Pharmacological regimens for eradication of Helicobacter pylori: an overview of systematic reviews and network meta-analysis.

BACKGROUND: Approximately half of the world's population is infected with Helicobacter pylori (H.pylori), a bacterium shown to be linked with a series of gastrointestinal diseases. A growing number of systematic reviews (SRs) have been published comparing the effectiveness of different treatments for H.pylori infection but have not reached a consistent conclusion. The objective of this study is to provide an overview of SRs of pharmacological therapies for the eradication of H.pylori. METHODS: Major electronic databases were searched to identify relevant SRs published between 2002 and February 2016. Studies were considered eligible if they included RCTs comparing different pharmacological regimens for treating patients diagnosed as H.pylori infected and pooled the eradication rates in a meta-analysis. A modified version of the 'A Measurement Tool to Assess Systematic Reviews' (AMSTAR) was used to assess the methodological quality. A Bayesian random effects network meta-analysis (NMA) was conducted to compare the different proton pump inhibitors (PPI) within triple therapy. RESULTS: 30 SRs with pairwise meta-analysis were included. In triple therapy, the NMA ranked the esomeprazole to be the most effective PPI, followed by rabeprazole, while no difference was observed among the three old generations of PPI for the eradication of H.pylori. When comparing triple and bismuth-based therapy, the relative effectiveness appeared to be dependent on the choice of antibiotics within the triple therapy; moxifloxacin or levofloxacin-based triple therapy were both associated with greater effectiveness than bismuth-based therapy as a second-line treatment, while bismuth-based therapy achieved similar or greater eradication rate compared to clarithromycin-based therapy. Inconsistent findings were reported regarding the use of levofloxacin/moxifloxacin in the first-line treatment; this could be due to the varied resistant rate to different antibiotics across regions and populations. Critical appraisal showed a low-moderate level of overall methodological quality of included studies. CONCLUSIONS: Our analysis suggests that the new generation of PPIs and use of moxifloxacin or levofloxacin within triple therapy as second-line treatment were associated with greater effectiveness. Given the varied antibiotic resistant rate across regions, the appropriateness of pooling results together in meta-analysis should be carefully considered and the recommendation of the choice of antibiotics should be localized.

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.

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.

Guidelines 2.0: systematic development of a comprehensive checklist for a successful guideline enterprise.

BACKGROUND: Although several tools to evaluate the credibility of health care guidelines exist, guidance on practical steps for developing guidelines is lacking. We systematically compiled a comprehensive checklist of items linked to relevant resources and tools that guideline developers could consider, without the expectation that every guideline would address each item. METHODS: We searched data sources, including manuals of international guideline developers, literature on guidelines for guidelines (with a focus on methodology reports from international and national agencies, and professional societies) and recent articles providing systematic guidance. We reviewed these sources in duplicate, extracted items for the checklist using a sensitive approach and developed overarching topics relevant to guidelines. In an iterative process, we reviewed items for duplication and omissions and involved experts in guideline development for revisions and suggestions for items to be added. RESULTS: We developed a checklist with 18 topics and 146 items and a webpage to facilitate its use by guideline developers. The topics and included items cover all stages of the guideline enterprise, from the planning and formulation of guidelines, to their implementation and evaluation. The final checklist includes links to training materials as well as resources with suggested methodology for applying the items. INTERPRETATION: The checklist will serve as a resource for guideline developers. Consideration of items on the checklist will support the development, implementation and evaluation of guidelines. We will use crowdsourcing to revise the checklist and keep it up to date.

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.

Exercise for preventing and treating osteoporosis in postmenopausal women.

BACKGROUND: Osteoporosis is a condition resulting in an increased risk of skeletal fractures due to a reduction in the density of bone tissue. Treatment of osteoporosis typically involves the use of pharmacological agents. In general it is thought that disuse (prolonged periods of inactivity) and unloading of the skeleton promotes reduced bone mass, whereas mechanical loading through exercise increases bone mass. OBJECTIVES: To examine the effectiveness of exercise interventions in preventing bone loss and fractures in postmenopausal women. SEARCH STRATEGY: During the update of this review we updated the original search strategy by searching up to December 2010 the following electronic databases: the Cochrane Musculoskeletal Group's Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2010 Issue 12); MEDLINE; EMBASE; HealthSTAR; Sports Discus; CINAHL; PEDro; Web of Science; Controlled Clinical Trials; and AMED. We attempted to identify other studies by contacting experts, searching reference lists and searching trial registers. SELECTION CRITERIA: All randomised controlled trials (RCTs) that met our predetermined inclusion criteria. DATA COLLECTION AND ANALYSIS: Pairs of members of the review team extracted the data and assessed trial quality using predetermined forms. For dichotomous outcomes (fractures), we calculated risk ratios (RRs) using a fixed-effect model. For continuous data, we calculated mean differences (MDs) of the percentage change from baseline. Where heterogeneity existed (determined by the I(2) statistic), we used a random-effects model. MAIN RESULTS: Forty-three RCTs (27 new in this update) with 4320 participants met the inclusion criteria. The most effective type of exercise intervention on bone mineral density (BMD) for the neck of femur appears to be non-weight bearing high force exercise such as progressive resistance strength training for the lower limbs (MD 1.03; 95% confidence interval (CI) 0.24 to 1.82). The most effective intervention for BMD at the spine was combination exercise programmes (MD 3.22; 95% CI 1.80 to 4.64) compared with control groups. Fractures and falls were reported as adverse events in some studies. There was no effect on numbers of fractures (odds ratio (OR) 0.61; 95% CI 0.23 to 1.64). Overall, the quality of the reporting of studies in the meta-analyses was low, in particular in the areas of sequence generation, allocation concealment, blinding and loss to follow-up. AUTHORS' CONCLUSIONS: Our results suggest a relatively small statistically significant, but possibly important, effect of exercise on bone density compared with control groups. Exercise has the potential to be a safe and effective way to avert bone loss in postmenopausal women.

Systems for grading the quality of evidence and the strength of recommendations II: pilot study of a new system.

BACKGROUND: Systems that are used by different organisations to grade the quality of evidence and the strength of recommendations vary. They have different strengths and weaknesses. The GRADE Working Group has developed an approach that addresses key shortcomings in these systems. The aim of this study was to pilot test and further develop the GRADE approach to grading evidence and recommendations. METHODS: A GRADE evidence profile consists of two tables: a quality assessment and a summary of findings. Twelve evidence profiles were used in this pilot study. Each evidence profile was made based on information available in a systematic review. Seventeen people were given instructions and independently graded the level of evidence and strength of recommendation for each of the 12 evidence profiles. For each example judgements were collected, summarised and discussed in the group with the aim of improving the proposed grading system. Kappas were calculated as a measure of chance-corrected agreement for the quality of evidence for each outcome for each of the twelve evidence profiles. The seventeen judges were also asked about the ease of understanding and the sensibility of the approach. All of the judgements were recorded and disagreements discussed. RESULTS: There was a varied amount of agreement on the quality of evidence for the outcomes relating to each of the twelve questions (kappa coefficients for agreement beyond chance ranged from 0 to 0.82). However, there was fair agreement about the relative importance of each outcome. There was poor agreement about the balance of benefits and harms and recommendations. Most of the disagreements were easily resolved through discussion. In general we found the GRADE approach to be clear, understandable and sensible. Some modifications were made in the approach and it was agreed that more information was needed in the evidence profiles. CONCLUSION: Judgements about evidence and recommendations are complex. Some subjectivity, especially regarding recommendations, is unavoidable. We believe our system for guiding these complex judgements appropriately balances the need for simplicity with the need for full and transparent consideration of all important issues.

GRADE guidelines: 10. Considering resource use and rating the quality of economic evidence.

OBJECTIVES: In this article, we describe how to include considerations about resource utilization when making recommendations according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. STUDY DESIGN AND SETTINGS: We focus on challenges with rating the confidence in effect estimates (quality of evidence) and incorporating resource use into evidence profiles and Summary of Findings (SoF) tables. RESULTS: GRADE recommends that important differences in resource use between alternative management strategies should be included along with other important outcomes in the evidence profile and SoF table. Key steps in considering resources in making recommendations with GRADE are the identification of items of resource use that may differ between alternative management strategies and that are potentially important to decision makers, finding evidence for the differences in resource use, making judgments regarding confidence in effect estimates using the same criteria used for health outcomes, and valuing the resource use in terms of costs for the specific setting for which recommendations are being made. CONCLUSIONS: With our framework, decision makers will have access to concise summaries of recommendations, including ratings of the quality of economic evidence, and better understand the implications for clinical decision making.

Developing and Evaluating Communication Strategies to Support Informed Decisions and Practice Based on Evidence (DECIDE): protocol and preliminary results.

BACKGROUND: Healthcare decision makers face challenges when using guidelines, including understanding the quality of the evidence or the values and preferences upon which recommendations are made, which are often not clear. METHODS: GRADE is a systematic approach towards assessing the quality of evidence and the strength of recommendations in healthcare. GRADE also gives advice on how to go from evidence to decisions. It has been developed to address the weaknesses of other grading systems and is now widely used internationally. The Developing and Evaluating Communication Strategies to Support Informed Decisions and Practice Based on Evidence (DECIDE) consortium (http://www.decide-collaboration.eu/), which includes members of the GRADE Working Group and other partners, will explore methods to ensure effective communication of evidence-based recommendations targeted at key stakeholders: healthcare professionals, policymakers, and managers, as well as patients and the general public. Surveys and interviews with guideline producers and other stakeholders will explore how presentation of the evidence could be improved to better meet their information needs. We will collect further stakeholder input from advisory groups, via consultations and user testing; this will be done across a wide range of healthcare systems in Europe, North America, and other countries. Targeted communication strategies will be developed, evaluated in randomized trials, refined, and assessed during the development of real guidelines. DISCUSSION: Results of the DECIDE project will improve the communication of evidence-based healthcare recommendations. Building on the work of the GRADE Working Group, DECIDE will develop and evaluate methods that address communication needs of guideline users. The project will produce strategies for communicating recommendations that have been rigorously evaluated in diverse settings, and it will support the transfer of research into practice in healthcare systems globally.

Grading quality of evidence and strength of recommendations.

Users of clinical practice guidelines and other recommendations need to know how much confidence they can place in the recommendations. Systematic and explicit methods of making judgments can reduce errors and improve communication. We have developed a system for grading the quality of evidence and the strength of recommendations that can be applied across a wide range of interventions and contexts. In this article we present a summary of our approach from the perspective of a guideline user. Judgments about the strength of a recommendation require consideration of the balance between benefits and harms, the quality of the evidence, translation of the evidence into specific circumstances, and the certainty of the baseline risk. It is also important to consider costs (resource utilisation) before making a recommendation. Inconsistencies among systems for grading the quality of evidence and the strength of recommendations reduce their potential to facilitate critical appraisal and improve communication of these judgments. Our system for guiding these complex judgments balances the need for simplicity with the need for full and transparent consideration of all important issues.