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Background: Negative pressure wound therapy (NPWT) is a widely used method of wound treatment. We performed a systematic review of randomised controlled trials (RCTs) comparing the patient-relevant benefits and harms of NPWT with standard wound therapy (SWT) in patients with wounds healing by secondary intention., Methods: We searched for RCTs in MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and study registries (last search: July 2018) and screened reference lists of relevant systematic reviews and health technology assessments. Manufacturers and investigators were asked to provide unpublished data. Eligible studies investigated at least one patient-relevant outcome (e.g. wound closure). We assessed publication bias and, if feasible, performed meta-analyses, grading the results into different categories (hint, indication or proof of a greater benefit or harm)., Results: We identified 48 eligible studies of generally low quality with evaluable data for 4315 patients and 30 eligible studies with missing data for at least 1386 patients. Due to potential publication bias (proportion of inaccessible data, 24%), we downgraded our conclusions. A meta-analysis of all wound healing data showed a significant effect in favour of NPWT (OR 1.56, 95% CI 1.15 to 2.13, p = 0.008). As further analyses of different definitions of wound closure did not contradict that analysis, we inferred an indication of a greater benefit of NPWT. A meta-analysis of hospital stay (in days) showed a significant difference in favour of NPWT (MD - 4.78, 95% CI - 7.79 to - 1.76, p = 0.005). As further analyses of different definitions of hospital stay/readmission did not contradict that analysis, we inferred an indication of a greater benefit of NPWT. There was neither proof (nor indication nor hint) of greater benefit or harm of NPWT for other patient-relevant outcomes such as mortality and adverse events., Conclusions: In summary, low-quality data indicate a greater benefit of NPWT versus SWT for wound closure in patients with wounds healing by secondary intention. The length of hospital stay is also shortened. The data show no advantages or disadvantages of NPWT for other patient-relevant outcomes. Publication bias is an important problem in studies on NPWT, underlining that all clinical studies need to be fully reported.

Background: Pay-for-Performance (P4P) is a payment model that rewards health care providers for meeting pre-defined targets for quality indicators or efficacy parameters to increase the quality or efficacy of care., Objectives: Our objective was to assess the impact of P4P for in-hospital delivered health care on the quality of care, resource use and equity. Our objective was not only to answer the question whether P4P works in general (simple perspective) but to provide a comprehensive and detailed overview of P4P with a focus on analyzing the intervention components, the context factors and their interrelation (more complex perspective)., Search Methods: We searched CENTRAL, MEDLINE, Embase, three other databases and two trial registers on 27 June 2018. In addition, we searched conference proceedings, gray literature and web pages of relevant health care institutions, contacted experts in the field, conducted cited reference searches and performed cross-checks of included references and systematic reviews on the same topic., Selection Criteria: We included randomized trials, cluster randomized trials, non-randomized clustered trials, controlled before-after studies, interrupted time series and repeated measures studies that analyzed hospitals, hospital units or groups of hospitals and that compared any kind of P4P to a basic payment scheme (e.g. capitation) without P4P. Studies had to analyze at least one of the following outcomes to be eligible: patient outcomes; quality of care; utilization, coverage or access; resource use, costs and cost shifting; healthcare provider outcomes; equity; adverse effects or harms., Data Collection and Analysis: Two review authors independently screened all citations for inclusion, extracted study data and assessed risk of bias for each included study. Study characteristics were extracted by one reviewer and verified by a second.We did not perform meta-analysis because the included studies were too heterogenous regarding hospital characteristics, the design of the P4P programs and study design. Instead we present a structured narrative synthesis considering the complexity as well as the context/setting of the intervention. We assessed the certainty of evidence using the GRADE approach and present the results narratively in 'Summary of findings' tables., Main Results: We included 27 studies (20 CBA, 7 ITS) on six different P4P programs. Studies analyzed between 10 and 4267 centers. All P4P programs targeted acute or emergency physical conditions and compared a capitation-based payment scheme without P4P to the same capitation-based payment scheme combined with a P4P add-on. Two P4P program used rewards or penalties; one used first rewards and than penalties; two used penalties only and one used rewards only. Four P4P programs were established and evaluated in the USA, one in England and one in France.Most studies showed no difference or a very small effect in favor of the P4P program. The impact of each P4P program was as follows.Premier Hospital Quality Incentive Demonstration Program: It is uncertain whether this program, which used rewards for some hospitals and penalties for others, has an impact on mortality, adverse clinical events, quality of care, equity or resource use as the certainty of the evidence was very low.Value-Based Purchasing Program: It is uncertain whether this program, which used rewards for some hospitals and penalties for others, has an impact on mortality, adverse clinical events or quality of care as the certainty of the evidence was very low. Equity and resource use outcomes were not reported in the studies, which evaluated this program.Non-payment for Hospital-Acquired Conditions Program: It is uncertain whether this penalty-based program has an impact on adverse clinical events as the certainty of the evidence was very low. Mortality, quality of care, equity and resource use outcomes were not reported in the studies, which evaluated this program.Hospital Readmissions Reduction Program: None of the studies that examined this penalty-based program reported mortality, adverse clinical events, quality of care (process quality score), equity or resource use outcomes.Advancing Quality Program: It is uncertain whether this reward-/penalty-based program has an impact on mortality as the certainty of the evidence was very low. Adverse clinical events, quality of care, equity and resource use outcomes were not reported in any study.Financial Incentive to Quality Improvement Program: It is uncertain whether this reward-based program has an impact on quality of care, as the certainty of the evidence was very low. Mortality, adverse clinical events, equity and resource use outcomes were not reported in any study.Subgroup analysis (analysis of modifying design and context factors)Analysis of P4P design factors provides some hints that non-payments compared to additional payments and payments for quality attainment (e.g. falling below specified mortality threshold) compared to quality improvement (e.g. reduction of mortality by specified percent points within one year) may have a stronger impact on performance., Authors' Conclusions: It is uncertain whether P4P, compared to capitation-based payments without P4P for hospitals, has an impact on patient outcomes, quality of care, equity or resource use as the certainty of the evidence was very low (or we found no studies on the outcome) for all P4P programs. The effects on patient outcomes of P4P in hospitals were at most small, regardless of design factors and context/setting. It seems that with additional payments only small short-term but non-sustainable effects can be achieved. Non-payments seem to be slightly more effective than bonuses and payments for quality attainment seem to be slightly more effective than payments for quality improvement.

Background: The removal of the acute appendix is one of the most frequently performed surgical procedures. Open surgery associated with therapeutic efficacy has been the treatment of choice for acute appendicitis. However, in consequence of the evolution of endoscopic surgery, the operation can also be performed with minimally invasive surgery. Due to smaller incisions, the laparoscopic approach may be associated with reduced postoperative pain, reduced wound infection rate, and shorter time until return to normal activity.This is an update of the review published in 2010., Objectives: To compare the effects of laparoscopic appendectomy (LA) and open appendectomy (OA) with regard to benefits and harms., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE and Embase (9 February 2018). We identified proposed and ongoing studies from World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov and EU Clinical Trials Register (9 February 2018). We handsearched reference lists of identified studies and the congress proceedings of endoscopic surgical societies., Selection Criteria: We included randomised controlled trials (RCTs) comparing LA versus OA in adults or children., Data Collection and Analysis: Two review authors independently selected studies, assessed the risk of bias, and extracted data. We performed the meta-analyses using Review Manager 5. We calculated the Peto odds ratio (OR) for very rare outcomes, and the mean difference (MD) for continuous outcomes (or standardised mean differences (SMD) if researchers used different scales such as quality of life) with 95% confidence intervals (CI). We used GRADE to rate the quality of the evidence., Main Results: We identified 85 studies involving 9765 participants. Seventy-five trials included 8520 adults and 10 trials included 1245 children. Most studies had risk of bias issues, with attrition bias being the largest source across studies due to incomplete outcome data.In adults, pain intensity on day one was reduced by 0.75 cm on a 10 cm VAS after LA (MD -0.75, 95% CI -1.04 to -0.45; 20 RCTs; 2421 participants; low-quality evidence). Wound infections were less likely after LA (Peto OR 0.42, 95% CI 0.35 to 0.51; 63 RCTs; 7612 participants; moderate-quality evidence), but the incidence of intra-abdominal abscesses was increased following LA (Peto OR 1.65, 95% CI 1.12 to 2.43; 53 RCTs; 6677 participants; moderate-quality evidence).The length of hospital stay was shortened by one day after LA (MD -0.96, 95% CI -1.23 to -0.70; 46 RCTs; 5127 participant; low-quality evidence). The time until return to normal activity occurred five days earlier after LA than after OA (MD -4.97, 95% CI -6.77 to -3.16; 17 RCTs; 1653 participants; low-quality evidence). Two studies showed better quality of life scores following LA, but used different scales, and therefore no pooled estimates were presented. One used the SF-36 questionnaire two weeks after surgery and the other used the Gastro-intestinal Quality of Life Index six weeks and six months after surgery (both low-quality evidence).In children, we found no differences in pain intensity on day one (MD -0.80, 95% CI -1.65 to 0.05; 1 RCT; 61 participants; low-quality evidence), intra-abdominal abscesses after LA (Peto OR 0.54, 95% CI 0.24 to 1.22; 9 RCTs; 1185 participants; low-quality evidence) or time until return to normal activity (MD -0.50, 95% CI -1.30 to 0.30; 1 RCT; 383 participants; moderate-quality evidence). However, wound infections were less likely after LA (Peto OR 0.25, 95% CI 0.15 to 0.42; 10 RCTs; 1245 participants; moderate-quality evidence) and the length of hospital stay was shortened by 0.8 days after LA (MD -0.81, 95% CI -1.01 to -0.62; 6 RCTs; 316 participants; low-quality evidence). Quality of life was not reported in any of the included studies., Authors' Conclusions: Except for a higher rate of intra-abdominal abscesses after LA in adults, LA showed advantages over OA in pain intensity on day one, wound infections, length of hospital stay and time until return to normal activity in adults. In contrast, LA showed advantages over OA in wound infections and length of hospital stay in children. Two studies reported better quality of life scores in adults. No study reported this outcome in children. However, the quality of evidence ranged from very low to moderate and some of the clinical effects of LA were small and of limited clinical relevance. Future studies with low risk of bias should investigate, in particular, the quality of life in children.

Background: Systematic information retrieval generally requires a two-step selection process for studies, which is conducted by two persons independently of one another (double-screening approach). To increase efficiency, two methods seem promising, which will be tested in the planned study: the use of text mining to prioritize search results as well as the involvement of only one person in the study selection process (single-screening approach). The aim of the present study is to examine the following questions related to the process of study selection: Can the use of the Rayyan or EPPI Reviewer tools to prioritize the results of study selection increase efficiency? How accurately does a single-screening approach identify relevant studies? Which advantages or disadvantages (e.g., shortened screening time or increase in the number of full texts ordered) does a single-screening versus a double-screening approach have?, Methods: Our study is a prospective analysis of study selection processes based on benefit assessments of drug and non-drug interventions. It consists of two parts: firstly, the evaluation of a single-screening approach based on a sample size calculation (11 study selection processes, including 33 single screenings) and involving different screening tools and, secondly, the evaluation of the conventional double-screening approach based on five conventional study selection processes. In addition, the advantages and disadvantages of the single-screening versus the double-screening approach with regard to the outcomes "number of full texts ordered" and "time required for study selection" are analyzed. The previous work experience of the screeners is considered as a potential effect modifier., Discussion: No study comparing the features of prioritization tools is currently available. Our study can thus contribute to filling this evidence gap. This study is also the first to investigate a range of questions surrounding the screening process and to include an a priori sample size calculation, thus enabling statistical conclusions. In addition, the impact of missing studies on the conclusion of a benefit assessment is calculated., Systematic Review Registration: Not applicable.

Objectives: The objective of this study was to test and evaluate a new decision-making process on the need for updating within the update of a German clinical practice guideline (CPG)., Study Design and Setting: The pilot study comprised (1) limited searches in Pubmed to identify new potentially relevant evidence, (2) an online survey among the members of the CPG group to assess the need for update, and (3) a consensus conference for determination and prioritization of guideline sections with a high need for update. Subsequently, we conducted a second online survey to evaluate the procedure., Results: The searches resulted in 902 abstracts that were graded as new potentially relevant evidence. Twenty five of 39 members of the CPG group (64%) participated in the online survey. Seventy six percent of those took part in the second online survey. The evaluation study found on average a grade of support of the procedure regarding the determination of the need for update of 3.65 (standard deviation: 0.76) on a likert scale with 1 = "no support" to 5 = "very strong support.", Conclusion: The conducted procedure presents a systematic approach for assessing whether and to what extent a CPG requires updating and enables setting priorities for which particular guideline section to update within a CPG., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The Ebola virus has been responsible for numerous outbreaks since the 1970s, with the most recent outbreak taking place between 2014 and 2016 and causing an international public health emergency. Ebola virus disease (EVD) has a high mortality rate and no approved targeted treatment exists to date. A number of established drugs are being considered as potential therapeutic agents for the treatment of EVD., Objective: We aimed to identify potential drug repositioning candidates and to assess the scientific evidence available on their efficacy., Methods: We conducted a systematic literature search in MEDLINE, Embase, and other relevant trial registry platforms for studies published between January 1976 and January 2017. We included drug screening, preclinical studies, and clinical studies on repurposed drugs for the treatment of EVD. The risk of bias for animal studies and nonrandomized clinical studies was assessed. The quality of reporting for case series and case reports was evaluated. Finally, we selected drugs approved by established regulatory authorities, which have positive in vitro study outcomes and at least one additional animal or clinical trial., Results: We identified 3301 publications, of which 37 studies fulfilled our inclusion criteria. Studies were highly heterogeneous in terms of study type, methodology, and intervention. The risk of bias was high for 13 out of 14 animal studies. We selected 11 drugs with potential anti-EVD therapeutic effects and summarized their evidence., Conclusions: Several established drugs may have therapeutic effects on EVD, but the quality and quantity of current scientific evidence is lacking. This review highlights the need for well-designed and conducted preclinical and clinical research to establish the efficacy of potential repurposed drugs against EVD.

Background: The recent Ebola epidemic in western Africa developed into an acute public health emergency of unprecedented level in modern times. The treatment provided in most cases has been limited to supportive care, as no approved therapies are available to date. Several established, licenced drugs have been suggested as potential repurposed therapeutic agents for Ebola. However, scientific data on their efficacy in treating Ebola is limited. The purpose of this review is to systematically assess scientific evidence on potential drugs targeting Ebola. In specific, we aim to (1) identify drug library screens involving therapeutic agents targeting the Ebola virus, (2) list potential approved drugs identified from drug screens and review their mechanism of action against the Ebola virus and (3) summarise the outcome of preclinical and clinical trials investigating approved drugs targeting the Ebola virus., Methods/design: We will develop comprehensive systematic search strategies and will perform a systematic literature search in MEDLINE, Embase and Cochrane Central Register of Controlled Trials (CENTRAL). Two authors will independently screen the titles, abstracts and the references of all selected articles on the basis of inclusion criteria. These include any available drug screening, preclinical studies and clinical studies examining the efficacy of approved therapeutic agents targeting the Ebola virus. There will be no restrictions on the type of participants, the type of comparator, time or setting. Data extraction and quality assessment will be undertaken by two review authors working independently., Discussion: This systematic review will provide systematic knowledge on potential repurposed therapeutic agents targeting Ebola. It aims to help guide future investigations on repurposed drugs and avoid repetitive studies., Systematic Review Registration: PROSPERO CRD42015024349.

Background: Increase in the diagnosis of prostate cancer has increased the incidence of radical prostatectomy. However, the literature assessing pain therapy for this procedure has not been systematically evaluated. Thus, optimal pain therapy for patients undergoing radical prostatectomy remains controversial., Methods: Medline, Embase, and Cochrane Central Register of Controlled Trials were searched for studies assessing the effects of analgesic and anesthetic interventions on pain after radical prostatectomy. All searches were conducted in October 2012 and updated in June 2015., Results: Most treatments studied improved pain relief and/or reduced opioid requirements. However, there were significant differences in the study designs and the variables evaluated, precluding quantitative analysis and consensus recommendations., Conclusions: This systematic review reveals that there is a lack of evidence to develop an optimal pain management protocol in patients undergoing radical prostatectomy. Most studies assessed unimodal analgesic approaches rather than a multimodal technique. There is a need for more procedure-specific studies comparing pain and analgesic requirements for open and minimally invasive surgical procedures. Finally, while we wait for appropriate procedure specific evidence from publication of adequate studies assessing optimal pain management after radical prostatectomy, we propose a basic analgesic guideline.

Background: Several systematic reviews (SRs) of randomised controlled trials (RCTs) comparing laparoscopic versus open appendectomy have been published, but there has been no overview of SRs of these two interventions. This overview (review of review) aims to summarise the results of such SRs in order to provide the most up to date evidence, and to highlight discordant results., Methods: Medline, Embase, Cinahl, the Cochrane Database of Systematic Reviews and the Database of Abstracts of Reviews of Effects were searched for SRs published up to August 2014. Study selection and quality assessment using the AMSTAR tool were carried out independently by two reviewers. We used standardised forms to extract data that were analysed descriptively., Results: Nine SRs met the inclusion criteria. All were of moderate to high quality. The number of randomized controlled trials (RCTs) they included ranged from eight to 67. The duration of surgery pooled by eight reviews was 7.6 to 18.3 minutes shorter using the open approach. Pain scores on the first postoperative day were lower after laparoscopic appendectomy in two out of three reviews. The risk of abdominal abscesses was higher for laparoscopic surgery in half of six meta-analyses. The occurrence of wound infections pooled by all reviews was lower after laparoscopic appendectomy. One review showed no difference in mortality. The laparoscopic approach shortened hospital stay from 0.16 to 1.13 days in seven out of eight meta-analyses, though the strength of the evidence was affected by strong heterogeneity., Conclusion: Laparoscopic and open appendectomy are both safe and effective procedures for the treatment of acute appendicitis. This overview shows discordant results with respect to the magnitude of the effect but not to the direction of the effect. The evidence from this overview may prove useful for the development of clinical guidelines and protocols.

Background: Non-adherence is widespread problem. Adherence is a crucial point for the success and the safe use of therapies. The objective of this overview (review of reviews) was to identify factors that influence adherence in chronic physical conditions., Methods: A systematic literature search was performed in Medline and Embase (1990 to July 2013). Publications were screened according to predefined inclusion criteria. The study quality was assessed using AMSTAR. Both process steps were carried out independently by two reviewers. Relevant data on study characteristics and results were extracted in piloted standardized tables by one reviewer and checked by a second. Data were synthesized using a standardized quantitative approach by two reviewers., Results: Seven systematic reviews were included. Higher education and employment seem to have a positive effect on adherence. Ethnic minorities seem to be less adherent. Co-payments and higher medication cost seems to have negative effect on adherence. In contrast financial status/income and marital status seem to have no influence on adherence. The effect of therapy related factors was mostly unclear or had no effect. Only the number of different medications in heart failure patients showed the tendency of an effect. Indicators of regime complexity showed consistently a negative effect direction. Duration of disease seems to have no effect on adherence. There is the tendency that higher or middle age is associated with higher adherence. But in more than half of the reviews the effect was unclear. There is no clear effect of physical as well as mental comorbidity. Only one review showed the tendency of an effect for mental comorbidity. Also for gender the effect is not clear because the effect direction was heterogenic between and within the systematic reviews., Conclusion: The presented overview shows factors than can potentially have influence on adherence. Only for a few factors the influence on adherence was consistent. Most factors showed heterogeneous results regarding statistical significance and/or effect direction. However, belonging to an ethnic minority, unemployment and cost for the patient for their medications showed consistently a negative effect on adherence which indicates that there is a social gradient.

Background: Total hip and knee replacements are very frequently performed operative procedures in German hospitals. Despite the high number of cases, only few data on treatment procedures of the clinical routine and their impact on postoperative length of stay and clinical outcome are available. The aim of our survey was to gain detailed insights of the treatment procedures in patients scheduled for elective hip or knee replacement in order to extract recommendations for improving patient care., Methods: In a nation-wide survey, we asked leading physicians of 694 trauma surgery and orthopaedic surgery departments and their corresponding colleagues in the departments of anaesthesia for treatment procedures including the process of patient admission, surgical techniques, postoperative analgesia, discharge management and follow-up. We used a multiple linear regression for analysing variables impacting on the postoperative length of stay., Results: Altogether, 303 replies representing 31.8 % of the contacted hospitals could be evaluated. For hip arthroplasty, the anterolateral approach was most commonly chosen. For knee arthroplasty, the parapatellar approach was most frequently used. Tourniquet and wound drainage (mostly removed on the second postoperative day) were widely used with more than 90 %. The avoidance of wound drainage was associated with a lower postoperative length of stay for patients following total hip or knee replacement. Only 70 % of the German departments followed up their patients after discharge checking especially the range of motion of the artificial joint replacement., Conclusion: The treatment procedures for elective hip and knee replacement are very heterogeneous in German hospitals. The quality of the clinical outcome cannot be related to a single procedure; in fact the choice and complementary interaction of interventions are essential for improving patient care. These results provide first important evidence to which extent organisational structures and treatment procedures affect patient care and length of stay. Therefore, the analyses show relevant indications for an optimised standard in patient care., (Georg Thieme Verlag KG Stuttgart · New York.)

Rationale: Laser desorption ionization for mass spectrometric measurements (LDI MS) is supported by nanostructured materials. This technique helps to overcome known limitations of matrix-assisted laser desorption/ionization (MALDI) and especially avoids interfering signals caused by matrix components. LDI can be supported by bionanostructures from the cell walls of diatoms. We explore how ionization efficiency can be improved by chemical modification of the cell walls., Methods: We introduce procedures to chemically modify these nanopatterned silicate structures using perfluorooctyldimethylchlorosilane or pentafluorophenylpropyldimethylchlorosilane. Using a conventional MALDI-MS instrument we compare ionization using the novel materials with that of unmodified cell walls. The functionalized bionanomaterial is comprehensively evaluated for the use in LDI MS using a broad range of analytes and two commercial drugs., Results: Chemical modifications lead to materials that support LDI significantly better than unmodified diatom cell walls. LDI signal intensity was up to 25-fold increased using the modified preparations. No interfering signals in the lower molecular weight range down to m/z 100 were observed, demonstrating the suitability of the method for small analytes. Crude solutions of commercial drugs, such as Aspirin complex(®) and IbuHEXAL(®) could be directly investigated without additional sample preparation., Conclusions: Chemically modified diatom cell walls represent a powerful tool to support ionization in LDI MS. The lack of background signals in the low molecular weight region of the mass spectra allows also the investigations of small analytes., (Copyright © 2014 John Wiley & Sons, Ltd.)

Single-cell investigations of the diatoms Coscinodsicus granii and Thalassiosira pseudonana were performed using laser desorption/ionization (LDI)-MS without the addition of chemical matrices. The unique cell wall architecture of these microalgae, more precisely the biomineralized nanostructured surface, supported the ionization of cellular as well as surface-related metabolites. In model experiments with purified diatom cell walls of eight species C. granii and T. pseudonana proved to promote the ionization of the polymer polyethylene glycol most efficiently. These species were therefore chosen for further experiments. Without any additional workup, living diatom cells can be washed, can be placed on the LDI target and can immediately be profiled using LDI-MS. Characteristic signals arising from the two species were assigned to common metabolites known from diatom metabolism. Among others, chlorophyll, phospholipids and amino acids were detected. Using these fingerprint signals, we were able to perform species-specific MS imaging down to a single-cell resolution of 20 by 20 µm. The larger C. granii cells can be directly visualized, while more than one of the smaller T. pseudonana cells is needed to generate high-quality images. The introduced technique will pave the way toward a chemotyping of phytoplankton that will enable the automated annotation of microalgal species. But also, an assignment of metabolic plasticity on a single-cell level that could answer fundamental questions about plankton diversity is now in reach., (Copyright © 2013 John Wiley & Sons, Ltd.)

Rationale: Organic matrices are the state-of-the-art ionization mediators in Laser Desorption/Ionization Mass Spectrometry (LDI-MS). Despite improvements in understanding matrix chemistry, interfering matrix-related signals complicate the analysis. Surface-assisted LDI techniques like desorption/ionization on silicon (DIOS) or nanostructure initiator mass spectrometry (NIMS) provide promising alternatives but rely often on elaborate materials., Methods: We introduce nanopatterned biomineralized cell walls of microalgae as easily accessible biological surfaces that support the ionization of embedded molecules in LDI-MS. Microalgae cell walls were cleaned through oxidation and washing before pipetting on a stainless-steel matrix-assisted laser desorption/ionization (MALDI) target. Added molecules were efficiently ionized in positive and negative ionization mode in common MALDI sources. The method was rigorously validated by comparison with established MALDI experiments., Results: Ionization of PEG600, D-sphingosine and raffinose was successfully mediated by nanostructured cell wall preparations from two different microalgae. Without any change in protocol, steric acid could be detected in the negative ionization mode. Ionization is also supported by commercially available celite, a material containing mineralized diatom cell walls. Characteristic ingredients of fresh coffee were detected in LDI-MS after pipetting it on celite without further sample preparation. Caffeine and saccharose were detected in positive and characteristic fatty acids in negative ionization mode. Detection limits were comparable to established MALDI experiments., Conclusions: Bionanostructure-enhanced ionization allows the analysis of a diverse selection of analytes including polymers, sugars, amino alcohols, and organic acids without interfering matrix signals. We also show that celite, a commercially available porous material containing mineralized algal bionanostructures, supports LDI-MS., (Copyright © 2012 John Wiley & Sons, Ltd.)

Background: Laparoscopic cholecystectomy is one of the most common surgical procedures in Europe (and the world) and has become the standard procedure for the management of symptomatic cholelithiasis or acute cholecystitis in patients without specific contraindications. Bile duct injuries (BDI) are rare but serious complications that can occur during a laparoscopic cholecystectomy. Prevention and management of BDI has given rise to a host of publications but very few recommendations, especially in Europe., Methods: A systematic research of the literature was performed. An international expert panel was invited to appraise the current literature and to develop evidence-based recommendations. Statements and recommendations were drafted after a consensus development conference in May 2011, followed by presentation and discussion at the annual congress of the EAES held in Torino in June 2011. Finally, full guidelines were consented and adopted by the expert panel via e-mail and web conference., Results: A total of 1,765 publications were identified through the systematic literature search and additional submission by panellists; 671 publications were selected as potentially relevant. Only 46 publications fulfilled minimal methodological criteria to support Clinical Practice Guidelines recommendations. Because the level of evidence was low for most of the studies, most statements or recommendations had to be based on consensus of opinion among the panel members. A total of 15 statements and recommendations were developed covering the following topics: classification of injuries, epidemiology, prevention, diagnosis, and management of BDI., Conclusions: Because BDI is a rare event, it is difficult to generate evidence for prevention, diagnosis, or the management of BDI from clinical studies. Nevertheless, the panel has formulated recommendations. Due to the currently limited evidence, a European registry should be considered to collect and analyze more valid data on BDI upon which recommendations can be based.

The first uncatalyzed and [Cu(R-box)L(2)](SbF(6))(2)-catalyzed {1,6}-transannular Gosteli-Claisen rearrangement of cyclic 2-alkoxycarbonyl-substituted allyl vinyl ethers to afford medium- and large-sized carbacycles is disclosed.

Background: Laparoscopic surgery for acute appendicitis has been proposed to have advantages over conventional surgery., Objectives: To compare the diagnostic and therapeutic effects of laparoscopic and conventional 'open' surgery., Search Strategy: We searched the Cochrane Library, MEDLINE, EMBASE, LILACS, CNKI, SciSearch, study registries, and the congress proceedings of endoscopic surgical societies., Selection Criteria: We included randomized clinical trials comparing laparoscopic (LA) versus open appendectomy (OA) in adults or children. Studies comparing immediate OA versus diagnostic laparoscopy (followed by LA or OA if necessary) were separately identified., Data Collection and Analysis: Two reviewers independently assessed trial quality. Missing information or data was requested from the authors. We used odds ratios (OR), relative risks (RR), and 95% confidence intervals (CI) for analysis., Main Results: We included 67 studies, of which 56 compared LA (with or without diagnostic laparoscopy) vs. OA in adults. Wound infections were less likely after LA than after OA (OR 0.43; CI 0.34 to 0.54), but the incidence of intraabdominal abscesses was increased (OR 1.87; CI 1.19 to 2.93). The duration of surgery was 10 minutes (CI 6 to 15) longer for LA. Pain on day 1 after surgery was reduced after LA by 8 mm (CI 5 to 11 mm) on a 100 mm visual analogue scale. Hospital stay was shortened by 1.1 day (CI 0.7 to 1.5). Return to normal activity, work, and sport occurred earlier after LA than after OA. While the operation costs of LA were significantly higher, the costs outside hospital were reduced. Seven studies on children were included, but the results do not seem to be much different when compared to adults. Diagnostic laparoscopy reduced the risk of a negative appendectomy, but this effect was stronger in fertile women (RR 0.20; CI 0.11 to 0.34) as compared to unselected adults (RR 0.37; CI 0.13 to 1.01)., Authors' Conclusions: In those clinical settings where surgical expertise and equipment are available and affordable, diagnostic laparoscopy and LA (either in combination or separately) seem to have various advantages over OA. Some of the clinical effects of LA, however, are small and of limited clinical relevance. In spite of the mediocre quality of the available research data, we would generally recommend to use laparoscopy and LA in patients with suspected appendicitis unless laparoscopy itself is contraindicated or not feasible. Especially young female, obese, and employed patients seem to benefit from LA.