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Red blood cell distribution width is a parameter measured automatically in every complete blood count that actually reflects the degree of anisocytosis of the red blood cell population. It is a cost-effective tool used in everyday clinical practice along with other parameters to define and narrow the cause of anemia. In a series of pathologic entities, such as cardiovascular diseases, autoimmune diseases, malignancy, chronic renal diseases and chronic respiratory diseases, where inflammation and oxidative stress comprise the major pathophysiologic insults, red cell distribution width behaves as a significant and competent marker able to predict and assess disease activity and severity. A number of clinical studies based on these observations have aimed to evaluate its potential utility as an index of activity in inflammatory bowel disease. In this narrative review we present data from the international literature regarding its ability to express disease activity and we look into its relation with clinical, laboratory and endoscopic indices used to identify active disease. According to the results of published clinical trials, red cell distribution width is considerably correlated with disease activity and might serve as an index to differentiate Crohn's disease from ulcerative colitis.

Background Beta-blockers are used for prophylaxis of variceal bleeding. Our aim was to assess the efficacy and safety of carvedilol for primary or secondary prevention of variceal bleeding in patients with cirrhosis. Methods We searched Medline, Embase, CENTRAL and gray literature sources for randomized controlled trials (RCTs) comparing carvedilol with placebo or any active intervention. We synthesized data using random effects models. We summarized the strength of evidence using GRADE criteria. Results We included 13 trials with 1598 patients. Carvedilol was as efficacious as endoscopic variceal ligation (EVL) (4 RCTs, risk ratio [RR] 0.74, 95% confidence interval [CI] 0.37-1.49) or propranolol (3 RCTs, RR 0.76, 95%CI 0.27-2.14) for primary prevention of variceal bleeding. Likewise, carvedilol was as efficacious as EVL (3 RCTs, RR 1.10, 95%CI 0.75-1.61), non-selective beta-blockers (NSBBs) plus isosorbide-5-mononitrate (2 RCTs, RR 1.02, 95%CI 0.70-1.51) or propranolol (2 RCTs, RR 0.39, 95%CI 0.15-1.03) for secondary prevention of variceal bleeding. Carvedilol was associated with lower all-cause mortality compared to EVL (3 RCTs, RR 0.51, 95%CI 0.33-0.79). There was no difference in any other efficacy outcome. Finally, there were no significant differences in the safety profiles compared with EVL and NSBBs. Our confidence in the effect estimates for all outcomes was very low. Conclusion Carvedilol is as efficacious and safe as standard-of-care interventions for the primary and secondary prevention of variceal bleeding.

Objectives We aimed to assess the comparative efficacy and safety of adjunctive interventions for the prevention of Clostridioides difficile recurrence. Methods We searched Medline, Embase, CENTRAL, and clinicaltrials.gov up to May 2021. We included randomized controlled trials comparing interventions added to antibiotic therapy for prevention of CDI recurrence, to placebo or each other. Efficacy outcomes were CDI and diarrhea recurrence. Safety outcomes included the incidence of any adverse event (AE), serious AEs, and discontinuation due to AEs. We performed random-effects network meta-analysis. We ranked interventions based on SUCRA (surface under the cumulative ranking curve) probabilities. We assessed confidence in estimates utilizing the CINeMA (Confidence in Network Meta-Analysis) framework. Results Fifteen trials (3909 patients) assessed 9 interventions. Oligofructose (OR 0.17; 95% CI, 0.07 to 0.46), NTCD-M3 (OR 0.29; 95% CI, 0.12 to 0.68), rifaximin (OR 0.47; 95% CI, 0.24 to 0.93), RBX2660 (OR 0.47; 95% CI, 0.22 to 0.99), the combination bezlotoxumab/actoxumab (OR 0.47; 95% CI, 0.37 to 0.60), and bezlotoxumab (OR, 0.53; 95% CI, 0.42 to 0.68) were associated with lower incidence of CDI recurrence than placebo (moderate confidence). Oligofructose was ranked highest, however data for oligofructose were derived solely from one small trial. Probiotics, actoxumab and SER-109 were not superior to placebo (low confidence). Probiotics were not well tolerated (low confidence) and actoxumab showed high rates of serious AEs (moderate confidence). Conclusion Add-on treatment with oligofructose, NTCD-M3 spores, rifaximin, RBX2660, and bezlotoxumab likely reduces the risk of CDI. Evidence on probiotics and SER-109 are uncertain, thus adequately powered trials are warranted.

Many of the challenges faced by the LHC experiments (aggregation of distributed computing resources, management of data across multiple storage facilities, integration of experiment-specific workflow management tools across multiple grid services) are similarly experienced by "midscale" high energy physics and astrophysics experiments, particularly as their data set volumes are increasing at comparable rates. Often these (international, multi-institution) collaborations have outgrown the computing resources offered by their home laboratories, or the capacities of any single member institution. Unlike the LHC experiments, however, these collaborations often lack the manpower required to build, integrate and operate the systems required to meet their scale. In the Open Science Grid, we have organized a team designed to support collaborative science organizations re-use proven software and patterns in distributed processing and data management, often but not restricted to software developed for the LHC. Examples are re-use of the Rucio and FTS3 software for reliable data transfer and management, XRootD for data access and caching, Ceph for large scale pre-processing storage, and Pegasus for workflow management across heterogeneous resources. We summarize experience with the VERITAS gamma ray observatory, the South Pole Telescope (CMB detector), and the XENON dark matter search experiment.

Background We performed a systematic review and network meta-analysis to compare probiotics to current therapies in the induction and maintenance of remission in ulcerative colitis (UC). Methods We systematically searched Medline, Embase, CENTRAL up to November 2018. We included randomised controlled trials (RCTs) in patients with mild to moderate UC that compared probiotics, sulfasalazine, mesalamine (low dose Results Forty-eight trials (probiotics 6 trials) of induction therapy and 30 trials (probiotics 6 trials) of maintenance therapy were included in the analysis. In studies with probiotics concomitant treatment, mainly mesalamine, were allowed. At induction, probiotics were not superior to placebo (OR 1.43; 95%CI 0.84–2.42) and they were inferior to combined oral and topical mesalamine therapy (OR 0.28; 95%CI 0.12–0.66) and combined mesalamine and beclomethasone therapy (OR 0.27; 95%CI 0.09–0.83). On SUCRA analysis, combination therapies (SUCRA 0.92 and 0.93) were ranked the highest followed by balsalazide (SUCRA 0.71), budesonide ΜΜΧ (SUCRA 0.68), standard dose mesalamine (SUCRA 0.52), beclomethasone (SUCRA 0.50), olsalazine (SUCRA 0.41), probiotics (SUCRA 0.29), low dose mesalamine (SUCRA 0.26) and sulfasalazine (SUCRA 0.23) in terms of inducing remission. Probiotics were well tolerated. At maintenance, probiotics (OR 0.35; 95%CI 0.19–0.62) and their combination with mesalamine (OR 0.38; 95%CI 0.15–0.99) had lower rate of relapse compared with placebo, but there were no differences when compared with other treatments. On SUCRA analysis, probiotics either alone or combined with mesalamine had comparable SUCRA values to standard dose mesalamine (SUCRA 0.59) and sulfasalazine (SUCRA 0.68). The combination of oral and rectal mesalamine was superior to placebo (OR 0.10; 95%CI 0.04–0.26) and all other treatments and it was ranked highest (SUCRA 0.99). Probiotics were ranked the best tolerated option in terms of discontinuation due to adverse events (SUCRA 0.80). Conclusion Probiotics are well tolerated but they are not effective in inducing remission in active UC. They may be effective when added to mesalamine therapy in preventing relapse of quiescent UC, but large, well-designed RCTs are needed.

Background & Aims We aimed to assess the accuracy of Baveno VI criteria for identification of high-risk varices (HRVs) and varices of any size in patients with compensated advanced chronic liver disease (cACLD). Methods We performed a systematic search of publications through December 2018 for studies that assessed the accuracy of Baveno VI criteria for screening for varices in patients with cACLD. We used hierarchical models to synthesize evidence. We also conducted a post hoc analysis to assess the accuracy of Expanded Baveno VI criteria. We appraised the confidence in estimates using the Grading of Recommendations Assessment, Development and Evaluation approach. Results We identified 30 studies (8469 participants). Pooled values of Baveno VI criteria for HRVs (26 studies) were a sensitivity of 0.97 (95% CI, 0.95–0.98) and a specificity of 0.32 (95% CI, 0.26–0.39). Pooled sensitivity of Expanded Baveno VI criteria for HRVs (12 studies) was 0.90 (95% CI, 0.85–0.93) and specificity was 0.51 (95% CI, 0.45–0.57). In 1000 patients with cACLD, with a prevalence of HRVs of 20%, Baveno VI criteria would prevent endoscopy in 262 patients, but 6 patients with HRVs would be missed. Instead, use of the Expanded Baveno VI criteria would result in 428 patients avoiding endoscopy, but 20 patients with HRVs would be missed. The credibility of our findings is moderate or low, mainly owing to the retrospective design of most studies. Conclusions Baveno VI criteria have high diagnostic accuracy as a triage test for screening for HRVs in patients with cACLD. Expanded Baveno VI criteria could reduce the proportion of unnecessary endoscopies further, nevertheless with a higher rate of missed HRVs.

Basal insulin analogues aim for protracted glycemic control with minimal adverse effects.To assess the comparative efficacy and safety of basal insulin analogues for adults with type 2 diabetes mellitus (T2DM).Several databases from inception to April 2018 without language restrictions, ClinicalTrials.gov to April 2018, references of reviews, and meeting abstract books.Randomized trials lasting at least 12 weeks that compared efficacy (change in hemoglobin A1c [HbA1c] level from baseline [primary outcome]; percentage of patients with HbA1c level7% at end of study and change in body weight [secondary outcomes]) and safety (hypoglycemia) of basal insulin analogues.Two authors independently extracted data and assessed risk of bias for each outcome. All authors evaluated overall confidence in the evidence.Thirty-nine trials (26 195 patients) assessed 10 basal insulin analogues. Low- to very-low-quality evidence indicated that thrice-weekly degludec (Deg-3TW) was inferior to most other regimens for reducing HbA1c level, with mean differences ranging from 0.21% (vs. degludec, 100 U/mL [Deg-100]) to 0.32% (vs. glargine, 300 U/mL [Glar-300]). High- to moderate-quality evidence suggested that detemir had a favorable weight profile versus all comparators, and Glar-300 was associated with less weight gain than glargine, 100 U/mL (Glar-100); Deg-100; degludec, 200 U/mL (Deg-200); Deg-3TW; and LY2963016. Low- and very-low-quality evidence suggested that Deg-100, Deg-200, and Glar-300 were associated with lower incidence of nocturnal hypoglycemia than detemir, Glar-100, LY2963016, and neutral protamine lispro (NPL). Incidence of severe hypoglycemia did not differ among regimens, except NPL, which was associated with increased risk versus Deg-100, detemir, Glar-100, and Glar-300.Results are based mostly on indirect comparisons. Confidence in summary estimates is low or very low due to individual-study limitations, imprecision, or inconsistency.Low-quality evidence suggests that basal insulin analogues for T2DM do not substantially differ in their glucose-lowering effect. Low- and very-low-quality evidence suggests some regimens may be associated with lower risk for nocturnal hypoglycemia (Deg-100, Deg-200, and Glar-300) or less weight gain (detemir and Glar-300).None. (PROSPERO: CRD42016037055).

BACKGROUND Patient-reported outcomes are important in the assessment of efficacy of intervention for ulcerative colitis (UC). AIM To compare the impact of interventions for moderate-to-severe UC on health-related quality of life (HRQL). METHODS We searched Medline, Embase, CENTRAL and grey literature sources through October 2017. We included randomised controlled trials (RCTs) that compared infliximab, adalimumab, golimumab, vedolizumab or tofacitinib to each other or placebo. Outcomes included the change in quality of life scores and the proportion of patients with improvement in quality of life. We performed random-effect pairwise and network meta-analysis. We assessed confidence in estimates using the CINeMA (Confidence in Network Meta-Analysis) framework. RESULTS Fourteen RCTs assessed HRQL using the Inflammatory Bowel Disease Questionnaire (IBDQ) (14 trials), the Short Form questionnaire-36 (SF-36) (seven trials) or the European Quality of Life-5 Dimensions questionnaire (EQ-5D) (three trials). At induction (13 trials), low to very low confidence evidence suggested that all agents significantly improved both generic and disease-specific HRQL scores compared to placebo. However, only infliximab (MD 18.58; 95% CI 13.19-23.97) and vedolizumab (MD 18.00; 95% CI 11.08-24.92) showed clinically meaningful improvement in IBDQ score. Differences among individual interventions were imprecise. For maintenance (four trials), very low confidence evidence suggested that vedolizumab, tofacitinib and adalimumab maintained improvement in HRQL. CONCLUSIONS Induction treatment with infliximab, adalimumab, golimumab, vedolizumab or tofacitinib improves quality of life compared to placebo. Evidence on maintenance therapy is sparse and uncertain. Head-to-head comparisons could enhance confidence in conclusions about differences between drugs in terms of HRQL.

Nonalcoholic fatty liver disease (NAFLD) is the most frequent cause of elevated transaminase levels and affects approximately one third of the general population. Patients with NAFLD are at increased risk for cardiovascular events, which represent the leading cause of death in this population. We discuss the safety and efficacy of statins in this population.We reviewed the most recent literature on the safety of statins in patients with NAFLD and on their effects on liver histology and cardiovascular events.It appears that statins can be safely administered to patients with NAFLD, including those with elevated transaminase levels (3 times the upper limit of normal). Post-hoc analyses of randomized controlled trials also suggest that statins might reduce cardiovascular morbidity in this population. On the other hand, there are few and controversial data on the effects of statins on liver histology in patients with NAFLD.Statins appear to be safe and might also reduce cardiovascular events in patients with NAFLD. Ongoing and future studies will clarify whether statins might also have a role in the treatment of NAFLD.

Aim To assess the efficacy and safety of recently approved once-weekly glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes. Methods We conducted a systematic review and meta-analysis of randomized controlled trials comparing any GLP-1 RA licensed for once-weekly dosing (albiglutide, dulaglutide or exenatide extended release) with placebo or other antidiabetic agents. We searched Medline, Embase, the Cochrane Library and grey literature for articles published up to December 2014 and extracted data in duplicate. Results In our systematic review we included 33 trials with a total of 16 003 participants. Compared with placebo the change in glycated haemoglobin (HbA1c) concentration was −0.66% [six studies; 95% confidence interval (CI) −1.14 to −0.19; I2 = 88%] with albiglutide, and −1.18% (seven studies; 95% CI −1.34 to −1.02; I2 = 65%) with dulaglutide. Based on data from placebo-controlled trials, we did not detect statistically significant weight-sparing benefits for albiglutide or dulaglutide. Compared with other antidiabetic agents, once-weekly GLP-1 RAs outperformed sitagliptin, daily exenatide and insulin glargine in terms of HbA1c-lowering (mean differences −0.40%; 95% CI −0.66 to −0.14; I2 = 85%, −0.44%; 95% CI −0.58 to −0.29; I2 = 40% and −0.28; 95% CI −0.45 to −0.10; I2 = 81%, respectively). The main adverse effects of treatment included gastrointestinal and injection site reactions. Conclusions Given their dosing scheme and overall efficacy and safety profile, once-weekly GLP-1 RAs are a convenient therapeutic option for use as add-on to metformin.

Background The aim of the study was to assess the efficacy and safety of tofacitinib and its impact on quality of life in patients with moderate-to-severe ulcerative colitis. Methods We conducted a systematic review and meta-analysis of randomized controlled trials comparing tofacitinib with placebo or any active comparator. We searched Medline, Embase, the Cochrane Library and gray literature for articles published up to May 2017. We synthesized data using a fixed-effect model. We conducted subgroup analysis based on prior exposure to anti-tumor necrosis factor (TNF). We summarized the strength of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results We included three trials with 1220 participants. Compared with placebo, tofacitinib was effective in inducing clinical remission (odds ratio [OR] 3.84, 95% confidence interval [CI] 2.29-6.44, I2: 41%, GRADE: moderate), clinical response (OR 2.95, 95%CI 2.21-3.95, I2: 0%, GRADE: high), mucosal healing (OR 2.70, 95%CI 1.81-4.03, I2: 0%, GRADE: high). Tofacitinib was effective in both anti-TNF-naive and -experienced patients. Tofacitinib had a favorable effect on quality of life. There were no significant differences in the safety profile in terms of the incidence of any or serious adverse events compared to placebo. The risk for infections was increased (OR 1.51, 95%CI 1.05-2.19, I2: 0%, GRADE: moderate), but the incidence of serious infections did not differ between tofacitinib and placebo. Conclusion In patients with moderate-to-severe ulcerative colitis, short-term treatment with tofacitinib is effective for induction of remission and improvement of quality of life.

Importance The potential role of the fecal immunochemical test (FIT) for screening patients at increased risk for colorectal cancer (CRC) has not yet been elucidated. Objective To assess the diagnostic accuracy of FIT for CRC or advanced neoplasia (AN) in asymptomatic patients at above-average risk. Data Sources MEDLINE, EMBASE, Cochrane Library, and gray literature sources through August 2016. Study Selection Diagnostic studies evaluating the accuracy of FIT for CRC or AN in patients with a personal or familial history of CRC using colonoscopy as the reference standard. Data Extraction and Synthesis Two authors (A.K. and P.P.) independently extracted data and evaluated study quality using the Quality Assessment of Diagnostic Accuracy Studies–2 tool, and evaluated the quality of the body of evidence by means of GRADE (Grading of Recommendations Assessment, Development, and Evaluation). Hierarchical models were used to synthesize available evidence. Main Outcomes and Measures The primary outcome was the diagnostic performance of FIT for detecting CRC or AN. Results We included 12 studies (6204 participants). Seven studies were deemed at high or unclear risk of bias. The average sensitivity of FIT for CRC was 93% (95% CI, 53%-99%), and the average specificity was 91% (95% CI, 89%-92%), yielding a positive likelihood ratio (LR+) of 10.30 (CI 7.7-13.9) and a negative likelihood ratio (LR−) of 0.08 (95% CI, 0.01-0.75) (GRADE: very low). The average sensitivity of FIT for AN was 48% (95% CI, 39%-57%); and the average specificity was 93% (95% CI, 91%-94%), yielding an LR+ of 6.55 (95% CI, 5.0-8.5) and an LR− of 0.57 (95% CI, 0.48-0.67) (GRADE: very low). Subgroup analyses indicated that FIT cutoff values between 15- and 25-μg/g feces provided the best combination of sensitivity and specificity for the diagnosis of CRC (93% and 94%, respectively). Quantitative and 1-sample FIT showed adequate test performance, but data on other FIT brands and multiple samples were insufficient. Conclusions and Relevance The FIT has high overall diagnostic accuracy for CRC but moderate accuracy for AN in patients at above-average personal or familial risk. Heterogeneity and wide confidence intervals limit the trustworthiness of our findings.

Background Emerging evidence suggests that faecal microbiota transplantation (FMT) can induce remission in patients with refractory to standard treatment ulcerative colitis (UC). Methods We performed a systematic review and network meta-analysis to assess the comparative efficacy and safety of FMT and current therapies as induction treatments in UC. We searched Medline, Embase, CENTRAL and grey literature sources up to October 2019. We included randomised controlled trials of patients with active UC that compared FMT, infliximab, adalimumab, golimumab, vedolizumab and tofacitinib to each other or placebo. Efficacy outcomes were clinical remission and response. Safety outcomes were incidence of any adverse event (AE), serious AEs and infections. We conducted random-effects network meta-analysis and ranked treatments based on the surface under the cumulative ranking (SUCRA) probabilities. Results Twenty trials (5177 patients) were included in the analysis. There was only one head to head RCT (vedolizumab vs. adalimumab). FMT was superior to placebo for induction of clinical remission (OR 2.80; 95% CI 1.50–5.23) and response (OR 2.53; 95% CI 1.53–4.20). No indirect comparisons between FMT and licensed treatments reached statistical significance for efficacy outcomes. On SUCRA analysis, FMT (SUCRA 0.57, 0.58) had comparable SUCRA values with golimumab (SUCRA 0.53, 0.39) and vedolizumab (SUCRA 0.58, 0.61) in terms of clinical remission and response respectively. Infliximab (SUCRA 0.71, 0.93) and tofacitinib (SUCRA 0.85, 0.75) were ranked highest while adalimumab (SUCRA 0.23, 0.21) was ranked lowest. There was no increase in the rates of any AEs for FMT and licensed therapies and no differences in indirect comparisons. Vedolizumab (SUCRA 0.81) was the safest option, followed by tofacitinib (SUCRA 0.55). FMT (SUCRA 0.38) had comparable SUCRA values with adalimumab (SUCRA 0.37) and golimumab (SUCRA 0.47). Only tofacitinib increased the incidence of infections compared with placebo (OR 1.51; 95%CI 1.05–2.19). Based on SUCRAs, FMT (SUCRA 0.83) was the safest in terms of infections. Vedolizumab had lower incidence of serious AEs compared with FMT and placebo, while FMT was ranked as the least safe treatment. In subgroup analysis, FMT through the lower gastrointestinal (GI) tract was superior to placebo (OR 3.92; 95%CI 1.94–7.92) and performed numerically better than FMT through the upper GI tract (OR 0.29; 95%CI 0.08–1.13). Conclusion Evidence suggests that FMT could be an efficacious and safe alternative induction therapy for refractory UC. Lower GI delivery of FMT might be more effective. Due to the absence of head-to-head trials and the limited size of FMT trials, conclusions must be interpreted with caution.

Objectives We performed a systematic review and meta-regression analysis of randomized control trials to investigate the association between response to initial treatment and survival outcomes in patients with newly diagnosed multiple myeloma (MM). Methods Response outcomes included complete response (CR) and the combined outcome of CR or very good partial response (VGPR), while survival outcomes were overall survival (OS) and progression-free survival (PFS). We used random-effect meta-regression models and conducted sensitivity analyses based on definition of CR and study quality. Results Seventy-two trials were included in the systematic review, 63 of which contributed data in meta-regression analyses. There was no association between OS and CR in patients without autologous stem cell transplant (ASCT) (regression coefficient: .02, 95% confidence interval [CI] −0.06, 0.10), in patients undergoing ASCT (−.11, 95% CI −0.44, 0.22) and in trials comparing ASCT with non-ASCT patients (.04, 95% CI −0.29, 0.38). Similarly, OS did not correlate with the combined metric of CR or VGPR, and no association was evident between response outcomes and PFS. Sensitivity analyses yielded similar results. Conclusions This meta-regression analysis suggests that there is no association between conventional response outcomes and survival in patients with newly diagnosed MM.

Nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease in Western countries with potential progression to nonalcoholic steatohepatitis (NASH) and cirrhosis, is associated with cardiovascular disease (CVD) mortality. Several studies have reported a relationship between uric acid and NAFLD/NASH and it seems that serum uric acid (SUA) is a significant independent factor for the development of NAFLD. Potential mediating mechanisms include insulin resistance, endothelial dysfunction, and activation of inflammasome, especially NLRP3. Moreover, emerging evidence indicates a strong association between elevated SUA, metabolic syndrome (MetS), NAFLD, and CVD. The emphasis of the present review is whether common therapy of elevated SUA levels and NAFLD can improve compliance. There are several drugs with "off target" properties that show some separate benefit on SUA reduction (e.g. losartan) or NAFLD/NASH (pioglitazone); however, there is no randomized controlled trial (RCT) of a single drug with beneficial outcome for both diseases. Allopurinol reduces SUA levels and ameliorates NAFLD/NASH; however, no RCTs have been performed up to now to explore potential survival benefits. Atorvastatin, which has proven safe in NAFLD/NASH, reduces SUA levels, ameliorates NAFLD/NASH, prevents liver fibrosis, and above all substantially reduces CVD morbidity and mortality in comparison with those on statins but without NAFLD/NASH. This drug could be a solution to improve compliance in both diseases, which are prevalent and becoming even more common with the obesity, MetS, and type 2 diabetes mellitus epidemic.

OBJECTIVE: To assess the efficacy and safety of dipeptidyl peptidase-4 (DPP-4) inhibitors compared with metformin as monotherapy, or with other commonly used hypoglycaemic drugs combined with metformin, in adults with type 2 diabetes mellitus. DESIGN: Systematic review and meta-analysis of randomised controlled trials. DATA SOURCES: Medline, Embase, the Cochrane Library, conference proceedings, trial registers, and drug manufacturers' websites. ELIGIBILITY CRITERIA: Randomised controlled trials of adults with type 2 diabetes mellitus that compared a DPP-4 with metformin as monotherapy or with a sulfonylurea, pioglitazone, a glucagon-like peptide-1 (GLP-1) agonist, or basal insulin combined with metformin on the change from baseline in glycated haemoglobin (HbA(1c)). DATA EXTRACTION: The primary outcome was the change in HbA(1c). Secondary outcomes included the proportion of patients achieving the goal of HbA(1c)

OBJECTIVE To estimate the accuracy of Neuropad for the diagnosis and staging of distal symmetric polyneuropathy (DPN) across different stages of neuropathy, using multiple-level likelihood ratios (LRs) to interpret the time necessary to complete the color change of the test. RESEARCH DESIGN AND METHODS We conducted a cross-sectional, cohort-type diagnostic accuracy study in 251 consecutive adult type 2 diabetic patients with no peripheral arterial disease or other potential causes of neuropathy, who were recruited between January 2005 and December 2008 from the diabetes outpatient clinics in Alexandroupolis Hospital, Greece. Patients were tested for DPN by means of the neuropathy disability score (NDS) and Neuropad. Multiple-level LRs for time to complete color change were calculated across different stages of neuropathy. RESULTS The areas under the curve for the diagnosis of any (NDS of ≥3), at least moderate (NDS of ≥6), or severe (NDS of ≥9) DPN were 0.91, 0.96, and 0.97, respectively. The calculation of multiple-level LRs showed that time to complete color change 1,200 s were strongly suggestive of moderate or severe DPN, respectively. CONCLUSIONS Neuropad could be used as a triage test for the diagnosis and staging of DPN in patients with type 2 diabetes, prompting referral to specialized care setting.

Objective Neuropad is an adhesive indicator test applied at the plantar surface of the foot that detects sweating through color change. We examined the diagnostic accuracy of this simple plaster as triage test for screening for clinically relevant diabetic sensorimotor polyneuropathy in adult outpatients with type 1 or type 2 diabetes. Materials/Methods Systematic review and meta-analysis of diagnostic accuracy studies. We searched Medline, Embase, Cochrane Library, Biosis Previews, Web of Science, Scopus and gray literature without date or language restrictions. We pooled estimates of sensitivity and specificity, and fitted hierarchical models to produce summary receiver operating characteristic curves. We assessed methodological quality of included studies utilizing the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Results Eighteen studies with 3470 participants met the inclusion criteria. Average sensitivity and specificity were 86% (95% CI 79 to 91) and 65% (95% CI 51 to 76) respectively. Likelihood ratios (LRs) were LR + = 2.44 and LR − = 0.22. Subgroup analyses per reference standard utilized provided similar estimates. Most studies were at risk of bias for patient selection and use of index or reference test, and had concerns regarding applicability due to patient selection. Conclusion The adhesive indicator test has reasonable sensitivity and could be used for triage of diabetic neuropathy to rule out foot at risk. Patients who tested positive should be referred to specialized care to establish a definite diagnosis. There is insufficient evidence for effectiveness on patient-important outcomes and cost-effectiveness of implementation in the diagnostic pathway compared with the standard clinical examination.

We appreciate Scheffel and Schaan’s response to our systematic review.1 2 Our meta-analysis provides evidence that dipeptidyl peptidase-4 (DPP-4) inhibitors are indeed inferior to metformin and GLP-1 agonists on the primary endpoint of change in glycated haemoglobin (HbA1c). However, we do not agree with their interpretation of …

Even though tuberculosis is considered rare in developed countries, its rising incidence, especially in high-risk populations, places intestinal tuberculosis in the differential diagnosis of patients with atypical abdominal symptoms or signs. We, herein, report the case of an immunocompetent woman, from a nonendemic area, who developed intestinal tuberculosis, emphasizing the diagnostic challenges caused due to nonspecific symptoms, inconclusive clinical, laboratory, and imaging findings, which could not rule in or rule out tuberculosis. Antituberculosis treatment was administered based on endoscopic findings and histological features of mucosal biopsies, which were indicative of intestinal tuberculosis, and the patient showed a marked clinical and laboratory improvement. We also review the evidence with regard to the diagnostic accuracy of the different available tests for intestinal tuberculosis.

Obesity is a rapidly expanding epidemic in Western societies, with rates of more than 30% across Europe, and it is associated with an increased risk of metabolic disturbances. Previous reports have documented an association of reduced physical activity and abstinence from the traditional Mediterranean diet (MD) with increased mortality rate and prevalence of obesity in a population of Greek subjects.The aim of the present study was to evaluate and analyze the dietary habits in a population of Greek overweight and obese subjects and to investigate the potential associations between those patterns and the prevalence of metabolic syndrome components.The study recruited 226 consecutive adult (30 men, 169 women) overweight or obese (body mass index25 kg/m(2)) individuals attending the Metabolic Diseases Unit. Medical history, dietary history, and anthropometric parameters were recorded during the first visit. Fasting blood samples were collected for biochemistry assaying.According to the nutrient intake history and Mediterranean Diet Scale (MDS), participants were divided into 3 groups: those adhering to the MD and those not following the MD, who were further subdivided into the high-carbohydrate (HC) and high-fat (HF) diet groups according to the source of maximum energy intake. Adherence to the MD was associated with a lower prevalence of metabolic syndrome (27.3%, 69.2%, and 60.4% in MD, HC, and HF respectively, p = 0.006), lower low-density lipoprotein cholesterol (p = 0.009, MD vs. HF), and lower postchallenge glucose values (p = 0.028, MD vs. HF).Adherence to the MD seems to be declining among Greek overweight and obese subjects, a phenomenon that is associated with an increase in the prevalence of the metabolic syndrome.

Background & Aims Guidelines advocate use of magnetic resonance imaging (MRI) to estimate concentrations of iron in liver, to identify patients with iron overload, and to guide titration of chelation therapy. However, this recommendation was not based on a systematic synthesis and analysis of the evidence for MRI's diagnostic accuracy. Methods We conducted a systematic review and meta-analysis to investigate the diagnostic accuracy of MRI in identifying liver iron overload in patients with hereditary hemochromatosis, hemoglobinopathy, or myelodysplastic syndrome; liver biopsy analysis was used as the reference standard. We searched MEDLINE and EMBASE databases, the Cochrane Library, and gray literature, and computed summary receiver operating curves by fitting hierarchical models. We assessed methodologic quality using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Results Our final analysis included 20 studies (819 patients, total). Sensitivity and specificity values varied greatly, ranging from 0.00 to 1.00 and from 0.50 to 1.00, respectively. Because of substantial heterogeneity and variable positivity thresholds, we calculated only summary receiver operating curves (and summary estimate points for studies that used the same MRI sequences). T2 spin echo and T2* gradient-recalled echo MRI sequences accurately identified patients without liver iron overload (liver iron concentration > 7 mg Fe/g dry liver weight) (negative likelihood ratios, 0.10 and 0.05 respectively). However, these MRI sequences are less accurate in establishing a definite diagnosis of liver iron overload (positive likelihood ratio, 8.85 and 4.86, respectively). Conclusions Based on a meta-analysis, measurements of liver iron concentration by MRI may be accurate enough to rule out iron overload, but not to definitely identify patients with this condition. Most studies did not use explicit and prespecified MRI thresholds for iron overload, therefore some patients may have been diagnosed inaccurately with this condition. More studies are needed of standardized MRI protocols and to determine the effects of MRI surveillance on the development of chronic liver disease and patient survival.

Nonalcoholic fatty liver disease (NAFLD) is the commonest liver disease in Western countries. Treatment of NAFLD is currently based on lifestyle measures and no effective pharmacologic treatment is available so far. Emerging evidence, mainly from animal studies, suggests that the renin-angiotensin-aldosterone system may be of major importance in the pathogenesis of NAFLD and indicates that angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARBs) as a potentially useful therapeutic approach. However, data from human studies are limited and contradictory. In addition, there are few randomized controlled trials (RCTs) on the effects of ACE-I or ARB in patients with NAFLD and most data are from retrospective studies, pilot prospective studies and post hoc analyses of clinical trials. Accordingly, more and larger RCTs are needed to directly assess the effectiveness of ACE-I and ARBs in NAFLD.