The effects of sugammadex vs. neostigmine on postoperative respiratory complications and advanced healthcare utilisation: a multicentre retrospective cohort study.

Reversing neuromuscular blockade with sugammadex can eliminate residual paralysis, which has been associated with postoperative respiratory complications. There are equivocal data on whether sugammadex reduces these when compared with neostigmine. We investigated the association of the choice of reversal drug with postoperative respiratory complications and advanced healthcare utilisation. We included adult patients who underwent surgery and received general anaesthesia with sugammadex or neostigmine reversal at two academic healthcare networks between January 2016 and June 2021. The primary outcome was postoperative respiratory complications, defined as post-extubation oxygen saturation < 90%, respiratory failure requiring non-invasive ventilation, or tracheal re-intubation within 7 days. Our main secondary outcome was advanced healthcare utilisation, a composite outcome including: 7-day unplanned intensive care unit admission; 30-day hospital readmission; or non-home discharge. In total, 5746 (6.9%) of 83,250 included patients experienced postoperative respiratory complications. This was not associated with the reversal drug (adjusted OR (95%CI) 1.01 (0.94-1.08); p = 0.76). After excluding patients admitted from skilled nursing facilities, 8372 (10.5%) patients required advanced healthcare utilisation, which was not associated with the choice of reversal (adjusted OR (95%CI) 0.95 (0.89-1.01); p = 0.11). Equivalence testing supported an equivalent effect size of sugammadex and neostigmine on both outcomes, and neostigmine was non-inferior to sugammadex with regard to postoperative respiratory complications or advanced healthcare utilisation. Finally, there was no association between the reversal drug and major adverse cardiovascular events (adjusted OR 1.07 (0.94-1.21); p = 0.32). Compared with neostigmine, reversal of neuromuscular blockade with sugammadex was not associated with a reduction in postoperative respiratory complications or post-procedural advanced healthcare utilisation.

Sublimation in bright spots on (1) Ceres.

The dwarf planet (1) Ceres, the largest object in the main asteroid belt with a mean diameter of about 950 kilometres, is located at a mean distance from the Sun of about 2.8 astronomical units (one astronomical unit is the Earth-Sun distance). Thermal evolution models suggest that it is a differentiated body with potential geological activity. Unlike on the icy satellites of Jupiter and Saturn, where tidal forces are responsible for spewing briny water into space, no tidal forces are acting on Ceres. In the absence of such forces, most objects in the main asteroid belt are expected to be geologically inert. The recent discovery of water vapour absorption near Ceres and previous detection of bound water and OH near and on Ceres (refs 5-7) have raised interest in the possible presence of surface ice. Here we report the presence of localized bright areas on Ceres from an orbiting imager. These unusual areas are consistent with hydrated magnesium sulfates mixed with dark background material, although other compositions are possible. Of particular interest is a bright pit on the floor of crater Occator that exhibits probable sublimation of water ice, producing haze clouds inside the crater that appear and disappear with a diurnal rhythm. Slow-moving condensed-ice or dust particles may explain this haze. We conclude that Ceres must have accreted material from beyond the 'snow line', which is the distance from the Sun at which water molecules condense.

Drugs for preventing postoperative nausea and vomiting in adults after general anaesthesia: an abridged Cochrane network meta-analysis.

Postoperative nausea and vomiting is a common adverse effect of anaesthesia. Although dozens of different anti-emetics are available for clinical practice, there is currently no comparative ranking of efficacy and safety of these drugs to inform clinical practice. We performed a systematic review with network meta-analyses to compare, and rank in terms of efficacy and safety, single anti-emetic drugs and their combinations, including 5-hydroxytryptamine3 , dopamine-2 and neurokinin-1 receptor antagonists; corticosteroids; antihistamines; and anticholinergics used to prevent postoperative nausea and vomiting in adults after general anaesthesia. We systematically searched for placebo-controlled and head-to-head randomised controlled trials up to November 2017 (updated in April 2020). We assessed how trustworthy the evidence was using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) and Confidence In Network Meta-Analysis (CINeMA) approaches for vomiting within 24 h postoperatively, serious adverse events, any adverse event and drug class-specific side-effects. We included 585 trials (97,516 participants, 83% women) testing 44 single drugs and 51 drug combinations. The studies' overall risk of bias was assessed as low in only 27% of the studies. In 282 trials, 29 out of 36 drug combinations and 10 out of 28 single drugs lowered the risk of vomiting at least 20% compared with placebo. In the ranking of treatments, combinations of drugs were generally more effective than single drugs. Single neurokinin-1 receptor antagonists were as effective as other drug combinations. Out of the 10 effective single drugs, certainty of evidence was high for aprepitant, with risk ratio (95%CI) 0.26 (0.18-0.38); ramosetron, 0.44 (0.32-0.59); granisetron, 0.45 (0.38-0.54); dexamethasone, 0.51 (0.44-0.57); and ondansetron, 0.55 (0.51-0.60). It was moderate for fosaprepitant, 0.06 (0.02-0.21) and droperidol, 0.61 (0.54-0.69). Granisetron and amisulpride are likely to have little or no increase in any adverse event compared with placebo, while dimenhydrinate and scopolamine may increase the number of patients with any adverse event compared with placebo. So far, there is no convincing evidence that other single drugs effect the incidence of serious, or any, adverse events when compared with placebo. Among drug class specific side-effects, evidence for single drugs is mostly not convincing. There is convincing evidence regarding the prophylactic effect of at least seven single drugs for postoperative vomiting such that future studies investigating these drugs will probably not change the estimated beneficial effect. However, there is still considerable lack of evidence regarding safety aspects that does warrant investigation.

Acceptance of a medication refill reminder service in German community pharmacy practice.

Medication refill reminder services (MRRS), having the potential to support the detection of non-adherence and to promote periodic medication refilling by addressing forgetfulness, are not generally available in community pharmacy practice. Based on a new software module, a MRRS was developed. The acceptance of this service was tested in community pharmacies in Germany. Patients were recruited by trained pharmacy staff. Supported by the software, the pharmacies reminded patients to refill their prescription. After 7 months, the service was evaluated by patients and pharmacy staff. The pharmacy owners/managers were interviewed. Ten pharmacies applied the service to 148 patients, with 806 refill reminders for 391 drugs. Seventy-five patients (50.7%) chose to be reminded by a phone call, followed by text message (n=25), and email (n=18). Of all patients, 75 (50.7%) completed the paper-based questionnaire. Sixty-eight (90.7%) rated the service as good or very good and 54 (72.0%) felt more satisfied with their pharmacy. Sixty-four patients (85.3%) considered the service as supportive and wanted to continue. Thirty-nine pharmacy staff members (61.9%) answered the online questionnaire. Twenty-four (61.5%) stated that they found it difficult to use and apply the MRRS; twenty-six (66.6%) experienced technical problems. The service was rated good by 16 (41.0%) pharmacy staff members. They regarded the service helpful for some patients and wanted to continue after the end of the study. The majority of the ten interviewed pharmacy owners/managers expressed the opinion that the service was not very suitable for increasing customer loyalty and not cost-effective. Nevertheless, six (60.0%) of them wanted to continue using the service. The MRRS seems to be feasible, apart from technical difficulties. Patients rated the service as supportive, and the personal contact seems to be of high importance; most patients would like to continue the service. However, offering the service to patients turned out to be challenging in daily German community pharmacy practice.

Influence of xenon on pulmonary mechanics and lung aeration in patients with healthy lungs.

BACKGROUND: The anaesthetic xenon shows potent organ-protective properties. Due to high density and dynamic viscosity, peak inspiratory pressure (Pmax) increases during xenon application. Thus, barotrauma may counteract organ protection. Accordingly, we investigated the influence of xenon on lung mechanics and lung aeration in patients with normal and reduced thoracic wall compliance. METHODS: After registration and ethical approval, 20 patients free of pulmonary disease undergoing routine xenon-based anaesthesia were mechanically ventilated. The primary outcome variable transpulmonary pressure (Ptp) was determined from plateau pressure and intraoesophageal pressure before and after xenon wash-in. We recorded Pmax, and calculated airway resistance (RAW), and static (Cstat) and dynamic (Cdyn) respiratory compliances. Finally, lung aeration was quantified by electrical impedance tomography-derived centre of ventilation index (CVI) and global inhomogeneity index (GI) in the awake state, before and during xenon. RESULTS: Xenon increased Pmax [20.8 (SD 3) vs 22.6 (3) cm H2O, P<0.001] and RAW [0.9 (0.2) vs 1.4 (0.3) cm H2O litre-1 s, P<0.001], without affecting Ptp [1.5 (4) vs 2.0 (4) cm H2O, P=0.15]. While Cstat remained unchanged, Cdyn was reduced [33.9 (7) vs 31.2 (6) ml (cm H2O)-1, P<0.001). A ventral tidal volume shift after anaesthesia induction [CVI 0.53 (0.03) vs 0.59 (0.04), P<0.001] was unaltered during xenon [CVI 0.59 (0.04), P=0.29]. Homogeneity of lung aeration was also unchanged during xenon [GI 0.37 (0.03) vs 0.37 (0.03), P=0.99]. There were no clinically meaningful differential BMI-related effects. CONCLUSIONS: Xenon increases calculated airway resistance and peak inspiratory pressure without affecting transpulmonary pressure, independent of BMI. CLINICAL TRIAL REGISTRATION: NCT02682758.

The hip fracture surgery in elderly patients (HIPELD) study to evaluate xenon anaesthesia for the prevention of postoperative delirium: a multicentre, randomized clinical trial.

BACKGROUND: Postoperative delirium occurs frequently in elderly hip fracture surgery patients and is associated with poorer overall outcomes. Because xenon anaesthesia has neuroprotective properties, we evaluated its effect on the incidence of delirium and other outcomes after hip fracture surgery. METHODS: This was a phase II, multicentre, randomized, double-blind, parallel-group, controlled clinical trial conducted in hospitals in six European countries (September 2010 to October 2014). Elderly (≥75yr-old) and mentally functional hip fracture patients were randomly assigned 1:1 to receive either xenon- or sevoflurane-based general anaesthesia during surgery. The primary outcome was postoperative delirium diagnosed through postoperative day 4. Secondary outcomes were delirium diagnosed anytime after surgery, postoperative sequential organ failure assessment (SOFA) scores, and adverse events (AEs). RESULTS: Of 256 enrolled patients, 124 were treated with xenon and 132 with sevoflurane. The incidence of delirium with xenon (9.7% [95% CI: 4.5 -14.9]) or with sevoflurane (13.6% [95% CI: 7.8 -19.5]) were not significantly different (P=0.33). Overall SOFA scores were significantly lower with xenon (least-squares mean difference: -0.33 [95% CI: -0.60 to -0.06]; P=0.017). For xenon and sevoflurane, the incidence of serious AEs and fatal AEs was 8.0% vs 15.9% (P=0.05) and 0% vs 3.8% (P=0.06), respectively. CONCLUSIONS: Xenon anaesthesia did not significantly reduce the incidence of postoperative delirium after hip fracture surgery. Nevertheless, exploratory observations concerning postoperative SOFA-scores, serious AEs, and deaths warrant further study of the potential benefits of xenon anaesthesia in elderly hip fracture surgery patients. CLINICAL TRIAL REGISTRATION: EudraCT 2009-017153-35; ClinicalTrials.gov NCT01199276.

Co-incubation of PMN and CaCo-2 cells modulates inflammatory potential.

Polymorphonuclear granulocytes (PMN) are activated in inflammatory reactions. Intestinal epithelial cells are relevant for maintaining the intestinal barrier. We examined interactions of PMN and intestinal epithelial cell-like CaCo-2 cells to elucidate their regulation of inflammatory signalling and the impact of cyclooxygenase (COX), nitric oxide (NO) and platelet-activating factor (PAF). Human PMN and CaCo-2 cells, separately and in co-incubation, were stimulated with the calcium ionophore A23187 or with N-Formyl-methionyl-leucyl-phenylalanin (fMLP) that activates PMN only. Human neutrophil elastase (HNE) and respiratory Burst were measured. To evaluate the modulation of inflammatory crosstalk we applied inhibitors of COX (acetyl salicylic acid; ASA), NO-synthase (N-monomethyl-L-arginin; L-NMMA), and the PAF-receptor (WEB2086). Unstimulated, co-incubation of CaCo-2 cells and PMN led to significantly reduced Burst and elevated HNE as compared to PMN. After stimulation with A23187, co-incubation resulted in an inhibition of Burst and HNE. Using fMLP co-incubation failed to modulate Burst but increased HNE. Without stimulation, all three inhibitors abolished the effect of co-incubation on Burst but did not change HNE.  ASA partly prevented modulation of Burst L-NMMA and WEB2086 did not change Burst but abolished mitigation of HNE. Without stimulation, co-incubation reduced Burst and elevated HNE. Activation of PMN and CaCo-2 cells by fMLP as compared to A23187 resulted in a completely different pattern of Burst and HNE, possibly due to single vs. dual cell activation. Anti-inflammatory effect of co-incubation might in part be due to due to COX-signalling governing Burst whereas NO- and PAF-dependent signalling seemed to control HNE release.

[Integration of palliative care into intensive care : Systematic review]. / Integration der Palliativmedizin in die Intensivmedizin : Systematische Übersichtsarbeit.

BACKGROUND: One of the prime aims of intensive care is to cure patients or at least to extend life duration, sometimes to the extent of losing quality of life. Palliative care aims to improve the quality of life of patients with life-limiting conditions; however, some patients need both intensive and palliative care. About 5-10% of all deaths in Germany and 20% of all deaths in the USA occur in an intensive care unit (ICU) and many of those as well as other patients may benefit from palliative care consultation. Palliative care consultations are increasingly available for intensive care patients but are still infrequently used. OBJECTIVES: We aimed to determine the current situation of palliative patients in ICU settings: what is the impact of palliative care interventions on the quality of care of ICU patients? To what extent is palliative care support at ICUs available and to what extent is it used? Which factors trigger palliative care consultations? METHOD: We set out with a search of PubMed, Scopus and other databases in English and on a) the impact of palliative care interventions on the quality of care of ICU patients, b) the utilization of palliative care support in ICUs and c) the factors which trigger palliative care consultations. We included both quantitative and qualitative studies to reflect the views of all parties involved. To emphasize the situation in German-speaking countries we also searched Google Scholar with search terms in German and added those results to the review. Additionally, hand-searched studies in English and in German were included. RESULTS: We screened 695 abstracts and identified 18 relevant articles of which 15 were from the USA and Great Britain, 1 each was from Austria, Germany and Switzerland. Palliative care is a meaningful addition to ICU standard treatment: it can improve quality of care and helps reduce length of stay in an ICU. It is unclear if the reduced length of stay leads to economic benefits; however, the utilization of palliative care is inconsistent and infrequent as is its acceptance among ICU physicians. Trigger factors can be used to improve the integration of palliative care support in ICUs and point out patients' unmet palliative needs. DISCUSSION: Trigger factors can reduce barriers which hold back the integration of palliative care in ICUs. Early integration of palliative care can improve quality of care by offering psychological support to patients and their families and by providing collegial consultation. An ongoing prospective study is investigating the acceptance of trigger factors in the daily routine among ICU physicians in Germany.

Interaction of DPP10a with Kv4.3 channel complex results in a sustained current component of human transient outward current Ito.

The sustained component of the K(+) outward current in human atrial myocytes is believed to be due to the slowly inactivating ultra-rapid potassium current I Kur and not to the fast inactivating transient outward current Ito. Here we provide evidence for contribution of Ito to this late current due to the effects of dipeptidyl peptidase-like protein (DPP) 10 (DPP10a) interacting with Kv4.3 channels. We studied the late current component of Ito in human atrial myocytes and CHO cells co-expressing Kv4.3 or Kv4.3/KChIP2 (control) and DPP proteins using voltage-clamp technique and a pharmacological approach. A voltage dependent and slowly inactivating late current (43% of peak amplitude) could be observed in atrial myocytes. We found a similar current in CHO cells expressing Kv4.3/KChIP2 + DPP10a, but not in cells co-expressing Kv4.3 + DPP or Kv4.3/KChIP2 + DPP6-S. Assuming that DPP10a influences atrial Ito, we detected DPP10 expression of three alternatively spliced mRNAs, DPP10 protein and colocalization of Kv4.3 and DPP10 proteins in human atrial myocytes. DPP10a did not affect properties of expressed Kv1.5 excluding a contribution to the sustained IKur in atrial cells. To test for the contribution of Kv4-based Ito on sustained K(+) outward currents in human atrial myocytes, we used 4-AP to block IKur, in combination with Heteropoda toxin 2 to block Kv4 channels. We could clearly separate an Ito fraction of about 19% contributing to the late current in atrial myocytes. Thus, the interaction of DPP10a, expressed in human atrium, with Kv4.3 channels generates a sustained current component of Ito, which may affect late repolarization phase of atrial action potentials.

Predictors for postoperative nausea and vomiting after xenon-based anaesthesia.

BACKGROUND: In contrast to volatile anaesthetics, xenon acts by antagonism at N-methyl-d-aspartate receptors and antagonizes 5-hydroxytryptamine type 3 receptors that mediate nausea and vomiting. Therefore, it is unknown whether the same risk factors for postoperative nausea and vomiting (PONV) after volatile anaesthetics apply to xenon-based anaesthesia. METHODS: With ethics committee approval and written informed consent, 502 consecutive patients undergoing xenon-based anaesthesia were included in a multicentre prospective observational study. Antiemetic prophylaxis was administered at the discretion of the attending anaesthetists. Postoperative nausea and vomiting and need for antiemetic rescue medication were assessed for 24 h after anaesthesia. Multivariate logistic regression analysis was performed to quantify risk factors for PONV and need for rescue medication. RESULTS: Four hundred and eighty-eight subjects were available for the final analysis. The incidence of PONV in subjects without prophylaxis was lower than expected according to the Apfel Score (28% observed; 42% expected, P<0.001). Independent predictors for PONV were (adjusted odds ratio; 95% confidence interval) female sex (1.76; 1.08-2.89), younger patient age (0.82 per 10 yr; 0.69-0.97), and longer duration of anaesthesia (1.36 per hour; 1.17-1.59). CONCLUSIONS: The incidence of PONV was significantly lower than predicted by the Apfel Score. Female sex, younger age, and longer duration of anaesthesia are risk factors for PONV after xenon-based anaesthesia. CLINICAL TRIAL REGISTRATION: German Federal Institute for Drugs and Medical Devices number AL-PMS-01/07GER.

Tanshinone II A sulfonate, but not tanshinone II A, acts as potent negative allosteric modulator of the human purinergic receptor P2X7.

Tanshinone II A sulfonate (TIIAS) was identified as a potent, selective blocker of purinergic receptor P2X7 in a compound library screen. In this study, a detailed characterization of the pharmacologic effects of TIIAS on P2X7 is provided. Because TIIAS is a derivative of tanshinone II A (TIIA) and both compounds have been used interchangeably, TIIA was included in some assays. Fluorometric and electrophysiologic assays were used to characterize effects of TIIAS and TIIA on recombinantly expressed human, rat, and mouse P2X7. Results were confirmed in human monocyte-derived macrophages expressing native P2X7. In all experiments, involvement of P2X7 was verified using established P2X7 antagonists. TIIAS, but not TIIA, reduces Ca(2+) influx via human P2X7 (hP2X7) with an IC50 of 4.3 µM. TIIAS was less potent at mouse P2X7 and poorly inhibited rat P2X7. Monitoring of YO-PRO-1 uptake confirmed these findings, indicating that formation of the hP2X7 pore is also suppressed by TIIAS. Electrophysiologic experiments revealed a noncompetitive mode of action. TIIAS time-dependently inhibits hP2X7 gating, possibly by binding to the intracellular domain of the receptor. Inhibition of native P2X7 in macrophages by TIIAS was confirmed by monitoring Ca(2+) influx, YO-PRO-1 uptake, and release of the proinflammatory cytokine interleukin-1ß. Fluorometric experiments involving recombinantly expressed rat P2X2 and human P2X4 were conducted and verified the compound's selectivity. Our data suggest that hP2X7 is a molecular target of TIIAS, but not of TIIA, a compound with different pharmacologic properties.

Accessory subunits alter the temperature sensitivity of Kv4.3 channel complexes.

In human atrial myocytes the transient outward current I(to) develops a conspicuous faster inactivation with increasing temperatures. Since ß-subunits are known to modulate I(to) current kinetics, we hypothesized that the temperature sensitivity of I(to) is not only determined by the property of the ion-passing α-subunit Kv4.3 but also by its interaction with accessory ß-subunits. We therefore studied the influence of the transmembrane ß-subunits KCNE1, KCNE2 and DPP6 on Kv4.3/KChIP2 channels in CHO cells at room temperature and at physiological temperature. Exposure to 37°C caused a significant acceleration of the channel kinetics, whereas current densities and voltage dependences remained unaltered at 37°C compared to 23°C. However, Kv4.3/KChIP2 channels without transmembrane ß-subunits showed the strongest temperature sensitivity with considerably increased rates of activation and inactivation at 37°C. KCNE2 significantly slowed the current kinetics at 37°C compared to Kv4.3/KChIP2 channels, whereas KCNE1 did not influence the channel properties at both temperatures. Interestingly, the accelerating effects of DPP6 on current kinetics described at 23°C were diminished at physiological temperature, thus at 37°C current kinetics became remarkably similar for channel complexes Kv4.3/KChIP2 with and without DPP6 isoforms. A Markov state model was developed on the basis of experimental measurements to simulate the influence of ß-subunits on Kv4.3 channel complex at both temperatures. In conclusion, the remarkably fast kinetics of the native I(to) at 37°C could be reproduced by co-expressing Kv4.3, KChIP2, KCNE2 and DPP6 in CHO cells, whereas the high temperature sensitivity of human I(to) could be not mimicked.

Cardiovascular stability and unchanged muscle sympathetic activity during xenon anaesthesia: role of norepinephrine uptake inhibition.

BACKGROUND: Intraoperative hypotension is associated with increased risk of perioperative complications. The N-methyl-d-aspartate (NMDA) receptor (NMDA-R) antagonist xenon (Xe) induces general anaesthesia without impairment of cardiac output and vascular resistance. Mechanisms involved in cardiovascular stability have not been identified. METHODS: Muscle sympathetic activity (MSA) (microneurography), sympathetic baroreflex gain, norepinephrine (NE) plasma concentration (high-performance liquid chromatography), anaesthetic depth (Narcotrend(®) EEG monitoring), and vital parameters were analysed in vivo during Xe mono-anaesthesia in human volunteers (n=8). In vitro, NE transporter (NET) expressing HEK293 cells and SH-SY5Y neuroblastoma cells were pre-treated with ketamine, MK-801, NMDA/glycine, or vehicle. Subsequently, cells were incubated with or without Xe (65%). NE uptake was measured by using a fluorescent NET substrate (n=4) or [(3)H]NE (n=6). RESULTS: In vivo, Xe anaesthesia increased mean (standard deviation) arterial pressure from 93 (4) to 107 (6) mm Hg and NE plasma concentration from 156 (55) to 292 (106) pg ml(-1), P<0.01. MSA and baroreflex gain were unaltered. In vitro, ketamine decreased NET activity (P<0.01) in NET-expressing HEK293 cells, while Xe, MK-801, and NMDA/glycine did not. Xe reduced uptake in SH-SY5Y cells expressing NET and NMDA-Rs (P<0.01). MK-801 (P<0.01) and ketamine (P<0.01) also reduced NET activity, but NMDA/glycine blocked the effect of Xe on [(3)H]NE uptake. CONCLUSIONS: In vivo, Xe anaesthesia does not alter sympathetic activity and baroreflex gain, despite increased mean arterial pressure. In vitro, Xe decreases the uptake of NE in neuronal cells by the inhibition of NET. This inhibition might be related to NMDA-R antagonism and explain increased NE concentrations at the synaptic cleft and in plasma, contributing to cardiovascular stability during Xe anaesthesia.

Ventilation with low tidal volumes during upper abdominal surgery does not improve postoperative lung function.

BACKGROUND: Prolonged postoperative decrease in lung function is common after major upper abdominal surgery. Evidence suggests that ventilation with low tidal volumes may limit the damage during mechanical ventilation. We compared postoperative lung function of patients undergoing upper abdominal surgery, mechanically ventilated with high or low tidal volumes. METHODS: This was a double-blind, prospective, randomized controlled clinical trial. One hundred and one patients (age ≥ 50 yr, ASA ≥ II, duration of surgery ≥ 3 h) were ventilated with: (i) high [12 ml kg(-1) predicted body weight (PBW)] or (ii) low (6 ml kg(-1) PBW) tidal volumes intraoperatively. The positive end-expiratory pressure was 5 cm H(2)O in both groups and breathing frequency adjusted to normocapnia. Time-weighted averages (TWAs) of forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV(1)) until 120 h after operation were compared (P<0.025 considered statistically significant). Secondary outcomes were oxygenation, respiratory and non-respiratory complications, length of stay and mortality. RESULTS: The mean (sd) values of TWAs of FVC and FEV(1) were similar in both groups: FVC: 6 ml group 1.8 (0.7) litre vs 12 ml group 1.6 (0.5) litre (P=0.12); FEV(1): 6 ml group 1.4 (0.5) litre vs 12 ml group 1.2 (0.4) litre (P=0.15). FVC and FEV(1) at any single time point and secondary outcomes did not differ significantly between groups. CONCLUSIONS: Prolonged impaired lung function after major abdominal surgery is not ameliorated by low tidal volume ventilation.

[Time required and associated costs for implementation of home medication review with associated pharmaceutical and medical evaluation in the ambulatory health care sector]. / Zeitbedarf und Kosten für die Umsetzung eines Medikamentenreviews und assoziierter pharmazeutischer und medizinischer Evaluation im ambulanten Versorgungssektor.

INTRODUCTION: We aimed to estimate the time which is needed to conduct a home medication review (HMR) in the context of the AGnES implementation studies (AGnES=GP-supporting, community-based, e-health-assisted, systemic intervention). In a subsequent step associated costs were calculated. METHODS: IT-supported HMR were conducted by specially qualified AGnES-practice assistants to detect selected drug-related problems (DRP). The patient received pharmaceutical care by their local pharmacist and medical evaluation by their GP, respectively. RESULTS: The data from 471 patients (w: 339; m: 132) were evaluated (median age: w=81; m=78). The interview to detect selected DRP was 6 min (median) long. The subsequent drug record took 14.4 min. There was an additional effort for documentation of 5 min. The local pharmacist needed a median time of 15 min for pharmaceutical evaluation, whereas the GP needed 8 min. The estimated costs accounted for: AGnES-practice assistant: 9.12 €; pharmacist: 11.05 €; GP: 6.30 €. The overall estimated costs were 26.47 €. CONCLUSION: For the first time we present objective costs which were associated with the implementation of HMR. Due to high DRP-induced costs the HMR should be mandatory for groups with a high risk like for the occurrence of DRP.

Influence of helix 12 of Ultraspiracle on Drosophila melanogaster ecdysone receptor function.

Although it has no ligand, helix 12 in the ligand binding domain of Ultraspiracle (USP) is locked in an antagonistic position. To investigate whether this position is of functional importance, we enhanced the flexibility of helix 12 by mutating two amino acids (259, located in L1-3 and F491 in helix 12). Mutated USP reduces the stability of USP and all isoforms of the ecdysone receptor (EcR) and impairs nuclear localization and DNA binding of EcR/USP(L259A/F491/A), resulting in lower levels of basal transcriptional activity. Although the affinity of the ligand ponasterone A to EcR/USP(L259/F491) is moderately diminished, hormone-induced stimulation of transcriptional activity is normal. Potentiation of the ecdysone response by juvenile hormone (JH) is selectively increased in mutated heterodimers with EcR-B1, demonstrating that the antagonistic position impairs functional interaction of the EcR complex with JHIII.

Cardiac resynchronization therapy: an updateimpaired left ventricular systolic function.

Cardiac resynchronization therapy has been shown to reduce hospitalization and mortality, and to improve heart failure symptoms, in patients with systolic dysfunction and ventricular dyssynchrony. We review the current guidelines for cardiac resynchronization therapy, the underlying evidence, the latest developments in the field and directions of future research.

[Epithelial neoplasia of the appendix: what has recently changed?]. / Néoplasie épithéliale de l'appendice: quoi de neuf?

Appendicular tumors are mostly found incidentally in up to 1.5% of all appendectomies. Neuroendocrine tumors are the commonest malignancies, and are associated with an excellent long-term prognosis. While small lesions located at the appendicular tip can be treated with simple appendectomy, advanced tumors require right hemicolectomy. Goblet cell carcinoids are rare tumors showing a mixed phenotype. Long-term outcome is impaired, and for most cases a right hemicolectomy is mandatory. Colonic-type adenocarcinomas have a similar behavior like conventional colonic cancer and should be treated similarly. Mucinous neoplasias possess the characteristic of extensive mucin production with intraperitoneal spread. Treatment options are ranging from right hemicolectomy to multivisceral resection with intraperitoneal chemotherapy.

[Preoperative nutrition in abdominal surgery: recommendations and reality]. / Nutrition préopératoire en chirurgie viscérale: recommandations et réalité.

Malnutrition concerns up to 50% at in-hospital admission. Its diagnosis and treatment are fundamental parts of the surgical approach because nutritional status directly influences the clinical outcome. The Nutritional Risk Score (NRS-2002) represents the recommended screening tool by the European Society of Parenteral and Enteral Nutrition (ESPEN). Patients with a score > or = 3 and aged > 70 years old, should receive a nutritional support during 7-14 day before surgery. Depending on patient's clinical conditions, the enteral route of administration should be preferred. Despite strong evidence in favor of nutritional supplementation, much effort must be done to implement these supportive strategies in the everyday clinical practice.