Background:Deep vein thrombosis (DVT) is a condition in which a clot forms in the deep veins, most commonly of the leg. It occurs in approximately one in 1000 people. If left untreated, the clot can travel up to the lungs and cause a potentially life-threatening pulmonary embolism (PE). Previously, a DVT was treated with the anticoagulants heparin and vitamin K antagonists. However, two forms of direct oral anticoagulants (DOACs) have been developed: oral direct thrombin inhibitors (DTIs) and oral factor Xa inhibitors, which have characteristics that may be favourable compared to conventional treatment, including oral administration, a predictable effect, lack of frequent monitoring or dose adjustment and few known drug interactions. DOACs are now commonly being used for treating DVT: recent guidelines recommended DOACs over conventional anticoagulants for both DVT and PE treatment. This Cochrane Review was first published in 2015. It was the first systematic review to measure the effectiveness and safety of these drugs in the treatment of DVT. This is an update of the 2015 review. OBJECTIVES: To assess the effectiveness and safety of oral DTIs and oral factor Xa inhibitors versus conventional anticoagulants for the long-term treatment of DVT. Search methods:The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 1 March 2022. Selection criteria:We included randomised controlled trials (RCTs) in which people with a DVT, confirmed by standard imaging techniques, were allocated to receive an oral DTI or an oral factor Xa inhibitor compared with conventional anticoagulation or compared with each other for the treatment of DVT. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were recurrent venous thromboembolism (VTE), recurrent DVT and PE. Secondary outcomes included all-cause mortality, major bleeding, post-thrombotic syndrome (PTS) and quality of life (QoL). We used GRADE to assess the certainty of evidence for each outcome. Main results:We identified 10 new studies with 2950 participants for this update. In total, we included 21 RCTs involving 30,895 participants. Three studies investigated oral DTIs (two dabigatran and one ximelagatran), 17 investigated oral factor Xa inhibitors (eight rivaroxaban, five apixaban and four edoxaban) and one three-arm trial investigated both a DTI (dabigatran) and factor Xa inhibitor (rivaroxaban). Overall, the studies were of good methodological quality. Meta-analysis comparing DTIs to conventional anticoagulation showed no clear difference in the rate of recurrent VTE (odds ratio (OR) 1.17, 95% confidence interval (CI) 0.83 to 1.65; 3 studies, 5994 participants; moderate-certainty evidence), recurrent DVT (OR 1.11, 95% CI 0.74 to 1.66; 3 studies, 5994 participants; moderate-certainty evidence), fatal PE (OR 1.32, 95% CI 0.29 to 6.02; 3 studies, 5994 participants; moderate-certainty evidence), non-fatal PE (OR 1.29, 95% CI 0.64 to 2.59; 3 studies, 5994 participants; moderate-certainty evidence) or all-cause mortality (OR 0.66, 95% CI 0.41 to 1.08; 1 study, 2489 participants; moderate-certainty evidence). DTIs reduced the rate of major bleeding (OR 0.58, 95% CI 0.38 to 0.89; 3 studies, 5994 participants; high-certainty evidence). For oral factor Xa inhibitors compared with conventional anticoagulation, meta-analysis demonstrated no clear difference in recurrent VTE (OR 0.85, 95% CI 0.71 to 1.01; 13 studies, 17,505 participants; moderate-certainty evidence), recurrent DVT (OR 0.70, 95% CI 0.49 to 1.01; 9 studies, 16,439 participants; moderate-certainty evidence), fatal PE (OR 1.18, 95% CI 0.69 to 2.02; 6 studies, 15,082 participants; moderate-certainty evidence), non-fatal PE (OR 0.93, 95% CI 0.68 to 1.27; 7 studies, 15,166 participants; moderate-certainty evidence) or all-cause mortality (OR 0.87, 95% CI 0.67 to 1.14; 9 studies, 10,770 participants; moderate-certainty evidence). Meta-analysis showed a reduced rate of major bleeding with oral factor Xa inhibitors compared with conventional anticoagulation (OR 0.63, 95% CI 0.45 to 0.89; 17 studies, 18,066 participants; high-certainty evidence). AUTHORS' CONCLUSIONS: The current review suggests that DOACs may be superior to conventional therapy in terms of safety (major bleeding), and are probably equivalent in terms of efficacy. There is probably little or no difference between DOACs and conventional anticoagulation in the prevention of recurrent VTE, recurrent DVT, pulmonary embolism and all-cause mortality. DOACs reduced the rate of major bleeding compared to conventional anticoagulation. The certainty of evidence was moderate or high.

Background: Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system, with an unpredictable course. Current MS therapies such as disease-modifying therapies focus on treating exacerbations, preventing new exacerbations and avoiding the progression of disability. Siponimod (BAF312) is an oral treatment, a selective sphingosine-1-phosphate (S1P) receptor modulator, for the treatment of adults with relapsing forms of MS including active, secondary progressive MS with relapses. Objectives: To assess the benefits and adverse effects of siponimod as monotherapy or combination therapy versus placebo or any active comparator for people diagnosed with MS. Search methods: On 18 June 2020, we searched the Cochrane Multiple Sclerosis and Rare Diseases of the CNS Trials Register, which contains studies from CENTRAL, MEDLINE and Embase, and the trials registry databases ClinicalTrials.gov and WHO International Clinical Trials Registry Platform (ICTRP). We also handsearched relevant journals and screened the reference lists of published reviews and retrieved articles and searched reports (2004 to June 2020) from the MS societies in Europe and America. Selection criteria: We included randomised parallel controlled clinical trials (RCTs) that evaluated siponimod, as monotherapy or combination therapy, versus placebo or any active comparator in people with MS. There were no restrictions on dose or administration frequency. Data collection and analysis: We used standard methodological procedures expected by Cochrane. We discussed disagreements and resolved them by consensus among the review authors. Our primary outcomes wereworsening disability, relapse and adverse events, and secondary outcomes were annualised relapse rate, gadolinium-enhancing lesions, new lesions or enlarged pre-existing lesions and mean change of brain volume. We independently evaluated the certainty of evidence using the GRADE approach. We contacted principal investigators of included studies for additional data or confirmation of data. Main results: Two studies (1948 participants) met our selection criteria, 608 controls and 1334 treated with siponimod. The included studies compared siponimod with placebo. Overall, all studies had a high risk of bias due to selective reporting and attrition bias. Comparing siponimod administered at a dose of 2 mg to placebo, we found that siponimod may reduce the number of participants with disability progression at six months (56 fewer people per 1000; risk ratio (RR) 0.78, 95% confidence interval (CI) 0.65 to 0.94; 1 study, 1641 participants; low-certainty evidence) and annualised relapse rate (RR 0.43, 95% CI 0.34 to 0.56; 2 studies, 1739 participants; low-certainty evidence). But it might lead to little reduction in the number of participants with new relapse (166 fewer people per 1000; RR 0.38, 95% CI 0.15 to 1.00; 1 study, 94 participants; very low-certainty evidence). We observed no evidence of a difference due to adverse events for siponimod at 2 mg compared to placebo (14 more people per 1000; RR 1.52, 95% CI 0.85 to 2.71; 2 studies, 1739 participants, low-certainty evidence). In addition, due to the high risk of inaccurate magnetic resonance imaging (MRI) data in the two included studies, we could not combine data for active lesions on MRI scans. Both studies had high attrition bias resulting from the unbalanced reasons for dropouts among groups and high risk of bias due to conflicts of interest. Siponimod may reduce the number of gadolinium-enhancing T1-weighted lesions at two years of follow-up (RR 0.14, 95% CI 0.10 to 0.19; P < 0.0001; 1 study, 1641 participants; very low-certainty evidence). There may be no evidence of a difference between groups in the number of participants with at least one serious adverse event excluding relapses (113 more people per 1000; RR 1.80, 95% CI 0.37 to 8.77; 2 studies, 1739 participants; low-certainty evidence) at six months. No data were available regarding cardiac adverse events. In terms of safety profile, the most common adverse events associated with siponimod were headache, back pain, bradycardia, dizziness, fatigue, influenza, urinary tract infection, lymphopenia, nausea, alanine amino transferase increase and upper respiratory tract infection. These adverse events have dose-related effects and rarely led to discontinuation of treatment. Authors' conclusions: Based on the findings of the RCTs included in this review, we are uncertain whether siponimod interventions are beneficial for people with MS. There was low-certainty evidence to support that siponimod at a dose of 2 mg orally once daily as monotherapy compared with placebo may reduce the annualised relapse rate and the number of participants who experienced disability worsening, at 6 months. However, the certainty of the evidence to support the benefit in reducing the number of people with a relapse is very low. The risk of withdrawals due to adverse events requires careful monitoring of participants over time. The duration of all studies was less than 24 months, so the efficacy and safety of siponimod over 24 months are still uncertain, and further exploration is needed in the future. There is no high-certainty data available to evaluate the benefit on MRI outcomes. We assessed the certainty of the body of evidence for all outcomes was low to very low, downgraded due to serious study limitations, imprecision and indirectness. We are uncertain whether siponimod is beneficial for people with MS. More new studies with robust methodology and longer follow-up are needed to evaluate the benefit of siponimod for the management of MS and to observe long-term adverse effects. Also, in addition to comparing with placebo, more new studies are needed to evaluate siponimod versus other therapeutic options

Background:This study aims to develop an evidence-based clinical practice guideline of acupuncture in the treatment of patients with moderate and severe cancer pain. Methods:The development of this guideline was triggered by a systematic review published in JAMA Oncology in 2020. We searched databases and websites for evidence on patient preferences and values, and other resources of using acupuncture for treatment of cancer pain. Recommendations were developed through a Delphi consensus of an international multidisciplinary panel including 13 western medicine oncologists, Chinese medicine/acupuncture clinical practitioners, and two patient representatives. The certainty of evidence, patient preferences and values, resources, and other factors were fully considered in formulating the recommendations. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was employed to rate the certainty of evidence and the strength of recommendations. Results:The guideline proposed three recommendations: (1) a strong recommendation for the treatment of acupuncture rather than no treatment to relieve pain in patients with moderate to severe cancer pain; (2) a weak recommendation for the combination treatments with acupuncture/acupressure to reduce pain intensity, decrease the opioid dose, and alleviate opioid-related side effects in moderate to severe cancer pain patients who are using analgesics; and (3) a strong recommendation for acupuncture in breast cancer patients to relieve their aromatase inhibitor-induced arthralgia. Conclusion:This proposed guideline provides recommendations for the management of patients with cancer pain. The small sample sizes of evidence limit the strength of the recommendations and highlights the need for additional research.

Purpose: To provide an overview of existing meta-analysis (MAs) on the efficacy and safety of acupuncture for depression, and assess the methodological quality and the strength of evidence of the included MAs. Methods: We searched MAs of randomized trials that have evaluated the effects of acupuncture on depression in three international and three Chinese databases from their inception until August 2019. The methodological quality of included MAs was evaluated with the Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2), and the strength of evidence with the Grading of Recommendations, Assessment, Development and Evaluation (GRADE). We used the intra-class correlation coefficient (ICC) to assess reviewer agreement in the pre-experiment. Results: We included 31 MAs and 59 RCTs. The results of included MAs were conflicting, our meta-analyses found that acupuncture may confer small benefit in reducing the severity of depression by end of treatment than no treatment/wait list/treatment as usual(SMD -0.74, 95% CI -1.06 to -0.41, eight trials, 624 participants), control acupuncture (invasive, non-invasive sham controls) (SMD 0.27, 95% CI -0.51 to -0.04, 20 trials, 1055 participants), antidepressants(Selective serotonin reuptake inhibitors (SSRI)/Tetracyclic antidepressants(TCAs)) (SMD -0.28, 95% CI -0.46 to -0.10, 30 trials, 3068 participants), acupuncture plus antidepressants versus antidepressants(SSRI/TCAs) (SMD -0.99, 95% CI -1.37 to -0.61, 17 trials, 1110 participants). Subgroup analyses showed that there was no difference between electro-acupuncture and invasive control (P = 0.37), electroacupuncture and non-invasive control (P = 0.90), manual acupuncture and Tetracyclic antidepressants (P = 0.57), electro-acupuncture and Tetracyclic antidepressants (P = 0.07). Six MAs concluded that acupuncture reduced the incidence of adverse events compared with antidepressants. The evaluation with AMSTAR-2 showed that the quality of included MAs was low or critically low. The results of the GRADE evaluation showed that the strength of evidence was low to very low for most outcomes. Conclusions: Although acupuncture appears to be more effective and safer than no treatment, control acupuncture and antidepressants, the quality of the available evidence was very low. Further methodologically rigorous and adequately powered primary studies are needed to confirm the effectiveness of acupuncture for depression.

Objectives Acupuncture is an alternative therapy for Parkinson’s disease (PD), but its efficacy and safety are controversial. This overview aimed to summarize the existing evidence from systematic reviews (SRs) and meta-analyses (MAs) in order to assess the effectiveness of acupuncture as a treatment for PD. Methods Seven electronic databases were searched from their inception until July 2019. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) and Assessment of Multiple Systematic Reviews 2 (AMSTAR2) checklists were used to assess evidence quality and methodological quality, respectively. The outcomes of study were calculated using mean differences (MDs) and risk ratios (RRs) with 95 % confidence intervals (CIs). A meta-analysis was performed using RevMan 5.3 software. Results A total of 12 SRs/MAs were included. All 12 SRs/MAs had more than one critical weakness in AMSTAR 2 and were considered of critically low methodological quality. The quality of evidence was unsatisfactory according to the GRADE checklist. Meta-analyses showed that acupuncture combined with drug for the treatment of PD can significantly improve the total effectiveness rate compared with drug alone (RR = 1.25, 95 % CI 1.16–1.34, P < 0.001). It was also found that acupuncture combined with drug significantly improved the UPDRS I–IV total summed scores (WMD=−6.18, 95 % CI -10.32 to –2.04, P < 0.001) and Webster scores (WMD=−4.20, 95 % CI -7.59 to –0.81, P < 0.001). Conclusion Acupuncture might improve the UPDRS score, Webster score, and total effective rate in treatment of PD. It might be a safe and useful adjunctive treatment for patients with PD. However, we should interpret the findings of these reviews with caution, considering the overall limited methodological and reporting quality.

Objective To determine the relative effectiveness of dietary macronutrient patterns and popular named diet programmes for weight loss and cardiovascular risk factor improvement among adults who are overweight or obese. Design Systematic review and network meta-analysis of randomised trials. Data sources Medline, Embase, CINAHL, AMED, and CENTRAL from database inception until September 2018, reference lists of eligible trials, and related reviews. Study selection Randomised trials that enrolled adults (≥18 years) who were overweight (body mass index 25-29) or obese (≥30) to a popular named diet or an alternative diet. Outcomes and measures Change in body weight, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, systolic blood pressure, diastolic blood pressure, and C reactive protein at the six and 12 month follow-up. Review methods Two reviewers independently extracted data on study participants, interventions, and outcomes and assessed risk of bias, and the certainty of evidence using the GRADE (grading of recommendations, assessment, development, and evaluation) approach. A bayesian framework informed a series of random effects network meta-analyses to estimate the relative effectiveness of the diets. Results 121 eligible trials with 21 942 patients were included and reported on 14 named diets and three control diets. Compared with usual diet, low carbohydrate and low fat diets had a similar effect at six months on weight loss (4.63 v 4.37 kg, both moderate certainty) and reduction in systolic blood pressure (5.14 mm Hg, moderate certainty v 5.05 mm Hg, low certainty) and diastolic blood pressure (3.21 v 2.85 mm Hg, both low certainty). Moderate macronutrient diets resulted in slightly less weight loss and blood pressure reductions. Low carbohydrate diets had less effect than low fat diets and moderate macronutrient diets on reduction in LDL cholesterol (1.01 mg/dL, low certainty v 7.08 mg/dL, moderate certainty v 5.22 mg/dL, moderate certainty, respectively) but an increase in HDL cholesterol (2.31 mg/dL, low certainty), whereas low fat (−1.88 mg/dL, moderate certainty) and moderate macronutrient (−0.89 mg/dL, moderate certainty) did not. Among popular named diets, those with the largest effect on weight reduction and blood pressure in comparison with usual diet were Atkins (weight 5.5 kg, systolic blood pressure 5.1 mm Hg, diastolic blood pressure 3.3 mm Hg), DASH (3.6 kg, 4.7 mm Hg, 2.9 mm Hg, respectively), and Zone (4.1 kg, 3.5 mm Hg, 2.3 mm Hg, respectively) at six months (all moderate certainty). No diets significantly improved levels of HDL cholesterol or C reactive protein at six months. Overall, weight loss diminished at 12 months among all macronutrient patterns and popular named diets, while the benefits for cardiovascular risk factors of all interventions, except the Mediterranean diet, essentially disappeared. Conclusions Moderate certainty evidence shows that most macronutrient diets, over six months, result in modest weight loss and substantial improvements in cardiovascular risk factors, particularly blood pressure. At 12 months the effects on weight reduction and improvements in cardiovascular risk factors largely disappear.

The systematic review has increasingly become a popular tool for researching health policy. However, due to the complexity and diversity in the health policy research, it has also encountered more challenges. We set out the Cochrane reviews on health policy research as a representative to provide the first examination of epidemiological and descriptive characteristics as well as the compliance of methodological quality with the AMSTAR. 99 reviews were included by inclusion criteria, 73% of which were Implementation Strategies, 15% were Financial Arrangements and 12% were Governance Arrangements; involved Public Health (34%), Theoretical Exploration (18%), Hospital Management (17%), Medical Insurance (12%), Pharmaceutical Policy (9%), Community Health (7%) and Rural Health (2%). Only 39% conducted meta-analysis, and 49% reported being updates, and none was rated low methodological quality. Our research reveals that the quantity and quality of the evidence should be improved, especially Financial Arrangements and Governance Arrangements involved Rural Health, Health Care Reform and Health Equity, etc. And the reliability of AMSTAR needs to be tested in larger range in this field.