A Framework for the Development of Living Practice Guidelines in Health Care.

BACKGROUND: Living practice guidelines are increasingly being used to ensure that recommendations are responsive to rapidly emerging evidence. OBJECTIVE: To develop a framework that characterizes the processes of development of living practice guidelines in health care. DESIGN: First, 3 background reviews were conducted: a scoping review of methods papers, a review of handbooks of guideline-producing organizations, and an analytic review of selected living practice guidelines. Second, the core team drafted the first version of the framework. Finally, the core team refined the framework through an online survey and online discussions with a multidisciplinary international group of stakeholders. SETTING: International. PARTICIPANTS: Multidisciplinary group of 51 persons who have experience with guidelines. MEASUREMENTS: Not applicable. RESULTS: A major principle of the framework is that the unit of update in a living guideline is the individual recommendation. In addition to providing definitions, the framework addresses several processes. The planning process should address the organization's adoption of the living methodology as well as each specific guideline project. The production process consists of initiation, maintenance, and retirement phases. The reporting should cover the evidence surveillance time stamp, the outcome of reassessment of the body of evidence (when applicable), and the outcome of revisiting a recommendation (when applicable). The dissemination process may necessitate the use of different venues, including one for formal publication. LIMITATION: This study does not provide detailed or practical guidance for how the described concepts would be best implemented. CONCLUSION: The framework will help guideline developers in planning, producing, reporting, and disseminating living guideline projects. It will also help research methodologists study the processes of living guidelines. PRIMARY FUNDING SOURCE: None.

An International Needs Assessment Survey of Guideline Developers Demonstrates Variability in Resources and Challenges to Collaboration between Organizations.

BACKGROUND: The development of rigorous, high-quality clinical guidelines increases the need for resources and skilled personnel within guideline-producing organizations. While collaboration between organizations provides a unique opportunity to pool resources and save time and effort, the collaboration presents its own unique challenges. OBJECTIVE: To assess the perceived needs and current challenges of guideline producers worldwide related to guideline development and collaboration efforts. DESIGN: Survey questions were developed by the Guidelines International Network and the US GRADE Network, pilot-tested among attendees of a guideline development workshop, and disseminated electronically using convenience and snowball sampling methods. PARTICIPANTS: A total of 171 respondents representing 30 countries and more than 112 unique organizations were included in this analysis. MAIN MEASURES: The survey included free-response, multiple-choice, and seven-point Likert-scale questions. Questions assessed respondents' perceived value of guidelines, resource availability and needs, guideline development processes, and collaboration efforts of their organization. KEY RESULTS: Time required to develop high-quality systematic reviews and guidelines was the most relevant need (median=7; IQR=5.5-7). In-house resources to conduct literature searches (median=4; IQR=3-6) and the resources to develop rigorous guidelines rapidly (median=4; IQR=2-5) were perceived as the least available resources. Difficulties reconciling differences in guideline methodology (median=6; IQR=4-7) and the time required to establish collaborative agreements (median=6; IQR=5-6) were the most relevant barriers to collaboration between organizations. Results also indicated a general need for improvement in conflict of interest (COI) disclosure policies. CONCLUSION: The survey identified organizational challenges in supporting rigorous guideline development, including the time, resources, and personnel required. Connecting guideline developers to existing databases of high-quality systematic reviews and the use of freely available online platforms may facilitate guideline development. Guideline-producing organizations may also consider allocating resources to hiring or training personnel with expertise in systematic review methodologies or utilizing resources more effectively by establishing collaborations with other organizations.

Intraoperative interventions for preventing surgical site infection: an overview of Cochrane Reviews.

BACKGROUND: Surgical site infection (SSI) rates vary from 1% to 5% in the month following surgery. Due to the large number of surgical procedures conducted annually, the costs of these SSIs can be considerable in financial and social terms. Many interventions are used with the aim of reducing the risk of SSI in people undergoing surgery. These interventions can be broadly delivered at three stages: preoperatively, intraoperatively and postoperatively. The intraoperative interventions are largely focused on decontamination of skin using soap and antiseptics; the use of barriers to prevent movement of micro-organisms into incisions; and optimising the patient's own bodily functions to promote best recovery. Both decontamination and barrier methods can be aimed at people undergoing surgery and operating staff. Other interventions focused on SSI prevention may be aimed at the surgical environment and include methods of theatre cleansing and approaches to managing theatre traffic. OBJECTIVES: To present an overview of Cochrane Reviews of the effectiveness and safety of interventions, delivered during the intraoperative period, aimed at preventing SSIs in all populations undergoing surgery in an operating theatre. METHODS: Published Cochrane systematic reviews reporting the effectiveness of interventions delivered during the intraoperative period in terms of SSI prevention were eligible for inclusion in this overview. We also identified Cochrane protocols and title registrations for future inclusion into the overview. We searched the Cochrane Library on 01 July 2017. Two review authors independently screened search results and undertook data extraction and 'Risk of bias' and certainty assessment. We used the ROBIS (risk of bias in systematic reviews) tool to assess the quality of included reviews, and we used GRADE methods to assess the certainty of the evidence for each outcome. We summarised the characteristics of included reviews in the text and in additional tables. MAIN RESULTS: We included 32 Cochrane Reviews in this overview: we judged 30 reviews as being at low risk of bias and two at unclear risk of bias. Thirteen reviews had not been updated in the past three years. Two reviews had no relevant data to extract. We extracted data from 30 reviews with 349 included trials, totaling 73,053 participants. Interventions assessed included gloving, use of disposable face masks, patient oxygenation protocols, use of skin antiseptics for hand washing and patient skin preparation, vaginal preparation, microbial sealants, methods of surgical incision, antibiotic prophylaxis and methods of skin closure. Overall, the GRADE certainty of evidence for outcomes was low or very low. Of the 77 comparisons providing evidence for the outcome of SSI, seven provided high- or moderate-certainty evidence, 39 provided low-certainty evidence and 31 very low-certainty evidence. Of the nine comparisons that provided evidence for the outcome of mortality, five provided low-certainty evidence and four very low-certainty evidence.There is high- or moderate-certainty evidence for the following outcomes for these intraoperative interventions. (1) Prophylactic intravenous antibiotics administered before caesarean incision reduce SSI risk compared with administration after cord clamping (10 trials, 5041 participants; risk ratio (RR) 0.59, 95% confidence interval (CI) 0.44 to 0.81; high-certainty evidence - assessed by review authors). (2) Preoperative antibiotics reduce SSI risk compared with placebo after breast cancer surgery (6 trials, 1708 participants; RR 0.74, 95% CI 0.56 to 0.98; high-certainty evidence - assessed by overview authors). (3) Antibiotic prophylaxis probably reduce SSI risk in caesarean sections compared with no antibiotics (82 relevant trials, 14,407 participants; RR 0.40, 95% CI 0.35 to 0.46; moderate-certainty evidence; downgraded once for risk of bias - assessed by review authors). (4) Antibiotic prophylaxis probably reduces SSI risk for hernia repair compared with placebo or no treatment (17 trials, 7843 participants; RR 0.67, 95% CI 0.54 to 0.84; moderate-certainty evidence; downgraded once for risk of bias - assessed by overview authors); (5) There is currently no clear difference in the risk of SSI between iodine-impregnated adhesive drapes compared with no adhesive drapes (2 trials, 1113 participants; RR 1.03, 95% CI 0.66 to 1.60; moderate-certainty evidence; downgraded once for imprecision - assessed by review authors); (6) There is currently no clear difference in SSI risk between short-term compared with long-term duration antibiotics in colorectal surgery (7 trials; 1484 participants; RR 1.05 95% CI 0.78 to 1.40; moderate-certainty evidence; downgraded once for imprecision - assessed by overview authors). There was only one comparison showing negative effects associated with the intervention: adhesive drapes increase the risk of SSI compared with no drapes (5 trials; 3082 participants; RR 1.23, 95% CI 1.02 to 1.48; high-certainty evidence - rated by review authors). AUTHORS' CONCLUSIONS: This overview provides the most up-to-date evidence on use of intraoperative treatments for the prevention of SSIs from all currently published Cochrane Reviews. There is evidence that some interventions are useful in reducing SSI risk for people undergoing surgery, such as antibiotic prophylaxis for caesarean section and hernia repair, and also the timing of prophylactic intravenous antibiotics administered before caesarean incision. Also, there is evidence that adhesive drapes increase SSI risk. Evidence for the many other treatment choices is largely of low or very low certainty and no quality-of-life or cost-effectiveness data were reported. Future trials should elucidate the relative effects of some treatments. These studies should focus on increasing participant numbers, using robust methodology and being of sufficient duration to adequately assess SSI. Assessment of other outcomes such as mortality might also be investigated as part of non-experimental prospective follow-up of people with SSI of different severity, so the risk of death for different subgroups can be better understood.

What do patients and the public know about clinical practice guidelines and what do they want from them? A qualitative study.

BACKGROUND: Guideline producers are increasingly producing versions of guidelines for the public. The aim of this study was to explore what patients and the public understand about the purpose and production of clinical guidelines, and what they want from clinical guidelines to support their healthcare decisions. METHODS: Participants were purposively selected to represent a range of the likely users of patient versions of guidelines, including individuals with health conditions (diabetes and depression), general members of the public, health communication professionals and a group of young people. Participants were asked about their awareness and understanding of clinical guidelines and presented with scenario recommendations, or draft materials from patient guidelines to prompt discussion. Each discussion was facilitated by one or two researchers. All focus groups were recorded and transcribed prior to analysis. Data were analysed using framework analysis. RESULTS: We ran nine focus groups involving 62 individuals, supplemented by four interviews with people experiencing homelessness. Eight groups were held in Scotland, one in England. The four interviews were held in Scotland. The framework analysis yielded five themes: access and awareness; what patients want to know; properties of guidelines; presenting evidence; and format. Awareness of guidelines was low. Participants emphasised the need for information that enables them to choose between treatment options, including harms. They would like help with this from healthcare professionals, especially general practitioners. Participants differed in their support for the inclusion of numerical information and graphs. CONCLUSIONS: Members of the public want information to help them choose between treatments, including information on harms, particularly to support shared decisions with health professionals. Presenting numerical information is a challenge and layered approaches that present information in stages may be helpful. Ignoring the themes identified in this study is likely to lead to materials that fail to support public and patient healthcare decision making.

Preoperative skin antiseptics for preventing surgical wound infections after clean surgery.

BACKGROUND: Surgical site infection rates in the month following clean surgery vary from 0.6% (knee prosthesis) to 5% (limb amputation). Due to the large number of clean surgical procedures conducted annually the costs of these surgical site infections (SSIs) can be considerable in financial and social terms. Preoperative skin antisepsis using antiseptics is performed to reduce the risk of SSIs by removing soil and transient organisms from the skin where a surgical incision will be made. Antiseptics are thought to be toxic to bacteria and therefore aid their mechanical removal. The effectiveness of preoperative skin preparation is thought to be dependent on both the antiseptic used and the method of application, however, it is unclear whether preoperative skin antisepsis actually reduces postoperative wound infection, and, if so, which antiseptic is most effective. OBJECTIVES: To determine whether preoperative skin antisepsis immediately prior to surgical incision for clean surgery prevents SSI and to determine the comparative effectiveness of alternative antiseptics. SEARCH METHODS: For this third update we searched just the Cochrane Wounds Group Specialised Register (searched 27 January 2015); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 12). SELECTION CRITERIA: Randomised controlled trials evaluating the use of preoperative skin antiseptics applied immediately prior to incision in clean surgery. There was no restriction on the inclusion of reports based on language of publication, date or publication status. DATA COLLECTION AND ANALYSIS: Data extraction and assessment of risk of bias were undertaken independently by two review authors. MAIN RESULTS: There were no new studies added to the review in the third updateThirteen studies were included in this review (2,623 participants). These evaluated several different types of skin antiseptics - leading to 11 different comparisons being made. Although the antiseptics evaluated differed between studies, all trials involved some form of iodine. Iodine in alcohol was compared to alcohol alone in one trial; one trial compared povidone iodine paint (solution type not reported) with soap and alcohol. Six studies compared different types of iodine-containing products with each other and five compared iodine-containing products with chlorhexidine-containing products.There was evidence from one study suggesting that preoperative skin preparation with 0.5% chlorhexidine in methylated spirits led to a reduced risk of SSI compared with an alcohol based povidone iodine solution: RR 0.47 (95% CI 0.27 to 0.82). However, it is important to note that the trial does not report important details regarding the interventions (such as the concentration of povidone iodine paint used) and trial conduct, such that risk of bias was unclear.There were no other statistically significant differences in SSI rates in the other comparisons of skin antisepsis. Overall the risk of bias in included studies was unclear.A mixed treatment comparison meta-analysis was conducted and this suggested that alcohol-containing products had the highest probability of being effective - however, again the quality of this evidence was low. AUTHORS' CONCLUSIONS: A comprehensive review of current evidence found some evidence that preoperative skin preparation with 0.5% chlorhexidine in methylated spirits was associated with lower rates of SSIs following clean surgery than alcohol-based povidone iodine paint. However this single study was poorly reported. Practitioners may therefore elect to consider other characteristics such as costs and potential side effects when choosing between alternatives.The design of future trials should be driven by the questions of high priority to decision makers. It may be that investment in at least one large trial (in terms of participants) is warranted in order to add definitive and hopefully conclusive data to the current evidence base. Ideally any future trial would evaluate the iodine-containing and chlorhexidine-containing solutions relevant to current practice as well as the type of solution used (alcohol vs. aqueous).

Patients, health information, and guidelines: A focus-group study.

BACKGROUND: Evidence-based clinical guidelines could support shared decision-making and help patients to participate actively in their care. However, it is not well known how patients view guidelines as a source of health information. This qualitative study aimed to assess what patients know about guidelines, and what they think of their presentation formats. RESEARCH QUESTION: What is the role of guidelines as health information for patients and how could the implementation of evidence-based information for patients be improved? METHODS: A qualitative study with focus groups that were built around a semi-structured topic guide. Focus groups were audiotaped and transcribed and analysed using a phenomenographic approach. RESULTS: Five focus groups were carried out in 2012 with a total of 23 participants. Patients searched for health information from the Internet or consulted health professionals or their personal networks. The concepts of guidelines included instructions or standards for health professionals, information given by a health professional to the patient, and material to protect and promote the interests of patients. Some patients did not have a concept for guidelines. Patients felt that health information was abundant and its quality sometimes difficult to assess. They respected conciseness, clarity, clear structure, and specialists or well-known organizations as authors of health information. Patients would like health professionals to deliver and clarify written materials to them or point out to them the relevant Internet sites. CONCLUSIONS: The concept of guidelines was not well known among our interviewees; however, they expressed an interest in having more communication on health information, both written information and clarifications with their health professionals.

Patient and public attitudes to and awareness of clinical practice guidelines: a systematic review with thematic and narrative syntheses.

BACKGROUND: Clinical practice guidelines are typically written for healthcare providers but there is increasing interest in producing versions for the public, patients and carers. The main objective of this review is to identify and synthesise evidence of the public's attitudes towards clinical practice guidelines and evidence-based recommendations written for providers or the public, together with their awareness of guidelines. METHODS: We included quantitative and qualitative studies of any design reporting on public, patient (and their carers) attitudes and awareness of guidelines written for providers or patients/public. We searched electronic databases including MEDLINE, PSYCHINFO, ERIC, ASSIA and the Cochrane Library from 2000 to 2012. We also searched relevant websites, reviewed citations and contacted experts in the field. At least two authors independently screened, abstracted data and assessed the quality of studies. We conducted a thematic analysis of first and second order themes and performed a separate narrative synthesis of patient and public awareness of guidelines. RESULTS: We reviewed 5415 records and included 26 studies (10 qualitative studies, 13 cross sectional and 3 randomised controlled trials) involving 24 887 individuals. Studies were mostly good to fair quality. The thematic analysis resulted in four overarching themes: Applicability of guidelines; Purpose of guidelines for patient; Purpose of guidelines for health care system and physician; and Properties of guidelines. Overall, participants had mixed attitudes towards guidelines; some participants found them empowering but many saw them as a way of rationing care. Patients were also concerned that the information may not apply to their own health care situations. Awareness of guidelines ranged from 0-79%, with greater awareness in participants surveyed on national guideline websites. CONCLUSION: There are many factors, not only formatting, that may affect the uptake and use of guideline-derived material by the public. Producers need to make clear how the information is relevant to the reader and how it can be used to make healthcare improvements although there were problems with data quality. Awareness of guidelines is generally low and guideline producers cannot assume that the public has a more positive perception of their material than of alternative sources of health information.

Preoperative skin antiseptics for preventing surgical wound infections after clean surgery.

BACKGROUND: Surgical site infection rates in the month following clean surgery vary from 0.6% (knee prosthesis) to 5% (limb amputation). Due to the large number of clean surgical procedures conducted annually the costs of these surgical site infections (SSIs) can be considerable in financial and social terms. Preoperative skin antisepsis using antiseptics is performed to reduce the risk of SSIs by removing soil and transient organisms from the skin where a surgical incision will be made. Antiseptics are thought to be toxic to bacteria and therefore aid their mechanical removal. The effectiveness of preoperative skin preparation is thought to be dependent on both the antiseptic used and the method of application, however, it is unclear whether preoperative skin antisepsis actually reduces postoperative wound infection, and, if so, which antiseptic is most effective. OBJECTIVES: To determine whether preoperative skin antisepsis immediately prior to surgical incision for clean surgery prevents SSI and to determine the comparative effectiveness of alternative antiseptics. SEARCH METHODS: For this second update we searched the The Cochrane Wounds Group Specialised Register (searched 7 August 2012), The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 7), Ovid MEDLINE  (1950 to July Week 4 2012), Ovid MEDLINE (In-Process & Other Non-Indexed Citations August 06, 2012), Ovid EMBASE (1980 to 2012 Week 31), EBSCO CINAHL (2007 to 3 August 2012). SELECTION CRITERIA: Randomised controlled trials evaluating the use of preoperative skin antiseptics applied immediately prior to incision in clean surgery. There was no restriction on the inclusion of reports based on language of publication, date or publication status. DATA COLLECTION AND ANALYSIS: Data extraction and assessment of risk of bias were undertaken independently by two review authors. MAIN RESULTS: Thirteen studies were included in this review (2,623 participants). These evaluated several different types of skin antiseptics - leading to 11 different comparisons being made. Although the antiseptics evaluated differed between studies, all trials involved some form of iodine. Iodine in alcohol was compared to alcohol alone in one trial; one trial compared povidone iodine paint (solution type not reported) with soap and alcohol. Six studies compared different types of iodine-containing products with each other and five compared iodine-containing products with chlorhexidine-containing products.There was evidence from one study suggesting that preoperative skin preparation with 0.5% chlorhexidine in methylated spirits led to a reduced risk of SSI compared with an alcohol based povidone iodine solution: RR 0.47 (95% CI 0.27 to 0.82). However, it is important to note that the trial does not report important details regarding the interventions (such as the concentration of povidone iodine paint used) and trial conduct, such that risk of bias was unclear.There were no other statistically significant differences in SSI rates in the other comparisons of skin antisepsis. Overall the risk of bias in included studies was unclear.A mixed treatment comparison meta-analysis was conducted and this suggested that alcohol-containing products had the highest probability of being effective - however, again the quality of this evidence was low. AUTHORS' CONCLUSIONS: A comprehensive review of current evidence found some evidence that preoperative skin preparation with 0.5% chlorhexidine in methylated spirits was associated with lower rates of SSIs following clean surgery than alcohol-based povidone iodine paint. However this single study was poorly reported. Practitioners may therefore elect to consider other characteristics such as costs and potential side effects when choosing between alternatives.The design of future trials should be driven by the questions of high priority to decision makers. It may be that investment in at least one large trial (in terms of participants) is warranted in order to add definitive and hopefully conclusive data to the current evidence base. Ideally any future trial would evaluate the iodine-containing and chlorhexidine-containing solutions relevant to current practice as well as the type of solution used (alcohol vs. aqueous).

Methods for living guidelines: early guidance based on practical experience. Paper 5: decisions on methods for evidence synthesis and recommendation development for living guidelines.

OBJECTIVES: Producing living guidelines requires making important decisions about methods for evidence identification, appraisal, and integration to allow the living mode to function. Clarifying what these decisions are and the trade-offs between options is necessary. This article provides living guideline developers with a framework to enable them to choose the most suitable model for their living guideline topic, question, or context. STUDY DESIGN AND SETTING: We developed this guidance through an iterative process informed by interviews, feedback, and a consensus process with an international group of living guideline developers. RESULTS: Several key decisions need to be made both before commencing and throughout the continual process of living guideline development and maintenance. These include deciding what approach is taken to the systematic review process; decisions about methods to be applied for the evidence appraisal process, including the use of unpublished data; and selection of "triggers" to incorporate new studies into living guideline recommendations. In each case, there are multiple options and trade-offs. CONCLUSION: We identify trade-offs and important decisions to be considered throughout the living guideline development process. The most appropriate, and most sustainable, mode of development and updating will be dependent on the choices made in each of these areas.

Methods for living guidelines: early guidance based on practical experience. Paper 3: selecting and prioritizing questions for living guidelines.

OBJECTIVES: This article is part of a series on methods for living guidelines, consolidating practical experiences from developing living guidelines. It focuses on methods for identification, selection, and prioritization of clinical questions for a living approach to guideline development. STUDY DESIGN AND SETTING: Members of the Australian Living Evidence Consortium, the National Institute of Health and Care Excellence and the US Grading of Recommendations, Assessment, Development and Evaluations Network, convened a working group. All members have expertize and practical experience in the development of living guidelines. We collated methods, documents on prioritization from each organization's living guidelines, conducted interviews and held working group discussions. We consolidated these to form best practice principles which were then edited and agreed on by the working group members. RESULTS: We developed best practice principles for (1) identification, (2) selection, and (3) prioritization, of questions for a living approach to guideline development. Several different strategies for undertaking prioritizing questions are explored. CONCLUSION: The article provides guidance for prioritizing questions in living guidelines. Subsequent articles in this series explore consumer involvement, search decisions, and methods decisions that are appropriate for questions with different priority levels.

Endogenous IL-13 plays a crucial role in liver granuloma maturation during Leishmania donovani infection, independent of IL-4Rα-responsive macrophages and neutrophils.

Previous studies comparing interleukin 4 receptor α (IL-4Rα)(-/-) and interleukin 4 (IL-4)(-/-) BALB/c mice have indicated that interleukin 13 (IL-13), whose receptor shares the IL-4Rα subunit with IL-4, plays a protective role during visceral leishmaniasis. We demonstrate that IL-13(-/-) BALB/c mice were less able to control hepatic growth of Leishmania donovani compared with wild-type mice. This correlated with significantly retarded granuloma maturation in IL-13(-/-) mice, defective interferon γ (IFN-γ) production, and elevated IL-4 and interleukin 10 (IL-10) levels. L. donovani-infected IL-13(-/-) mice also responded poorly to sodium stibogluconate-mediated chemotherapy compared with wild-type BALB/c mice. Because murine lymphocytes do not have IL-13 receptors, we examined the ability of macrophage/neutrophil-specific IL-4Rα(-/-) mice to control primary infection with L. donovani and to respond to chemotherapy. Macrophage/neutrophil-specific IL-4Rα(-/-) mice were as resistant to leishmaniasis as wild-type mice, and chemotherapy retained its efficacy. Consequently, in L. donovani infected BALB/c mice, IL-13 promotes hepatic granuloma formation and controls parasite burdens independently of direct effects on macrophages/neutrophils.

A memorandum of understanding has facilitated guideline development involving collaborating groups.

OBJECTIVE: Collaboration between groups can facilitate the development of high-quality guidelines. While collaboration is often desirable, misunderstandings can occur. One method to minimize misunderstandings is the pre-specification of terms of engagement in a memorandum of understanding (MOU). This study considered when an MOU may be most helpful, and which key elements should be included. STUDY DESIGN AND SETTING: An international panel of representatives from guideline groups was convened. A literature review to identify publications and other documents relevant to the establishment of MOUs between two or more guideline groups, supplemented by available source documents, was used to inform development of a draft MOU resource. This was iteratively refined until consensus was achieved. RESULTS: The level of detail in an MOU may vary based on institutional preferences and the particular collaboration. Elements within an MOU include those pertaining to: (1) scope and purpose; (2) leadership and team; (3) methods and commitment; (4) review and endorsement; and (5) publication and dissemination. CONCLUSION: Since groups may have different expectations regarding how a collaboration will unfold, an MOU may mitigate preventable misunderstandings. The result may be a higher likelihood of producing a guideline without disruption and delay.

The UpPriority tool supported prioritization processes for updating clinical guideline questions.

OBJECTIVE: We aim to 1) use the UpPriority tool to identify which clinical questions (CQs) within the clinical guidelines (CGs) need to be prioritized for updating and 2) assess the implementation of the tool in a real-world set of CGs. STUDY DESIGN AND SETTING: We systematically assessed CQs from a sample of CGs developed in the Spanish National Health System CG program. We applied the UpPriority tool to each CG using a step-by-step process that included: 1) establishment of the UpPriority Implementation Working Group, 2) mapping of the original CG questions and recommendations, 3) development of a survey to prioritize CQs, 4) assessment of CQ's priority according to six items, 5) calculation and ranking of priority scores, 6) decision of prioritized CQs for updating, and 7) development of the priority report. We assessed the tool implementation process (appraisers' experience when using the tool) and the inter-observer reliability of the tool, and we provided suggestions for improvement. RESULTS: We included four CGs with a total of 107 CQs on the following topics: chronic heart failure (10 CQs), inherited retinal dystrophies (39 CQs), menopause (20 CQs), and open-angle glaucoma (38 CQs). We included a total of 30 participants, most of them clinicians that were members of the original CG development groups. CQs were classified in three groups: 1) high priority (CQs prioritized for updating [16/107; 15.0%]), 2) medium priority (CQs that could be prioritized for updating [47/107; 43.9%]), and low priority (CQs that were not prioritized for updating [44/107; 41.1%]). The mean time each appraiser needed to assess the CQs with the tool was 3.8 hours (range 0.5 to 10). Agreement among the appraisers varied among the CGs. Appraisers considered that the tool was useful. We suggest some areas for consideration when using the tool including: 1) identification of key appraisers, 2) customization of training materials, 3) establishment of priority thresholds, and 4) provision of methodological support. CONCLUSION: The UpPriority is a useful tool to identify which CQs within a CG need to be prioritized for update in a real-world scenario. Recruitment and training of topic experts are the main challenges when using the tool.

Improving the precision of search strategies for guideline surveillance.

INTRODUCTION AND AIM: NICE guideline surveillance determines whether previously published guidelines need updating. The surveillance process must balance time constraints with methodological rigor. It includes a rapid review to identify new evidence to contradict, reinforce or clarify guideline recommendations. Despite this approach, the screening burden can still be high. Applying additional search techniques may increase the precision of the database searches. METHODS: A retrospective analysis was conducted on five surveillance reviews with less than 2% of the studies included after screening. Modified searches were run in MEDLINE, Embase and PsycINFO (where appropriate) to test the impact of additional search techniques: focused subject headings, subheadings, frequency operators and title only searches. Modified searches were compared to original search results to determine: the retrieval of included studies, the precision of the search and the number needed to read. Studies not retrieved by the modified search were checked to determine if the surveillance decision would have been affected. RESULTS: The additional search techniques tested indicated that a combination of focused subject headings and frequency operators could improve the precision of surveillance searches. The modified search retrieved all the original studies included in the surveillance review for three of the reviews tested. Some of the original included studies were not retrieved for two reviews but the missing studies would not have affected the surveillance decision. CONCLUSIONS: Combining focused subject headings and frequency operators is a viable option for improving the precision of surveillance searches without compromising recall and without impacting the surveillance decision.

The UpPriority tool was developed to guide the prioritization of clinical guideline questions for updating.

OBJECTIVE: The objective of the study is to develop a pragmatic tool to prioritize clinical guideline (CG) questions for updating, the UpPriority tool. STUDY DESIGN AND SETTING: The development of this tool consisted of the following: (1) establishment of the working group, (2) generation of the initial version, (3) optimization of the tool (including an initial feasibility test, semistructured interviews, Delphi consensus survey, second feasibility test, external review, and pilot test), and (4) approval of the final version. RESULTS: A total of 87 participants including methodologists, clinicians, and other relevant stakeholders contributed to the development of the UpPriority tool. The tool consists of six items: (1) impact of outdated recommendations on safety, (2) availability of new relevant evidence, (3) context relevance of the clinical question, (4) methodological applicability of the clinical question, (5) user's interest, and (6) impact on access to health care. The UpPriority tool includes detailed guidance for using the tool and rating each item (using a 7-point Likert scale), for calculating and ranking the questions, and for summarizing results. CONCLUSION: The UpPriority tool could be useful for standardizing prioritization processes when updating CGs and for fostering more efficient use of resources in the CG field.

Functionalized nanoparticles for bioanalysis by SERRS.

Metallic nanoparticles can be used as basic materials for a wide variety of purposes including building blocks for nanoassemblies, substrates for enhanced spectroscopies such as fluorescence and Raman and as labels for biomolecules. In the present paper, we report how silver and gold nanoparticles can be functionalized with specific biomolecular probes to interact in a specific manner with a target molecule to provide a change in the properties of the nanoparticles which can be measured to indicate the molecular recognition event. Examples of this approach include DNA hybridization to switch on SERRS (surface-enhanced resonance Raman scattering) when a specific target sequence is present, the use of nanoparticles for in vivo SERRS imaging and the use of nanoparticles functionalized with antibodies to provide a new type of immunoassay. These examples indicate how nanoparticles can be used to provide highly sensitive and informative data from a variety of biological systems when used in combination with SERRS.

Rapid cell mapping using nanoparticles and SERRS.

Bone marrow-derived immune cells (macrophages) treated with gold and silver nanoparticles before fixation and dye staining have been analysed by multiple wavelength line scanning surface enhanced resonance Raman scattering (SERRS) mapping. The method yields high selectivity and sensitivity within short analysis times, identifying nanoparticle aggregates in secondary lysosomes. Using routine cell stains, the output from fluorescence, Raman and SERRS is quantified at four wavelengths of excitation, demonstrating the potential at longer biologically compatible wavelengths of using nanoparticles with cell stains for superior cell mapping.

IL-4 Mediated Resistance of BALB/c Mice to Visceral Leishmaniasis Is Independent of IL-4Rα Signaling via T Cells.

Previous studies infecting global IL-4Rα-/-, IL-4-/-, and IL-13-/-mice on a BALB/c background with the visceralizing parasite Leishmania donovani have shown that the T helper 2 cytokines, IL-4, and IL-13, play influential but not completely overlapping roles in controlling primary infection. Subsequently, using macrophage/neutrophil-specific IL-4Rα deficient BALB/c mice, we demonstrated that macrophage/neutrophil unresponsiveness to IL-4 and IL-13 did not have a detrimental effect during L. donovani infection. Here we expand on these findings and show that CD4+ T cell-(Lckcre), as well as pan T cell-(iLckcre) specific IL-4Rα deficient mice, on a BALB/c background, unlike global IL-4Rα deficient mice, are also not adversely affected in terms of resistance to primary infection with L. donovani. Our analysis suggested only a transient and tissue specific impact on disease course due to lack of IL-4Rα on T cells, limited to a reduced hepatic parasite burden at day 30 post-infection. Consequently, the protective role(s) demonstrated for IL-4 and IL-13 during L. donovani infection are mediated by IL-4Rα-responsive cell(s) other than macrophages, neutrophils and T cells.