The reporting checklist for public versions of guidelines: RIGHT-PVG.

BACKGROUND: Public or patient versions of guidelines (PVGs) are derivative documents that "translate" recommendations and their rationale from clinical guidelines for health professionals into a more easily understandable and usable format for patients and the public. PVGs from different groups and organizations vary considerably in terms of quality of their reporting. In order to address this issue, we aimed to develop a reporting checklist for developers of PVGs and other potential users. METHODS: First, we collected a list of potential items through reviewing a sample of PVGs, existing guidance for developing and reporting PVGs or other similar evidence-based patient tools, as well as qualitative studies on original studies of patients' needs about the content and/or reporting of information in PVGs or similar evidence-based patient tools. Second, we conducted a two-round Delphi consultation to determine the level of consensus on the items to be included in the final reporting checklist. Third, we invited two external reviewers to provide comments on the checklist. RESULTS: We generated the initial list of 45 reporting items based on a review of a sample of 30 PVGs, four PVG guidance documents, and 46 relevant studies. After the two-round Delphi consultation, we formed a checklist of 17 items grouped under 12 topics for reporting PVGs. CONCLUSION: The RIGHT-PVG reporting checklist provides an international consensus on the important criteria for reporting PVGs.

[A reporting tool for practice guidelines in health care: the RIGHT statement]. / Ein Instrument zur Erstellung von Leitlinienberichten: das RIGHT-Statement.

The quality of reporting practice guidelines is often poor, and there is no widely accepted guidance or standards for such reporting in health care. The international RIGHT (Reporting Items for practice Guidelines in HealThcare) Working Group was established to address this gap. The group followed an existing framework for developing guidelines for health research reporting and the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) Network approach. A checklist and an explanation and elaboration statement were developed. The RIGHT checklist includes 22 items that are considered essential for good reporting of practice guidelines: basic information (items 1 to 4), background (items 5 to 9), evidence (items 10 to 12), recommendations (items 13 to 15), review and quality assurance (items 16 and 17), funding and declaration and management of interests (items 18 and 19), and other information (items 20 to 22). The RIGHT checklist can assist developers in reporting guidelines, support journal editors and peer reviewers when considering guideline reports, and help health care practitioners understand and implement a guideline.

A Reporting Tool for Practice Guidelines in Health Care: The RIGHT Statement.

The quality of reporting practice guidelines is often poor, and there is no widely accepted guidance or standards for such reporting in health care. The international RIGHT (Reporting Items for practice Guidelines in HealThcare) Working Group was established to address this gap. The group followed an existing framework for developing guidelines for health research reporting and the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) Network approach. It developed a checklist and an explanation and elaboration statement. The RIGHT checklist includes 22 items that are considered essential for good reporting of practice guidelines: basic information (items 1 to 4), background (items 5 to 9), evidence (items 10 to 12), recommendations (items 13 to 15), review and quality assurance (items 16 and 17), funding and declaration and management of interests (items 18 and 19), and other information (items 20 to 22). The RIGHT checklist can assist developers in reporting guidelines, support journal editors and peer reviewers when considering guideline reports, and help health care practitioners understand and implement a guideline.

Estimating Information Processing in a Memory System: The Utility of Meta-analytic Methods for Genetics.

Genetic studies in Drosophila reveal that olfactory memory relies on a brain structure called the mushroom body. The mainstream view is that each of the three lobes of the mushroom body play specialized roles in short-term aversive olfactory memory, but a number of studies have made divergent conclusions based on their varying experimental findings. Like many fields, neurogenetics uses null hypothesis significance testing for data analysis. Critics of significance testing claim that this method promotes discrepancies by using arbitrary thresholds (α) to apply reject/accept dichotomies to continuous data, which is not reflective of the biological reality of quantitative phenotypes. We explored using estimation statistics, an alternative data analysis framework, to examine published fly short-term memory data. Systematic review was used to identify behavioral experiments examining the physiological basis of olfactory memory and meta-analytic approaches were applied to assess the role of lobular specialization. Multivariate meta-regression models revealed that short-term memory lobular specialization is not supported by the data; it identified the cellular extent of a transgenic driver as the major predictor of its effect on short-term memory. These findings demonstrate that effect sizes, meta-analysis, meta-regression, hierarchical models and estimation methods in general can be successfully harnessed to identify knowledge gaps, synthesize divergent results, accommodate heterogeneous experimental design and quantify genetic mechanisms.

Hyperbaric versus plain bupivacaine for spinal anesthesia for cesarean delivery.

BACKGROUND: Bupivacaine is an amide local anesthetic used in hyperbaric and plain forms administered as spinal anesthesia for cesarean delivery. In this systematic review, we summarized the effectiveness and safety of hyperbaric versus plain bupivacaine in providing anesthesia for cesarean delivery. We considered the adequacy of anesthesia for completion of cesarean delivery and the need for interventions to treat complications. METHODS: We searched the CENTRAL, MEDLINE, and EMBASE databases. We imposed no language restriction. We included all randomized controlled trials involving patients undergoing spinal anesthesia for elective cesarean delivery that compared the use of hyperbaric bupivacaine with plain bupivacaine. RESULTS: We included 6 studies with a total of 394 patients in this review. These studies have small sample size, few observed events, differences in methodology, and insufficient information pertaining to assessment of risk of bias. This prevented us from calculating pooled estimates. Results show that there is no compelling evidence in favor of the use of intrathecal plain or hyperbaric bupivacaine for spinal anesthesia for cesarean delivery. CONCLUSIONS: There is a lack of clear evidence regarding the superiority of hyperbaric compared with plain bupivacaine for spinal anesthesia for cesarean delivery. The need for conversion to general anesthesia because of failed spinal anesthesia is an important clinical outcome, but current data are insufficient to compare spinal anesthesia induced with hyperbaric compared with plain bupivacaine for this outcome. Further research is required.

Rationale, Methodology, and Implementation of a Dispatcher-assisted Cardiopulmonary Resuscitation Trial in the Asia-Pacific (Pan-Asian Resuscitation Outcomes Study Phase 2).

Abstract Background. Survival outcomes from out-of-hospital cardiac arrest (OHCA) in Asia are poor (2-11%). Bystander cardiopulmonary resuscitation (CPR) rates are relatively low in Asia. Dispatcher-assisted CPR (DA-CPR) has recently emerged as a potentially cost-effective intervention to increase bystander CPR and survival from OHCA. The Pan-Asian Resuscitation Outcomes Study (PAROS), an Asia-Pacific cardiac arrest registry, was set up in 2009, with the aim of understanding OHCA as a disease in Asia and improving OHCA survival. The network has adopted DA-CPR as part of its strategy to improve OHCA survival. Objective. This article aims to describe the conceptualization, study design, potential benefits, and difficulties for implementation of DA-CPR trial in the Asia-Pacific. Methods. Two levels of intervention, basic and comprehensive, will be offered to PAROS participating sites. The basic level consists of implementation of a DA-CPR protocol and training program, while the comprehensive level consists of implementation of the basic level, with the addition of a dispatch quality measurement tool, quality improvement program, and community education program. Sites that are not able to implement the package will contribute control data. The primary outcome of the study is survival to hospital discharge or survival to 30 days post cardiac arrest. DA-CPR and bystander CPR are secondary outcomes. Conclusion. Implementation of DA-CPR requires concerted efforts by EMS leaders and supervisors, dispatchers, hospital stakeholders, policy makers, and the general public. The DA-CPR trial implemented by the PAROS sites, if successful, can serve as a model for other countries considering such an intervention in their EMS systems.

Cost-effectiveness analysis of liver resection versus transplantation for early hepatocellular carcinoma within the Milan criteria.

UNLABELLED: Both liver resection (LR) and cadaveric liver transplantation (CLT) are potentially curative treatments for patients with hepatocellular carcinoma (HCC) within the Milan criteria and with adequate liver function. Adopting either as a first-line therapy carries major cost and resource implications. The objective of this study was to estimate the relative cost-effectiveness of LR against CLT for patients with HCC within the Milan criteria using a decision analytic model. A Markov cohort model was developed to simulate a cohort of patients aged 55 years with HCC within the Milan criteria and Child-Pugh A/B cirrhosis, undergoing LR or CLT, and followed up over their remaining life expectancy. Analysis was performed in different geographical cost settings: the USA, Switzerland and Singapore. Transition probabilities were obtained from systematic literature reviews, supplemented by databases from Singapore and the Organ Procurement and Transplantation Network (USA). Utility and cost data were obtained from open sources. LR produced 3.9 quality-adjusted life years (QALYs) while CLT had an additional 1.4 QALYs. The incremental cost-effectiveness ratio (ICER) of CLT versus LR ranged from $111,821/QALY in Singapore to $156,300/QALY in Switzerland, and was above thresholds for cost-effectiveness in all three countries. Sensitivity analysis revealed that CLT-related 5-year cumulative survival, one-time cost of CLT, and post-LR 5-year cumulative recurrence rates were the most sensitive parameters in all cost scenarios. ICERs were reduced below threshold when CLT-related 5-year cumulative survival exceeded 84.9% and 87.6% in Singapore and the USA, respectively. For Switzerland, the ICER remained above the cost-effectiveness threshold regardless of the variations. CONCLUSION: In patients with HCC within the Milan criteria and Child-Pugh A/B cirrhosis, LR is more cost-effective than CLT across three different costing scenarios: the USA, Switzerland, Singapore.

Early versus late initiation of epidural analgesia for labour.

BACKGROUND: Pain during childbirth is arguably the most severe pain some women may experience in their lifetime. Epidural analgesia is an effective form of pain relief during labour. Many women have concerns regarding its safety. Furthermore, epidural services and anaesthetic support may not be available consistently across all centres. Observational data suggest that early initiation of epidural may be associated with an increased risk of caesarean section, but the same findings were not seen in recent randomised controlled trials. More recent guidelines suggest that in the absence of a medical contraindication, maternal request is a sufficient medical indication for pain relief during labour. The choice of analgesic technique, agent, and dosage is based on many factors, including patient preference, medical status, and contraindications. There is no systematically reviewed evidence on the maternal and foetal outcomes and safety of this practice. OBJECTIVES: This systematic review aimed to summarise the effectiveness and safety of early initiation versus late initiation of epidural analgesia in women. We considered the obstetric and fetal outcomes relevant to women and side effects of the treatments, including risk of caesarean section, instrumental birth and time to birth. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (12 February 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 1), MEDLINE (January 1966 to February 2014), Embase (January 1980 to February 2014) and reference lists of retrieved studies. SELECTION CRITERIA: We included all randomised controlled trials involving women undergoing epidural labour analgesia that compared early initiation versus late initiation of epidural labour analgesia. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion, extracted the data and assessed the trial quality. Data were checked for accuracy. MAIN RESULTS: We included nine studies with a total of 15,752 women.The overall risk of bias of the studies was low, with the exception of performance bias (blinding of participants and personnel).The nine studies showed no clinically meaningful difference in risk of caesarean section with early initiation versus late initiation of epidural analgesia for labour (risk ratio (RR) 1.02; 95% confidence interval (CI) 0.96 to 1.08, nine studies, 15,499 women, high quality evidence). There was no clinically meaningful difference in risk of instrumental birth with early initiation versus late initiation of epidural analgesia for labour (RR 0.93; 95% CI 0.86 to 1.01, eight studies, 15,379 women, high quality evidence). The duration of second stage of labour showed no clinically meaningful difference between early initiation and late initiation of epidural analgesia (mean difference (MD) -3.22 minutes; 95% CI -6.71 to 0.27, eight studies, 14,982 women, high quality evidence). There was significant heterogeneity in the duration of first stage of labour and the data were not pooled.There was no clinically meaningful difference in Apgar scores less than seven at one minute (RR 0.96; 95% CI 0.84 to 1.10, seven studies, 14,924 women, high quality evidence). There was no clinically meaningful difference in Apgar scores less than seven at five minutes (RR 0.96; 95% CI 0.69 to 1.33, seven studies, 14,924 women, high quality evidence). There was no clinically meaningful difference in umbilical arterial pH between early initiation and late initiation (MD 0.01; 95% CI -0.01 to 0.03, four studies, 14,004 women, high quality evidence). There was no clinically meaningful difference in umbilical venous pH favouring early initiation (MD 0.01; 95% CI -0.00 to 0.02, four studies, 14,004 women, moderate quality evidence). AUTHORS' CONCLUSIONS: There is predominantly high-quality evidence that early or late initiation of epidural analgesia for labour have similar effects on all measured outcomes. However, various forms of alternative pain relief were given to women who were allocated to delayed epidurals to cover that period of delay, so that is it hard to assess the outcomes clearly. We conclude that for first time mothers in labour who request epidurals for pain relief, it would appear that the time to initiate epidural analgesia is dependent upon women's requests.

Phototherapy for treating pressure ulcers.

BACKGROUND: A pressure ulcer is defined as "an area of localized injury to the skin and/or underlying tissue, usually over a bony prominence, as a result of pressure, or pressure in combination with shear". The use of phototherapy - that is, light (or laser) used as an adjuvant, non-surgical intervention, with the aim of having a therapeutic effect on healing - has increased recently. OBJECTIVES: To determine the effects of phototherapy on the healing of pressure ulcers. SEARCH METHODS: In January 2014, we searched the Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid EMBASE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); and EBSCO CINAHL. We did not restrict the search by language or publication date. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing the effects of phototherapy (in addition to standard treatment) with sham phototherapy (in addition to standard treatment), another type of phototherapy (in addition to standard treatment) or standard or conventional treatment alone. DATA COLLECTION AND ANALYSIS: Two review authors assessed studies for relevance and design according to the selection criteria, extracted data and evaluated study quality. The authors made attempts to obtain missing data by contacting study authors. Disagreement was resolved by consensus and discussion with a third review author. MAIN RESULTS: We identified seven RCTs involving 403 participants. All the trials were at unclear risk of bias. Trials compared the use of phototherapy with standard care only (six trials) or sham phototherapy (one trial). Only one of the trials included a third arm in which another type of phototherapy was applied. Overall, there was insufficient evidence to determine the relative effects of phototherapy for healing pressure ulcers. Time to complete healing was reported in three studies. Two studies showed the ultraviolet (UV) treated group had a shorter mean time to complete healing than the control group (mean difference -2.13 weeks (95% CI -3.53 to -0.72, P value 0.003)). One study reported that the laser group had a longer mean time to complete healing than the control group (mean difference 5.77 weeks; 95% CI -0.25 to 11.79). However, this result should be interpreted with caution, as these were small studies and the findings may have been due to chance. Three studies reported proportions of ulcers healed with a variety of results. One study reported a different outcome measure, and the other two studies had different treatment durations. These variations did not allow us to pool the studies and draw any conclusions as to whether phototherapy is effective or not. Adverse effects were reported in only two studies that compared phototherapy with control; the risk ratio for adverse events was imprecise. One study reported risk ratio (RR) 0.72 (95%CI 0.18 to 2.80). However, another study reported RR 0.89 (95% CI: 0.71 to 1.12) based on the number of events in each group, rather than the number of people with events. Among five studies reporting the rate of change in ulcer area, three studies found no statistically significant difference between the two groups. Pooling was not undertaken because of differences in outcome measures reported. The results were based on data from trials with unclear risk of bias for which generation of the randomisation sequence, concealment allocation and blinding of outcome assessors were unclear. No studies reported on quality of life, length of hospital stay, pain or cost. AUTHORS' CONCLUSIONS: We are very uncertain as to the effects of phototherapy in treating pressure ulcers. The quality of evidence is very low due to the unclear risk of bias and small number of trials available for analysis. The possibility of benefit or harm of this treatment cannot be ruled out. Further research is recommended.

Pitfalls in evidence assessment: the case of chlorhexidine and alcohol in skin antisepsis.

Chlorhexidine has attracted increasing attention for its role in skin antisepsis in recent years. It was tested in several prominent clinical trials and subsequently recommended in important guidelines for blood culture collection, vascular catheter insertion and surgical skin preparation. We noticed and subsequently reported a widespread misinterpretation of evidence surrounding chlorhexidine and its role in skin antisepsis. Multiple clinical trial reports and systematic reviews that had assessed the clinical efficacy of chlorhexidine/alcohol combinations for skin antisepsis had attributed efficacy solely to the chlorhexidine component. This misinterpretation was carried over into the tertiary literature, including evidence-based guidelines. Here we discuss some of the scientific, ethical, patient safety and infection control implications of this misinterpretation, as well as broader implications for evidence-based medicine.

Adenosine 2A receptor promotes collagen production by human fibroblasts via pathways involving cyclic AMP and AKT but independent of Smad2/3.

Activation of adenosine A2A receptor (A2AR) promotes fibrosis and collagen synthesis. However, the underlying mechanism is still unclear, not least because cAMP, its principal effector, has been found to inhibit TGFß1-induced collagen synthesis. Here, we show that in primary normal human dermal fibroblasts, A2AR stimulation with CGS21680 elicits a modest cAMP increase (150 ± 12% of control; EC50 54.8 nM), which stimulates collagen1 (Col1) and collagen3 (Col3), but maximal cAMP resulting from direct activation of adenylyl cyclase by forskolin (15,689 ± 7038% of control; EC50 360.7 nM) inhibits Col1 and increases Col3. Similar to Col1 expression, fibroblast proliferation increased following physiological cAMP increases by CGS21680 but was inhibited by cAMP increases beyond the physiological range by forskolin. The A2AR-mediated increase of Col1 and Col3 was mediated by AKT, while Col3, but not Col1, expression was dependent on p38 and repressed by ERK. TGFß1 induced phosphorylation of Smad2/3 and increased Col3 expression, which was prevented by Smad3 depletion. In contrast, CGS21680 did not activate Smad2/3, and Smad2/3 knockdown did not prevent CGS21680-induced Col1 or Col3 increases. Our results indicate that cAMP is a concentration-dependent switch for collagen production via noncanonical, AKT-dependent, Smad2/3-independent signaling. These observations explain the paradoxical effects of cAMP on collagen expression.

Mechanisms of action of methotrexate.

As one of the most utilized disease-modifying anti-rheumatic drugs, methotrexate (MTX) has revolutionized the treatment of rheumatoid arthritis as well as many other non-rheumatic chronic inflammatory diseases. Far from a simple anti- proliferative agent as was once thought, our understanding of how it exerts its anti-inflammatory effects has grown over the years. The mechanisms of action of MTX are reviewed here, and we look at how this knowledge helps to explain some of its most common side effects.

Extracellular generation of adenosine by the ectonucleotidases CD39 and CD73 promotes dermal fibrosis.

Adenosine has an important role in inflammation and tissue remodeling and promotes dermal fibrosis by adenosine receptor (A2AR) activation. Adenosine may be formed intracellularly from adenine nucleotides or extracellularly through sequential phosphohydrolysis of released ATP by nucleoside triphosphate diphosphohydrolase (CD39) and ecto-5'-nucleotidase (CD73). Because the role of these ecto-enzymes in fibrosis appears to be tissue specific, we determined whether these ectonucleotidases were directly involved in diffuse dermal fibrosis. Wild-type and mice globally deficient in CD39 knockout (CD39KO), CD73 (CD73KO), or both (CD39/CD73DKO) were challenged with bleomycin. Extracellular adenosine levels and dermal fibrosis were quantitated. Adenosine release from skin cultured ex vivo was increased in wild-type mice after bleomycin treatment but remained low in skin from CD39KO, CD73KO, or CD39/CD73DKO bleomycin-treated mice. Deletion of CD39 and/or CD73 decreased the collagen content, and prevented skin thickening and tensile strength increase after bleomycin challenge. Decreased dermal fibrotic features were associated with reduced expression of the profibrotic mediators, transforming growth factor-ß1 and connective tissue growth factor, and diminished myofibroblast population in CD39- and/or CD73-deficient mice. Our work supports the hypothesis that extracellular adenosine, generated in tandem by ecto-enzymes CD39 and CD73, promotes dermal fibrogenesis. We suggest that biochemical or biological inhibitors of CD39 and/or CD73 may hold promise in the treatment of dermal fibrosis in diseases such as scleroderma.

Use of hyperbaric versus isobaric bupivacaine for spinal anaesthesia for caesarean section.

BACKGROUND: Bupivacaine is an amide local anaesthetic used in hyperbaric and isobaric forms. These are administered intrathecally into the spine to provide regional anaesthesia for caesarean section. Several trials have compared hyperbaric and isobaric bupivacaine but none have conclusively shown benefit of either. OBJECTIVES: This systematic review aimed to summarize the effectiveness and safety of hyperbaric versus isobaric bupivacaine in providing anaesthesia for caesarean section. We considered the adequacy of anaesthesia for completion of caesarean section and the need for interventions to treat complications. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 4), MEDLINE (January 1966 to May 2011) and EMBASE (January 1980 to May 2011). We handsearched journals. We imposed no language restriction. We reran our search in the above databases from January 2011 to January 2013; the studies are awaiting assessment and will be dealt with when we update the review. SELECTION CRITERIA: We included all randomized controlled trials involving parturients undergoing spinal anaesthesia for elective caesarean section that compared the use of hyperbaric with isobaric bupivacaine. DATA COLLECTION AND ANALYSIS: Two authors independently extracted the data. The data that were extracted included the number of events and the sample sizes in both the intervention and control groups. For continuous outcomes, we extracted mean and standard deviation.We reported odds ratios and risk ratios (RR) for binary outcomes and mean differences (MD) for continuous outcomes. MAIN RESULTS: We included six studies with a total of 394 patients in this review. Anaesthesia performed with hyperbaric bupivacaine appeared to be less likely to need conversion to general anaesthesia (two studies, 158 patients included in meta-analysis; RR 0.17, 95% confidence interval (CI) 0.03 to 0.94). There was no difference in the need for supplemental analgesics. The time till sensory block to the T4 level was also shorter with hyperbaric bupivacaine (two studies, 126 patients; MD -1.06 minutes, 95% CI -1.80 to -0.31). There were no other significant differences between the two anaesthetics. AUTHORS' CONCLUSIONS: The criteria for conversion to general anaesthesia should be clearly defined in future research. This review found that intrathecal hyperbaric bupivacaine had a more rapid onset of sensory blockade at the T4 level than isobaric bupivacaine. It may also result in less need for conversion to general anaesthesia and supplemental analgesia. However, due to the rarity of this outcome, variability in the dose, use of adjuvant drugs and differences in the technique used for regional anaesthesia the evidence is weak. Any apparent advantage of hyperbaric bupivacaine needs to be confirmed in larger randomized trials. There were no differences in the adverse effects studied.

Adenosine A(2A) receptors promote collagen production by a Fli1- and CTGF-mediated mechanism.

INTRODUCTION: Adenosine, acting through the A(2A) receptor, promotes tissue matrix production in the skin and the liver and induces the development of dermal fibrosis and cirrhosis in murine models. Since expression of A(2A) receptors is increased in scleroderma fibroblasts, we examined the mechanisms by which the A(2A) receptor produces its fibrogenic effects. METHODS: The effects of A(2A) receptor ligation on the expression of the transcription factor, Fli1, a constitutive repressor for the synthesis of matrix proteins, such as collagen, is studied in dermal fibroblasts. Fli1 is also known to repress the transcription of CTGF/CCN2, and the effects of A(2A) receptor stimulation on CTGF and TGF-ß1 expression are also examined. RESULTS: A(2A) receptor occupancy suppresses the expression of Fli1 by dermal fibroblasts. A(2A) receptor activation induces the secretion of CTGF by dermal fibroblasts, and neutralization of CTGF abrogates the A(2A) receptor-mediated enhancement of collagen type I production. A(2A)R activation, however, resulted in a decrease in TGF-ß1 protein release. CONCLUSIONS: Our results suggest that Fli1 and CTGF are important mediators of the fibrogenic actions of adenosine and the use of small molecules such as adenosine A(2A) receptor antagonists may be useful in the therapy of dermal fibrosis in diseases such as scleroderma.

The forgotten role of alcohol: a systematic review and meta-analysis of the clinical efficacy and perceived role of chlorhexidine in skin antisepsis.

BACKGROUND: Skin antisepsis is a simple and effective measure to prevent infections. The efficacy of chlorhexidine is actively discussed in the literature on skin antisepsis. However, study outcomes due to chlorhexidine-alcohol combinations are often attributed to chlorhexidine alone. Thus, we sought to review the efficacy of chlorhexidine for skin antisepsis and the extent of a possible misinterpretation of evidence. METHODS: We performed a systematic literature review of clinical trials and systematic reviews investigating chlorhexidine compounds for blood culture collection, vascular catheter insertion and surgical skin preparation. We searched PubMed, CINAHL, the Cochrane Library, the Agency for Healthcare Research and Quality website, several clinical trials registries and a manufacturer website. We extracted data on study design, antiseptic composition, and the following outcomes: blood culture contamination, catheter colonisation, catheter-related bloodstream infection and surgical site infection. We conducted meta-analyses of the clinical efficacy of chlorhexidine compounds and reviewed the appropriateness of the authors' attribution. RESULTS: In all three application areas and for all outcomes, we found good evidence favouring chlorhexidine-alcohol over aqueous competitors, but not over competitors combined with alcohols. For blood cultures and surgery, we found no evidence supporting chlorhexidine alone. For catheters, we found evidence in support of chlorhexidine alone for preventing catheter colonisation, but not for preventing bloodstream infection. A range of 29 to 43% of articles attributed outcomes solely to chlorhexidine when the combination with alcohol was in fact used. Articles with ambiguous attribution were common (8-35%). Unsubstantiated recommendations for chlorhexidine alone instead of chlorhexidine-alcohol were identified in several practice recommendations and evidence-based guidelines. CONCLUSIONS: Perceived efficacy of chlorhexidine is often in fact based on evidence for the efficacy of the chlorhexidine-alcohol combination. The role of alcohol has frequently been overlooked in evidence assessments. This has broader implications for knowledge translation as well as potential implications for patient safety.

Immunotherapy for diabetic amyotrophy.

BACKGROUND: People with diabetes mellitus (DM) sometimes present with acute or subacute, progressive, asymmetrical pain and weakness of the proximal lower limb muscles. The various names for the condition include diabetic amyotrophy or diabetic lumbosacral radiculoplexus neuropathies. Some studies suggest that it may be due to immune-mediated inflammatory microvasculitis causing ischaemic damage of the nerves. Immunotherapies would therefore be expected to be beneficial. This is an update of a review first published in 2009. OBJECTIVES: We aimed to review the evidence from randomised trials for the efficacy of any form of immunotherapy in the treatment of diabetic amyotrophy. SEARCH METHODS: We searched the Cochrane Neuromuscular Disease Group Specialized Register (7 February 2012), CENTRAL (2012 Issue 1), MEDLINE (January 1966 to January 2012) and EMBASE (January 1980 to January 2012), and contacted authors of relevant publications and other experts to obtain additional references, unpublished trials, and ongoing trials. SELECTION CRITERIA: We intended to include all randomised and quasi-randomised trials of any immunotherapy in participants with the condition fulfilling all the following: diabetes mellitus as defined by internationally recognised criteria, acute or subacute onset of pain and lower motor neuron weakness involving predominantly the proximal muscles of the lower limbs, weakness that is not confined to one nerve or nerve root distribution and exclusion of other causes of lumbosacral radiculopathies and plexopathy. DATA COLLECTION AND ANALYSIS: Two authors independently examined all references retrieved by the search to select those meeting the inclusion criteria. MAIN RESULTS: We found only one completed controlled trial using intravenous methylprednisolone in diabetic amyotrophy (Dyck 2006). The results have not been fully published and were not available for analyses. We found no additional trials when the searches were updated in 2012. AUTHORS' CONCLUSIONS: There is presently no evidence from randomised trials to support any recommendation on the use of any immunotherapy treatment in diabetic amyotrophy.

Methotrexate in atherogenesis and cholesterol metabolism.

Methotrexate is a disease-modifying antirheumatic drug commonly used to treat inflammatory conditions such as rheumatoid arthritis which itself is linked to increased cardiovascular risk. Treatments that target inflammation may also impact the cardiovascular system. While methotrexate improves cardiovascular risk, inhibition of the cyclooxygenase (COX)-2 enzyme promotes atherosclerosis. These opposing cardiovascular influences may arise from differing effects on the expression of proteins involved in cholesterol homeostasis. These proteins, ATP-binding cassette transporter (ABC) A1 and cholesterol 27-hydroxylase, facilitate cellular cholesterol efflux and defend against cholesterol overload. Methotrexate upregulates expression of cholesterol 27-hydroxylase and ABCA1 via adenosine release, while COX-2 inhibition downregulates these proteins. Adenosine, acting through the A(2A) and A(3) receptors, may upregulate proteins involved in reverse cholesterol transport by cAMP-PKA-CREB activation and STAT inhibition, respectively. Elucidating underlying cardiovascular mechanisms of these drugs provides a framework for developing novel cardioprotective anti-inflammatory medications, such as selective A(2A) receptor agonists.