Background Metabolic disorders exhibit strong inflammatory underpinnings and vice versa. This study aimed to investigate the association between metabolic health status, genetic predisposition, and the risk of inflammatory bowel disease (IBD), and to explore the potential benefits of maintaining ideal metabolic status for individuals with a predetermined genetic risk of IBD. Method This population-based prospective study included 385,820 unrelated European descent participants from the UK Biobank. Using multivariable Cox regression, we assessed the relationship of metabolic phenotypes with risk of IBD and its subtypes. We also developed a polygenic risk score to examine how metabolic health status interacted with genetic risk in relation to IBD risk. Results During the follow-up period of 4,328,895 person-years, 2,044 newly-diagnosed IBD cases were identified. Higher genetic risk and an increasing number of abnormal metabolic phenotypes were associated with elevated IBD risk (p-trend <0.001). Individuals with high genetic risk and poor metabolic health had a significantly higher risk of IBD (HR=4.56, 95 % CI=3.27–6.36) compared to those with low genetic risk and ideal metabolic health. These results remained consistent for IBD subtypes. Maintaining ideal metabolic status reduced IBD risk within each genetic risk category and jointly decreased subsequent risk by 40 % in high genetic risk individuals. Conclusion Our study reveals a combined impact of poor metabolic health and genetic risk on IBD incidence. Those with low genetic risk and optimal metabolic health exhibit the lowest IBD risk, offering insights into potential management strategies for individuals at predefined genetic risk.

BackgroundChildhood obesity is a global public health issue, and the status of clinical practice guidelines (CPGs) as instruction manuals for the management of childhood obesity remains unclear. This study aims to identify and apprise the methodological and reporting quality of CPGs focused on childhood obesity and provide an overview of key recommendations.MethodsDatabases and websites reporting guidelines were searched from January, 2018 to September, 2023. The methodological quality was graded using the AGREE II, and RIGHT was used to assess the reporting completeness.ResultsAmong the six included CPGs, two were rated as high quality and considered "Recommended" and three were reported no less than 80%. CPGs included 184 recommendations cover diagnosis, assessment and management of complications, interventions and prevention. The diagnostic criteria for children with obesity over 2 years of age are based on normative BMI percentiles, depending on sex and age. CPGs recommended the delivery of multi-component behavior-changed interventions included controlling diet and increasing physical activity. Pharmacological interventions and bariatric surgery are considered as complementary therapies.ConclusionCPGs for childhood obesity should emphasize the impact of psychological factors and consider the provision of interventions from multiple settings, and could consider the role of complementary alternative therapies.ImpactSix guidelines have been published in the past 5 years focusing children obesity.Recommendations covered diagnosis, multiple intervention and prevention.Guidelines should focus on the role of complementary alternative therapies.Guidelines should emphasize the impact of psychological factors.Guidelines should consider the provision of interventions from multiple settings.

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 Molnupiravir has been considered a promising candidate for COVID-19. Its efficacy and safety in non-severe COVID-19 patients and the differences between patients with different risk factors need further evaluation. Methods We conducted a systematic review and meta-analysis of randomized controlled trials that allocated adult patients with non-severe COVID-19 to molnupiravir or a control. We used random-effects models, and conducted subgroup analyses and meta-regression for COVID-19 patients with high-risk factors. The GRADE approach was used to rate the certainty of evidence. Results Fourteen trials with 34 570 patients were included. Moderate- to low-certainty evidence showed that molnupiravir was associated with a reduction in the risk of hospitalization (relative risk [RR] = 0.63, 95% CI: 0.47-0.85), risk of mechanical ventilation (RR = 0.37, 95% CI: 0.19-0.72) and time to symptom resolution (mean differences [MD] = -2.91 days, 95% CI: -3.66 to -2.16). However, no significant differences were found in adverse events, all-cause mortality, rate of and time to viral clearance, or duration of hospitalization. For the rate of viral clearance, subgroup effects were found between trials with low and high risk of bias (P = 0.001) and between trials with male or female majority (P < 0.001). For admission to hospital, subgroup effects were also found between trials with & GE;50% and <50% of the participants being female (P = 0.04). Meta-regression showed a significant association between higher trial mean age and elevated risk of hospitalization (P = 0.011), and female majority and elevated risk of hospitalization (P = 0.011). Conclusions Molnupiravir was found to be effective in non-severe COVID-19, but the efficacy varied with age and sex.

BackgroundPharmacological treatment is common in practice and widely used for the management of insomnia. However, evidence comparing the relative effectiveness, safety, and certainty of evidence among drug classes and individual drugs for insomnia are still lacking. This study aimed to determine the relative effectiveness, safety, and tolerability of drugs for insomnia.MethodsIn this systematic review and network meta-analysis we systematically searched PubMed, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, and ClinicalTrials.gov, from inception to January 10, 2022 to identify randomized controlled trials that compared insomnia drugs with placebo or an active comparator in adults with insomnia. We conducted random-effects frequentist network meta-analyses to summarize the evidence, and used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty, categorize interventionsand present the findings.ResultsA total of 148 articles met our eligibility criteria; these included 153 trials which enrolled 46,412 participants and assessed 36 individual drugs from eight drug classes. Compared with placebo, both subjectively and objectively measured total sleep time were significantly improved with non-benzodiazepine (subjective: mean difference [MD] 25.07, 95% confidence interval [CI] 15.49-34.64, low certainty; objective: MD 22.34, 95% CI 7.64-37.05, high certainty), antidepressants (subjective: MD 54.40, 95% CI 34.96-75.83, low certainty; objective: MD 35.64, 95% CI 13.05-58.24, high certainty), and orexin receptor antagonists (subjective: MD 21.62, 95% CI 0.84-42.40, high certainty; objective: MD 31.81, 95% CI 2.66-60.95, high certainty); of which doxepin, almorexant, suvorexant, and lemborexant were among the relatively effective drugs with relatively good tolerability and lower risks of any adverse events (AEs). Both subjectively and objectively measured sleep onset latency were significantly shortened with non-benzodiazepines (subjective: MD - 10.12, 95% CI - 13.84 to - 6.40, moderate certainty; objective: MD - 12.11, 95% CI - 19.31 to - 4.90, moderate certainty) and melatonin receptor agonists (subjective: MD - 7.73, 95% CI - 15.21 to - 0.26, high certainty; objective: MD - 7.04, 95% CI - 12.12 to - 1.95, moderate certainty); in particular, zopiclone was among the most effective drugs with a lower risk of any AEs but worse tolerability. Non-benzodiazepines could significantly decrease both subjective and objective measured wake time after sleep onset (subjective: MD - 16.67, 95% CI - 21.79 to - 11.56, moderate certainty; objective: MD - 13.92, 95% CI - 22.71 to - 5.14, moderate certainty).ConclusionsNon-benzodiazepines probably improve total sleep time, sleep onset latency, and wake time after sleep onset. Other insomnia drug classes and individual drugs also showed potential benefits in improving insomnia symptoms. However, the choice of insomnia drugs should be based on the phenotype of insomnia presented, as well as each drug's safety and tolerability.Protocol registration PROSPERO (CRD42019138790).

Background: Multiple studies and meta-analyses have reported the diagnostic value of C-reactive protein (CRP) in several diseases. However, the precision, and influence of potential bias regarding the diagnostic values of existing evidence may have implications for clinical practice. Methods: We performed an umbrella review of diagnostic test accuracy studies of CRP for diseases by searching PubMed, Embase, China National Knowledge Infrastructure, and WanFang databases up to March 7, 2021. Five independent reviewers evaluated eligibility, extracted data, and assessed methodological quality. We descriptively analyzed the diagnostic accuracy of CRP for multiple diseases, heterogeneity between studies, and publication bias. Results: Seventy-four meta-analyses were included, with 13 diseases classified according to the International Classification of Diseases-11 (ICD-11). The methodological quality of the included meta-analyses was mostly low, with only 16 meta-analyses rated as moderate or high, including seven diseases classified by ICD-11. CRP had a relatively greater diagnostic accuracy for two of these diseases. For postoperative infectious complications after bariatric surgery, sensitivity and specificity were 0.81 (0.34-1) and 0.91 (0.73-1), respectively. For anastomotic leakage after colorectal surgery, sensitivity and specificity were 0.95 (0.75-0.99) and 0.95 (0.75-0.99), respectively. Conclusions: The diagnostic accuracy of CRP for multiple diseases has been extensively studied; however, most studies have low methodological quality. Evidence indicates that CRP has a relatively greater diagnostic accuracy for inflammation and infection diseases, especially for postoperative infectious complications after bariatric surgery and anastomotic leakage after colorectal surgery.

White rice is the food more than half of the world's population depends on. White rice intake can significantly increase the glycemic load of consumers and bring some adverse health effects. However, the quality of evidence implicating white rice in adverse health outcomes remains unclear. To evaluate the association between white rice consumption and the risk of cardiometabolic and cancer outcomes, a systematic review and dose-response meta-analysis of the relevant publications were performed. Twenty-three articles including 28 unique prospective cohorts with 1,527,198 participants proved eligible after a comprehensive search in four databases. For the risk of type 2 diabetes mellitus (T2DM), the pooled RR was 1.18 (16 more per 1000 persons) for comparing the highest with the lowest category of white rice intake, with moderate certainty evidence. Females presented a higher risk (23 more per 1000 persons) in subgroup analysis. And every additional 150 grams of white rice intake per day was associated with a 6% greater risk of T2DM (5 more per 1000 persons) with a linear positive trend. We found no significant associations between white rice intake and risk of cardiovascular diseases (CVD), CVD mortality, cancer, and metabolic syndrome. In conclusion, moderate certainty evidence demonstrated that white rice intake was associated with T2DM risk, with a linear positive trend. However, low to very low certainty of evidence suggested that no substantial associations were found between white rice intake and other cardiometabolic and cancer outcomes. More cohorts are needed to strength the evidence body.

Background: The coronavirus disease 2019 (COVID-19) continues to spread globally. Due to the higher risk of mortality, the treatment of severe or critical patients is a top priority. Traditional Chinese medicine (TCM) treatment has played an extremely important role in the fight against COVID-19 in China; a timely evidence summary on TCM in managing COVID-19 is crucial to update the knowledge of healthcare for better clinical management of COVID-19. This study aimed to assess the effects and safety of TCM treatments for severe/critical COVID-19 patients by systematically collecting and synthesizing evidence from randomized controlled trials (RCTs) and observational studies (e.g., cohort). Methods: We searched nine databases up to 19th March 2022 and the reference lists of relevant publications. Pairs of reviewers independently screened studies, extracted data of interest, and assessed risk of bias. We performed qualitative systematic analysis with visual presentation of results and compared the direction and distribution of effect estimates for each patient's important outcome. We performed sensitivity analyses to observe the robustness of results by restricting analysis to studies with low risk of bias. Results: The search yielded 217,761 records, and 21 studies (6 RCTs and 15 observational studies) proved eligible. A total of 21 studies enrolled 12,981 severe/critical COVID-19 patients with a mean age of 57.21 years and a mean proportion of men of 47.91%. Compared with usual supportive treatments, the effect estimates of TCM treatments were consistent in direction, illustrating that TCM treatments could reduce the risk of mortality, rate of conversion to critical cases, and mechanical ventilation, and showed significant advantages in shortening the length of hospital stay, time to viral clearance, and symptom resolution. The results were similar when we restricted analyses to low-risk-bias studies. No serious adverse events were reported with TCM treatments, and no significant differences were observed between groups. Conclusion: Encouraging evidence suggests that TCM presents substantial advantages in treating severe/critical COVID-19 patients. TCM has a safety profile that is comparable to that of conventional treatment alone. TCMs have played an important role in China's prevention and treatment of COVID-19, which sets an example of using traditional medicine in preventing and treating COVID-19 worldwide.

Background: Acupuncture has been widely practiced for primary insomnia (PI). However, the relative benefit and harm among acupuncture therapies remain uncertain.Objectives: To compare and evaluate the effect differences of multiple acupuncture therapies for patients with PI.Methods: Systematic literature search for randomized controlled trials (RCTs). Pairs of reviewers independently conducted literature screening, data extraction, and risk of bias assessment. Meta-analysis was conducted using R and Stata software. The Grading of Recommendations Assessment, Development, and Evaluation system (GRADE) was used to assess certainty of evidence and interpret results.Results: Fifty-seven RCTs with 4678 patients were included. Compared with usual treatment, multiple acupuncture therapies showed a better effect for Pittsburgh sleep quality index score. And acupoints catgut embedding (ACE) was proved to be the most effective with a moderate certainty of evidence; auricular acupressure or auricular acupuncture plus manual acupuncture (AP + MA), electroacupuncture plus acupoint application (EA + APA), and intradermal needle (IN) might be also the most effective with low certainty of evidence. ACE, ACE + MA, AP + MA, EA, EA + APA, HPN, MA and PBN + MA showed significantly improvement in effective rate when compared with usual treatment. Insufficient evidence reported on Epworth Sleepiness Scale, Athens Insomnia Scale, and recurrence rate. The most common slight adverse events mainly included hematoma, pain, headache, and bleeding.Conclusions: With moderate to low certainty of evidence, multiple acupuncture therapies showed impressive insomnia improvement, especially ACE, AP + MA, and EA + APA. Differences between therapies were small or insignificant and based-on low or very low certainty of evidence.(c) 2022 Elsevier B.V. All rights reserved.

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