Comparative efficacy of once-weekly semaglutide and SGLT-2 inhibitors in type 2 diabetic patients inadequately controlled with metformin monotherapy: a systematic literature review and network meta-analysis

<p><b>Objective:</b> Treatment intensification with additional anti-diabetic agents is recommended in type 2 diabetes (T2D) for patients inadequately controlled on metformin monotherapy. The present network meta-analysis (NMA) evaluated comparative efficacy and safety of once-weekly semaglutide and sodium-glucose co-transporter 2 inhibitors (SGLT-2is) in T2D patients inadequately controlled with metformin.</p> <p><b>Methods:</b> Randomized controlled trials with ≥20 weeks duration were searched in EMBASE, MEDLINE, and CENTRAL. Primary efficacy outcomes were: change from baseline in HbA_1c, weight, systolic blood pressure (SBP), post-prandial blood glucose (PPG), and fasting blood glucose (FPG). Treatment effects at 26 (±4) weeks were compared using Bayesian NMAs. Meta-regression and sensitivity analysis were used to address the trial heterogeneity.</p> <p><b>Results:</b> Eight trials were found eligible for this NMA. Statistically significant reductions in HbA1c were observed with both 1.0 mg and 0.5 mg doses of once-weekly semaglutide when compared to SGLT-2is. The mean differences in change from baseline in HbA_1c for once-weekly semaglutide 1.0 mg vs SGLT-2is ranged from −0.66% for canagliflozin 300 mg (95% Credible Intervals [CrI]: −0.82, −0.50%) to −1.11% for dapagliflozin 5 mg (95% CrI: −1.37, −0.85%). Once-weekly semaglutide 1.0 mg performed significantly better than all SGLT-2is of interest in reducing weight and improving FPG levels: however, SBP reduction was not statistically differentiable. Results of sensitivity analysis and meta-regressions aligned with base-case results. NMAs were not possible for PPG and safety outcomes, due to lack of data.</p> <p><b>Conclusion:</b> Once-weekly semaglutide treatment is significantly better compared to SGLT-2is in achieving adequate glycemic control in T2D patients inadequately controlled with metformin monotherapy.</p

Diagnostic utility of a line probe assay for multidrug resistant-TB in smear-negative pulmonary tuberculosis

<div><p>Objective</p><p>To evaluate the performance of Genotype MTBDRplus VER 2.0 in the diagnosis of <i>Mycobacterium tuberculosis</i> (MTB) in sputum smear-negative pulmonary TB cases.</p><p>Methods</p><p>A total of 572 Ziehl-Neelsen sputum smear-negative samples were selected and subjected to line probe assay (Genotype MTBDRplus VER 2.0), and culture in mycobacterial growth indicator tube (MGIT-960). Immunochromatographic test was used to confirm the MTB-complex (MTBC) in culture-positive samples and phenotypic drug-susceptibility testing was done using MGIT-960.</p><p>Results</p><p>The line probe assay was able to diagnose MTBC in 38.2% (213/558) of specimens after excluding 14 nontuberculous mycobacteria. Sensitivity and specificity of the assay were 68.4% and 89.3% respectively, considering MGIT-960 culture as gold standard after excluding contaminated and invalid results. On comparing with composite reference standard, the assay had 71.5% sensitivity and 100% specificity in the diagnosis of tuberculosis. The sensitivity and specificity for detecting resistance to rifampicin (RMP) were 100% and 99.24% respectively and for resistance to isoniazid (INH) were 97.62% and 98.55%, respectively.</p><p>Conclusion</p><p>Genotype MTBDRplus VER 2.0 is a rapid and precise diagnostic tool for detection of MTB in sputum smear-negative samples. It also facilitates accurate diagnosis of RMP and INH resistance within turn around-time.</p></div

Diagnostic accuracy of LPA version 2.0 with and without CRS.

<p>Diagnostic accuracy of LPA version 2.0 with and without CRS.</p

Study Design.

<p>*A total of 47 cultures were contaminated including three samples with invalid result by Xpert MTB/RIF and one sample with error by Xpert MTB/RIF. Two other samples which gave “error” by Xpert MTB/RIF were culture negative but were excluded from the study.</p

Rifampin susceptibility testing by Xpert MTB/RIF and phenotypic DST.

<p>Sensitivity<b>-</b> 94.5% (88.6–97.4)</p><p>Specificity<b>-</b> 97.7% (95.4–98.9)</p><p>Positive Predictive Value- 93.6% (87.5–96.9)</p><p>Negative Predictive Value- 98.0% (95.8–99.1)</p><p>Data are presented as whole numbers. RIF- Rifampin, DST- Drug susceptibility testing</p><p>Rifampin susceptibility testing by Xpert MTB/RIF and phenotypic DST.</p

Pattern of gene mutations in <i>Mycobacterium tuberculosis</i> strains using LPA version 2.0.

<p>Pattern of gene mutations in <i>Mycobacterium tuberculosis</i> strains using LPA version 2.0.</p

Performance parameter of LPA version 2.0.

<p>Performance parameter of LPA version 2.0.</p

Diagnostic performance of Xpert MTB/RIF assay in different respiratory samples.

<p>PPV-Positive predictive value, NPV- Negative predictive value. Values in parantheses are 95% confidence intervals</p><p>Diagnostic performance of Xpert MTB/RIF assay in different respiratory samples.</p

DataSheet1_Sorafenib increases cytochrome P450 lipid metabolites in patient with hepatocellular carcinoma.PDF

Hepatocellular carcinoma (HCC) is a leading cause of cancer death, and medical treatment options are limited. The multikinase inhibitor sorafenib was the first approved drug widely used for systemic therapy in advanced HCC. Sorafenib might affect polyunsaturated fatty acids (PUFA)-derived epoxygenated metabolite levels, as it is also a potent inhibitor of the soluble epoxide hydrolase (sEH), which catalyzes the conversion of cytochrome-P450 (CYP)-derived epoxide metabolites derived from PUFA, such as omega-6 arachidonic acid (AA) and omega-3 docosahexaenoic acid (DHA), into their corresponding dihydroxy metabolites. Experimental studies with AA-derived epoxyeicosatrienoic acids (EETs) have shown that they can promote tumor growth and metastasis, while DHA-derived 19,20-epoxydocosapentaenoic acid (19,20-EDP) was shown to have anti-tumor activity in mice. In this study, we found a significant increase in EET levels in 43 HCC patients treated with sorafenib and a trend towards increased levels of DHA-derived 19,20-EDP. We demonstrate that the effect of sorafenib on CYP- metabolites led to an increase of 19,20-EDP and its dihydroxy metabolite, whereas DHA plasma levels decreased under sorafenib treatment. These data indicate that specific supplementation with DHA could be used to increase levels of the epoxy compound 19,20-EDP with potential anti-tumor activity in HCC patients receiving sorafenib therapy.</p

Representative patterns of line probe assay (GenoType MTBDR-plus) strip.

<p>Lane 1, susceptible to rifampicin (RIF) and isoniazid (INH); Lane 2, MDR- TB (<i>rpoB</i> S531L mutation and<i>inhA</i> C15T mutation); Lane 3, rifampicin monoresistant (mutation at rpoB530–533 gene region); Lane 4, absence of TUB band; Lan 5, isoniazid monoresistant (<i>katG</i> S315T1 mutation); Lane 6, DNA positive control (sensitive to rifampicin and isoniazid); Lane 7, DNA negative control.</p