistance on the empirical treatment. In all, 197 episodes of S. aureus bacteraemia were included in the study, of which 106 were included in the intervention group. Median time from MALDI-TOF MS identification to GeneXpert MRSA result was 97 min (range 25-250). Detection of methicillin resistance using GeneXpert MRSA had a sensitivity of 99% and a specificity of 100%. There was less unnecessary coverage of MRSA in the intervention group (17.1% versus 29.2%, p 0.09). GeneXpert MRSA was highly reliable in diagnosing methicillin resistance when performed directly on positive blood cultures. This could help to avoid unnecessary prescriptions of anti-MRSA agents and promote the introduction of earlier adequate coverage in unsuspected cases.

Documenting a time-bound, circular view of hierarchies: a microanalysis of parent-infant dyadic interaction.

This article presents a new theory that separates the levels of communication and relates them circularly, namely, by separating time from space/meaning variables. Documenting this proposition requires sequential microdescriptions--a far-out project in the field of family therapy. In an extensive study of clinical and nonclinical families, starting with available microanalytic data on nonverbal parent-infant dialogue, distinct time organizations have been found to modify the degree of circularity between the levels of interaction according to the observed types of engagement, that is, consensual, conflictual, and paradoxical. The double description of the dyad as a totality versus the dyad as a framing/developing organization imparts crucial information on how development proceeds in dyadic, co-evolutive systems, and presumably in larger ones too. In this perspective, a model is elaborated and then applied to a case description in our therapeutic consultation.

Metabolic intervention on lipid synthesis converging pathways abrogates prostate cancer growth.

One of the most conserved features of all cancers is a profound reprogramming of cellular metabolism, favoring biosynthetic processes and limiting catalytic processes. With the acquired knowledge of some of these important changes, we have designed a combination therapy in order to force cancer cells to use a particular metabolic pathway that ultimately results in the accumulation of toxic products. This innovative approach consists of blocking lipid synthesis, at the same time that we force the cell, through the inhibition of AMP-activated kinase, to accumulate toxic intermediates, such as malonyl-coenzyme A (malonyl-CoA) or nicotinamide adenine dinucleotide phosphate. This results in excess of oxidative stress and cancer cell death. Our new therapeutic strategy, based on the manipulation of metabolic pathways, will certainly set up the basis for new upcoming studies defining a new paradigm of cancer treatment.

Profile order and time-dependent artifacts in contrast-enhanced coronary MR angiography at 3T: origin and prevention.

To enhance the clinical value of coronary magnetic resonance angiography (MRA), high-relaxivity contrast agents have recently been used at 3T. Here we examine a uniform bilateral shadowing artifact observed along the coronary arteries in MRA images collected using such a contrast agent. Simulations were performed to characterize this artifact, including its origin, to determine how best to mitigate this effect, and to optimize a data acquisition/injection scheme. An intraluminal contrast agent concentration model was used to simulate various acquisition strategies with two profile orders for a slow-infusion of a high-relaxivity contrast agent. Filtering effects from temporally variable weighting in k-space are prominent when a centric, radial (CR) profile order is applied during contrast infusion, resulting in decreased signal enhancement and underestimation of vessel width, while both pre- and postinfusion steady-state acquisitions result in overestimation of the vessel width. Acquisition during the brief postinfusion steady-state produces the greatest signal enhancement and minimizes k-space filtering artifacts.

Relationship between time of day and periprocedural myocardial infarction after elective angioplasty.

Objectives: To test if the time of day significantly influences the occurrence of type 4A myocardial infarction in elective patients undergoing percutaneous coronary intervention (PCI). Background: Recent studies have suggested an influence of circadian rhythms on myocardial infarction size and mortality among patients with ST-elevation myocardial infarction. The aim of the study is to investigate whether periprocedural myocardial infarction (PMI) is influenced by the time of day in elective patients undergoing PCI. Methods: All consecutive patients undergoing elective PCI between 2007 and 2011 at our institutions with known post-interventional troponin were retrospectively included. Patients (n = 1021) were divided into two groups according to the starting time of the PCI: the morning group (n = 651) between 07:00 and 11:59, and the afternoon group (n = 370) between 12:00 and 18:59. Baseline and procedural characteristics as well as clinical outcome defined as the occurrence of PMI were compared between groups. In order to limit selection bias, all analyses were equally performed in 308 pairs using propensity score (PS) matching. Results: In the overall population, the rate of PMI was statistically lower in the morning group compared to the afternoon group (20% vs. 30%, p < 0.001). This difference remained statistically significant after PS-matching (21% vs. 29%, p = 0.03). Multivariate analysis shows that being treated in the afternoon independently increases the risk for PMI with an odds ratio of 2.0 (95%CI: 1.1-3.4; p = 0.02). Conclusions: This observational PS-matched study suggests that the timing of an elective PCI influences the rate of PMI.

Predictors of Weight Change in Sedentary Smokers Receiving a Standard Smoking Cessation Intervention.

INTRODUCTION: Quitting smoking is associated with weight gain, which may threaten motivation to engage or sustain a quit attempt. The pattern of weight gained by smokers treated according to smoking cessation guidelines has been poorly described. We aimed to determine the weight gained after smoking cessation and its predictors, by smokers receiving individual counseling and nicotine replacement therapies for smoking cessation. METHODS: We performed an ancillary analysis of a randomized controlled trial assessing moderate physical activity as an aid for smoking cessation in addition to standard treatment in sedentary adult smokers. We used mixed longitudinal models to describe the evolution of weight over time, thus allowing us to take every participant into account. We also fitted a model to assess the effect of smoking status and reported use of nicotine replacement therapy at each time point. We adjusted for intervention group, sex, age, nicotine dependence, and education. RESULTS: In the whole cohort, weight increased in the first 3 months, and stabilized afterwards. Mean 1-year weight gain was 3.3kg for women and 3.9kg for men (p = .002). Higher nicotine dependence and male sex were associated with more weight gained during abstinence. Age over median was associated with continuing weight gain during relapse. There was a nonsignificant trend toward slower weight gain with use of nicotine replacement therapies. CONCLUSION: Sedentary smokers receiving a standard smoking cessation intervention experience a moderate weight gain, limited to the first 3 months. Older age, male sex, and higher nicotine dependence are predictors of weight gain.

Acute neurorehabilitation: does a neurosensory and coordinated interdisciplinary programme reduce tracheostomy weaning time and weaning failure?

BACKGROUND/PURPOSE: A new coordinated interdisciplinary unit was created in the acute section of the department of clinical neurosciences, the Acute NeuroRehabilitation (NRA) unit. The objective was to evaluate the impact of the unit and its neurosensory programme on the management of tracheostomy patients in terms of reduction in the average time taken for weaning, weaning success rate and therapeutic efficiency. METHODS: This 49-month retrospective study compares 2 groups of tracheostomy patients before (n = 34) and after (n = 46) NRA intervention. The outcome measures evaluate the benefits of the NRA unit intervention (time to decannulation, weaning and complication rates) and the benefits of the coordination (time to registration in a rehabilitation centre and rate of non-compliance with standards of care). RESULTS: Weaning failure rate was reduced from 27.3% to 9.1%, no complications or recannulations were observed in the post-intervention group after weaning and time to decannulation following admission to our unit decreased from 19.13 to 12.75 days. The rate of non-compliance with patient standards of care was significantly reduced from 45% to 30% (Mann-Whitney p = 0.003). DISCUSSION/CONCLUSIONS: This interdisciplinary weaning programme helped to reduce weaning time and weaning failure, without increased complications, in the sample studied. Coordination improved the efficiency of the interdisciplinary team in the multiplicity and complexity of the different treatments.

Beyond Centre and Margin: (Self-)translation and the Ecopoetics of Space in Geetanjali Shree's "Mai"

Croisant les concepts de traduction culturelle et une approche « queer » de l'identité, notre article propose une lecture de l'utilisation de tropes végétaux ou organiques dans le roman de Geetanjali Shree, Mai, comme critique de la logique binaire du centre et de la marge qui caractérise autant l'orientalisme que le système patriarcal. Ecrit à la première personne, le roman invente un nouvel espace d'énonciation en narrant l'enfance et la jeunesse d'une jeune femme et la constitution de son identité à travers la relation complexe qu'elle entretient avec sa mère, son milieu familial issu de la classe moyenne du Nord de l'Inde, et la société indienne contemporaine aux prises avec la globalisation. Toutefois, ce cercle ou centre est en constante évolution puisque le contexte postcolonial dans lequel ces identités féminines se situent nous amène à considérer d'autres modes d'intervention (agency) qui opèrent non seulement à travers la prise de parole mais aussi à travers l'usage stratégique du silence. Fleurissant entre l'anglais et le hindi, ces identités hybrides nous poussent à revoir nos cartographies critiques et à investiguer et investir des lieux liminaux dans lesquels des subjectivités traversent les frontières et transgressent les limites imposées par l'ordre patriarcal et les cartographies imposées par les centres de pouvoir.