Neuraxial vs general anaesthesia for total hip and total knee arthroplasty: a systematic review of comparative-effectiveness research.

BACKGROUND: This systematic review evaluated the evidence comparing patient-important outcomes in spinal or epidural vs general anaesthesia for total hip and total knee arthroplasty. METHODS: MEDLINE, Ovid EMBASE, EBSCO CINAHL, Thomson Reuters Web of Science, and the Cochrane Central Register of Controlled Trials from inception until March 2015 were searched. Eligible randomized controlled trials or prospective comparative studies investigating mortality, major morbidity, and patient-experience outcomes directly comparing neuraxial (spinal or epidural) with general anaesthesia for total hip arthroplasty, total knee arthroplasty, or both were included. Independent reviewers working in duplicate extracted study characteristics, validity, and outcomes data. Meta-analysis was conducted using the random-effects model. RESULTS: We included 29 studies involving 10 488 patients. Compared with general anaesthesia, neuraxial anaesthesia significantly reduced length of stay (weighted mean difference -0.40 days; 95% confidence interval -0.76 to -0.03; P=0.03; I2 73%; 12 studies). No statistically significant differences were found between neuraxial and general anaesthesia for mortality, surgical duration, surgical site or chest infections, nerve palsies, postoperative nausea and vomiting, or thromboembolic disease when antithrombotic prophylaxis was used. Subgroup analyses failed to find statistically significant interactions (P>0.05) based on risk of bias, type of surgery, or type of neuraxial anaesthesia. CONCLUSION: Neuraxial anaesthesia for total hip or total knee arthroplasty, or both appears equally effective without increased morbidity when compared with general anaesthesia. There is limited quantitative evidence to suggest that neuraxial anaesthesia is associated with improved perioperative outcomes. Future investigations should compare intermediate and long-term outcome differences to better inform anaesthesiologists, surgeons, and patients on importance of anaesthetic selection.

The risk of asthma exacerbation after reducing inhaled corticosteroids: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Asthma guidelines suggest reducing controller medications when asthma is stable. METHODS: The purpose of the study is to estimate the risk of asthma exacerbation in stable asthmatics who reduce inhaled corticosteroids (ICS) compared to those who maintain a stable ICS dose. We identified articles from a systematic review of English and non-English articles using MEDLINE, EMBASE, Web of Science, and CENTRAL (inception to May 25, 2013). We included randomized controlled trials (RCTs) with a stable asthma run-in period of 4 weeks or more, an intervention to reduce ICS, and a follow-up period of at least 3 months. RESULTS: The search strategy identified 2253 potential articles, of which 206 were reviewed at the full-text level and 6 met criteria for inclusion. The relative risk of an asthma exacerbation in individuals who reduced ICS compared to those who maintained the same ICS dose was 1.25 (95% CI 0.96, 1.62; P = 0.10; I(2)  = 0%) in studies with a mean follow-up of 22 weeks. Individuals who reduced ICS had a decreased% predicted FEV1 of 0.87% (95% CI -1.58%,3.33%; P = 0.49, I(2)  = 58%) and a decreased mean morning peak expiratory flow of 9.57 l/min (95% CI 1.25, 17.90; P = 0.02; I(2)  = 74%) compared to those individuals who maintained a stable ICS dose. CONCLUSIONS: Asthma exacerbations were statistically no more likely among individuals who reduced ICS compared to those who maintained their ICS dose, supporting current guidelines which recommend decreasing ICS by 50% after a period of asthma stability.

Falls and major orthopaedic surgery with peripheral nerve blockade: a systematic review and meta-analysis.

The objective of this systematic review with meta-analysis was to determine the risk for falls after major orthopaedic surgery with peripheral nerve blockade. Electronic databases from inception through January 2012 were searched. Eligible studies evaluated falls after peripheral nerve blockade in adult patients undergoing major lower extremity orthopaedic surgery. Independent reviewers working in duplicate extracted study characteristics, validity, and outcomes data. The Peto odds ratio (OR) with 95% confidence intervals (CIs) were estimated from each study that compared continuous lumbar plexus blockade with non-continuous blockade or no blockade using a fixed effects model. Ten studies (4014 patients) evaluated the number of falls as an outcome. Five studies did not contain comparison groups. The meta-analysis of five studies [four randomized controlled trials (RCTs) and one cohort] compared continuous lumbar plexus blockade (631 patients) with non-continuous blockade or no blockade (964 patients). Fourteen falls occurred in the continuous lumbar plexus block group when compared with five falls within the non-continuous block or no block group (attributable risk 1.7%; number needed to harm 59). Continuous lumbar plexus blockade was associated with a statistically significant increase in the risk for falls [Peto OR 3.85; 95% CI (1.52, 9.72); P=0.005; I(2)=0%]. Evidence was low (cohort) to high (RCTs) quality. Continuous lumbar plexus blockade in adult patients undergoing major lower extremity orthopaedic surgery increases the risk for postoperative falls compared with non-continuous blockade or no blockade. However, attributable risk was not outside the expected probability of postoperative falls after orthopaedic surgery.

Meta-Analysis of Randomized Controlled Trials on Androgens versus Erythropoietin for Anaemia of Chronic Kidney Disease: Implications for Developing Countries.

Androgens which are relatively cheap were used in the treatment of anaemia in dialysis patients before the advent of Erythropoietin (EPO). However, there are concerns about their efficacy and side effects. Aims. To examine the efficacy and harms of androgens for the treatment of anaemia of chronic kidney disease (CKD) compared to EPO. Settings and Design. A systematic review and meta-analysis using an a priori protocol. Methods and Materials. We searched several databases for randomized controlled trials using the key terms anaemia, chronic kidney disease, and androgens, without language restrictions. We also searched reference lists of relevant articles. Statistical Analysis Used. Data was analyzed using Review manger 5 software. We summarized treatment effects as relative risks and mean differences, with 95% confidence intervals using a random-effect model. We tested for heterogeneity with Chi(2) and the I(2) statistics. Results. We identified four eligible trials involving 114 participants, majority (83.33%) of whom were males, mostly over 50 years of age. The pooled difference in mean haemoglobin between the nandrolone and EPO arms at the end of the trials was -0.11 (CI -0.80 to 0.58) which is not statistically significant. Conclusions. This meta-analysis revealed no difference between nandrolone and EPO for the treatment of anaemia of CKD in men over 50 years. Therefore, nandrolone can be used for the treatment of anaemia of CKD in this category of patients, in resource-limited countries. However, further studies are needed to determine the long-term safety of nandrolone in men over 50 years old, as well as its effectiveness and safety in females in general, and males less than 50 years of age.

Diagnostic performance of body mass index to identify obesity as defined by body adiposity: a systematic review and meta-analysis.

OBJECTIVE: We performed a systematic review and meta-analysis of studies that assessed the performance of body mass index (BMI) to detect body adiposity. DESIGN: Data sources were MEDLINE, EMBASE, Cochrane, Database of Systematic Reviews, Cochrane CENTRAL, Web of Science, and SCOPUS. To be included, studies must have assessed the performance of BMI to measure body adiposity, provided standard values of diagnostic performance, and used a body composition technique as the reference standard for body fat percent (BF%) measurement. We obtained pooled summary statistics for sensitivity, specificity, positive and negative likelihood ratios (LRs), and diagnostic odds ratio (DOR). The inconsistency statistic (I2) assessed potential heterogeneity. RESULTS: The search strategy yielded 3341 potentially relevant abstracts, and 25 articles met our predefined inclusion criteria. These studies evaluated 32 different samples totaling 31 968 patients. Commonly used BMI cutoffs to diagnose obesity showed a pooled sensitivity to detect high adiposity of 0.50 (95% confidence interval (CI): 0.43-0.57) and a pooled specificity of 0.90 (CI: 0.86-0.94). Positive LR was 5.88 (CI: 4.24-8.15), I (2)=97.8%; the negative LR was 0.43 (CI: 0.37-0.50), I (2)=98.5%; and the DOR was 17.91 (CI: 12.56-25.53), I (2)=91.7%. Analysis of studies that used BMI cutoffs >or=30 had a pooled sensitivity of 0.42 (CI: 0.31-0.43) and a pooled specificity of 0.97 (CI: 0.96-0.97). Cutoff values and regional origin of the studies can only partially explain the heterogeneity seen in pooled DOR estimates. CONCLUSION: Commonly used BMI cutoff values to diagnose obesity have high specificity, but low sensitivity to identify adiposity, as they fail to identify half of the people with excess BF%.

Fluoroquinolone prophylaxis in patients with neutropenia: a meta-analysis of randomized placebo-controlled trials.

A recent meta-analysis, which included non-placebo open-labeled trials, showed that fluoroquinolone prophylaxis reduces mortality in neutropenic patients, whereas two recent large trials failed to show a similar benefit. Therefore, we performed a meta-analysis of randomized, blinded, placebo-controlled trials of fluoroquinolone prophylaxis in neutropenic patients. We searched several databases for relevant trials in any language. We used random effects models for pooling dichotomous data and assessed the between-study inconsistency with I (2). Two investigators independently assessed the eligibility and quality of the included trials. A total of 2,721 patients were randomized in eight eligible trials. Compared to the placebo, there was a statistically non-significant but consistent decrease in mortality with fluoroquinolone prophylaxis (4.5% vs. 3.9%, relative risk (RR) 0.76, 95% confidence interval (CI) 0.54, 1.08, p = 0.13, I (2) = 0%). Significant inconsistency, however, accompanied the pooled analysis of febrile episode (39% vs. 31%, RR 0.76, 95% CI 0.55, 1.03, p = 0.08, I (2) = 96.5%). To an extent, this inconsistency was explained in the subgroup analyses by the type of patient population studied and the type of fluoroquinolone used (p for interaction

The effect of online status on the impact factors of general internal medicine journals.

BACKGROUND: We sought to determine the effects of becoming available online on impact factors of general medicine journals. METHODS: Through MEDLI NE with an institutional subscription, the 2004 online status of "Medicine, General and Internal" journals listed in the Institute for Scientific Information (ISI ) Journal Citation Reports (JCR) was classified as full text on the Net (FU TON), abstract only, or no abstract available (NAA)/unavailable in MEDLI NE. Similarly, through use of a home computer without an institutional subscription, the 2004 online status of the same journals was determined. For each journal, impact factors for 1992 to 2003 were obtained. RESULTS: Of the 102 "Medicine, General and Internal" journals listed in the ISI JCR, 71 (70%) existed in both pre-Internet (1992) and Internet (2003) eras. Of these 71 journals, those available as FU TON in 2004 had higher median impact factors than non-FU TON journals in 1992 (p < 0.0001> and 2003 (p < 0.0001). Journals that became available online, at least partially, had significant increases in median impact factors from 1992 to 2003 (p< 0.0001 for journals that became available as FUTON and for journals that provided an abstract only. However, journals that became available as FUTON had a greater increase in median impact from 1992 to 2003 than other journals (p = 0.002). Similar results were obtained using impact factor data according to journal online status through use of a home computer without an institutional subscription and for English-language journals only. CONCLUSION: Becoming available online as FUTON is associated with a significant increase in journal impact factor.

Interleukin 10-deficient colitis: new similarities to human inflammatory bowel disease.

BACKGROUND: Interleukin (IL) 10 is a potent anti-inflammatory cytokine. Disruption of the IL-10 gene in C57/Black6 mice results in enterocolitis in the presence of intestinal bacteria. This study investigated gut mucosal barrier function sequentially during the development of colitis in this model. METHODS: Animals were bred in specific pathogen-free conditions and transferred to conventional housing at 4 weeks. Mice were evaluated at 6, 8, 10, 12, 14 and 15 weeks of age. Barrier function was assessed by measuring intestinal permeability and antibody response to systemic endotoxaemia (antibody to the core glycolipid region of lipopolysaccharide; EndoCAb). Colons were harvested and a histological injury score (HIS) was calculated. RESULTS: The HIS increased progressively until 12 weeks, with an associated increase in intestinal permeability, and immunoglobulin (Ig) M and IgG EndoCAb. The HIS correlated positively with both intestinal permeability and IgM and IgG EndoCAb. Intestinal permeability showed a positive correlation with EndoCAb. CONCLUSION: IL-10 knockout mice develop colitis with an associated disturbance in gut mucosal barrier function, as measured by increased permeability and endotoxaemia. The colitis found in the IL-10 knockout mouse shares these histological, physiological and biochemical features with human inflammatory bowel disease and is therefore suitable for therapeutic trials. A measure of endotoxaemia correlated directly with intestinal permeability in this model.

Lipopolysaccharide binding protein in acute pancreatitis.

OBJECTIVE: To assess the expression of plasma lipopolysaccharide binding protein (LBP) concentrations and its relationship to markers of the systemic inflammatory response syndrome during acute pancreatitis. DESIGN: A prospective study. SETTING: General surgical units of university teaching hospitals in the Belfast area. PATIENTS: The study included 18 patients admitted with established diagnosis of acute pancreatitis on the basis of elevated serum amylase or by contrast radiology. Patients were retrospectively stratified using the Modified Glasgow Criteria into severe (n = 7) and mild (n = 11) disease. INTERVENTIONS AND MEASUREMENTS: Blood samples were obtained at admission (day 1) and for a further 3 days for the measurement of LBP, C-reactive protein (CRP), tumor necrosis factor, and interleukin (IL)-6. Acute Physiology and Chronic Health Evaluation (APACHE) II scores were calculated on day 1 and day 2. MAIN RESULTS: LBP and CRP concentrations were significantly increased from healthy control values in acute pancreatitis patients at presentation. In the mild group LBP, CRP and IL-6 concentrations remained relatively constant throughout the study period. By comparison, severe acute pancreatitis was associated with significantly higher LBP concentrations and a marked systemic inflammatory response as evidenced by increased CRP, IL-6, and APACHE II scores. The rise in LBP occurred after the observed increase of these markers. Significant correlations were found among CRP and LBP, IL-6 and LBP, and IL-6 and APACHE II scores. There were no fatalities in the mild group, whereas four of the seven patients with severe disease died. CONCLUSIONS: LBP was significantly raised in patients with severe acute pancreatitis but would seem to be of limited use in predicting disease severity. This acute phase protein may have a role in the progression of systemic complications associated with acute pancreatitis.

Characterization of the Kupffer cell response to exogenous endotoxin in a rodent model of obstructive jaundice.

BACKGROUND: Sepsis and endotoxaemia occur frequently in biliary obstruction. Impaired Kupffer cell endocytosis is implicated in these events. Tumour necrosis factor and interleukin 6, secreted by Kupffer cells, are important mediators of sepsis. Kupffer cell clearance of endotoxin and secretion of cytokines in experimental obstructive jaundice were investigated. METHODS: Wistar rats were randomized to bile duct ligation, sham operation or control. Groups (n = 8) were studied 1 and 3 weeks after operation. Kupffer cell function was assessed using in situ hepatic perfusion. RESULTS: Clearance of endotoxin was significantly depressed 1 week (median (interquartile range) 20.3 (10.5-27.1) per cent) and 3 weeks (22.1 (20.2-23.2) per cent) after bile duct ligation compared with that in respective sham animals (35.5 (29.9-41.6) and 40.9 (37.7-47.0) per cent) and controls (39.5 (37.3-46.8) per cent). Secretion of tumour necrosis factor was significantly greater 1 week (1113.7 (706.5-1436. 8) pg/ml) and 3 weeks (1118.2 (775.7-1484.1) pg/ml) following bile duct ligation compared with that in respective sham animals (114.3 (0-178.5) and 107.6 (63.7-166.4) pg/ml) and controls (0 (0-20.7) pg/ml). Interleukin 6 was not secreted by sham or control animals but was present in the perfusate from jaundiced animals at 1 and 3 weeks (52.5 (9.9-89.5) and 66.2 (60.2-193.1) pg/ml). CONCLUSION: These data demonstrate simultaneous impairment of Kupffer cell clearance of endotoxin and increased secretion of proinflammatory cytokines in experimental obstructive jaundice. These diverse responses may contribute to the development of sepsis-related complications in biliary obstruction.

Lower limb ischaemia-reperfusion injury causes endotoxaemia and endogenous antiendotoxin antibody consumption but not bacterial translocation.

BACKGROUND: It has been suggested that reperfusion of the acutely ischaemic lower limb alters gut permeability. The effect of lower limb ischaemia-reperfusion on systemic endotoxin and antiendotoxin antibody concentrations and the incidence of bacterial translocation was investigated. METHODS: Systemic endotoxin and antiendotoxin antibody concentrations were measured in five groups of male Wistar rats: control, after 3 h of bilateral hind limb ischaemia alone, and after 3 h of bilateral hind limb ischaemia followed by 1, 2 or 3 h of reperfusion. A second experiment examined translocation of indigenous bacteria following 2 h of reperfusion in a similar model. RESULTS: Ischaemia followed by reperfusion for 1, 2 or 3 h caused a significant increase in plasma endotoxin concentration to mean(s.e.m.) 10.0(3.0), 44.8(19.2) and 20.2(6.2) pg/ml compared with that in control animals (2.58(0.91) pg/ml) or animals in the ischaemia alone group (1.2(0.9) pg/ml) (P < 0.05). This was associated with a significant reduction in endogenous antiendotoxin antibody (immunoglobulin (Ig) G and IgM) concentration. No significant bacterial translocation was detected in any of the groups studied. CONCLUSION: These results demonstrate that a remote and isolated ischaemia-reperfusion injury to the lower limb, in the absence of infection or bacterial translocation, causes endotoxaemia. Further studies are needed to evaluate the role of endogenous antiendotoxin antibodies in this situation.

Lactulose as an antiendotoxin in experimental colitis.

The efficacy of lactulose as an antiendotoxin was studied and the effect of lactulose or colistin on faecal flora was investigated in a hapten-induced rat model of colitis. Enteral administration of lactulose to rats with colitis was associated with a significant reduction in the systemic concentration of endotoxin (median (range) 5.4 (0-19.9) versus 23.7 (0-145.0) pg/ml in colitic rats treated with water; 4.6 (0-10.8) pg/ml in healthy animals). Enteral administration of colistin significantly reduced the faecal count of aerobic Gram-negative bacilli (median (range) 2.84 (1.40-8.43) versus 8.26 (4.50-10.40) log10 colony-forming units per g faeces after treatment with water) but not the faecal load of endotoxin. Patients with inflammatory bowel disease may benefit from enteral treatment with lactulose to prevent systemic endotoxaemia and/or with colistin to modify enteric bacteria.

Enteral and parenteral anti-endotoxin treatment in experimental colitis.

Systemic endotoxemia has been described in ulcerative colitis and Crohn's disease and shown to correlate positively with disease activity and the extent of intestinal ulceration. This study evaluated the efficacy of antibiotic and anti-endotoxic treatment in reducing systemic endotoxemia in a hapten-induced rat model of colitis. Enteral administration of paromomycin was associated with a significant reduction in systemic endotoxin concentrations (7.4 +/- 1.2 pg/ml) when compared with controls (39.8 +/- 12.6 pg/ml; p = 0.032). Intravenous injection of taurolidine was also found to significantly reduce systemic endotoxemia (3.1 +/- 1.3 pg/ml) in comparison with controls receiving saline injection (17.5 +/- 4.2 pg/ml; p = 0.008). Enteral neomycin, parenteral polymyxin or metronidazole and cefuroxime were ineffective anti-endotoxin treatments in this model. Enteral paromomycin or parenteral tauro-lidine therapy are potential methods of preventing and treating systemic endotoxemia in patients with inflammatory bowel disease.

Colonic bacteria and bacterial translocation in experimental colitis.

The indigenous intestinal flora and an intact mucosa are vital components of body defences against luminal pathogenic bacteria. Disruption of these defences in inflammatory bowel disease may permit bacterial translocation and contribute to disease severity. Support for this hypothesis comes from this study of a hapten-induced rat model of colitis. Induction of colitis was associated with a significantly increased colonic Gram-negative aerobic bacilli count. The results, expressed as log10 [colony-forming units per gram tissue] were: colitic 6.97-8.86 versus control 4.90-6.69 (P < 0.05). Colitis was also associated with a decreased Gram-positive cocci count at 4.00-8.04 versus control 6.45-8.30 (P < 0.05). Bacteria translocated to the mesenteric lymph nodes in five of eight colitic rats (P = 0.01), to the spleen in four (P = 0.04) and to the liver in five (P = 0.01) but to these organs in none of the eight control animals. There was a positive correlation between the severity of colonic inflammation and extent of bacterial translocation in colitic animals (rs = 0.86, P = 0.007).

Adsorbents as antiendotoxin agents in experimental colitis.

The intestinal mucosa protects the body from a large reservoir of intraluminal pathogenic bacteria and endotoxins. This mucosal barrier is disrupted by the inflammation and ulceration of inflammatory bowel disease and may permit the absorption of toxic bacterial products. Systemic endotoxaemia has been demonstrated in ulcerative colitis and Crohn's disease and correlates with the extent and activity of disease. In this study the efficacy of absorbents as antiendotoxin agents in a hapten induced rat model of colitis is investigated. Induction of colitis was associated with systemic endotoxaemia. Enteral administration of terra fullonica and kaolin, but not of charcoal, significantly reduced systemic endotoxaemia (terra fullonica 4.2 (1.40) pg/ml; kaolin 5.29 (1.86) pg/ml; charcoal 32.7 (16.6) pg/ml; water 39.8 (12.6) pg/ml). Data expressed as mean (SE). With increasing severity of colitis, there was a decreasing ability of adsorbent therapy (terra fullonica) to control systemic endotoxaemia. Enteral administration of adsorbents controls gut derived systemic endotoxaemia in experimental colitis in animals and may be a useful antiendotoxin treatment in patients with inflammatory bowel disease.