Because we are not certain that they are beneficial, it is also reasonable not to prescribe them. According to the GRADE approach, recommendations can be strong or weak and for or against a course of ...action.33 High quality evidence of an effect on surrogate outcomes do not trigger strong recommendations. All tests for relative subgroup effects may be underpowered to detect true differences because the effect sizes are small, especially for mortality. ...we cannot be certain that a true subgroup effect does not exist. Several trials of corticosteroids for pneumonia or acute respiratory distress syndrome have enrolled patients who did not have sepsis; we did not consider these trials. ...clinicians treating these conditions should also consider evidence2324 and guidelines12 applicable to patients who have pneumonia and acute respiratory distress syndrome.
What you need to know: The recommendations apply to patients under 60 years old with patent foramen ovale (PFO) who have had a cryptogenic ischaemic stroke, when extensive workup for other ...aetiologies of stroke is negative; For patients who are open to all options, we make a weak recommendation for PFO closure plus antiplatelet therapy rather than anticoagulant therapy; For patients in whom anticoagulation is contraindicated or declined, we make a strong recommendation for PFO closure plus antiplatelet therapy versus antiplatelet therapy alone; For patients in whom closure is contraindicated or declined, we make a weak recommendation for anticoagulant therapy rather than antiplatelet therapy; Further research may alter the recommendations that involve anticoagulant therapy. Options for the secondary prevention of stroke in patients younger than 60 years who have had a cryptogenic ischaemic stroke thought to be secondary to patent foramen ovale (PFO) include PFO closure (with antiplatelet therapy), antiplatelet therapy alone, or anticoagulants. International guidance and practice differ on which option is preferable. The BMJ Rapid Recommendations panel used a linked systematic review1 triggered by three large randomised trials published in September 2017 that suggested PFO closure might reduce the risk of ischaemic stroke more than alternatives.234 The panel felt that the studies, when considered in the context of the full body of evidence, might change current clinical practice.5 The linked systematic review finds that PFO closure prevents recurrent stroke relative to antiplatelet therapy, but possibly not relative to anticoagulants, and is associated with procedural complications and persistent atrial fibrillation.1 The review also presents evidence regarding the role of anticoagulants or antiplatelet therapy when PFO closure is not acceptable or is contraindicated.
AbstractUpdate to this articleIn October 2022, three years after the initial publication of this guideline, the first trial of the effect of colonoscopy screening was published. The implications of ...this new evidence for the current recommendations were evaluated by the guideline panel in January 2023. The guideline panel judged that this new evidence did not alter the current recommendations, and therefore that an update of the following guideline was not needed (see table 2 for details).Clinical questionRecent 15-year updates of sigmoidoscopy screening trials provide new evidence on the effectiveness of colorectal cancer screening. Prompted by the new evidence, we asked: “Does colorectal cancer screening make an important difference to health outcomes in individuals initiating screening at age 50 to 79? And which screening option is best?”Current practiceNumerous guidelines recommend screening, but vary on recommended test, age and screening frequency. This guideline looks at the evidence and makes recommendations on screening for four screening options: faecal immunochemical test (FIT) every year, FIT every two years, a single sigmoidoscopy, or a single colonoscopy.RecommendationsThese recommendations apply to adults aged 50-79 years with no prior screening, no symptoms of colorectal cancer, and a life expectancy of at least 15 years. For individuals with an estimated 15-year colorectal cancer risk below 3%, we suggest no screening (weak recommendation). For individuals with an estimated 15-year risk above 3%, we suggest screening with one of the four screening options: FIT every year, FIT every two years, a single sigmoidoscopy, or a single colonoscopy (weak recommendation). With our guidance we publish the linked research, a graphic of the absolute harms and benefits, a clear description of how we reached our value judgments, and linked decision aids.How this guideline was createdA guideline panel including patients, clinicians, content experts and methodologists produced these recommendations using GRADE and in adherence with standards for trustworthy guidelines. A linked systematic review of colorectal cancer screening trials and microsimulation modelling were performed to inform the panel of 15-year screening benefits and harms. The panel also reviewed each screening option’s practical issues and burdens. Based on their own experience, the panel estimated the magnitude of benefit typical members of the population would value to opt for screening and used the benefit thresholds to inform their recommendations.The evidenceOverall there was substantial uncertainty (low certainty evidence) regarding the 15-year benefits, burdens, and harms of screening. Best estimates suggested that all four screening options resulted in similar colorectal cancer mortality reductions. FIT every two years may have little or no effect on cancer incidence over 15 years, while FIT every year, sigmoidoscopy, and colonoscopy may reduce cancer incidence, although for FIT the incidence reduction is small compared with sigmoidoscopy and colonoscopy. Screening related serious gastrointestinal and cardiovascular adverse events are rare. The magnitude of the benefits is dependent on the individual risk, while harms and burdens are less strongly associated with cancer risk.Understanding the recommendationBased on benefits, harms, and burdens of screening, the panel inferred that most informed individuals with a 15-year risk of colorectal cancer of 3% or higher are likely to choose screening, and most individuals with a risk of below 3% are likely to decline screening. Given varying values and preferences, optimal care will require shared decision making.
An updated meta-analysis incorporating nine randomized trials (
= 816) investigating low-to-moderate dose prolonged glucocorticoid treatment in acute respiratory distress syndrome (ARDS) show ...moderate-to-high quality evidence that glucocorticoid therapy is safe and reduces (i) time to endotracheal extubation, (ii) duration of hospitalization, and (iii) mortality (number to treat to save one life = 7), and increases the number of days free from (i) mechanical ventilation, (ii) intensive care unit stay, and (iii) hospitalization. Recent guideline suggests administering methylprednisolone in patients with early moderate-to-severe (1 mg/kg/day) and late persistent (2 mg/kg/day) ARDS (conditional recommendation based on moderate quality of evidence).
What you need to know: PSA testing has increased the number of men diagnosed with and treated for prostate cancer, but many of these men would never have experienced any symptoms or death from ...prostate cancer; This guideline makes a weak recommendation against offering systematic PSA screening based on an updated systematic review. The recommendation is weak because there may be a small, though uncertain, benefit of screening on prostate cancer mortality; Men who place more value on avoiding complications from biopsies and cancer treatment are likely to decline screening. In contrast, men who put more value in even a small reduction of prostate cancer mortality (such as men at high baseline risk because of family history or African descent, or those concerned to rule out the diagnosis) may opt for screening; Shared decision making is needed for men considering screening to make a decision consistent with their individual values and preferences. However, clinicians need not feel obligated to systematically raise the issue of PSA screening with their patients. What is the role of prostate-specific antigen (PSA) screening in prostate cancer? An expert panel produced these recommendations based on a linked systematic review.1 The review was triggered by a large scale, cluster randomised trial on PSA screening in men without a previous diagnosis of prostate cancer published in 2018 (box 1).2 It found no difference between one-time PSA screening and standard practice in prostate cancer mortality but found an increase in the detection of low risk prostate cancer after a median follow-up of 10 years.
Abstract Context Pharmacological thromboprophylaxis involves a trade-off between a reduction in venous thromboembolism (VTE) and increased bleeding. No guidance specific for procedure and patient ...factors exists in urology. Objective To inform estimates of absolute risk of symptomatic VTE and bleeding requiring reoperation in urological non-cancer surgery. Evidence acquisition We searched for contemporary observational studies and estimated the risk of symptomatic VTE or bleeding requiring reoperation in the 4 wk after urological surgery. We used the GRADE approach to assess the quality of the evidence. Evidence synthesis The 37 eligible studies reported on 11 urological non-cancer procedures. The duration of prophylaxis varied widely both within and between procedures; for example, the median was 12.3 d (interquartile range IQR 3.1–55) for open recipient nephrectomy (kidney transplantation) studies and 1 d (IQR 0–1.3) for percutaneous nephrolithotomy, open prolapse surgery, and reconstructive pelvic surgery studies. Studies of open recipient nephrectomy reported the highest risks of VTE and bleeding (1.8–7.4% depending on patient characteristics and 2.4% for bleeding). The risk of VTE was low for 8/11 procedures (0.2–0.7% for patients with low/medium risk; 0.8–1.4% for high risk) and the risk of bleeding was low for 6/7 procedures (≤0.5%; no bleeding estimates for 4 procedures). The quality of the evidence supporting these estimates was low or very low. Conclusions Although inferences are limited owing to low-quality evidence, our results suggest that extended prophylaxis is warranted for some procedures (eg, kidney transplantation procedures in high-risk patients) but not others (transurethral resection of the prostate and reconstructive female pelvic surgery in low-risk patients). Patient summary The best evidence suggests that the benefits of blood-thinning drugs to prevent clots after surgery outweigh the risks of bleeding in some procedures (such as kidney transplantation procedures in patients at high risk of clots) but not others (such as prostate surgery in patients at low risk of clots).
What are the benefits and harms of sodium-glucose cotransporter 2 (SGLT-2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists when added to usual care (lifestyle interventions and/or ...other diabetes drugs) in adults with type 2 diabetes at different risk for cardiovascular and kidney outcomes?
Clinical decisions about treatment of type 2 diabetes have been led by glycaemic control for decades. SGLT-2 inhibitors and GLP-1 receptor agonists are traditionally used in people with elevated glucose level after metformin treatment. This has changed through trials demonstrating atherosclerotic cardiovascular disease (CVD) and chronic kidney disease (CKD) benefits independent of medications' glucose-lowering potential.
The guideline panel issued risk-stratified recommendations concerning the use of SGLT-2 inhibitors or GLP-1 receptor agonists in adults with type 2 diabetes• Three or fewer cardiovascular risk factors without established CVD or CKD: Weak recommendation against starting SGLT-2 inhibitors or GLP-1 receptor agonists.• More than three cardiovascular risk factors without established CVD or CKD: Weak recommendation for starting SGLT-2 inhibitors and weak against starting GLP-1 receptor agonists.• Established CVD or CKD: Weak recommendation for starting SGLT-2 inhibitors and GLP-1 receptor agonists.• Established CVD and CKD: Strong recommendation for starting SGLT-2 inhibitors and weak recommendation for starting GLP-1 receptor agonists.• For those committed to further reducing their risk for CVD and CKD outcomes: Weak recommendation for starting SGLT-2 inhibitors rather than GLP-1 receptor agonists.
An international panel including patients, clinicians, and methodologists created these recommendations following standards for trustworthy guidelines and using the GRADE approach. The panel applied an individual patient perspective.
A linked systematic review and network meta-analysis (764 randomised trials included 421 346 participants) of benefits and harms found that SGLT-2 inhibitors and GLP-1 receptor agonists generally reduce overall death, and incidence of myocardial infarctions, and end-stage kidney disease or kidney failure (moderate to high certainty evidence). These medications exert different effects on stroke, hospitalisations for heart failure, and key adverse events in different subgroups. Absolute effects of benefit varied widely based on patients' individual risk (for example, from five fewer deaths in the lowest risk to 48 fewer deaths in the highest risk, for 1000 patients treated over five years). A prognosis review identified 14 eligible risk prediction models, one of which (RECODe) informed most baseline risk estimates in evidence summaries to underpin the risk-stratified recommendations. Concerning patients' values and preferences, the recommendations were supported by evidence from a systematic review of published literature, a patient focus group study, a practical issues summary, and a guideline panel survey.
We stratified the recommendations by the levels of risk for CVD and CKD and systematically considered the balance of benefits, harms, other considerations, and practical issues for each risk group. The strong recommendation for SGLT-2 inhibitors in patients with CVD and CKD reflects what the panel considered to be a clear benefit. For all other adults with type 2 diabetes, the weak recommendations reflect what the panel considered to be a finer balance between benefits, harms, and burdens of treatment options. Clinicians using the guideline can identify their patient's individual risk for cardiovascular and kidney outcomes using credible risk calculators such as RECODe. Interactive evidence summaries and decision aids may support well informed treatment choices, including shared decision making.
AbstractClinical questionWhat is the role of gastrointestinal bleeding prophylaxis (stress ulcer prophylaxis) in critically ill patients? This guideline was prompted by the publication of a new large ...randomised controlled trial.Current practiceGastric acid suppression with proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs) is commonly done to prevent gastrointestinal bleeding in critically ill patients. Existing guidelines vary in their recommendations of which population to treat and which agent to use.RecommendationsThis guideline panel makes a weak recommendation for using gastrointestinal bleeding prophylaxis in critically ill patients at high risk (>4%) of clinically important gastrointestinal bleeding, and a weak recommendation for not using prophylaxis in patients at lower risk of clinically important bleeding (≤4%). The panel identified risk categories based on evidence, with variable certainty regarding risk factors. The panel suggests using a PPI rather than a H2RA (weak recommendation) and recommends against using sucralfate (strong recommendation).How this guideline was createdA guideline panel including patients, clinicians, and methodologists produced these recommendations using standards for trustworthy guidelines and the GRADE approach. The recommendations are based on a linked systematic review and network meta-analysis. A weak recommendation means that both options are reasonable.The evidenceThe linked systematic review and network meta-analysis estimated the benefit and harm of these medications in 12 660 critically ill patients in 72 trials. Both PPIs and H2RAs reduce the risk of clinically important bleeding. The effect is larger in patients at higher bleeding risk (those with a coagulopathy, chronic liver disease, or receiving mechanical ventilation but not enteral nutrition or two or more of mechanical ventilation with enteral nutrition, acute kidney injury, sepsis, and shock) (moderate certainty). PPIs and H2RAs might increase the risk of pneumonia (low certainty). They probably do not have an effect on mortality (moderate certainty), length of hospital stay, or any other important outcomes. PPIs probably reduce the risk of bleeding more than H2RAs (moderate certainty).Understanding the recommendationIn most critically ill patients, the reduction in clinically important gastrointestinal bleeding from gastric acid suppressants is closely balanced with the possibility of pneumonia. Clinicians should consider individual patient values, risk of bleeding, and other factors such as medication availability when deciding whether to use gastrointestinal bleeding prophylaxis. Visual overviews provide the relative and absolute benefits and harms of the options in multilayered evidence summaries and decision aids available on MAGICapp.
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