A comparison of four risk models for the prediction of cardiovascular complications in patients with a history of atrial fibrillation undergoing non-cardiac surgery.

It is unclear how best to predict peri-operative cardiovascular risk in patients with atrial fibrillation undergoing non-cardiac surgery. This study examined the accuracy of the revised cardiac risk index and three atrial fibrillation thrombo-embolic risk models for predicting 30-day cardiovascular events after non-cardiac surgery in patients with a pre-operative history of atrial fibrillation. We conducted a prospective cohort study in 28 centres from 2007 to 2013 of 40,004 patients ≥ 45 years of age undergoing inpatient non-cardiac surgery who were followed until 30 days after surgery for cardiovascular events (defined as myocardial injury, heart failure, stroke, resuscitated cardiac arrest or cardiovascular death). The 2088 patients with a pre-operative history of atrial fibrillation were at higher risk of peri-operative cardiovascular events compared with the 34,830 patients without a history of atrial fibrillation (29% vs. 13%, respectively, adjusted odds ratio 1.30 (95%CI 1.17-1.45). Compared with the revised cardiac risk index (c-index 0.60), all atrial fibrillation thrombo-embolic risk scores were significantly better at predicting peri-operative cardiovascular events: CHADS2 (c-index 0.62); CHA2 DS2 -VASc (c-index 0.63); and R2 CHADS2 (c-index 0.65), respectively. Although the three thrombo-embolic risk prediction models were significantly better than the revised cardiac risk index for prediction of peri-operative cardiovascular events, none of the four models exhibited strong discrimination metrics. There remains a need to develop a better peri-operative risk prediction model.

Efficiency of pragmatic search strategies to update clinical guidelines recommendations.

BACKGROUND: A major challenge in updating clinical guidelines is to efficiently identify new, relevant evidence. We evaluated the efficiency and feasibility of two new approaches: the development of restrictive search strategies using PubMed Clinical Queries for MEDLINE and the use of the PLUS (McMaster Premium Literature Service) database. METHODS: We evaluated a random sample of recommendations from a national guideline development program and identified the references that would potentially trigger an update (key references) using an exhaustive approach. We designed restrictive search strategies using the minimum number of Medical Subject Headings (MeSH) terms and text words required from the original exhaustive search strategies and applying broad and narrow filters. We developed PLUS search strategies, matching Medical Subject Headings (MeSH) and Systematized Nomenclature of Medicine (SNOMED) terms with guideline topics. We compared the number of key references retrieved by these approaches with those retrieved by the exhaustive approach. RESULTS: The restrictive approach retrieved 68.1 % fewer references than the exhaustive approach (12,486 versus 39,136), and identified 89.9 % (62/69) of key references and 88 % (22/25) of recommendation updates. The use of PLUS retrieved 88.5 % fewer references than the exhaustive approach (4,486 versus 39,136) and identified substantially fewer key references (18/69, 26.1 %) and fewer recommendation updates (10/25, 40 %). CONCLUSIONS: The proposed restrictive approach is a highly efficient and feasible method to identify new evidence that triggers a recommendation update. Searching only in the PLUS database proved to be a suboptimal approach and suggests the need for topic-specific tailoring.

[Development of clinical practice guidelines for patients with comorbidity and multiple diseases]. / Desarrollo de guías de práctica clínica en pacientes con comorbilidad y pluripatología.

The management of patients with comorbidity and polypathology represents a challenge for all healthcare systems. Clinical practice guidelines (CPGs) have limitations when applied to this population. The aim of this study is to propose the terminology and methodology for optimally approach comorbidity and polypathology in the CPGs. Based on a literature review, we suggest a number of proposals for the approach in different phases of CPG preparation, with special attention to the inclusion of clusters of comorbidity in the initial questions the implementation of indirect evidence, the burden of disease management for patients and their environment, when establishing recommendations, as well as the strategies of dissemination and implementation. These proposals should be developed in greater depth with the implication of more agents in order to have valid and useful tools for this population.

Guideline registries and libraries: a mixed-methods approach identified issues to be addressed with content.

OBJECTIVE: To establish what GIN guideline community members see as the desirable features of a guidelines library and registry of guidelines in development STUDY DESIGN AND SETTING: An explorative mixed-methods study was undertaken, including scoping activity and semi-structured interviews with guideline developers and endorsers from nine member organizations of the Guidelines International Network. RESULTS: A small number of desirable features of a guideline library were identified: comprehensiveness; single source of information to avoid searching multiple sites; inclusion of related materials; being up to date; searchability and ease of use. No existing library of guidelines was considered to have all of these features. A number of issues arose out of the desire to have a comprehensive library of guidelines, including inclusion of 'high quality guidelines' and limiting the scope to include only national guidelines. For registries of guidelines in development, the data set should be limited to avoid placing undue burden on those entering information. CONCLUSION: Our findings identify ongoing issues for the guideline community, including the tension between comprehensiveness and ease of use, which can result in limited uptake, reporting of guideline quality and the need for clarity on the purpose of any library or registry.

Grading quality of evidence and strength of recommendations in clinical practice guidelines part 3 of 3. The GRADE approach to developing recommendations.

This is the third and last article in the series about the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to grading the quality of evidence and the strength of recommendations in clinical practice guidelines and its application in the field of allergy. We describe the factors that influence the strength of recommendations about the use of diagnostic, preventive and therapeutic interventions: the balance of desirable and undesirable consequences, the quality of a body of evidence related to a decision, patients' values and preferences, and considerations of resource use. We provide examples from two recently developed guidelines in the field of allergy that applied the GRADE approach. The main advantages of this approach are the focus on patient important outcomes, explicit consideration of patients' values and preferences, the systematic approach to collecting the evidence, the clear separation of the concepts of quality of evidence and strength of recommendations, and transparent reporting of the decision process. The focus on transparency facilitates understanding and implementation and should empower patients, clinicians and other health care professionals to make informed choices.

Grading quality of evidence and strength of recommendations in clinical practice guidelines. Part 1 of 3. An overview of the GRADE approach and grading quality of evidence about interventions.

The GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) approach provides guidance to grading the quality of underlying evidence and the strength of recommendations in health care. The GRADE system's conceptual underpinnings allow for a detailed stepwise process that defines what role the quality of the available evidence plays in the development of health care recommendations. The merit of GRADE is not that it eliminates judgments or disagreements about evidence and recommendations, but rather that it makes them transparent. This first article in a three-part series describes the GRADE framework in relation to grading the quality of evidence about interventions based on examples from the field of allergy and asthma. In the GRADE system, the quality of evidence reflects the extent to which a guideline panel's confidence in an estimate of the effect is adequate to support a particular recommendation. The system classifies quality of evidence as high, moderate, low, or very low according to factors that include the study methodology, consistency and precision of the results, and directness of the evidence.

Grading quality of evidence and strength of recommendations in clinical practice guidelines: Part 2 of 3. The GRADE approach to grading quality of evidence about diagnostic tests and strategies.

The GRADE approach to grading the quality of evidence and strength of recommendations provides a comprehensive and transparent approach for developing clinical recommendations about using diagnostic tests or diagnostic strategies. Although grading the quality of evidence and strength of recommendations about using tests shares the logic of grading recommendations for treatment, it presents unique challenges. Guideline panels and clinicians should be alert to these special challenges when using the evidence about the accuracy of tests as the basis for clinical decisions. In the GRADE system, valid diagnostic accuracy studies can provide high quality evidence of test accuracy. However, such studies often provide only low quality evidence for the development of recommendations about diagnostic testing, as test accuracy is a surrogate for patient-important outcomes at best. Inferring from data on accuracy that using a test improves outcomes that are important to patients requires availability of an effective treatment, improved patients' wellbeing through prognostic information, or - by excluding an ominous diagnosis - reduction of anxiety and the opportunity for earlier search for an alternative diagnosis for which beneficial treatment can be available. Assessing the directness of evidence supporting the use of a diagnostic test requires judgments about the relationship between test results and patient-important consequences. Well-designed and conducted studies of allergy tests in parallel with efforts to evaluate allergy treatments critically will encourage improved guideline development for allergic diseases.

Colorectal cancer guidelines seldom include the patient perspective.

OBJECTIVES: This study aimed to describe how colorectal practice guidelines (PGs) incorporate the patient perspective. STUDY DESIGN AND SETTING: We searched in the Guidelines International Network library, MEDLINE, National Guideline Clearinghouse, NHS Evidence database, and TRIP database. Two authors independently selected the PGs. We considered recommendations rated or worded as weak or conditional or suggesting multiple options, as potentially preference sensitive. Two authors independently evaluated if, in potentially sensitive recommendations, the patient perspective was incorporated. RESULTS: We included 28 PGs that contained 588 recommendations, being 256 potentially preference sensitive. Ten PGs (36%) included patients in the development process, and 12 (43%) provided information about patients' perspectives. Nine PGs (32%) included recommendations in which the patient perspective was explicitly considered, and 13 (46.4%) that recommended a discussion with the patient. From a total of 588 recommendations, 9.7% (25/256) of potentially preference-sensitive recommendations considered the patient perspective. The inclusion of patients in the development process was associated with a more frequent incorporation of the patient perspective in potentially preference sensitive recommendations (70% vs. 0%; P < 0.001). CONCLUSIONS: Guideline users should be aware that the incorporation of the patient perspective in colorectal cancer PGs is suboptimal. Guideline developers should make efforts to incorporate the patient perspective, especially in preference-sensitive recommendations.

Self-monitoring of oral anticoagulation: a systematic review and meta-analysis.

BACKGROUND: Near-patient testing has made self-monitoring of anticoagulation with warfarin feasible, and several trials have suggested that such monitoring might be equal to or better than standard monitoring. We did a systematic review and meta-analysis of all randomised controlled trials that assessed the effects of self-monitoring or self-management (self-testing and self-dosage) of anticoagulation compared with standard monitoring. METHODS: We searched the Cochrane Register of Controlled Trials, MEDLINE, EMBASE to April 2005, and contacted manufacturers and authors of relevant studies. Outcomes analysed were: major haemorrhage, thromboembolic events, death, tests in range, minor haemorrhage, frequency of testing, and feasibility of self-monitoring. FINDINGS: We identified 14 randomised trials of self-monitoring: pooled estimates showed significant reductions in thromboembolic events (odds ratio 0.45, 95% CI 0.30-0.68), all-cause mortality (0.61, 0.38-0.98), and major haemorrhage (0.65, 0.42-0.99). Trials of combined self-monitoring and self-adjusted therapy showed significant reductions in thromboembolic events (0.27, 0.12-0.59) and death (0.37, 0.16-0.85), but not major haemorrhage (0.93, 0.42-2.05). No difference was noted in minor haemorrhage. 11 trials reported improvements in the mean proportion of international normalisation ratios in range. INTERPRETATION: Self-management improves the quality of oral anticoagulation. Patients capable of self-monitoring and self-adjusting therapy have fewer thromboembolic events and lower mortality than those who self-monitor alone. However, self-monitoring is not feasible for all patients, and requires identification and education of suitable candidates.

Calcitonin for metastatic bone pain.

BACKGROUND: Pain is the most frequent symptom experienced by cancer patients, its intensity dependent on the site of the tumour. Tumours that compromise bone or nervous structures due to the bone destruction process are the most painful. There are several treatments to deal with pain (and other symptoms) caused by bone metastases. The hormone, calcitonin, has the potential to relieve pain, and also retain bone density, thus reducing the risk of fractures. This review is an update of a previously published review in The Cochrane Library (Issue 3, 2003) on this topic. OBJECTIVES: To assess the effectiveness of calcitonin in controlling metastatic bone pain and reducing bone complications (hypercalcemia, fractures and nerve compression) in patients with bone metastases. SEARCH STRATEGY: Electronic searches were performed in MEDLINE (1966 to 2005), EMBASE (1974 to 2005), the Cochrane Central Register of Controlled Trials (Issue 2, 2005), specialised registers of the Cochrane Cancer Network and of the Cochrane Pain, Palliative and Supportive Care Group. Registers of clinical trials in progress were also searched. SELECTION CRITERIA: Studies were included if they were randomised, double-blind clinical trials of patients with metastatic bone pain, treated with calcitonin, where the major outcome measure was pain, assessed at four weeks or longer. DATA COLLECTION AND ANALYSIS: Study selection and data extraction were performed by two independent review authors. Only two studies (90 patients) were eligible for inclusion in the review and therefore meta-analysis of the data was not possible. Intention-to-treat analysis was performed by imputing all missing values as adverse outcomes. MAIN RESULTS: Of the two small studies included in the review, one study showed a non-significant effect of calcitonin in the number of patients with total pain reduction (RR 2.50; CI 95%, 0.55 to 11.41). The second study provided no evidence that calcitonin reduced analgesia consumption (RR 1.05; CI 95%, 0.90 to 1.21) in patients with painful bone metastases. There was no evidence that calcitonin was effective in controlling complications due to bone metastases; for improving quality of life; or patients' survival. Although not statistically significant, a greater number of adverse effects were observed in the groups given calcitonin in the two included studies (RR 3.35, CI 95%, 0.72 to 15.66). AUTHORS' CONCLUSIONS: The limited evidence currently available does not support the use of calcitonin to control pain from bone metastases. Since the last version of this review, none of the new relevant studies have provided additional information on this treatment, in contrast to other therapeutic approaches that should be considered.

Laxatives for the treatment of hemorrhoids.

BACKGROUND: Symptomatic hemorrhoids are a common medical condition, which increase in prevalence in women during pregnancy and postpartum. Although the evidence appears to be inconclusive, narrative reviews and clinical practice guidelines recommend the use of laxatives (and fiber) for the treatment of hemorrhoids and relief of symptoms. This is due to their safety and low cost. OBJECTIVES: To evaluate the impact of laxatives on a wide range of symptoms in people with symptomatic hemorrhoids. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2005), MEDLINE (1966 to 2005), EMBASE (1980 to 2005), CINAHL (1982 to 2005), BIOSIS, and AMED (Allied and Alternative Medicine Database), for eligible trials (including conference proceedings). We sought missing and additional information from authors, industry, and experts in the field. SELECTION CRITERIA: We selected all published and unpublished randomised controlled trials that compared any type of laxative to placebo or no therapy in any patient population. DATA COLLECTION AND ANALYSIS: Two authors independently screened studies for inclusion and retrieved all potentially relevant studies. Data were extracted from studies that met our selection criteria on study population, intervention used, pre-specified outcomes, and methodology. We extracted methodological information for the assessment of internal validity: existence and method of generation of the randomization schedule, and method of allocation concealment; blinding of caregivers and outcomes assessors; numbers of and reasons for participants lost to follow up; and use of validated outcome measures. MAIN RESULTS: Seven randomised trials enrolling a total of 378 participants to fiber or a non-fiber control were identified. Meta-analyses using random-effects models showed that laxatives in the form of fiber had a beneficial effect in the treatment of symptomatic hemorrhoids. The risk of not improving hemorrhoids and having persisting symptoms decreased by 53% in the fiber group (risk reduction (RR) 0.47, 95% CI 0.32 to 0.68). These results are compatible with large treatment effects regarding prolapse, pain, itching, although the pooled analyses showed a tendency toward no-effect for these parametres. The effect on bleeding showed a significant difference in favour of the fiber (RR 0.50, 95% CI 0.28 to 0.89). Studies including data on multiple follow ups (usually after six weeks and three months) showed consistent results over time. However, we have to stress two possible limitations of this review: the risk of publication bias, and only moderate study quality. AUTHORS' CONCLUSIONS: The use of fiber shows a consistent beneficial effect for relieving overall symptoms and bleeding in the treatment of symptomatic hemorrhoids.

Postoperative atrial fibrillation in non-cardiac and cardiac surgery: an overview.

Postoperative atrial fibrillation (POAF) is the most common perioperative cardiac arrhythmia. A major risk factor for POAF is advanced age, both in non-cardiac and cardiac surgery. Following non-cardiac surgery, it is important to correct reversible conditions such as electrolytes imbalances to prevent the occurrence of POAF. Management of POAF consists of rate control and therapeutic anticoagulation if POAF persists for > 48 h and CHADS2 score > 2. After cardiac surgery, POAF affects a larger amount of patients. In addition to age, valve surgery carries the greatest risk for new AF. Rate control is the mainstay therapy in these patients. Prediction, prevention, and management of POAF should be further studied.

The prediction of postoperative stroke or death in patients with preoperative atrial fibrillation undergoing non-cardiac surgery: a VISION sub-study.

BACKGROUND: The optimal means of pre-operative risk stratification in patients with atrial fibrillation (AF) is uncertain. OBJECTIVE: To examine the accuracy of AF thromboembolic risk models (the CHADS2, CHA2DS2-VASc, and R2CHADS2 scores) for predicting 30-day stroke and/or all-cause mortality after non-cardiac surgery in patients with preoperative AF, and to compare these risk scores with the Revised Cardiac Risk Index (RCRI). PATIENTS/METHODS: A multicentre (8 countries, 2007-2011) prospective cohort study of patients ≥ 45 years of age undergoing inpatient non-cardiac surgery, who were followed until 30 days after surgery. We calculated c-statistics for each risk prediction model and net reclassification improvements (NRIs) compared with the RCRI. RESULTS: The 961 patients with preoperative AF were at higher risk of any cardiovascular event in the 30 days postoperatively compared with the 13 001 patients without AF: 26.6% vs. 9.0%; adjusted odds ratio, 1.58; 95% confidence interval [CI], 1.33-1.88. All thromboembolic risk scores predicted postoperative death just as well as the RCRI (with c-indices between 0.67 and 0.72). Compared with the RCRI (which had a c-index of 0.64 for 30-day stroke/death), the CHADS2 (c-index, 0.67; NRI, 0.31; 95% CI, 0.02-0.61) significantly improved postoperative stroke/mortality risk prediction, largely due to improved discrimination of patients who did not subsequently have an event. CONCLUSIONS: In AF patients, the three thromboembolic risk scores performed similarly to the RCRI in predicting death within 30 days and the CHADS2 score was the best predictor of postoperative stroke/death regardless of type of surgery.

Calcitonin for metastatic bone pain.

BACKGROUND: Pain is the most frequent symptom experienced by cancer patients, its intensity dependent on the site of the tumour. Tumours that compromise bone or nervous structures due to the bone destruction process are the most painful. There are several treatments to deal with pain (and other symptoms) caused by bone metastasis. The hormone, calcitonin, has the potential to relieve pain, and also retain bone density, thus reducing the risk of fractures. OBJECTIVES: To assess the effectiveness of calcitonin in controlling metastatic bone pain and reducing bone complications (hypercalcemia, fractures and nervous compression) in patients with bone metastases. SEARCH STRATEGY: Electronic searches were performed in MEDLINE (1966-2001), EMBASE (1974-2001), the Cochrane Central Register of Controlled Trials (Issue 2, 2001), specialised registers of the Cochrane Cancer Network and of the Cochrane Pain, Palliative and Supportive Care Group. Registers of clinical trials in progress were also searched. SELECTION CRITERIA: Studies were included if they were randomised, double-blind clinical trials of patients with metastatic bone pain, treated with calcitonin, where the major outcome measure was pain, assessed at four weeks or longer. DATA COLLECTION AND ANALYSIS: Study selection and data extraction were performed by two independent reviewers. Only two studies (90 patients) were eligible for inclusion in the review and therefore meta-analysis of the data was not possible. Intention-to-treat analysis was performed by imputing all missing values as adverse outcomes. MAIN RESULTS: Of the two small studies included in the review, one study showed a non-significant effect of calcitonin in the number of patients with total pain reduction (RR 2.50; CI 95%, 0.55 to 11.41). The second study provided no evidence that calcitonin reduced analgesia consumption (RR 1.05; CI 95%, 0.90 to 1.21) in patients with painful bone metastases. There was no evidence that calcitonin was effective in controlling complications due to bone metastases; for improving quality of life; or patients' survival. Although not statistically significant, a greater number of adverse effects were observed in the groups given calcitonin in the two included studies (RR 3.35, CI 95%, 0.72 to 15.66). REVIEWER'S CONCLUSIONS: The limited evidence currently available for systematic review does not support the use of calcitonin to control pain from bone metastases. Until new studies provide additional information on this treatment, other therapeutic approaches should be considered.

Development of clinical practice guidelines for patients with comorbidity and multiple diseases. / Desarrollo de guías de práctica clínica en pacientes con comorbilidad y pluripatología.

The management of patients with comorbidity and polypathology represents a challenge for all healthcare systems. Clinical practice guidelines (CPGs) have limitations when applied to this population. The aim of this study is to propose the terminology and methodology for optimally approach comorbidity and polypathology in the CPGs. Based on a literature review, we suggest a number of proposals for the approach in different phases of CPG preparation, with special attention to the inclusion of clusters of comorbidity in the initial questions the implementation of indirect evidence, the burden of disease management for patients and their environment, when establishing recommendations, as well as the strategies of dissemination and implementation. These proposals should be developed in greater depth with the implication of more agents in order to have valid and useful tools for this population.