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.

Arthroscopic surgery for degenerative knee disease (osteoarthritis including degenerative meniscal tears).

BACKGROUND: Arthroscopic knee surgery remains a common treatment for symptomatic knee osteoarthritis, including for degenerative meniscal tears, despite guidelines strongly recommending against its use. This Cochrane Review is an update of a non-Cochrane systematic review published in 2017. OBJECTIVES: To assess the benefits and harms of arthroscopic surgery, including debridement, partial menisectomy or both, compared with placebo surgery or non-surgical treatment in people with degenerative knee disease (osteoarthritis, degenerative meniscal tears, or both). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and two trials registers up to 16 April 2021, unrestricted by language. SELECTION CRITERIA: We included randomised controlled trials (RCTs), or trials using quasi-randomised methods of participant allocation, comparing arthroscopic surgery with placebo surgery or non-surgical interventions (e.g. exercise, injections, non-arthroscopic lavage/irrigation, drug therapy, and supplements and complementary therapies) in people with symptomatic degenerative knee disease (osteoarthritis or degenerative meniscal tears or both). Major outcomes were pain, function, participant-reported treatment success, knee-specific quality of life, serious adverse events, total adverse events and knee surgery (replacement or osteotomy). DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, extracted data, and assessed risk of bias and the certainty of evidence using GRADE. The primary comparison was arthroscopic surgery compared to placebo surgery for outcomes that measured benefits of surgery, but we combined data from all control groups to assess harms and knee surgery (replacement or osteotomy). MAIN RESULTS: Sixteen trials (2105 participants) met our inclusion criteria. The average age of participants ranged from 46 to 65 years, and 56% of participants were women. Four trials (380 participants) compared arthroscopic surgery to placebo surgery. For the remaining trials, arthroscopic surgery was compared to exercise (eight trials, 1371 participants), a single intra-articular glucocorticoid injection (one trial, 120 participants), non-arthroscopic lavage (one trial, 34 participants), non-steroidal anti-inflammatory drugs (one trial, 80 participants) and weekly hyaluronic acid injections for five weeks (one trial, 120 participants). The majority of trials without a placebo control were susceptible to bias: in particular, selection (56%), performance (75%), detection (75%), attrition (44%) and selective reporting (75%) biases. The placebo-controlled trials were less susceptible to bias and none were at risk of performance or detection bias. Here we limit reporting to the main comparison, arthroscopic surgery versus placebo surgery. High-certainty evidence indicates arthroscopic surgery leads to little or no difference in pain or function at three months after surgery, moderate-certainty evidence indicates there is probably little or no improvement in knee-specific quality of life three months after surgery, and low-certainty evidence indicates arthroscopic surgery may lead to little or no difference in participant-reported success at up to five years, compared with placebo surgery. Mean post-operative pain in the placebo group was 40.1 points on a 0 to 100 scale (where lower score indicates less pain) compared to 35.5 points in the arthroscopic surgery group, a difference of 4.6 points better (95% confidence interval (CI) 0.02 better to 9 better; I2 = 0%; 4 trials, 309 participants). Mean post-operative function in the placebo group was 75.9 points on a 0 to 100 rating scale (where higher score indicates better function) compared to 76 points in the arthroscopic surgery group, a difference of 0.1 points better (95% CI 3.2 worse to 3.4 better; I2 = 0%; 3 trials, 302 participants). Mean post-operative knee-specific health-related quality of life in the placebo group was 69.7 points on a 0 to 100 rating scale (where higher score indicates better quality of life) compared with 75.3 points in the arthroscopic surgery group, a difference of 5.6 points better (95% CI 0.36 better to 10.68 better; I2 = 0%; 2 trials, 188 participants). We downgraded this evidence to moderate certainty as the 95% confidence interval does not rule in or rule out a clinically important change. After surgery, 74 out of 100 people reported treatment success with placebo and 82 out of 100 people reported treatment success with arthroscopic surgery at up to five years (risk ratio (RR) 1.11, 95% CI 0.66 to 1.86; I2 = 53%; 3 trials, 189 participants). We downgraded this evidence to low certainty due to serious indirectness (diversity in definition and timing of outcome measurement) and serious imprecision (small number of events). We are less certain if the risk of serious or total adverse events increased with arthroscopic surgery compared to placebo or non-surgical interventions. Serious adverse events were reported in 6 out of 100 people in the control groups and 8 out of 100 people in the arthroscopy groups from eight trials (RR 1.35, 95% CI 0.64 to 2.83; I2 = 47%; 8 trials, 1206 participants). Fifteen out of 100 people reported adverse events with control interventions, and 17 out of 100 people with surgery at up to five years (RR 1.15, 95% CI 0.78 to 1.70; I2 = 48%; 9 trials, 1326 participants). The certainty of the evidence was low, downgraded twice due to serious imprecision (small number of events) and possible reporting bias (incomplete reporting of outcome across studies). Serious adverse events included death, pulmonary embolism, acute myocardial infarction, deep vein thrombosis and deep infection. Subsequent knee surgery (replacement or high tibial osteotomy) was reported in 2 out of 100 people in the control groups and 4 out of 100 people in the arthroscopy surgery groups at up to five years in four trials (RR 2.63, 95% CI 0.94 to 7.34; I2 = 11%; 4 trials, 864 participants). The certainty of the evidence was low, downgraded twice due to the small number of events. AUTHORS' CONCLUSIONS: Arthroscopic surgery provides little or no clinically important benefit in pain or function, probably does not provide clinically important benefits in knee-specific quality of life, and may not improve treatment success compared with a placebo procedure. It may lead to little or no difference, or a slight increase, in serious and total adverse events compared to control, but the evidence is of low certainty. Whether or not arthroscopic surgery results in slightly more subsequent knee surgery (replacement or osteotomy) compared to control remains unresolved.

Prophylaxis against covid-19: living systematic review and network meta-analysis.

UPDATES: This is the second version (first update) of the living systematic review, replacing the previous version (available as a data supplement). When citing this paper please consider adding the version number and date of access for clarity. OBJECTIVE: To determine and compare the effects of drug prophylaxis on severe acute respiratory syndrome coronavirus virus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (covid-19). DESIGN: Living systematic review and network meta-analysis (NMA). DATA SOURCES: World Health Organization covid-19 database, a comprehensive multilingual source of global covid-19 literature to 4 March 2022. STUDY SELECTION: Randomised trials in which people at risk of covid-19 were allocated to prophylaxis or no prophylaxis (standard care or placebo). Pairs of reviewers independently screened potentially eligible articles. METHODS: After duplicate data abstraction, we conducted random-effects bayesian network meta-analysis. We assessed risk of bias of the included studies using a modification of the Cochrane risk of bias 2.0 tool and assessed the certainty of the evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach. RESULTS: The second iteration of this living NMA includes 32 randomised trials which enrolled 25 147 participants and addressed 21 different prophylactic drugs; adding 21 trials (66%), 18 162 participants (75%) and 16 (76%) prophylactic drugs. Of the 16 prophylactic drugs analysed, none provided convincing evidence of a reduction in the risk of laboratory confirmed SARS-CoV-2 infection. For admission to hospital and mortality outcomes, no prophylactic drug proved different than standard care or placebo. Hydroxychloroquine and vitamin C combined with zinc probably increase the risk of adverse effects leading to drug discontinuation­risk difference for hydroxychloroquine (RD) 6 more per 1000 (95% credible interval (CrI) 2 more to 10 more); for vitamin C combined with zinc, RD 69 more per 1000 (47 more to 90 more), moderate certainty evidence. CONCLUSIONS: Much of the evidence remains very low certainty and we therefore anticipate future studies evaluating drugs for prophylaxis may change the results for SARS-CoV-2 infection, admission to hospital and mortality outcomes. Both hydroxychloroquine and vitamin C combined with zinc probably increase adverse effects. SYSTEMATIC REVIEW REGISTRATION: This review was not registered. The protocol established a priori is included as a supplement. FUNDING: This study was supported by the Canadian Institutes of Health Research (grant CIHR-IRSC:0579001321).

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.

Probiotics for the prevention of Clostridium difficile-associated diarrhea: a systematic review and meta-analysis.

BACKGROUND: Antibiotic treatment may disturb the resistance of gastrointestinal flora to colonization. This may result in complications, the most serious of which is Clostridium difficile­associated diarrhea (CDAD). PURPOSE: To assess the efficacy and safety of probiotics for the prevention of CDAD in adults and children receiving antibiotics. DATA SOURCES: Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, Allied and Complementary Medicine Database, Web of Science, and 12 gray-literature sources. STUDY SELECTION: Randomized, controlled trials including adult or pediatric patients receiving antibiotics that compared any strain or dose of a specified probiotic with placebo or with no treatment control and reported the incidence of CDAD. DATA EXTRACTION: Two reviewers independently screened potentially eligible articles; extracted data on populations, interventions, and outcomes; and assessed risk of bias. The Grading of Recommendations Assessment, Development and Evaluation guidelines were used to independently rate overall confidence in effect estimates for each outcome. DATA SYNTHESIS: Twenty trials including 3818 participants met the eligibility criteria. Probiotics reduced the incidence of CDAD by 66% (pooled relative risk, 0.34 [95% CI, 0.24 to 0.49]; I(2) = 0%). In a population with a 5% incidence of antibiotic-associated CDAD (median control group risk), probiotic prophylaxis would prevent 33 episodes (CI, 25 to 38 episodes) per 1000 persons. Of probiotic-treated patients, 9.3% experienced adverse events, compared with 12.6% of control patients (relative risk, 0.82 [CI, 0.65 to 1.05]; I(2) = 17%). LIMITATIONS: In 13 trials, data on CDAD were missing for 5% to 45% of patients. The results were robust to worst-plausible assumptions regarding event rates in studies with missing outcome data. CONCLUSION: Moderate-quality evidence suggests that probiotic prophylaxis results in a large reduction in CDAD without an increase in clinically important adverse events. PRIMARY FUNDING SOURCE: None.

Probiotics for the prevention of pediatric antibiotic-associated diarrhea.

BACKGROUND: Antibiotics alter the microbial balance within the gastrointestinal tract. Probiotics may prevent antibiotic-associated diarrhea (AAD) via restoration of the gut microflora. Antibiotics are prescribed frequently in children and AAD is common in this population. OBJECTIVES: The primary objectives were to assess the efficacy and safety of probiotics (any specified strain or dose) used for the prevention of AAD in children. SEARCH METHODS: MEDLINE, EMBASE, CENTRAL, CINAHL, AMED, and the Web of Science (inception to May 2010) were searched along with specialized registers including the Cochrane IBD/FBD review group, CISCOM (Centralized Information Service for Complementary Medicine), NHS Evidence, the International Bibliographic Information on Dietary Supplements as well as trial registries. Letters were sent to authors of included trials, nutra/pharmaceutical companies, and experts in the field requesting additional information on ongoing or unpublished trials. Conference proceedings, dissertation abstracts, and reference lists from included and relevant articles were also searched. SELECTION CRITERIA: Randomized, parallel, controlled trials in children (0 to 18 years) receiving antibiotics, that compare probiotics to placebo, active alternative prophylaxis, or no treatment and measure the incidence of diarrhea secondary to antibiotic use were considered for inclusion. DATA COLLECTION AND ANALYSIS: Study selection, data extraction as well as methodological quality assessment using the risk of bias instrument was conducted independently and in duplicate by two authors. Dichotomous data (incidence of diarrhea, adverse events) were combined using a pooled relative risk and risk difference (adverse events), and continuous data (mean duration of diarrhea, mean daily stool frequency) as weighted mean differences, along with their corresponding 95% confidence intervals. For overall pooled results on the incidence of diarrhea, sensitivity analyses included available case versus extreme-plausible analyses and random- versus fixed-effect models. To explore possible explanations for heterogeneity, a priori subgroup analysis were conducted on probiotic strain, dose, definition of antibiotic-associated diarrhea, antibiotic agent as well as risk of bias. MAIN RESULTS: Sixteen studies (3432 participants) met the inclusion criteria. Trials included treatment with either Bacillus spp., Bifidobacterium spp., Lactobacilli spp., Lactococcus spp., Leuconostoc cremoris, Saccharomyces spp., or Streptococcus spp., alone or in combination. Nine studies used a single strain probiotic agent, four combined two probiotic strains, one combined three probiotic strains, one product included ten probiotic agents, and one study included two probiotic arms that used three and two strains respectively. The risk of bias was determined to be high in 8 studies and low in 8 studies. Available case (patients who did not complete the studies were not included in the analysis) results from 15/16 trials reporting on the incidence of diarrhea show a large, precise benefit from probiotics compared to active, placebo or no treatment control. The incidence of AAD in the probiotic group was 9% compared to 18% in the control group (2874 participants; RR 0.52; 95% CI 0.38 to 0.72; I(2) = 56%). This benefit was not statistically significant in an extreme plausible (60% of children loss to follow-up in probiotic group and 20% loss to follow-up in the control group had diarrhea) intention to treat (ITT) sensitivity analysis. The incidence of AAD in the probiotic group was 16% compared to 18% in the control group (3392 participants; RR 0.81; 95% CI 0.63 to 1.04; I(2) = 59%). An a priori available case subgroup analysis exploring heterogeneity indicated that high dose (≥5 billion CFUs/day) is more effective than low probiotic dose (< 5 billion CFUs/day), interaction P value = 0.010. For the high dose studies the incidence of AAD in the probiotic group was 8% compared to 22% in the control group (1474 participants; RR 0.40; 95% CI 0.29 to 0.55). For the low dose studies the incidence of AAD in the probiotic group was 8% compared to 11% in the control group (1382 participants; RR 0.80; 95% CI 0.53 to 1.21). An extreme plausible ITT subgroup analysis was marginally significant for high dose probiotics. For the high dose studies the incidence of AAD in the probiotic group was 17% compared to 22% in the control group (1776 participants; RR 0.72; 95% CI 0.53 to 0.99; I(2) = 58%). None of the 11 trials (n = 1583) that reported on adverse events documented any serious adverse events. Meta-analysis excluded all but an extremely small non-significant difference in adverse events between treatment and control (RD 0.00; 95% CI -0.01 to 0.02). AUTHORS' CONCLUSIONS: Despite heterogeneity in probiotic strain, dose, and duration, as well as in study quality, the overall evidence suggests a protective effect of probiotics in preventing AAD. Using 11 criteria to evaluate the credibility of the subgroup analysis on probiotic dose, the results indicate that the subgroup effect based on dose (≥5 billion CFU/day) was credible. Based on high-dose probiotics, the number needed to treat (NNT) to prevent one case of diarrhea is seven (NNT 7; 95% CI 6 to 10). However, a GRADE analysis indicated that the overall quality of the evidence for the primary endpoint (incidence of diarrhea) was low due to issues with risk of bias (due to high loss to follow-up) and imprecision (sparse data, 225 events). The benefit for high dose probiotics (Lactobacillus rhamnosus or Saccharomyces boulardii) needs to be confirmed by a large well-designed randomized trial. More refined trials are also needed that test strain specific probiotics and evaluate the efficacy (e.g. incidence and duration of diarrhea) and safety of probiotics with limited losses to follow-up. It is premature to draw conclusions about the efficacy and safety of other probiotic agents for pediatric AAD. Future trials would benefit from a standard and valid outcomes to measure AAD.