Differential contractile response of critically ill patients to neuromuscular electrical stimulation

BACKGROUND: Neuromuscular electrical stimulation (NMES) has been investigated as a preventative measure for intensive care unit-acquired weakness. Trial results remain contradictory and therefore inconclusive. As it has been shown that NMES does not necessarily lead to a contractile response, our aim was to characterise the response of critically ill patients to NMES and investigate potential outcome benefits of an adequate contractile response. METHODS: This is a sub-analysis of a randomised controlled trial investigating early muscle activating measures together with protocol-based physiotherapy in patients with a SOFA score ≥ 9 within the first 72 h after admission. Included patients received protocol-based physiotherapy twice daily for 20 min and NMES once daily for 20 min, bilaterally on eight muscle groups. Electrical current was increased up to 70 mA or until a contraction was detected visually or on palpation. Muscle strength was measured by a blinded assessor at the first adequate awakening and ICU discharge. RESULTS: One thousand eight hundred twenty-four neuromuscular electrical stimulations in 21 patients starting on day 3.0 (2.0/6.0) after ICU admission were included in this sub-analysis. Contractile response decreased from 64.4% on day 1 to 25.0% on day 7 with a significantly lower response rate in the lower extremities and proximal muscle groups. The electrical current required to elicit a contraction did not change over time (day 1, 50.2 [31.3/58.8] mA; day 7, 45.3 [38.0/57.5] mA). The electrical current necessary for a contractile response was higher in the lower extremities. At the first awakening, patients presented with significant weakness (3.2 [2.5/3.8] MRC score). When dividing the cohort into responders and non-responders (> 50% vs. ≤ 50% contractile response), we observed a significantly higher SOFA score in non-responders. The electrical current necessary for a muscle contraction in responders was significantly lower (38.0 [32.8/42.9] vs. 54.7 [51.3/56.0] mA, p < 0.001). Muscle strength showed higher values in the upper extremities of responders at ICU discharge (4.4 [4.1/4.6] vs. 3.3 [2.8/3.8] MRC score, p = 0.036). CONCLUSION: Patients show a differential contractile response to NMES, which appears to be dependent on the severity of illness and also relevant for potential outcome benefits. TRIAL REGISTRATION: ISRCTN ISRCTN19392591 , registered 17 February 201

CARbon DIoxide for the treatment of Febrile seizures: rationale, feasibility, and design of the CARDIF-study

Background: 2-8% of all children aged between 6 months and 5 years have febrile seizures. Often these seizures cease spontaneously, however depending on different national guidelines, 20-40% of the patients would need therapeutic intervention. For seizures longer than 3-5 minutes application of rectal diazepam, buccal midazolam or sublingual lorazepam is recommended. Benzodiazepines may be ineffective in some patients or cause prolonged sedation and fatigue. Preclinical investigations in a rat model provided evidence that febrile seizures may be triggered by respiratory alkalosis, which was subsequently confirmed by a retrospective clinical observation. Further, individual therapeutic interventions demonstrated that a pCO2-elevation via re-breathing or inhalation of 5% CO2 instantly stopped the febrile seizures. Here, we present the protocol for an interventional clinical trial to test the hypothesis that the application of 5% CO2 is effective and safe to suppress febrile seizures in children. Methods: The CARDIF (CARbon DIoxide against Febrile seizures) trial is a monocentric, prospective, double-blind, placebo-controlled, randomized study. A total of 288 patients with a life history of at least one febrile seizure will be randomized to receive either carbogen (5% CO2 plus 95% O2) or placebo (100% O2). As recurrences of febrile seizures mainly occur at home, the study medication will be administered by the parents through a low-pressure can fitted with a respiratory mask. The primary outcome measure is the efficacy of carbogen to interrupt febrile seizures. As secondary outcome parameters we assess safety, practicability to use the can, quality of life, contentedness, anxiousness and mobility of the parents. Prospect: The CARDIF trial has the potential to develop a new therapy for the suppression of febrile seizures by redressing the normal physiological state. This would offer an alternative to the currently suggested treatment with benzodiazepines. This study is an example of academic translational research from the study of animal physiology to a new therapy

The Impact of Climate Policy on U.S. Aviation

Abstract and PDF report are also available on the MIT Joint Program on the Science and Policy of Global Change website (http://globalchange.mit.edu/).We evaluate the impact of an economy-wide cap-and-trade policy on U.S. aviation taking the American Clean Energy and Security Act of 2009 (H.R.2454) as a representative example. We use an economywide model to estimate the impact of H.R. 2454 on fuel prices and economic activity, and a partial equilibrium model of the aviation industry to estimate changes in aviation carbon dioxide (CO2) emissions and operations. Between 2012 and 2050, with reference demand growth benchmarked to ICAO/GIACC (2009) forecasts, we find that aviation emissions increase by 130%. In our climate policy scenarios, emissions increase by between 97% and 122%. A key finding is that, under the core set of assumptions in our analysis, H.R. 2454 reduces average fleet efficiency, as increased air fares reduce demand and slow the introduction of new aircraft. Assumptions relating to the sensitivity of aviation demand to price changes, and the degree to which higher fuel prices stimulate advances in the fuel efficiency of new aircraft play an important role in this result.U.S. Federal Aviation Administration Office of Environment and Energy under FAA Award Number: 06HCHNEHMIT, Amendment Nos. 018 and 028. ErichHBecker Foundation. The Joint Program on the Science and Policy of Global Change is funded by the U.S. Department of Energy and a consortium of government and industrial sponsors

Development of Slowed Down Beams at the Fragment Separator for FAIR

The feasibility studies of the slowed down beam setup involving deceleration of a 64Ni beam at 250 MeV/u to 13 MeV/u in a thick Al degrader was performed at the FRagment Separator (FRS) at GSI. The experimentally measured energy spread and the nuclear reaction yields in the degrader are in good agreement with simulations

Inflammatory response in the acute phase of deep vein thrombosis

AbstractObjective: Deep vein thrombosis (DVT) is a multifactorial disease. Recently, inflammation has been suggested as a risk factor for DVT. The question is whether inflammation is a cause of venous thrombosis or rather a result of the thrombotic process. Methods: We studied the inflammatory response in the acute phase of DVT with interleukin-6, interleukin-8, and C-reactive protein (CRP) as inflammatory markers. Plasma concentrations were measured on the day of admission (day 0) in 40 patients with acute DVT confirmed with phlebography and in 33 patients with clinical suspicion of DVT but negative phlebography results (controls). In patients with DVT, inflammatory markers were also examined on five subsequent days. Results: On day 0, the median concentrations in plasma of interleukin-6, interleukin-8, and CRP were 15.0 pg/mL (range, <3 to 70 pg/mL), 7.0 pg/mL (range, <3 to 76 pg/mL), 37.5 mg/L (range, <7 to 164 mg/L), respectively, in the patient group and less than 3 pg/mL (range, <3 to 11 pg/mL; P <.001), 6.0 pg/mL (range, <3 to 52 pg/mL; P =.08), and 5.0 pg/L (range, <7 to 66 pg/L; P <.001), respectively, in the controls. During the next days, interleukin-6 concentration showed a gradual decline in patients with DVT from 15.0 to 5.5 pg/mL (P <.001), interleukin-8 concentration was relatively constant in time, and CRP concentration declined from 37.5 to 21.5 mg/L (P =.01). Conclusion: Our data show an apparent inflammatory response with highest measured concentrations of inflammatory markers on the day of admission and a subsequent decrease during the next days. This response supports the hypothesis that elevated inflammatory markers are a result rather than a cause of venous thrombosis. (J Vasc Surg 2002;35:701-6.

Impact of protocol‐based physiotherapy on insulin sensitivity and peripheral glucose metabolism in critically ill patients

Background: The impact of physiotherapy on insulin sensitivity and peripheral glucose metabolism in critically ill patients is not well understood. Methods: This pooled analysis investigates the impact of different physiotherapeutic strategies on insulin sensitivity in critically ill patients. We pooled data from two previous trials in adult patients with sequential organ failure assessment score (SOFA)>= 9 within 72 h of intensive care unit (ICU) admission, who received hyperinsulinaemic euglycaemic (HE) clamps. Patients were divided into three groups: standard physiotherapy (sPT, n = 22), protocol-based physiotherapy (pPT, n = 8), and pPT with added muscle activating measures (pPT+, n = 20). Insulin sensitivity index (ISI) was determined by HE clamp. Muscle metabolites lactate, pyruvate, and glycerol were measured in the M. vastus lateralis via microdialysis during the HE clamp. Histochemical visualization of glucose transporter-4 (GLUT4) translocation was performed in surgically extracted muscle biopsies. All data are reported as median (25th/75th percentile) (trial registry: ISRCTN77569430 and ISRCTN19392591/ethics approval: Charite-EA2/061/06 and Charite-EA2/041/10). Results Fifty critically ill patients (admission SOFA 13) showed markedly decreased ISIs on Day 17 (interquartile range) 0.029 (0.022/0.048) (mg/min/kg)/(mU/L) compared with healthy controls 0.103 (0.087/0.111), P < 0.001. ISI correlated with muscle strength measured by medical research council (MRC) score at first awakening (r = 0.383, P = 0.026) and at ICU discharge (r = 0.503, P = 0.002). Different physiotherapeutic strategies showed no effect on the ISI [sPT 0.029 (0.019/0.053) (mg/min/kg)/(mU/L) vs. pPT 0.026 (0.023/0.041) (mg/min/kg)/(mU/L) vs. pPT+ 0.029 (0.023/0.042) (mg/min/kg)/(mU/L); P = 0.919]. Regardless of the physiotherapeutic strategy metabolic flexibility was reduced. Relative change of lactate/pyruvate ratio during HE clamp is as follows: sPT 0.09 (-0.13/0.27) vs. pPT 0.07 (-0.16/0.31) vs. pPT+ -0.06 (-0.19/0.16), P = 0.729, and relative change of glycerol concentration: sPT -0.39 (-0.8/-0.12) vs. pPT -0.21 (-0.33/0.07) vs. pPT+ -0.21 (-0.44/-0.03), P = 0.257. The majority of ICU patients showed abnormal localization of GLUT4 with membranous GLUT4 distribution in 37.5% (3 of 8) of ICU patients receiving sPT, in 42.9% (3 of 7) of ICU patients receiving pPT, and in 53.8% (7 of 13) of ICU patients receiving pPT+ (no statistical testing possible). Conclusions: Our data suggest that a higher duration of muscle activating measures had no impact on insulin sensitivity or metabolic flexibility in critically ill patients with sepsis-related multiple organ failure

Direct observation of long-lived isomers in 212^{212}Bi

Long-lived isomers in 212Bi have been studied following 238U projectile fragmentation at 670 MeV per nucleon. The fragmentation products were injected as highly charged ions into the GSI storage ring, giving access to masses and half-lives. While the excitation energy of the first isomer of 212Bi was confirmed, the second isomer was observed at 1478(30) keV, in contrast to the previously accepted value of >1910 keV. It was also found to have an extended Lorentz-corrected in-ring halflife >30 min, compared to 7.0(3) min for the neutral atom. Both the energy and half-life differences can be understood as being due a substantial, though previously unrecognised, internal decay branch for neutral atoms. Earlier shell-model calculations are now found to give good agreement with the isomer excitation energy. Furthermore, these and new calculations predict the existence of states at slightly higher energy that could facilitate isomer de-excitation studies.Comment: published in PRL 110, 12250

Type of treatment, symptoms and patient satisfaction play an important role in primary care contact during prostate cancer follow-up:Results from the population-based PROFILES registry

BACKGROUND: With the increasing attention for the role of General Practitioners (GPs) after cancer treatment, it is important to better understand the involvement of GPs following prostate cancer treatment. This study investigates factors associated with GP contact during follow-up of prostate cancer survivors, such as patient, treatment and symptom variables, and satisfaction with, trust in, and appraised knowledge of GPs. METHODS: Of 787 prostate cancer survivors diagnosed between 2007 and 2013, and selected from the Netherlands Cancer Registry, 557 (71%) responded to the invitation to complete a questionnaire. Multivariable logistic regression analyses were performed to investigate which variables were associated with GP contact during follow- up. RESULTS: In total, 200 (42%) prostate cancer survivors had contact with their GP during follow-up, and 76 (16%) survivors preferred more contact. Survivors who had an intermediate versus low educational level (OR = 2.0) were more likely to have had contact with their GP during follow-up. Survivors treated with surgery (OR = 2.8) or hormonal therapy (OR = 3.5) were also more likely to seek follow-up care from their GP compared to survivors who were treated with active surveillance. Patient reported bowel symptoms (OR = 1.4), hormonal symptoms (OR = 1.4), use of incontinence aids (OR = 1.6), and being satisfied with their GP (OR = 9.5) were also significantly associated with GP contact during follow-up. CONCLUSIONS: Education, treatment, symptoms and patient satisfaction were associated with GP contact during prostate cancer follow-up. These findings highlight the potential for adverse side-effects to be managed in primary care. In light of future changes in cancer care, evaluating prostate cancer follow-up in primary care remains important

Reducing work pressure and IT problems and facilitating IT integration and audit &amp; feedback help adherence to perioperative safety guidelines: a survey among 95 perioperative professionals

Background: To improve perioperative patient safety, guidelines for the preoperative, peroperative, andpostoperative phase were introduced in the Netherlands between 2010 and 2013. To help the implementation ofthese guidelines, we aimed to get a better understanding of the barriers and drivers of perioperative guidelineadherence and to explore what can be learned for future implementation projects in complex organizations.Methods: We developed a questionnaire survey based on the theoretical framework of Van Sluisveld et al. forclassifying barriers and facilitators. The questionnaire contained 57 statements derived from (a) an instrument formeasuring determinants of innovations by the Dutch Organization for Applied Scientific Research, (b) interviewswith quality and safety policy officers and perioperative professionals, and (c) a publication of Cabana et al. Thetarget group consisted of 232 perioperative professionals in nine hospitals. In addition to rating the statements on afive-point Likert scale (which were classified into the seven categories of the framework: factors relating to theintervention, society, implementation, organization, professional, patients, and social factors), respondents wereinvited to rank their three most important barriers in a separate, extra open-ended question.Results: Ninety-five professionals (41%) completed the questionnaire. Fifteen statements (26%) were considered tobe barriers, relating to social factors (N = 5), the organization (N = 4), the professional (N = 4), the patient (N = 1),and the intervention (N = 1). An integrated information system was considered an important facilitator (70.4%) aswell as audit and feedback (41.8%). The Barriers Top-3 question resulted in 75 different barriers in nearly allcategories. The most frequently reported barriers were as follows: time pressure (16% of the total number ofbarriers), emergency patients (8%), inefficient IT structure (4%), and workload (3%).Conclusions: We identified a wide range of barriers that are believed to hinder the use of the perioperative safetyguidelines, while an integrated information system and local data collection and feedback will also be necessary toengage perioperative teams. These barriers need to be locally prioritized and addressed by tailored implementationstrategies. These results may also be of relevance for guideline implementation in general in complex organizations.Trial registration: Dutch Trial Registry: NTR3568.Keywords: Guideline adherence, Implementation, Implementation barriers, Implementation facilitators, Patientsafety, Perioperative car