Paschalis Paschos

Dipeptidyl peptidase-4 inhibitors for treatment of type 2 diabetes mellitus in the clinical setting: systematic review and meta-analysis.

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 (HbA1c). Data extraction The primary outcome was the change in HbA1c. Secondary outcomes included the proportion of patients achieving the goal of HbA1c <7%, the change in body weight, discontinuation rate because of any adverse event, occurrence of any serious adverse event, all cause mortality, and incidence of hypoglycaemia, nasopharyngitis, urinary tract infection, upper respiratory infection, nausea, vomiting, and diarrhoea. Results 27 reports of 19 studies including 7136 patients randomised to a DPP-4 inhibitor and 6745 patients randomised to another hypoglycaemic drug were eligible for the systematic review and meta-analysis. Overall risk of bias for the primary outcome was low in three reports, unclear in nine, and high in 14. Compared with metformin as monotherapy, DPP-4 inhibitors were associated with a smaller decline in HbA1c (weighted mean difference 0.20, 95% confidence interval 0.08 to 0.32) and in body weight (1.5, 0.9 to 2.11). As a second line treatment, DPP-4 inhibitors were inferior to GLP-1 agonists (0.49, 0.31 to 0.67) and similar to pioglitazone (0.09, −0.07 to 0.24) in reducing HbA1c and had no advantage over sulfonylureas in the attainment of the HbA1c goal (risk ratio in favour of sulfonylureas 1.06, 0.98 to 1.14). DPP-4 inhibitors had a favourable weight profile compared with sulfonylureas (weighted mean difference −1.92, −2.34 to −1.49) or pioglitazone (−2.96, −4.13 to −1.78), but not compared with GLP-1 agonists (1.56, 0.94 to 2.18). Only a minimal number of hypoglycaemias were observed in any treatment arm in trials comparing a DPP-4 inhibitor with metformin as monotherapy or with pioglitazone or a GLP-1 agonist as second line treatment. In most trials comparing a DPP-4 inhibitor with sulfonylureas combined with metformin, the risk for hypoglycaemia was higher in the group treated with a sulfonylurea. Incidence of any serious adverse event was lower with DPP-4 inhibitors than with pioglitazone. Incidence of nausea, diarrhoea, and vomiting was higher in patients receiving metformin or a GLP-1 agonist than in those receiving a DPP-4 inhibitor. Risk for nasopharyngitis, upper respiratory tract infection, or urinary tract infection did not differ between DPP-4 inhibitors and any of the active comparators. Conclusion In patients with type 2 diabetes who do not achieve the glycaemic targets with metformin alone, DPP-4 inhibitors can lower HbA1c, in a similar way to sulfonylureas or pioglitazone, with neutral effects on body weight. Increased unit cost, which largely exceeds that of the older drugs, and uncertainty about their long term safety, however, should also be considered.

Nonalcoholic fatty liver disease and the renin-angiotensin system: Implications for treatment

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.

Nonalcoholic fatty liver disease and statins

OBJECTIVE 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. MATERIALS/METHODS 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. RESULTS 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. CONCLUSIONS 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.

The protective role of the Mediterranean diet on the prevalence of metabolic syndrome in a population of Greek obese subjects.

Background: 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. Objective: 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. Methods: The study recruited 226 consecutive adult (30 men, 169 women) overweight or obese (body mass index >25 kg/m2) 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. Results: 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). Conclusions: 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.

Efficacy and safety of once‐weekly glucagon‐like peptide 1 receptor agonists for the management of type 2 diabetes: a systematic review and meta‐analysis of randomized controlled trials

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.

Intestinal tuberculosis: a diagnostic challenge--case report and review of the literature.

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.

Accuracy of the Neuropad Test for the Diagnosis of Distal Symmetric Polyneuropathy in Type 2 Diabetes

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 <360 s suggested the absence of neuropathy. Values between 360 and 1,000 s were indicative of mild neuropathy. Finally, values between 1,000 and 1,200 or >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.

Accuracy of Magnetic Resonance Imaging in Diagnosis of Liver Iron Overload: A Systematic Review and Meta-analysis

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 MRIs 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.

A simple plaster for screening for diabetic neuropathy: A diagnostic test accuracy systematic review and meta-analysis

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.

Diagnostic Accuracy of Fecal Immunochemical Test in Patients at Increased Risk for Colorectal Cancer: A Meta-analysis

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-&mgr;g/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.