WHAT IS THE ROLE OF DUAL ANTIPLATELET THERAPY AFTER HIGH RISK TRANSIENT ISCHAEMIC ATTACK OR MINOR STROKE? SPECIFICALLY, DOES DUAL ANTIPLATELET THERAPY WITH A COMBINATION OF ASPIRIN AND CLOPIDOGREL ...LEAD TO A GREATER REDUCTION IN RECURRENT STROKE AND DEATH OVER THE USE OF ASPIRIN ALONE WHEN GIVEN IN THE FIRST 24 HOURS AFTER A HIGH RISK TRANSIENT ISCHAEMIC ATTACK OR MINOR ISCHAEMIC STROKE? AN EXPERT PANEL PRODUCED A STRONG RECOMMENDATION FOR INITIATING DUAL ANTIPLATELET THERAPY WITHIN 24 HOURS OF THE ONSET OF SYMPTOMS, AND FOR CONTINUING IT FOR 10-21 DAYS CURRENT PRACTICE IS TYPICALLY TO USE A SINGLE DRUG.
What is the comparative effectiveness of available therapies for chronic pain associated with temporomandibular disorders (TMD)?
TMD are the second most common musculoskeletal chronic pain disorder ...after low back pain, affecting 6-9% of adults globally. TMD are associated with pain affecting the jaw and associated structures and may present with headaches, earache, clicking, popping, or crackling sounds in the temporomandibular joint, and impaired mandibular function. Current clinical practice guidelines are largely consensus-based and provide inconsistent recommendations.
For patients living with chronic pain (≥3 months) associated with TMD, and compared with placebo or sham procedures, the guideline panel issued: (1) strong recommendations in favour of cognitive behavioural therapy (CBT) with or without biofeedback or relaxation therapy, therapist-assisted mobilisation, manual trigger point therapy, supervised postural exercise, supervised jaw exercise and stretching with or without manual trigger point therapy, and usual care (such as home exercises, stretching, reassurance, and education); (2) conditional recommendations in favour of manipulation, supervised jaw exercise with mobilisation, CBT with non-steroidal anti-inflammatory drugs (NSAIDS), manipulation with postural exercise, and acupuncture; (3) conditional recommendations against reversible occlusal splints (alone or in combination with other interventions), arthrocentesis (alone or in combination with other interventions), cartilage supplement with or without hyaluronic acid injection, low level laser therapy (alone or in combination with other interventions), transcutaneous electrical nerve stimulation, gabapentin, botulinum toxin injection, hyaluronic acid injection, relaxation therapy, trigger point injection, acetaminophen (with or without muscle relaxants or NSAIDS), topical capsaicin, biofeedback, corticosteroid injection (with or without NSAIDS), benzodiazepines, and β blockers; and (4) strong recommendations against irreversible oral splints, discectomy, and NSAIDS with opioids.
An international guideline development panel including patients, clinicians with content expertise, and methodologists produced these recommendations in adherence with standards for trustworthy guidelines using the GRADE approach. The MAGIC Evidence Ecosystem Foundation (MAGIC) provided methodological support. The panel approached the formulation of recommendations from the perspective of patients, rather than a population or health system perspective.
Recommendations are informed by a linked systematic review and network meta-analysis summarising the current body of evidence for benefits and harms of conservative, pharmacologic, and invasive interventions for chronic pain secondary to TMD.
These recommendations apply to patients living with chronic pain (≥3 months duration) associated with TMD as a group of conditions, and do not apply to the management of acute TMD pain. When considering management options, clinicians and patients should first consider strongly recommended interventions, then those conditionally recommended in favour, then conditionally against. In doing so, shared decision making is essential to ensure patients make choices that reflect their values and preference, availability of interventions, and what they may have already tried. Further research is warranted and may alter recommendations in the future.
Activity-based funding (ABF) of hospitals is a policy intervention intended to re-shape incentives across health systems through the use of diagnosis-related groups. Many countries are adopting or ...actively promoting ABF. We assessed the effect of ABF on key measures potentially affecting patients and health care systems: mortality (acute and post-acute care); readmission rates; discharge rate to post-acute care following hospitalization; severity of illness; volume of care.
We undertook a systematic review and meta-analysis of the worldwide evidence produced since 1980. We included all studies reporting original quantitative data comparing the impact of ABF versus alternative funding systems in acute care settings, regardless of language. We searched 9 electronic databases (OVID MEDLINE, EMBASE, OVID Healthstar, CINAHL, Cochrane CENTRAL, Health Technology Assessment, NHS Economic Evaluation Database, Cochrane Database of Systematic Reviews, and Business Source), hand-searched reference lists, and consulted with experts. Paired reviewers independently screened for eligibility, abstracted data, and assessed study credibility according to a pre-defined scoring system, resolving conflicts by discussion or adjudication.
Of 16,565 unique citations, 50 US studies and 15 studies from 9 other countries proved eligible (i.e. Australia, Austria, England, Germany, Israel, Italy, Scotland, Sweden, Switzerland). We found consistent and robust differences between ABF and no-ABF in discharge to post-acute care, showing a 24% increase with ABF (pooled relative risk = 1.24, 95% CI 1.18-1.31). Results also suggested a possible increase in readmission with ABF, and an apparent increase in severity of illness, perhaps reflecting differences in diagnostic coding. Although we found no consistent, systematic differences in mortality rates and volume of care, results varied widely across studies, some suggesting appreciable benefits from ABF, and others suggesting deleterious consequences.
Transitioning to ABF is associated with important policy- and clinically-relevant changes. Evidence suggests substantial increases in admissions to post-acute care following hospitalization, with implications for system capacity and equitable access to care. High variability in results of other outcomes leaves the impact in particular settings uncertain, and may not allow a jurisdiction to predict if ABF would be harmless. Decision-makers considering ABF should plan for likely increases in post-acute care admissions, and be aware of the large uncertainty around impacts on other critical outcomes.
The management of type 2 diabetes predominantly focuses on reducing hemoglobin A1C (HbA1c). We examined the association between the magnitude of reduction in HbA1c and cardiovascular outcomes for new ...diabetes medications: sodium-glucose cotransporter-2 SGLT2 inhibitors, glucagon-like peptide-1 GLP1 agonists, and dipeptidyl peptidase-4 DPP4 inhibitors.
We reviewed all published, placebo-controlled, randomized cardiovascular outcome trials. Meta-regression was performed to evaluate the association between HbA1c reduction (i.e., post-intervention HbA1c for active drug – pre-intervention HbA1c for active drug – post-intervention HbA1c for placebo – pre-intervention HbA1c for placebo) and the composite cardiovascular outcome (i.e., stroke, myocardial infarction, or cardiovascular death).
We identified 14 cardiovascular outcome clinical trials, the median sample size was 9401, the median age was 64 years, the median time since diagnosis of diabetes was 12 years, and the median duration of trial follow-up was 120 weeks. Within individual medication classes, each additional 0.5% reduction in HbA1c in the active drug arm, relative to placebo, was associated with a lower incidence of cardiovascular events for GLP1 agonists (0.82, 0.68–0.98) but not for SGLT2 (0.97, 0.69–1.36) or DPP4 (1.03, 0.39–2.74) inhibitors.
Our study provides further support that reducing the risk of cardiovascular events for adults with diabetes is partly explained by a reduction in HbA1c.
•Among over 130,000 adults with diabetes, reduction in hemoglobin A1c was associated with a decrease in cardiovascular risk•The association between hemoglobin A1c reduction and decreased cardiovascular risk varies by medication class•For GLP-1 agonists, there is a strong correlation between hemoglobin A1c reduction and decreased cardiovascular risk•For SGLT2 inhibitors, there was no association between hemoglobin A1c reduction and cardiovascular risk
Most systematic reviews of opioids for chronic pain have pooled treatment effects across individual opioids under the assumption they provide similar benefits and harms. We examined the comparative ...effects of individual opioids for chronic non-cancer pain through a network meta-analysis of randomised controlled trials.
We searched MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials to March 2021 for studies that enrolled patients with chronic non-cancer pain, randomised them to receive different opioids, or opioids vs placebo, and followed them for at least 4 weeks. Certainty of evidence was evaluated using the GRADE approach.
We identified 82 eligible trials (22 619 participants) that evaluated 14 opioids. Compared with placebo, several opioids showed superiority to others for analgesia and improvement in physical function; however, when restricted to pooled-effect estimates supported by moderate certainty evidence, no differences between opioids were evident. Among opioids with moderate certainty evidence, all increased the risk of gastrointestinal adverse events compared with placebo, although no opioids were more harmful than others. Low to very low certainty evidence suggests that extended-release vs immediate-release opioids may provide similar benefits for pain relief and physical functioning, and gastrointestinal harms.
Our findings support the pooling of effect estimates across different types and formulations of opioids to inform effectiveness for chronic non-cancer pain.
Purpose
Motivated by a new randomized trial (the PEPTIC trial) that raised the issue of an increase in mortality with proton pump inhibitors (PPIs) relative to histamine-2 receptor antagonists ...(H2RAs), we updated our prior systematic review and network meta-analysis (NMA) addressing the impact of pharmacological gastrointestinal bleeding prophylaxis in critically ill patients.
Methods
We searched for randomized controlled trials that examined the efficacy and safety of gastrointestinal bleeding prophylaxis with PPIs, H2RAs, or sucralfate versus one another or placebo or no prophylaxis in adult critically ill patients. We performed Bayesian random-effects NMA and conducted analyses using all PEPTIC data as well as a restricted analysis using only PEPTIC data from high compliance centers. We used the GRADE approach to quantify absolute effects and assess the certainty of evidence.
Results
Seventy-four trials enrolling 39 569 patients proved eligible. Both PPIs (risk ratio (RR) 1.03, 95% credible interval 0.93 to 1.14, moderate certainty) and H2RAs (RR 0.98, 0.89 to 1.08, moderate certainty) probably have little or no impact on mortality compared with no prophylaxis. There may be no important difference between PPIs and H2RAs on mortality (RR 1.05, 0.97 to 1.14, low certainty), the 95% credible interval of the complete analysis has not excluded an important increase in mortality with PPIs. Both PPIs (RR 0.46, 0.29 to 0.66) and H2RAs (RR 0.67, 0.48 to 0.94) probably reduce clinically important gastrointestinal bleeding; the magnitude of reduction is probably greater in PPIs than H2RAs (RR 0.69, 0.45 to 0.93), and the difference may be important in higher, but not lower bleeding risk patients. PPIs (RR 1.08, 0.88 to 1.45, low certainty) and H2RAs (RR 1.07, 0.85 to 1.37, low certainty) may have no important impact on pneumonia compared with no prophylaxis.
Conclusion
This updated NMA confirmed that PPIs and H2RAs are most likely to have a similar effect on mortality compared to each other and compared to no prophylaxis; however, the possibility that PPIs may slightly increase mortality cannot be excluded (low certainty evidence). PPIs and H2RAs probably achieve important reductions in clinically important gastrointestinal bleeding; for higher bleeding risk patients, the greater benefit of PPIs over H2RAs may be important. PPIs or H2RAs may not result in important increases in pneumonia but the certainty of evidence is low.
AbstractObjectivesThe aim of the study was to develop a Grading of Recommendations, Assessment, Development and Evaluation (GRADE) summary of findings (SoF) table format that displays the critical ...information from a network meta-analysis (NMA). Study Design and SettingWe applied a user experience model for data analysis based on four rounds of semistructured interviews. ResultsWe interviewed 32 stakeholders who conduct or use MA. Four rounds of interviews produced six candidate NMA-SoF tables. Users found a final NMA-SoF table that included the following components highly acceptable: (1) details of the clinical question (PICO), (2) a plot depicting network geometry, (3) relative and absolute effect estimates, (4) certainty of evidence, (5) ranking of treatments, and (6) interpretation of findings. ConclusionUsing stakeholder feedback, we developed a new GRADE NMA-SoF table that includes the relevant components that facilitate understanding NMA findings and health decision-making.
PDF
