Narrowing geographic inequality in life expectancy in Brazil: a multilevel analysis between 1991 and 2010.

OBJECTIVES: To analyze the geographic inequalities in life expectancy (LE) and the probability of survival up to 40 and 60 years in Brazil between 1991 and 2010, to partition the variance of these indicators by including municipalities, states, and macroregions in the analysis, and to test the association between municipal socio-economic and health services indicators with life expectancy. STUDY DESIGN: Multilevel analysis. METHODS: Census data from 1991, 2000, and 2010 were used to calculate the outcomes and the socio-economic variables. Municipalities were separated into centiles according to their values in each outcome. Absolute and relative differences were calculated for each year. Multilevel linear regression models were performed, taking into account three levels: regions, states, and municipalities. Municipal socio-economic and health services variables were included in the model with the 2010 data. RESULTS: All 5545 Brazilian counties showed improvement in the three indicators, but the magnitude varied significantly across the country. The highest gains in LE were observed in the North and Northeast regions. The gap in LE between the 1st and 99th percentile decreased from 19.6 years to 12.2 years. The relative difference also fell, from 1.37 to 1.18. Most counties' socio-economic and health services indicators were associated with the outcomes and explained 86.7%, 31.2%, and 32.4% of the variation in LE attributable to regions, states, and counties, respectively. CONCLUSIONS: The average life expectancy increased between 1991 and 2010. Concomitantly, a reduction in geographic disparities was observed. The counties' socio-economic and health services variables explained much of the variation of the outcomes in 2010.

The effect of inhalational anaesthesia during deceased donor organ procurement on post-transplantation graft survival.

Many deceased by neurologic criteria donors are administered inhalational agents during organ recovery surgery-a process that is characterised by warm and cold ischaemia followed by warm reperfusion. In certain settings, volatile anaesthetics (VA) are known to precondition organs to protect them from subsequent ischaemia-reperfusion injury. As such, we hypothesised that exposure to VA during organ procurement would improve post-graft survival. Lifebanc (organ procurement organisation [OPO] for NE Ohio) provided the investigators with a list of death by neurologic criteria organ donors cared for at three large tertiary hospitals in Cleveland between 2006 and 2016-details about the surgical recovery phase were extracted from the organ donors' medical records. De-identified data on graft survival were obtained from the United Network for Organ Sharing (UNOS). The collated data underwent comparative analysis based on whether or not VA were administered during procurement surgery. Records from 213 donors were obtained for analysis with 138 exposed and 75 not exposed. Demographics, medical histories, and organ procurement rates were similar between the two cohorts. For the primary endpoint, there were no significant differences observed in either early (30-day) or late (five-year) graft survival rates for kidney, liver, lung, or heart transplants. Our findings from this retrospective review of a relatively small cohort do not support the hypothesis that the use of VA during the surgical procurement phase improves graft survival. Reviews of larger datasets and/or a prospective study may be required to provide a definitive answer.

Linear and non-linear heart rate metrics for the assessment of anaesthetists' workload during general anaesthesia.

BACKGROUND: Excessive workload may impact the anaesthetists' ability to adequately process information during clinical practice in the operation room and may result in inaccurate situational awareness and performance. This exploratory study investigated heart rate (HR), linear and non-linear heart rate variability (HRV) metrics and subjective ratings scales for the assessment of workload associated with the anaesthesia stages induction, maintenance and emergence. METHODS: HR and HRV metrics were calculated based on five min segments from each of the three anaesthesia stages. The area under the receiver operating characteristics curve (AUC) of the investigated metrics was calculated to assess their ability to discriminate between the stages of anaesthesia. Additionally, a multiparametric approach based on logistic regression models was performed to further evaluate whether linear or non-linear heart rate metrics are suitable for the assessment of workload. RESULTS: Mean HR and several linear and non-linear HRV metrics including subjective workload ratings differed significantly between stages of anaesthesia. Permutation Entropy (PeEn, AUC=0.828) and mean HR (AUC=0.826) discriminated best between the anaesthesia stages induction and maintenance. In the multiparametric approach using logistic regression models, the model based on non-linear heart rate metrics provided a higher AUC compared with the models based on linear metrics. CONCLUSIONS: In this exploratory study based on short ECG segment analysis, PeEn and HR seem to be promising to separate workload levels between different stages of anaesthesia. The multiparametric analysis of the regression models favours non-linear heart rate metrics over linear metrics.

Comparing propofol versus sevoflurane anesthesia for epileptogenic focus detection during positron emission tomography in pediatric patients.

BACKGROUND: Fluoro-D-deoxyglucose positron emission tomography (FDG-PET) is a standard procedure for interictal assessment and accurate pre-surgical evaluation of presumed epileptogenic zone localization. Profound sedation or general anesthesia is frequently required to reduce movement artefacts in young or cognitively impaired patients during image acquisition. This study compares the impact of propofol and sevoflurane anesthesia on overall quality of PET images, detectability of a hypometabolic lesion and demarcation of the detected lesion in pediatric patients suffering from focal epilepsia. METHODS: Pediatric patients with focal epilepsia were anesthesized using propofol (N.=37) or sevoflurane (N.=43). Two independent blinded investigators rated the PET-scans on a 3-point Likert scale with respect to overall quality of PET images, detectability of a hypometabolic lesion and demarcation of the detected lesion. Mann-Whitney-U-Test was conducted to compare the rating results between the two anesthesia regimes. Inter-rater reliability was calculated using Cohen's Kappa. RESULTS: Anesthesia was throughout uneventful and there was no clinical evidence for peridiagnostic seizures. Differences in neither single dimension ratings nor in sum scores (mean 5.8 ± SD 1.5 for propofol, and 5.7 ± SD 1.5 for sevoflurane; P=0.567) were statistically significant. Cohen's Kappa was between 0.428 and 0.499. CONCLUSION: For surgical planning in patients with epilepsy, FDG-PET imaging is an indispensable functional imaging technique to detect hypometabolism. We conclude that both, sevoflurane and propofol based anesthetic regimes are suitable to detect hypometabolic cerebral lesions during FDG-PET.

Cardiopulmonary resuscitation performance during simulator-based trainings: a comparative retrospective analysis of adherence to 2005 and 2010 guidelines.

BACKGROUND: New cardiopulmonary resuscitation (CPR) guidelines have been published in 2010 emphasizing the importance of minimizing interruptions during chest compression. The aim of our study was to compare the simulator-based CPR training performance of physicians not specialized in anaesthesia and intensive care nurses before and after implementation of new resuscitation guidelines. METHODS: In autumn 2010, a total of 74 scenarios during six 1.5 day simulation-based CPR trainings were performed. Four of them were conducted after the implementation of the 2010 guidelines. During each simulated scenario a programmed script standardized the conditions of the simulator and its reactions on the trainees' actions. CPR relevant parameters were extracted on the basis of the simulator's log files and no-flow-time fraction and median cardiac output of the simulator were calculated. Results before and after the guideline implementation were compared using the Wilcoxon Two Sample Test. RESULTS: Thirty-four out of 74 scenarios were included into the analysis. During training according to the 2010 guidelines, the no-flow-time fraction was lower (median: 21.8% [IQR: 16.1-27.1%] vs. 29.1 % [IQR: 25.0-30.9 %]; P=0.04). The median cardiac output increased from 1.60 L/min-1 [IQR: 1.50-1.65 L/min-1] to 1.90 L/min-1 [IQR: 1.80-2.10 L/min-1]; P<0.001) when the CPR training was conducted according to the 2010 resuscitation guidelines. CONCLUSION: Non-anesthesiological physicians and intensive care nurses training demonstrated an improved CPR performance in a high-fidelity human patient simulator with respect to the median cardiac output and duration of no-flow-time when 2010 CPR guidelines were applied.

Alterations in rotation thromboelastometry (ROTEM®) parameters: point-of-care testing vs analysis after pneumatic tube system transport.

BACKGROUND: Thromboelastometry as point-of-care (POC) testing enables the analysis of the clotting process at the bedside, providing rapid results to guide haemostatic therapy. However, POC testing utilizes medical staff who are managing critically ill patients, as non-laboratory personnel may not be sufficiently trained to run the devices. To resolve these problems, thromboelastometry can be performed in the central laboratory and rapid transport of samples can be accomplished via a pneumatic tube system (PTS). This study compares thromboelastometry parameters of blood samples analysed immediately with those analysed after PTS transport. METHODS: In patients with normal haemostasis, two arterial blood samples were collected from each patient (n=92) in citrated plastic tubes to investigate the assays INTEM (n=35), EXTEM (n=27), and FIBTEM (n=30). One blood sample was analysed immediately, the other sample after PTS transport. Thromboelastometry was performed using a single ROTEM(®) device. RESULTS: The mean clot firmness values were significantly lower for PTS samples in both the INTEM (-0.7 mm cf. -1.1 mm) and EXTEM (-1.4 cf. -1.7 mm) assays. INTEM coagulation time (CT) was significantly lower in PTS samples with a mean difference of -13 s. EXTEM CT was significantly higher in PTS samples with a mean difference of +3.9 s. CONCLUSIONS: Thromboelastometry parameters of blood samples analysed after PTS transport are significantly altered compared with those analysed immediately. However, in patients with normal haemostasis, the alterations were small and without clinical consequence, implying that analysis after PTS transport is an acceptable alternative to prompt analysis at the bedside. Further studies should focus on patients with impaired haemostasis.

The mu-opioid receptor agonist remifentanil induces acute dysphoria irrespective of its analgesic properties.

Mu-opioidergic agonists are believed to induce euphoria, whereas kappa-agonists are thought to lead to dysphoria. Our study investigated mood effects of remifentanil, a mu-receptor opioid agonist, in healthy male volunteers. Moreover, we examined interactions between mood and pain. Three conditions were investigated in 21 volunteers: saline, 0.05 and 0.15 microg kg(-1) min(- 1) remifentanil. Each condition was investigated during non-painful heat and during painful heat stimulation. Mood was measured with the von Zerssen's mood scale (Bf-S score) and pain intensity using a Visual Analogue Scale (VAS). High Bf-S scores are reflecting discontent and dysphoria. Changes were tested for significance using a linear mixed model approach. Remifentanil significantly increased Bf-S scores during painful heat (+91.4%), indicating a negative mood effect, although it reduced VAS scores of painful heat intensity (-49.0%). The type of sensory stimulation (non-painful versus painful) had no effect on mood. There was no interaction between remifentanil dose and type of stimulation. Our results provide evidence for negative mood effects of remifentanil. These effects occur with and without pain. Taken into account that remifentanil reduces pain, one could have expected analgesia-related amelioration of mood instead. In clinical practice, these remifentanil effects should be considered and a comedication might be advisable.

[Postoperative acute mitral regurgitation. Unexpected finding after minor non-cardiac surgery]. / Akute perioperative Mitralklappeninsuffizienz. Unerwarteter Befund nach nichtkardiochirurgischem Bagatelleingriff.

This report describes the case of a 59-year-old man who was scheduled for general anesthesia with propofol, sufentanil and sevoflurane for removal of a metal implant. The patient was classified as American Society of Anesthesiologists (ASA) II status because of an asymptomatic mitral valve prolapse and medically treated arterial hypertension. During induction of narcosis a pulsoxymetrically measured inadequate increase in oxygen saturation after preoxygenation was noticed and a moderate respiratory obstruction occurred intraoperatively, but anesthesia was uneventfully completed and the patient was extubated. However, 3 h later the patient developed severe dyspnea, hypoxia, tachycardia and arterial hypotension. Physical examination revealed a new grade 4/6 systolic murmur radiating to the axilla and X-ray showed bilateral pulmonary edema. Neither electrocardiographic nor biochemical manifestations of acute myocardial infarction were identified but transthoracic echocardiography revealed fluttering of the posterior leaflet of the mitral valve with grade III regurgitation and dilation of the left atrium. Coronary angiography was normal and left ventriculography confirmed severe mitral regurgitation. Mitral valve repair was successfully performed 22 h after presentation of symptoms. Mitral regurgitation is a common finding on echocardiography, seen to some degree in over 75% of the population. The etiology of mitral valve insufficiency which can be caused by pathologic changes of one or more of the components of the mitral valve, including the leaflets, annulus, chordae tendineae, papillary muscles, or by abnormalities of the surrounding left ventricle and/or atrium are discussed. Rupture of mitral chordae tendineae is infrequent and causes acute hemodynamic deterioration and needs corrective surgery. Valve replacement should be performed only if mitral valve repair is not possible. Echocardiography is an invaluable tool in determining the severity of regurgitation, the integrity of the mitral valve apparatus, the extent of left ventricular enlargement, and the ejection fraction. Acute mitral valve regurgitation caused by a rupture of chordae tendineae should be considered in the differential diagnosis of perioperative acute pulmonary edema.

Efficacy and safety of pregabalin in treatment refractory patients with various neuropathic pain entities in clinical routine.

AIMS: Conventional approaches to the management of neuropathic pain (NeP) often yield unsatisfactory results. We aimed to investigate pregabalin, a gamma-aminobutyric acid (GABA)-analogue, in a wide range of pregabalin naive patients with treatment refractory NeP. METHODS: Investigator-initiated, 4-week, open, prospective multicentre study in tertiary care. Pregabalin was prescribed at physicians' discretion based on patients' individual responses and tolerability, with or without concomitant analgesics. Consecutive patients were requested to fill in questionnaires at baseline and after 14 and 28 days with numerical pain rating scales (0, none; 10, worst possible), sleep rating scales, parts of the Brief Pain Inventory, Pain Experience Scale, Short Questionnaire on Current Burden and the SF-12 health-related quality of life scale. RESULTS: In 55 patients, the mean pregabalin dose was 142 +/- 26 mg at day 1 and 348 +/- 161 mg at day 28. The mean pain score decreased from 6.5 +/- 1.7 to 5.5 +/- 1.9 at day 14 and to 4.9 +/- 1.8 at day 28 (-24.6%, p < 0.0001). Significant and rapid improvements were noted in the sleep interference score (p < 0.00001), Short Questionnaire on Current Burden (p < 0.01) and SF-12 (somatic score p < 0.001; psychological score p < 0.01). Pregabalin was well tolerated, and only three patients (5%) discontinued treatment prematurely. CONCLUSIONS: Our findings suggest that pregabalin is an effective and well-tolerated drug in difficult-to-treat NeP patients under daily clinical practice conditions. A flexible dosing approach appears appropriate to ensure patient compliance and treatment success.

[Antibiotic prophylaxis in cesarean section -- piperacillin versus piperacillin/tazobactam in 300 cesarean sections]. / Antibiotikaprophylaxe bei Sectio Caesarea -- Piperacillin 4 g versus Piperacillin/Tazobactam 4.5 g.

INTRODUCTION: Antibiotic prophylaxis is a standard procedure in obstetric surgery and has been discussed in various investigations. Use of treatment is judged by high efficacy and good tolerance. METHOD: In 300 patients undergoing cesarean sections we compared results of application of Piperacillin 4 g and Piperacillin/Tazobactam 4.5 g after cut of umbilical cord. Tazobactam/Piperacillin is a combination of a broad-spectrum penicillin and a beta-lactamase inhibitor with increased toxicity against staph. aureus, enterobacter, and other germs responsible for local and systemic infections in obstetric surgery. RESULTS: We did not observe any severe adverse effects. Rate of severe wound infections was 1.3 % (Tazobactam/Piperacillin) and 2 % (Piperacillin alone). The difference showed no statistic significance (p > 0.01). During postoperative course we found a higher increase of CRP (p < 0.01) in the Piperacillin group. CRP proved to be a useful objective parameter to distinguish between patients with or without postoperative infections. No differences were found in the number of leucocytes, time in hospital and other parameters.

[Risks and complications of epidural neurolysis -- a review with case report]. / Schwerwiegende Risiken und Komplikationen der epiduralen Neurolyse nach Racz.

Racz's minimal invasive epidural catheter procedure, also known as "epidural neuroplasty" is not only utilized in patients suffering from failed spine surgery ("failed back surgery syndrome") but also increasingly applied to non-surgical back pain patients to prevent chronification or deterioration. Its hypothesized principle of action is local epidural lysis of adhesions, neurolysis of vertebral nerve roots and local lavage of proinflammatory mediators by repeated injection of local anesthetics, corticosteroids, hyaluronidase and hypertonic saline solution. However adverse events are well known to occur in epidural neuroplasty. Complications of epidural neuroplasty are due to the procedure itself or due to specific drugs-related side effects. Unintended dural puncture, administration of the drugs to the subarachnoid or subdural space, catheter shearing, infection and severe hemodynamic instability during application are most commonly observed adverse events. Complications related to the procedure itself occur immediately, while complications relating to drug administration show later onset. Within this context, we report a case of severe meningitis with neurologic sequelae in a patient who received Racz catheter-treatment for unspecific low-back pain and provide an overview of the literature on other potential severe complications. As a consequence, we recommend that the Racz catheter procedure as yet should be restricted to controlled clinical trials with rigorous inclusion- and exclusion criteria.

[Perioperative pain therapy for knee endoprosthetics]. / Perioperative Schmerztherapie in der Kniegelenkendoprothetik.

Total knee arthroplasty (TKA) is associated with significant postoperative pain. Adequate analgesics and techniques are required for early mobilization, continuous passive motion and intensified physical therapy as well as for high-quality postoperative analgesia.However, in the immediate postoperative setting the excessive nociceptive input can be blocked by using doses which are most frequently associated with adverse effects like dizziness, nausea and vomiting, sedation and risk of respiratory depression. The use of peripheral nerve blocks is recommended after orthopaedic surgery. After TKA, the continuous "3 in 1 nerve block" has been proven to be more effective than conventional patient controlled intravenous opioid therapy as well as than epidural analgesia accompanied by side effects. Postoperative analgesic techniques influence surgical outcome, duration of hospitalization and re-convalescence. The use of regional analgesia after TKA may initially lead to higher costs but it is counterbalanced by a reduction in morbidity and mortality, decrease in hospitalization, improved re-convalescence and a better functional outcome.

The G20210A prothrombin-gene mutation and the plasminogen activator inhibitor (PAI-1) 5G/5G genotype are associated with early onset of severe preeclampsia.

Hereditary risk determinants of venous thrombosis have been reported to be associated with severe preeclampsia. So far there are no data to support whether these risk determinants are related to the time of onset of severe preeclampsia. We used a case-control design, studying 97 women with severe preeclampsia in previous pregnancies and 277 normal women, to assess hereditary risk factors of venous thrombosis as risk determinants for severe preeclampsia. A case-only design comprising solely the 97 women with a history of preeclampsia was used to evaluate these risk factors as risk determinants for early onset of severe preeclampsia. Using the case-control design, there was no significant risk association of the hereditary risk factors with severe preeclampsia [factor V Leiden, odds ratio (OR) 0.9, 95% confidence interval (CI) 0.4, 2.2; prothrombin mutation, OR 1.9, 95% CI 0.5, 7.0; methylentetrahydrofolate reductase 677TT genotype, OR 0.8, 95% CI 0.4, 1.8; plasminogen activator inhibitor (PAI-1) 4G/4G genotype, OR 1.2, 95% CI 0.7, 2.1; PAI-1 5G/5G genotype, OR 1.0, 95% CI 0.5, 1.8]. However, the onset of severe preeclampsia was significantly earlier in women with the G20210A prothrombin gene mutation (24.5 weeks vs. 30.1 weeks, P = 0.046) and in women with the PAI-1 5G/5G genotype (25.7 weeks vs. 30.8 weeks, P = 0.024). Hereditary risk factors for venous thrombosis do not predispose for severe preeclampsia. However, women who are carriers of the G20210A prothrombin gene mutation and the PAI-1 5G/5G genotype are at risk for early onset of severe preeclampsia. It appears that these risk factors do not induce the pathomechanism but accelerate the course of preeclampsia.

Transcriptional regulation by the Wilms' tumour suppressor protein WT1.

Wilms' tumour is a paediatric malignancy of the kidneys and is the most common solid tumour found in children. The Wilms' tumour suppressor protein WT1 is mutated in approximately 15% of Wilms' tumours, and is aberrantly expressed in many others. WT1 can manifest both tumour suppressor and oncogenic activities, but the reasons for this are not yet clear. The Wilms' tumour suppressor protein WT1 is a transcriptional activator, the function of which is under cell-context-specific control. We have previously described a small region at the N-terminus of WT1 (suppression domain) that inhibits the transcriptional activation domain by contacting a co-suppressor protein. We recently identified BASP1 as one of the components of the co-suppressor. Here, we analyse the mechanism of action of the WT1 suppression domain, and discuss its function in the context of the role of WT1 as a regulator of development.

C-terminal truncation of WT1 delays but does not abolish hematopoiesis in embryoid bodies.

The effect of mutations that truncate the WT1 protein on in vitro hematopoietic differentiation from embryonal stem cells has been examined by CFU-A assay, o-dianisidine staining for heme, and RT-PCR analysis of the expression of fetal and adult globins. In two independently isolated ES cell lines the mutations delay but do not abolish hematopoiesis. Analysis of replated CFU-A colonies indicates that the delay occurs prior to the formation of hematopoietic stem cells. The results demonstrate a role for WT1 at the onset of hematopoiesis.

Truncation of WT1 results in downregulation of cyclin G1 and IGFBP-4 expression.

Mutations in the WT1 gene are found in a subset of Wilms' tumours and in certain other disorders such as Denys-Drash syndrome. The WT1 gene product is a zinc finger transcription factor for which many target genes have been suggested. Here we utilise gene targeting to generate cells containing only truncated forms of WT1, in which the DNA-binding region is disrupted. Examination of gene expression in these cells using cDNA macroarrays suggests two novel WT1 transcriptional targets, cyclin G1 (Ccng1), and insulin-like growth factor binding protein 4 (Igfbp4).

Dose-dependent regional cerebral blood flow changes during remifentanil infusion in humans: a positron emission tomography study.

BACKGROUND: The current study investigated dose-dependent effects of the mu-selective agonist remifentanil on regional cerebral blood flow (rCBF) in volunteers using positron emission tomography (PET). METHODS: Ten right-handed male volunteers were included in a 15O-water PET study. Seven underwent three conditions: control (saline), low remifentanil (0.05 microg x kg(-1) x min(-1)), and moderate remifentanil (0.15 microg x kg(-1) x min(-1)). The remaining three participated in the low and moderate conditions. A semirandomized study protocol was used with control and remifentanil conditions 3 or more months apart. The order of low and moderate conditions was randomized. Cardiovascular and respiratory parameters were monitored. Categoric comparisons between the control, low, and moderate conditions and a pixelwise correlation analysis across the three conditions were performed (P < 0.05, corrected for multiple comparisons) using statistical parametric mapping. RESULTS: Cardiorespiratory parameters were maintained constant over time. At the low remifentanil dose, significant increases in relative rCBF were noted in the lateral prefrontal cortices, inferior parietal cortices, and supplementary motor area. Relative rCBF decreases were observed in the basal mediofrontal cortex, cerebellum, superior temporal lobe, and midbrain gray matter. Moderate doses further increased rCBF in mediofrontal and anterior cingulate cortices, occipital lobe transition, and caudal periventricular grey. Significant decreases were detected in the inferior parietal lobes. These dose-dependent effects of remifentanil on rCBF were confirmed by a correlation analysis. CONCLUSION: Remifentanil induced dose-dependent changes in relative rCBF in areas involved in pain processing. At moderate doses, rCBF responses were additionally detected in structures known to participate in modulation of vigilance and alertness. Insight into the mechanisms of opioid analgesia within the pain-processing neural network may lead to a better understanding of antinociception and opioid treatment.