Management of chronic pain associated with temporomandibular disorders: a clinical practice guideline.

CLINICAL QUESTION: What is the comparative effectiveness of available therapies for chronic pain associated with temporomandibular disorders (TMD)? CURRENT PRACTICE: 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. 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 ß blockers; and (4) strong recommendations against irreversible oral splints, discectomy, and NSAIDS with opioids. HOW THIS GUIDELINE WAS CREATED: 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. THE EVIDENCE: 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. UNDERSTANDING THE RECOMMENDATION: 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.

Comparison of seven popular structured dietary programmes and risk of mortality and major cardiovascular events in patients at increased cardiovascular risk: systematic review and network meta-analysis.

OBJECTIVE: To determine the relative efficacy of structured named diet and health behaviour programmes (dietary programmes) for prevention of mortality and major cardiovascular events in patients at increased risk of cardiovascular disease. DESIGN: Systematic review and network meta-analysis of randomised controlled trials. DATA SOURCES: AMED (Allied and Complementary Medicine Database), CENTRAL (Cochrane Central Register of Controlled Trials), Embase, Medline, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and ClinicalTrials.gov were searched up to September 2021. STUDY SELECTION: Randomised trials of patients at increased risk of cardiovascular disease that compared dietary programmes with minimal intervention (eg, healthy diet brochure) or alternative programmes with at least nine months of follow-up and reporting on mortality or major cardiovascular events (such as stroke or non-fatal myocardial infarction). In addition to dietary intervention, dietary programmes could also include exercise, behavioural support, and other secondary interventions such as drug treatment. OUTCOMES AND MEASURES: All cause mortality, cardiovascular mortality, and individual cardiovascular events (stroke, non-fatal myocardial infarction, and unplanned cardiovascular interventions). REVIEW METHODS: Pairs of reviewers independently extracted data and assessed risk of bias. A random effects network meta-analysis was performed using a frequentist approach and grading of recommendations assessment, development and evaluation (GRADE) methods to determine the certainty of evidence for each outcome. RESULTS: 40 eligible trials were identified with 35 548 participants across seven named dietary programmes (low fat, 18 studies; Mediterranean, 12; very low fat, 6; modified fat, 4; combined low fat and low sodium, 3; Ornish, 3; Pritikin, 1). At last reported follow-up, based on moderate certainty evidence, Mediterranean dietary programmes proved superior to minimal intervention for the prevention of all cause mortality (odds ratio 0.72, 95% confidence interval 0.56 to 0.92; patients at intermediate risk: risk difference 17 fewer per 1000 followed over five years), cardiovascular mortality (0.55, 0.39 to 0.78; 13 fewer per 1000), stroke (0.65, 0.46 to 0.93; 7 fewer per 1000), and non-fatal myocardial infarction (0.48, 0.36 to 0.65; 17 fewer per 1000). Based on moderate certainty evidence, low fat programmes proved superior to minimal intervention for prevention of all cause mortality (0.84, 0.74 to 0.95; 9 fewer per 1000) and non-fatal myocardial infarction (0.77, 0.61 to 0.96; 7 fewer per 1000). The absolute effects for both dietary programmes were more pronounced for patients at high risk. There were no convincing differences between Mediterranean and low fat programmes for mortality or non-fatal myocardial infarction. The five remaining dietary programmes generally had little or no benefit compared with minimal intervention typically based on low to moderate certainty evidence. CONCLUSIONS: Moderate certainty evidence shows that programmes promoting Mediterranean and low fat diets, with or without physical activity or other interventions, reduce all cause mortality and non-fatal myocardial infarction in patients with increased cardiovascular risk. Mediterranean programmes are also likely to reduce stroke risk. Generally, other named dietary programmes were not superior to minimal intervention. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016047939.

Prophylactic Therapies for Morbidity and Mortality After Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Network Meta-Analysis of Randomized Trials.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is associated with high mortality and morbidity. We aimed to determine the relative benefits of pharmacological prophylactic treatments in patients with aneurysmal subarachnoid hemorrhage by performing a network meta-analysis of randomized trials. METHODS: We searched Medline, Web of Science, Embase, Scopus, ProQuest, and Cochrane Central to February 2020. Pairs of reviewers independently identified eligible trials, extracted data, and assessed the risk of bias. Eligible trials compared the prophylactic effects of any oral or intravenous medications or intracranial drug-eluting implants to one another or placebo or standard of care in adult hospitalized patients with confirmed aneurysmal subarachnoid hemorrhage. We used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to assess the certainty of the evidence. RESULTS: We included 53 trials enrolling 10 415 patients. Nimodipine likely reduces all-cause mortality compared to placebo (odds ratio [OR],0.73 [95% CI, 0.53-1.00]; moderate certainty; absolute risk reduction (ARR), -3.35%). Nimodipine (OR, 1.46 [95% CI, 1.07-1.99]; high certainty; absolute risk increase, 8.25%) and cilostazol (OR, 3.73 [95% CI, 1.14-12.18]; moderate certainty; absolute risk increase, 23.15%) were the most effective treatments in improving disability at the longest follow-up. Compared to placebo, clazosentan (10 mg/kg; OR, 0.39 [95% CI, 0.22-0.68]; high certainty; ARR, -16.65%), nicardipine (OR, 0.48 [95% CI, 0.24-0.94]; moderate certainty; ARR, -13.70%), fasudil (OR, 0.55 [95% CI, 0.31-0.98]; moderate certainty; ARR, -11.54%), and magnesium (OR, 0.66 [95% CI, 0.46-0.94]; high certainty; ARR, -8.37%) proved most effective in reducing the likelihood of delayed cerebral ischemia. CONCLUSIONS: Nimodipine and cilostazol are likely the most effective treatments in preventing morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage. Clazosentan, nicardipine, fasudil, and magnesium showed beneficial effects on delayed cerebral ischemia and vasospasm but they were not found to reduce mortality or disability. Future trials are warranted to elaborately investigate the prophylactic effects of medications that may improve mortality and long-term functional outcomes, such as cilostazol and clazosentan. REGISTRATION: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42019122183.

Human and Bovine Colostrum for Prevention of Necrotizing Enterocolitis: A Meta-analysis.

CONTEXT: Human and bovine colostrum (HBC) administration has been linked to beneficial effects on morbidity and mortality associated with necrotizing enterocolitis (NEC). OBJECTIVES: To determine the effectiveness and safety of HBC for reducing NEC, mortality, sepsis, time to full-feed and feeding intolerance in preterm infants. DATA SOURCES: We conducted searches through Medline, Embase, Cumulative Index of Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, and gray literature. STUDY SELECTION: Randomized controlled trials comparing human or bovine colostrum to placebo. DATA EXTRACTION: Two reviewers independently did screening, review, and extraction. RESULTS: Eight studies (385 infants) proved eligible. In comparison with placebo, HBC revealed no effect on the incidence of severe NEC (relative risk [RR]: 0.99; 95% confidence interval [CI] 0.48 to 2.02, I2 = 2.2%; moderate certainty of evidence), all-cause mortality (RR: 0.88; 95% CI 0.39 to 1.82, I2 = 0%; moderate certainty), culture-proven sepsis (RR: 0.78; 95% CI 0.53 to 1.14, I2 = 0%; moderate certainty), and feed intolerance (RR: 0.97; 95% CI 0.37 to 2.56, I2 = 55%; low certainty). HBC revealed a significant effect on reducing the mean days to reach full enteral feed (mean difference: -3.55; 95% CI 0.33 to 6.77, I2 = 41.1%; moderate certainty). The indirect comparison of bovine versus human colostrum revealed no difference in any outcome. LIMITATIONS: The number of patients was modest, whereas the number of NEC-related events was low. CONCLUSIONS: Bovine or human colostrum has no effect on severe NEC, mortality, culture-proven sepsis, feed intolerance, or length of stay. Additional research focused on the impact on enteral feeding may be needed to confirm the findings on this outcome.

Association of Placebo, Indomethacin, Ibuprofen, and Acetaminophen With Closure of Hemodynamically Significant Patent Ductus Arteriosus in Preterm Infants: A Systematic Review and Meta-analysis.

Importance: Despite increasing emphasis on conservative management of patent ductus arteriosus (PDA) in preterm infants, different pharmacotherapeutic interventions are used to treat those developing a hemodynamically significant PDA. Objectives: To estimate the relative likelihood of hemodynamically significant PDA closure with common pharmacotherapeutic interventions and to compare adverse event rates. Data Sources and Study Selection: The databases of MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from inception until August 15, 2015, and updated on December 31, 2017, along with conference proceedings up to December 2017. Randomized clinical trials that enrolled preterm infants with a gestational age younger than 37 weeks treated with intravenous or oral indomethacin, ibuprofen, or acetaminophen vs each other, placebo, or no treatment for a clinically or echocardiographically diagnosed hemodynamically significant PDA. Data Extraction and Synthesis: Data were independently extracted in pairs by 6 reviewers and synthesized with Bayesian random-effects network meta-analyses. Main Outcomes and Measures: Primary outcome: hemodynamically significant PDA closure; secondary: included surgical closure, mortality, necrotizing enterocolitis, and intraventricular hemorrhage. Results: In 68 randomized clinical trials of 4802 infants, 14 different variations of indomethacin, ibuprofen, or acetaminophen were used as treatment modalities. The overall PDA closure rate was 67.4% (2867 of 4256 infants). A high dose of oral ibuprofen was associated with a significantly higher odds of PDA closure vs a standard dose of intravenous ibuprofen (odds ratio [OR], 3.59; 95% credible interval [CrI], 1.64-8.17; absolute risk difference, 199 [95% CrI, 95-258] more per 1000 infants) and a standard dose of intravenous indomethacin (OR, 2.35 [95% CrI, 1.08-5.31]; absolute risk difference, 124 [95% CrI, 14-188] more per 1000 infants). Based on the ranking statistics, a high dose of oral ibuprofen ranked as the best pharmacotherapeutic option for PDA closure (mean surface under the cumulative ranking [SUCRA] curve, 0.89 [SD, 0.12]) and to prevent surgical PDA ligation (mean SUCRA, 0.98 [SD, 0.08]). There was no significant difference in the odds of mortality, necrotizing enterocolitis, or intraventricular hemorrhage with use of placebo or no treatment compared with any of the other treatment modalities. Conclusions and Relevance: A high dose of oral ibuprofen was associated with a higher likelihood of hemodynamically significant PDA closure vs standard doses of intravenous ibuprofen or intravenous indomethacin; placebo or no treatment did not significantly change the likelihood of mortality, necrotizing enterocolitis, or intraventricular hemorrhage. Trial Registration: PROSPERO Identifier: CRD42015015797.

Knee arthroscopy versus conservative management in patients with degenerative knee disease: a systematic review.

OBJECTIVE: To determine the effects and complications of arthroscopic surgery compared with conservative management strategies in patients with degenerative knee disease. DESIGN: Systematic review. MAIN OUTCOME MEASURES: Pain, function, adverse events. DATA SOURCES: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Google Scholar and Open Grey up to August 2016. ELIGIBILITY CRITERIA: For effects, randomised clinical trials (RCTs) comparing arthroscopic surgery with a conservative management strategy (including sham surgery) in patients with degenerative knee disease. For complications, RCTs and observational studies. REVIEW METHODS: Two reviewers independently extracted data and assessed risk of bias for patient-important outcomes. A parallel guideline committee (BMJ Rapid Recommendations) provided input on the design and interpretation of the systematic review, including selection of patient-important outcomes. We used the GRADE approach to rate the certainty (quality) of the evidence. RESULTS: We included 13 RCTs and 12 observational studies. With respect to pain, the review identified high-certainty evidence that knee arthroscopy results in a very small reduction in pain up to 3 months (mean difference =5.4 on a 100-point scale, 95% CI 2.0 to 8.8) and very small or no pain reduction up to 2 years (mean difference =3.1, 95% CI -0.2 to 6.4) when compared with conservative management. With respect to function, the review identified moderate-certainty evidence that knee arthroscopy results in a very small improvement in the short term (mean difference =4.9 on a 100-point scale, 95% CI 1.5 to 8.4) and very small or no improved function up to 2 years (mean difference =3.2, 95% CI -0.5 to 6.8). Alternative presentations of magnitude of effect, and associated sensitivity analyses, were consistent with the findings of the primary analysis. Low-quality evidence suggested a very low probability of serious complications after knee arthroscopy. CONCLUSIONS: Over the long term, patients who undergo knee arthroscopy versus those who receive conservative management strategies do not have important benefits in pain or function. TRIAL REGISTRATION NUMBER: PROSPERO CRD42016046242.