Efficacy and safety of anti‐obesity drugs in children and adolescents: systematic review and meta‐analysis

We undertook a meta‐analysis of randomized controlled trials to summarize the efficacy of anti‐obesity drugs in reducing BMI and improving health in children and adolescents. Data sources included Medline, Embase, the Cochrane controlled trials register and other registers of controlled trials, together with reference lists of identified articles. All data sources were searched from January 1996 to July 2008. We searched for double blind randomized placebo controlled trials of approved anti‐obesity drugs used in children and adolescents (age <20) with primary obesity for ≥6 months. Six trials, 4 of sibutramine (total patients = 686) and 2 of orlistat (n = 573) met inclusion criteria. No trials of rimonabant were identified. Compared with placebo, sibutramine together with behavioural support reduced BMI by 2.20 kg/m² (95% CI: 1.57 to 2.83) and orlistat together with behavioural support reduced BMI by 0.83 kg/m² (95% CI 0.47 to 1.19). Sibutramine improved waist circumference, triglycerides and high density lipoprotein (HDL)‐cholesterol, but raised systolic and diastolic blood pressure and pulse. Orlistat increased rates of gastrointestinal side‐effects. We conclude that sibutramine in adolescents produces clinically meaningful reductions in BMI and waist circumference of approximately 0.63 SD, with improvements in cardiometabolic risk. Orlistat modestly reduces BMI (effect size approximately 0.24 SD) with a high prevalence of gastrointestinal adverse effects.     

Impact of antisecretory treatment on respiratory symptoms of gastroesophageal reflux disease in children

The effect of antisecretory treatment on extraesophageal symptoms of gastroesophageal reflux disease was evaluated. Seventy‐eight children presenting with typical and extraesophageal symptoms of gastroesophageal reflux disease underwent a multichannel intraluminal impedance and pH monitoring (MII/pH). Children with a positive MII/pH were randomly treated with proton pump inhibitors (PPIs) or histamine H₂‐receptor antagonists (H₂RAs) during 3 months. At the end of the treatment period, all patients were recalled. A second treatment period of 3 months was given to those patients who were not symptom‐free after 3 months. Thirty‐five of the forty‐one (85.4%) children with a pathologic MII/pH presented with extraesophageal symptoms and were treated with PPIs (omeprazole; n:19) or H₂RAs (ranitidine; n:16) for 12 weeks. After 3 months, 11/19 (57.9%) PPI‐treated patients had a complete resolution of symptoms; 6/8 nonresponders were treated with PPI for another 3 months and became all symptom‐free. The other two underwent a Nissen fundoplication. Only 5/16 (31.2 %) patients treated with H₂RAs had a complete resolution of symptoms after 3 months; 1/11 was treated again with H₂RAs during 3 months, and 10/11 were changed to PPIs. In 3/10, a partial resolution of symptoms was achieved, while in 7/10, a complete remission was obtained (P < 0.05). Antisecretory reflux treatment improves extraesophageal reflux symptoms. The efficacy of PPIs is superior to that of H₂RAs in these children.     

Intraoperative mechanical ventilation strategies for obese patients: a systematic review and network meta‐analysis

Several intraoperative ventilation strategies are available for obese patients. However, the same ventilation interventions have exhibited different effects on PaO₂/FIO₂ concerning obese patients in different trials, and the issue remains controversial. Therefore, we conducted a network meta‐analysis to identify the optimal mechanical ventilation strategy. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, Embase, MEDLINE, CINAHL and Web of Science for studies published up to June 2014, and the PaO₂/FIO₂ in obese patients given different mechanical ventilation strategies was assessed. We assessed the studies for eligibility and extracted data and then pooled the data and used a Bayesian fixed‐effect model to combine direct comparisons with indirect evidence. Eligible studies evaluated different ventilation strategies for obese patients and reported the intraoperative PaO₂/FIO₂ ratio, atelectasis and pulmonary compliance. Thirteen randomized controlled trials were included for network meta‐analysis, including 476 patients who received 1 of 12 ventilation strategies. Volume‐controlled ventilation with higher PEEP plus single recruitment manoeuvres (VCV + higher PEEP + single RM) was associated with the highest PaO₂/FiO₂ ratio, improving intraoperative pulmonary compliance and reducing the incidence of intraoperative atelectasis.     

Nocturnal acid breakthrough: pH, drugs and bugs

Nocturnal acid breakthrough (NAB) was defined by Peghini et al. in 1998 as the presence of at least 60 continuous minutes of intragastric pH < 4 during the overnight period (22:00-06:00 h) in patients taking a proton pump inhibitor (PPI) twice-daily before meals. NAB was shown to occur in more than 70% of patients on PPI therapy but can be decreased or eliminated by adding a histamine-2 receptor antagonist (H2RA) at bedtime. Helicobacter pylori status influences intragastric acid control on PPI therapy: H. pylori-positive patients having better gastric acid control compared with their H. pylori-negative counterparts. Recent data indicate that NAB might not occur in H. pylori-positive subjects on twice-daily PPI, suggesting there is no need for combined PPI twice-daily and H2RA therapy to control night-time gastric acid secretion in these individuals. The clinical importance of NAB has been debated ever since this concept was introduced. The importance of NAB in healthy subjects and asymptomatic, uncomplicated gastro-oesophageal reflux disease patients on PPI therapy may be low, but ignoring it in patients with poor oesophageal motility and Barrett's oesophagus may result in suboptimal treatment. Further studies are warranted to investigate whether leaving H. pylori to 'assist'acid suppression obtained by PPI twice-daily, adding bedtime H2RAs after successful H. pylori eradication or other approaches to eliminate NAB results in better clinical outcomes.     

Second‐look endoscopy after endoscopic submucosal dissection for gastric neoplasms

Routine second‐look endoscopy after gastric endoscopic submucosal dissection (ESD) remains controversial. The aim of the present study was to systematically evaluate the efficacy of second‐look endoscopy for gastric ESD. PubMed, the Cochrane library, and the Igaku‐chuo‐zasshi database were searched in order to identify randomized trials eligible for inclusion in the systematic review. Data were combined to calculate a pooled odds ratio (OR) for developing post‐ESD bleeding. The database search yielded three randomized trials (854 patients). Compared with second‐look endoscopy, the pooled OR for post‐ESD bleeding without second‐look endoscopy was 0.69 (95% confidence interval [CI]: 0.38–1.26, P = 0.228), without significant heterogeneity. There were no significant differences between second‐look endoscopy and no second‐look endoscopy with regard to large tumor size (>20 mm). This systematic review and meta‐analysis showed that second‐look endoscopy had no advantage for the prevention of post‐ESD bleeding in patients without a high risk of bleeding.     

Comparison of tiotropium plus formoterol to tiotropium alone in stable chronic obstructive pulmonary disease: a meta-analysis

Background and objective: It is not clear whether combination therapy with tiotropium plus formoterol has greater efficacy, without increasing the burden of adverse events, compared with tiotropium alone. This meta‐analysis was performed to evaluate the differences in efficacy and adverse events associated with combination therapy compared with tiotropium alone, in patients with stable COPD. Methods: MEDLINE, EMBASE, CINAHL and the Cochrane trials database were searched for this analysis. Randomized controlled trials of 2 or more weeks of treatment with tiotropium plus formoterol or arformoterol, compared with tiotropium alone, were reviewed. Studies were pooled to yield odds ratio (OR) or weighted mean differences (WMD), with 95% confidence interval (CI). Results: Eight trials, involving 1868 randomized patients, met the inclusion criteria. Treatment with tiotropium plus formoterol significantly improved the average FEV₁ (WMD 105 mL, 95% CI: 69–142), average FVC (WMD 135 mL, 95% CI: 96–174) and trough FEV₁ (WMD 53 mL, 95% CI: 30–76), compared with tiotropium alone, although the difference was not statistically significant for trough FVC. The mean change in transitional dyspnoea index (TDI) was markedly greater with tiotropium plus formoterol (WMD 1.50, 95% CI: 1.01–1.99) than with tiotropium alone, and there was a similar difference in the proportion of patients with a clinically significant change in TDI (OR 2.34, 95% CI: 1.58–3.46). There tended to be fewer adverse events and COPD exacerbations with tiotropium plus formoterol, compared with tiotropium alone, but the differences were not statistically significant. Conclusions: Tiotropium plus formoterol significantly improved lung function and symptom scores compared with tiotropium alone. There was a trend towards a reduction in adverse events, although the difference was not statistically significant. Long‐term trials are necessary to evaluate the effects of tiotropium plus formoterol and to clarify the role of combination therapy, compared with tiotropium alone.     

Systematic review and meta-analysis of randomized trials on probiotics for hepatic encephalopathy

Aim: The objective of this systematic review and meta‐analysis was to assess the efficacy of probiotics and synbiotics in patients with hepatic encephalopathy. Methods: Eligible trials were identified by searching electronic databases including MEDLINE, the Cochrane Library, Science Citation Index and Embase, abstract proceedings, reference lists and ongoing trial registers until 13 October 2010. We included randomized controlled trials comparing probiotics and synbiotics with no intervention, placebo or lactulose in patients with hepatic encephalopathy. The primary outcome measure was improvement in hepatic encephalopathy. Results were expressed as risk rates (RR) with confidence intervals (CI) and intertrial heterogeneity as I². Results: Seven trials with a total of 393 patients were analyzed. Compared to placebo or lactulose, treatment with probiotics or synbiotics significantly improved hepatic encephalopathy (RR = 1.40, 95% CI = 1.05–1.86, I² = 5%). Probiotics decreased arterial ammonia (weighted mean difference 15.95; 95% CI = 26.72–3.28; I² = 68%), but not venous ammonia (weighted mean difference 5.23; 95% CI = 21.77–11.30; I² = 89%). Treatment with probiotics or synbiotics did not significantly affect the psychometric tests. Overall adverse events were reported in four trials with no difference between probiotics and placebo groups (RR = 0.32, 95% CI = 0.04–2.57; I² = 59%). Regression analysis showed evidence of small‐study effects. Conclusion: The present meta‐analysis suggests that probiotics may be an effective treatment of hepatic encephalopathy, though rigorous evaluation in standardized, randomized, clinical trial with clinically relevant outcomes is still needed.     

Prospective randomized controlled trial to compare the effects of omeprazole and famotidine in preventing delayed bleeding and promoting ulcer healing after endoscopic submucosal dissection

Background and Aims: Proton pump inhibitors (PPIs) are generally used to prevent delayed bleeding after endoscopic submucosal dissection (ESD) and to heal the artificial ulcers. However, it remains controversial whether PPIs or histamine‐2 receptor antagonists (H₂RAs) are more effective in preventing delayed bleeding after ESD. We prospectively compared the effects of omeprazole and famotidine in preventing delayed bleeding and promoting artificial ulcer healing after ESD. Methods: A total of 158 patients (155 early gastric cancers and three adenomas) were randomly assigned to the PPI group (omeprazole 20 mg/day) or H₂RA group (famotidine 40 mg/day) in a prospective randomized controlled trial. The primary end point was the incidence of hematemesis, melena, and/or a decrease in hemoglobin level of 2 g/dL or more requiring endoscopic hemostatic treatment. ESD‐induced ulcer healing and changes in ulcer size were also compared at 6 weeks after ESD as a secondary end point. Results: Of the 158 patients, two were excluded from analysis because they had been treated with a PPI before the present study. Accordingly, data from 77 PPI and 79 H₂RA subjects were included for analysis. Delayed bleeding after ESD occurred in 6.5% of subjects (PPI group) and in 6.3% (H₂RA group); there was no significant difference between the two groups. Likewise, the two groups were not significantly different with respect to ulcer stage or ulcer size reduction rate. Conclusions: Proton pump inhibitors are not superior to H₂RAs for the prevention of delayed bleeding or the healing of artificially induced ulcers after ESD.     

The short‐ and long‐term outcomes of percutaneous intervention with drug‐eluting stent vs bare‐metal stent in saphenous vein graft disease: An updated meta‐analysis of all randomized clinical trials

The use of drug‐eluting stents (DES) vs bare‐metal stents (BMS) in saphenous vein graft (SVG) lesions remains controversial. We conducted a meta‐analysis of all randomized clinical trials comparing the outcomes of DES with BMS in SVG percutaneous coronary interventions. A search of PubMed, Embase, the Cochrane Register of Controlled Trials, and Clinicaltrials.gov was performed for all randomized clinical trials. We evaluated the short‐ and long‐term clinical outcomes of the following: all‐cause mortality, major adverse cardiovascular events (MACE), definite/probable stent thrombosis, target lesion revascularization (TLR), and target‐vessel revascularization (TVR). From a total of 1582 patients in 6 randomized clinical trials, 797 had DES and 785 had BMS. Patients with DES had lower short‐term MACE, TLR, and TVR in comparison with BMS (odds ratio [OR]: 0.56, 95% confidence interval [CI]: 0.35–0.91, P = 0.02; OR: 0.43, 95% CI: 0.19–0.99, P = 0.05; and OR: 0.45, 95% CI: 0.22–0.95, P = 0.04, respectively). However, there were no different outcomes for all‐cause mortality (P = 0.63) or stent thrombosis (P = 0.21). With long‐term follow‐up, there were no significant reductions of MACE (P = 0.20), TLR (P = 0.57), TVR (P = 0.07), all‐cause mortality (P = 0.29), and stent thrombosis (P = 0.76). The use of DES in SVG lesions was associated with lower short‐term MACE, TLR, and TVR in comparison with BMS. However, there were no significant differences with long‐term follow‐up.     

Effects of initiation and titration of a single pre-prandial dose of insulin glulisine while continuing titrated insulin glargine in type 2 diabetes: a 6-month 'proof-of-concept' study

Aim: Stepwise intensification of insulin treatment to match the progressive decline of endogenous insulin secretion has been shown to be an effective management strategy in type 2 diabetes mellitus (T2DM). The efficacy of initiating and titrating a single bolus dose of insulin glulisine to baseline insulin glargine plus oral hypoglycaemic agents (OHAs) was investigated. Methods: This was a 6‐month, parallel‐group, randomized, open‐label, Phase IV study conducted in the US, UK and Russia. People with T2DM (HbA_1c 7.5–9.5%) using any basal insulin underwent a 3‐month run‐in period on insulin glargine titrated to optimize fasting blood glucose (BG) control. Those with HbA_1c >7.0% were randomized to either continue prior therapy (n = 57) or to add a single dose of insulin glulisine (n = 49) immediately prior to the main meal for a further 3 months. Two different titration algorithms were employed for the bolus dose, targeting 2‐h postprandial BG ≤135 mg/dL (≤7.5 mmol/l; Russia and UK) or pre‐meal/bedtime BG 100–120 mg/dl (5.5–6.7 mmol/l; US). Results: HbA_1c and fasting plasma glucose levels decreased during the run‐in period. In the 3 months after randomization, more participants in the basal‐plus‐bolus group reached HbA_1c <7.0% than the basal‐only control group (22.4 vs. 8.8%; p < 0.05), with significantly greater reduction of HbA_1c (?0.37 vs. ?0.11%; p = 0.0290). Rates of hypoglycaemia and mean weight change were comparable between the treatment groups. Conclusions: In people with T2DM inadequately controlled on basal insulin plus OHAs, adding a single injection of insulin glulisine prior to the main meal significantly improves glucose control without undesired side effects.     

Proton pump inhibitors therapy vs H2 receptor antagonists therapy for upper gastrointestinal bleeding after endoscopy: A meta-analysis

AIM: To compare the therapeutic effects of proton pump inhibitors vs H₂ receptor antagonists for upper gastrointestinal bleeding in patients after successful endoscopy.METHODS: We searched the Cochrane library, MEDLINE, EMBASE and PubMed for randomized controlled trials until July 2014 for this study. The risk of bias was evaluated by the Cochrane Collaboration’s tool and all of the studies had acceptable quality. The main outcomes included mortality, re-bleeding, received surgery rate, blood transfusion units and hospital stay time. These outcomes were estimated using odds ratios (OR) and mean difference with 95% confidence interval (CI). RevMan 5.3.3 software and Stata 12.0 software were used for data analyses.RESULTS: Ten randomized controlled trials involving 1283 patients were included in this review; 678 subjects were in the proton pump inhibitors (PPI) group and the remaining 605 subjects were in the H₂ receptor antagonists (H₂RA) group. The meta-analysis results revealed that after successful endoscopic therapy, compared with H₂RA, PPI therapy had statistically significantly decreased the recurrent bleeding rate (OR = 0.36; 95%CI: 0.25-0.51) and receiving surgery rate (OR = 0.29; 95%CI: 0.09-0.96). There were no statistically significant differences in mortality (OR = 0.46; 95%CI: 0.17-1.23). However, significant heterogeneity was present in both the numbers of patients requiring blood transfusion after treatment [weighted mean difference (WMD), -0.70 unit; 95%CI: -1.64 - 0.25] and the time that patients remained hospitalized [WMD, -0.77 d; 95%CI: -1.87 - 0.34]. The Begg’s test (P = 0.283) and Egger’s test (P = 0.339) demonstrated that there was no publication bias in our meta-analysis.CONCLUSION: In patients with upper gastrointestinal bleeding after successful endoscopic therapy, compared with H₂RA, PPI may be a more effective therapy.     

The once‐daily human glucagon‐like peptide‐1 analog,liraglutide, improves β‐cell function in Japanese patients with type 2 diabetes

Aims/Introduction: β‐cell function was evaluated by homeostasis model assessment of β‐cell function (HOMA‐B) index, proinsulin:insulin and proinsulin:C‐peptide ratios in adult, Japanese type 2 diabetes patients receiving liraglutide. Materials and Methods: Data from two randomized, controlled clinical trials (A and B) including 664 Japanese type 2 diabetes patients (mean values: glycated hemoglobin [HbA_1c] 8.61–9.32%; body mass index [BMI] 24.4–25.3 kg/m²) were analyzed. In two 24‐week trials, patients received liraglutide 0.9 mg (n = 268) or glibenclamide 2.5 mg (n = 132; trial A), or liraglutide 0.6, 0.9 mg (n = 176) or placebo (n = 88) added to previous sulfonylurea therapy (trial B). Results: Liraglutide was associated with improved glycemic control vs sulfonylurea monotherapy or placebo. In liraglutide‐treated groups in trials A and B, area under the curve (AUC) _{insulin 0–3 h} was improved (P < 0.001 for all) and the AUC_{insulin 0–3 h}:AUC_{glucose 0–3 h} ratio was increased (estimated treatment difference [liraglutide–comparator] 0.058 [0.036, 0.079]). HOMA‐B significantly increased with liraglutide relative to comparator in trial B (P < 0.05), but not in trial A. The reduction in fasting proinsulin:insulin ratio was 50% greater than in comparator groups. Conclusions: In Japanese type 2 diabetes patients, liraglutide was associated with effective glycemic control, restoration of prandial insulin response and indications of improved β‐cell function. This trial was registered with Clinicaltrials.gov (trial A: no. NCT00393718/JapicCTI‐060328 and trial B: no. NCT00395746/JapicCTI‐060324). (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2012.00193.x, 2012)     

Meditation for asthma: Systematic review and meta-analysis

Objective: To conduct a comprehensive review and meta-analysis of the effectiveness of meditation on a variety of asthma outcomes. Methods: We searched MEDLINE, EMBASE, CINAHL, PsycINFO and AMED in June 2016 to identify randomized controlled trials (RCTs) investigating the effectiveness of meditation in adults with asthma. No restriction was put on language or year of publication. Study quality was assessed using The Cochrane Risk of Bias Assessment Tool. Meta-analysis was carried out using RevMan 5.3. Results: Four RCTs involving 201 patients met the inclusion criteria. Quality of studies was inconsistent with only one study reporting adequate allocation concealment. Disease-specific quality of life was assessed in two trials; a pooled result involving 62 intervention and 65 control participants indicated a significant improvement in quality of life in the meditation group compared to the control group (SMD 0.40, 95% CI 0.05–0.76). A pooled result from all four studies indicated the uncertain effect of meditation in forced expiratory volume in 1 s (FEV₁) (SMD ?0.67, 95% CI ?2.17 to 0.82). Results from the individual trials suggest that meditation may be helpful in reducing perceived stress and the use of short-term rescue medication. Conclusion: Our review suggests that there is some evidence that meditation is beneficial in improving quality of life in asthma patients. As two out of four studies in our review were of poor quality, further trials with better methodological quality are needed to support or refute this finding.     

Change in glycated haemoglobin levels after initiating second‐line therapy in type 2 diabetes: a primary care database study

The aim of the present study was to compare the absolute reduction in glycated haemoglobin (HbA1c) levels at 6 months after initiating second‐line glucose‐lowering therapy in patients with type 2 diabetes treated with metformin monotherapy in general practices. A total of 7009 patients were identified (Disease Analyser Germany: January 2004 to December 2014). The patients' mean ± standard deviation (s.d.) age was 63 ± 11 years, 55.5% were male and their mean ± s.d. HbA1c level was 8.0 ± 1.6%. The initiated second‐line therapies included: dipeptidyl peptidase‐4 (DPP‐4) inhibitors (38.7%); sulphonylureas (36.3%); insulin (13.3%); glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs; 2.5%); thiazolidinediones (5%); and other agents (glinides, aldose‐reductase inhibitors; 4.1%). The mean absolute HbA1c change from baseline was ?0.9% (DPP‐4 inhibitors, ?0.9%; sulphonylureas, ?0.9%; insulin, ?1.1%; GLP‐1RAs, ?0.7%; thiazolidinediones, ?0.9%; and other, ?0.7%; all p < 0.001). Overall, 58% of patients reached the HbA1c target of <7% (DPP‐4 inhibitors, 61.7%; sulphonylureas, 56.7%; insulin, 45.6%; GLP‐1RAs, 62.2%; thiazolidinediones, 69.7%; and other, 57.5%). Compared with sulphonlyureas, DPP‐4 inhibitors, GLP‐1RAs and thiazolidinediones were associated with an increased odds of reaching HbA1c <7% [odds ratio (OR) 1.24, 95% confidence interval (CI) 1.09–1.40; OR 1.43, 95% CI 1.01–2.04; and OR 1.70, 95% CI 1.30–2.23, respectively], whereas insulin was related to a lower odds (0.66, 95% CI 0.55–0.78). In conclusion, in patients with type 2 diabetes very similar reductions in HbA1c after 6 months of second‐line therapy were achieved regardless of the type of therapy.     

The safety of dipeptidyl peptidase‐4 (DPP‐4) inhibitors or sodium‐glucose cotransporter 2 (SGLT‐2) inhibitors added to metformin background therapy in patients with type 2 diabetes mellitus: a systematic review and meta‐analysis

The aim of the present meta‐analysis was to assess the safety profile of dipeptidyl peptidase‐4 (DPP‐4) inhibitors and sodium‐glucose cotransporter 2 (SGLT‐2) inhibitors in comparison with placebo as add‐on to metformin therapy in patients with type 2 diabetes. Randomized controlled trials and controlled clinical trials were identified by searching Pubmed, Embase and the Cochrane Central Register of Controlled Trials database until 15 July 2013. All included studies were critically appraised and analysed with the use of Review Manager 5.1.0 software according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses statement protocol. Twenty randomized and double‐blinded studies published in 22 articles fulfilled the inclusion criteria for meta‐analysis. The overall results demonstrated that the use of oral antidiabetic agents (analysed separately and together) was not associated with any significantly increased risk of any serious adverse events including hypoglycaemia and gastrointestinal disorders. Moreover, the use of DPP‐4 or SGLT‐2 inhibitors significantly decreased risk of diarrhoea compared with placebo, when given concomitantly with metformin. However, we found that the SGLT‐2 inhibitors were more likely to cause a genital infection. Despite some limitations, the findings of this meta‐analysis indicate that DPP‐4 or SGLT‐2 inhibitors have favourable safety profile, and such therapy, when combined with metformin is well tolerated. Copyright © 2013 John Wiley & Sons, Ltd.     

Colchicine for alcoholic and non‐alcoholic liver fibrosis or cirrhosis

Abstract: Aims/Background: Colchicine is an anti‐inflammatory and anti‐fibrotic drug. Several randomized clinical trials have addressed the question whether colchicine has any efficacy in patients with alcoholic as well as non‐alcoholic fibrosis and cirrhosis. The objectives were to assess the efficacy of colchicine evaluated in randomized trials on mortality, liver related mortality, liver related complications, liver fibrosis markers, liver histology, alcohol consumption, quality of life, and health economics in patients with alcoholic and non‐alcoholic fibrosis or cirrhosis. Methods: Interventions encompassed peroral colchicine at any dose versus placebo or no intervention. The trials could be double‐blind, single‐blind or unblinded. The trials could be unpublished or published as an article, an abstract, or a letter, and no language limitations were applied. All analyses were performed according to the intention‐to‐treat method. MEDLINE, The Cochrane Controlled Trials Register, The Cochrane Hepato‐Biliary Group Controlled Trials Register and full text searches were combined. Results: Combining the results of 14 randomized clinical trials including 1138 patients demonstrated no significant effects of colchicine on mortality (odds ratio (OR): 0.91; 95% confidence interval (CI) 0.64, 1.31), liver related mortality (OR: 0.98; CI 0.56, 1.74), complications (OR: 1.06; CI 0.65, 1.73), and the other outcomes. Colchicine was associated with a significantly increased risk of adverse events (OR: 4.41; CI 2.24, 8.70; p< 0.001). Conclusions: Colchicine should not be used for liver fibrosis or liver cirrhosis irrespective of etiology. Future trials on colchicine for liver diseases ought to be large.     

Effect of semaglutide versus other glucagon-like peptide-1 receptor agonists on cardio-metabolic risk factors in patients with type 2 diabetes: A systematic review and meta-analysis of head-to-head,phase 3, randomized controlled trials

IntroductionGlucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as a cornerstone treatment for type 2 diabetes mellitus (T2DM). The aim of the present meta-analysis was to assess whether semaglutide exerts greater effects on glycemia and other cardio-metabolic risk factors compared to other GLP-1RAs.MethodsPubMed and Cochrane Library databases, along with grey literature sources, were searched form inception to 8th February 2023, in order to retrieve head-to-head, phase 3 randomized controlled trials (RCTs) assessing the effect of semaglutide versus other GLP-1RAs on glycemia and other cardio-metabolic risk factors in T2DM.ResultsWe finally pooled data from 5 RCTs in a total of 3760 randomized participants. Semaglutide compared to other GLP-1RAs provided a significantly greater reduction in HbA1c levels by 0.44 %, in fasting plasma glucose by 0.48 mmol/L, in body weight by 2.53 kg and in body mass index by 0.91 kg/m². Subjects receiving semaglutide experienced significantly greater odds for achieving target and optimal HbA1c, along with significantly greater odds for weight loss >5 % and 10 %. However, subjects randomized to semaglutide also experienced significantly greater odds for gastrointestinal adverse events and treatment discontinuation.ConclusionSemaglutide is more effective than rest GLP-1RAs, in terms of improvement in glycemia and other cardio-metabolic risk factors, among individuals with T2DM.     

Long‐term outcomes of late course accelerated hyper‐fractionated radiotherapy for localized esophageal carcinoma in Mainland China: a meta‐analysis

Published data on the long‐term survival results of patients with localized esophageal carcinoma receiving late course accelerated hyper‐fractionated radiotherapy (LCAF RT) versus conventional fractionated radiotherapy (CF RT) are inconclusive. In order to derive a more precise estimation of the both treatment‐regimes, a meta‐analysis based on systematic review of published articles was performed. A meta‐analysis was performed using trials identified through Pubmed and Chinese national knowledge infrastructure. Results in 5‐year survival and 5‐year local control were collected from randomized trials comparing LCAF RT with CF RT. Review Manager (The Cochrane Collaboration, Oxford, England) and Stata software (Stata Corporation, College Station, TX, USA) were used for data management. A total of 11 trials were involved in this analysis with 572 cases and 567 controls. Our results showed that LCAF RT, compared with CF RT, significantly improved the 5‐year survival (odds ratio [OR]= 2.93, 95% confidence interval [CI]: 2.15–4.00, P < 0.00001) and 5‐year local control (OR = 3.96, 95% CI: 2.91–5.38, P < 0.00001). LCAF RT was more therapeutically beneficial than CF RT in the localized esophageal carcinoma.     

Comparison of twice-daily injections of biphasic insulin lispro and basal-bolus therapy: glycaemic control and quality-of-life of insulin-naïve type 2 diabetic patients

Objective: The aim of this study was to evaluate twice‐daily injections of biphasic insulin lispro vs. basal–bolus (BB) therapy with regard to quality‐of‐life (QOL) and glycaemic control in insulin‐naïve type 2 diabetic patients. Methods: Twenty‐eight patients with type 2 diabetes were randomized to receive either twice‐daily 50/50 premixed insulin lispro (Mix50 group) or BB (NPH insulin at bedtime and preprandial insulin lispro) therapy (BB group) for 12 weeks. Glycated haemoglobin (HbA1C), 1,5‐anhydroglucitol (1,5‐AG), blood plasma glucose level, body mass index (BMI), daily total insulin dosage and insulin therapy–related QOL (ITR‐QOL) were studied. Results: ITR‐QOL was significantly better in the Mix50 than in the BB group (103.1 ± 9.8 vs. 90.6 ± 19.4; p < 0.05). HbA_1c improved in both groups (from 11.1 ± 2.1 to 6.9 ± 1.0% with Mix50 vs. from 11.0 ± 2.3 to 6.6 ± 0.8% with BB therapy). Conclusion: These results might suggest that twice‐daily injections of premixed rapid‐acting insulin analogue therapy could achieve good glycaemic control and better QOL compared with BB therapy in insulin‐naïve type 2 diabetes.