New anti-diabetic agents for the treatment of non-alcoholic fatty liver disease: a systematic review and network meta-analysis of randomized controlled trials

ObjectivesThis network meta-analysis aims to compare the efficacy and safety of new anti-diabetic medications for the treatment of non-alcoholic fatty liver disease (NAFLD).Materials and methodsPubMed and Scopus were searched from inception to 27th March 2022 to identify all randomized controlled trials (RCTs) in NAFLD patients. Outcomes included reductions in intrahepatic steatosis (IHS) and liver enzyme levels. The efficacy and safety of DPP-4 inhibitors, GLP-1 agonists, SGLT-2 inhibitors, and other therapies were indirectly compared using a NMA approach. Unstandardized mean difference (USMD) with 95% confidence intervals (CI) were calculated.Results2,252 patients from 31 RCTs were included. “Add-on” GLP-1 agonists with standard of care (SoC) treatment showed significantly reduced IHS compared to SoC alone [USMD (95%CI) -3.93% (-6.54%, -1.33%)]. Surface under the cumulative ranking curve (SUCRA) identified GLP-1 receptor agonists with the highest probability to reduce IHS (SUCRA 88.5%), followed by DPP-4 inhibitors (SUCRA 69.6%) and pioglitazone (SUCRA 62.2%). “Add-on” GLP-1 receptor agonists were also the most effective treatment for reducing liver enzyme levels; AST [USMD of -5.04 (-8.46, -1.62)], ALT [USMD of -9.84 (-16.84, -2.85)] and GGT [USMD of -15.53 (-22.09, -8.97)] compared to SoC alone. However, GLP-1 agonists were most likely to be associated with an adverse event compared to other interventions.ConclusionGLP-1 agonists may represent the most promising anti-diabetic treatment to reduce hepatic steatosis and liver enzyme activity in T2DM and NAFLD patients. Nevertheless, longer-term studies are required to determine whether this delays progression of liver cirrhosis in patients with NAFLD and T2DM.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42021259336.1

Quality of life after great saphenous vein ablation in Thai patients with great saphenous vein reflux

SummaryBackground/ObjectiveTo determine the quality of life (QoL) in Thais after intervention for great saphenous vein (GSV) reflux.MethodsPatients with Clinical Etiologic Anatomic Pathophysiologic classes 2 and 3 were enrolled in this study. QoL was measured using the EuroQol descriptive system (EQ-5D) questionnaire, and patients chose to receive either endovenous treatment or surgery after consulting with their surgeons. The QoL before the intervention, at 1 week, and at 1 month after the intervention were evaluated. Patients who reported “no problem” in each domain of the EQ-5D questionnaire before and 1 month after the intervention were compared. Utility gain was estimated from the questionnaire and compared between clinical classes. The proportion of worsening QoL at 1 week after the intervention was compared between patients receiving endovenous procedures and surgery.ResultsA total of 83 patients—56 received endovenous procedures [23 received ultrasound-guided foam sclerotherapy (UGFS) and 33 received radiofrequency ablation (RFA)] and 27 received surgery—were enrolled. QoLs were significantly better in all domains after the intervention: pain/discomfort (58%), mobility (42%), anxiety/depression (38%), usual activities (19%), and self-care (9%). Utility gain was 0.255 (95% confidence interval: 0.197–0.313) and higher in class 3. At 1 week after the intervention, surgery had significantly higher patients with worse mobility scores. Among endovenous procedures, UGFS had higher patients with worse pain/discomfort scores than RFA at 1 week after the intervention (16% vs. 0%, p = 0.025).ConclusionGSV ablation for GSV reflux in Thai patients with CEAP C2 and C3 categories significantly improves both physical and mental QoL; patients who received endovenous procedures were found to have better early physical QoL

Effect of immediate neonatal zidovudine on prevention of vertical transmission of human immunodeficiency virus type 1

AbstractObjectives: To describe the effects of various short zidovudine (ZDV) prophylactic regimens on vertical transmission of human immunodeficiency virus type 1 (HIV-1) infection, especially the effect of immediate neonatal ZDV prophylaxis.Materials and Methods: The study included children of HIV-1-infected mothers who were born at a teaching hospital in Bangkok. The ZDV prophylaxis regimens varied by time periods that included: (1) no ZDV (1991–1996); (2) antenatal oral ZDV, 250 mg given twice a day starting at 34 to 36 weeks' gestation and continued until labor (1995–1998); (3) antenatal oral ZDV plus immediate neonatal oral ZDV, 6 mg/0.6 mL/dose started within the first 2 hours after birth and continued at 6-hour intervals for 4 to 6 weeks (1997–1998); and (4) intrapartum intravenous ZDV given in addition to regimen 3 (1998–1999). Neonatal ZDV was administered within 2 hours after birth in 95% of the neonates.Results: In a cohort of 136 children born at least 9 months before the analysis date, the HIV-1 vertical infection rates were: (1) no ZDV, 11 of 48 (22.9%, 95% confidence interval [Cl] = 12.0–37.3); (2) late antenatal ZDV, 10 of 47 (21.3%, 95% Cl = 10.7–35.7); (3) late antenatal ZDV plus immediate neonatal ZDV, 0 of 28 (0%, 95% Cl = 0–12.3); (4) late antenatal, intrapartum intravenous ZDV, plus immediate neonatal ZDV, 0 of 13 (0%, 95% Cl = 0–24.7). An estimated 0% (95% Cl = 0–8.6) of the infants who received immediate neonatal ZDV with or without intrapartum ZDV were infected, as compared with 22.1% (95% Cl = 14.2–31.8 ) of those who received no ZDV or only late antenatal ZDV (P < 0.001).Conclusion: The results of this study suggests high protective effect of immediate administration of neonatal ZDV. Perinatal components of antiretroviral prophylaxis provided the best results for protecting against vertical HIV-1 transmission

Cost-utility analysis of direct-acting antivirals for treatment of chronic hepatitis C genotype 1 and 6 in Vietnam

Objective: Very few cost-utility analyses have either evaluated direct-acting antivirals (DAAs) on hepatitis C virus (HCV) genotype 6 patients or undertaken societal perspective. Recently, DAAs have been introduced into the Vietnamese health insurance drug list for chronic hepatitis C (CHC) treatment without empirical cost-effectiveness evidence. This study was conducted to generate these data on DAAs among CHC patients with genotypes 1 and 6 in Vietnam. Methods: A hybrid decision-tree and Markov model was employed to compare costs and quality-adjusted life-years (QALYs) of available DAAs, including (1) sofosbuvir/ledipasvir, (2) sofosbuvir/velpatasvir, and (3) sofosbuvir plus daclatasvir, with pegylated-interferon plus ribavirin (PR). Primary data collection was conducted in Vietnam to identify costs and utility values. Incremental cost-effectiveness ratios were estimated from societal and payer perspectives. Uncertainty and scenario analyses and value of information analyses were performed. Results: All DAAs were cost-saving as compared with PR in CHC patients with genotypes 1 and 6 in Vietnam, and sofosbuvir/velpatasvir was the most cost-saving regimen, from both societal and payer perspectives. From the societal perspective, DAAs were associated with the increment of quality-adjusted life-years by 1.33 to 1.35 and decrement of costs by $6519 to$7246. Uncertainty and scenario analyses confirmed the robustness of base-case results, whereas the value of information analyses suggested the need for further research on relative treatment efficacies among DAA regimens. Conclusions: Allocating resources for DAA treatment for HCV genotype 1 and 6 is surely a rewarding public health investment in Vietnam. It is recommended that the government rapidly scale up treatment and enable financial accessibility for HCV patients

Work- and Travel-related Physical Activity and Alcohol Consumption: Relationship With Bone Mineral Density and Calcaneal Quantitative Ultrasonometry

AbstractA number of healthy workers rarely exercise because of a lack of time or resources. Physical activity related to work and everyday travel may be more feasible, but evidence of its beneficial effect on bone health is scarce. We assessed if this form of physical activity was associated with higher bone mineral density (BMD) and stiffness index (SI) when adjusted for recreational physical activity, age, body mass index, smoking, alcohol consumption, education, and serum level of 25-hydroxyvitamin D. Healthy workers, aged 25–54 yr, of the Electricity Generating Authority of Thailand were surveyed. The outcomes were BMD (lumbar spine, femoral neck, and total hip) and calcaneal SI. Physical activity was estimated using the global physical activity questionnaire and considered active when >600 metabolic equivalent tasks (min). Of 2268 subjects, 74% were men. Active male subjects had significantly higher BMD at the femoral neck and total hip (p < 0.005). However, the association was not significant with male lumbar spine BMD, male SI, or any bone parameters in women (p > 0.05). In men, work and travel physical activity seems beneficial to male bone health; hence, it should be encouraged. Furthermore, smoking appeared harmful while moderate alcohol consumption was beneficial

Comparative cardiovascular benefits of individual SGLT2 inhibitors in type 2 diabetes and heart failure: a systematic review and network meta-analysis of randomized controlled trials

BackgroundIn patients with type 2 diabetes (T2D) and a history of heart failure (HF), sodium–glucose cotransporter-2 inhibitors (SGLT2is) have demonstrated cardiovascular (CV) benefits. However, the comparative efficacy of individual SGLT2is remains uncertain. This network meta-analysis (NMA) compared the efficacy and safety of five SGLT2is (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, and sotagliflozin) on CV outcomes in these patients.Materials and methodsPubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched up to September 23, 2022, to identify all randomized controlled trials (RCTs) comparing SGLT2is to placebo in T2D patients with HF. The main outcomes included composite CV death/heart failure hospitalization (HFH), HFH, CV death, all-cause mortality, and adverse events. Pairwise and NMA approaches were applied.ResultsOur analysis included 11 RCTs with a total of 20,438 patients with T2D and HF. All SGLT2is significantly reduced HFH compared to standard of care (SoC) alone. “Add-on” SGLT2is, except ertugliflozin, significantly reduced composite CV death/HFH relative to SoC alone. Moreover, canagliflozin had lower composite CV death/HFH compared to dapagliflozin. Based on the surface under the cumulative ranking curve (SUCRA), the top-ranked SGLT2is for reducing HFH were canagliflozin (95.5%), sotagliflozin (66.0%), and empagliflozin (57.2%). Head-to-head comparisons found no significant differences between individual SGLT2is in reducing CV death. “Add-on” SGLT2is reduced all-cause mortality compared with SoC alone, although only dapagliflozin was statistically significant. No SGLT2is were significantly associated with serious adverse events. A sensitivity analysis focusing on HF-specific trials found that dapagliflozin, empagliflozin, and sotagliflozin significantly reduced composite CV death/HFH, consistent with the main analysis. However, no significant differences were identified from their head-to-head comparisons in the NMA. The SUCRA indicated that sotagliflozin had the highest probability of reducing composite CV death/HFH (97.6%), followed by empagliflozin (58.4%) and dapagliflozin (44.0%).ConclusionSGLT2is significantly reduce the composite CV death/HFH outcome. Among them, canagliflozin may be considered the preferred treatment for patients with diabetes and a history of heart failure, but it may also be associated with an increased risk of any adverse events compared to other SGLT2is. However, a sensitivity analysis focusing on HF-specific trials identified sotagliflozin as the most likely agent to reduce CV death/HFH, followed by empagliflozin and dapagliflozin.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022353754

Germline Missense Changes in the APC Gene and Their Relationship to Disease

Familial adenomatous polyposis (FAP) is characterized by the presence of hundreds to thousands of adenomas that carpet the entire colon and rectum. Nonsense and frameshift mutations in the adenomatous polyposis coli (APC) gene account for the majority of mutations identified to date and predispose primarily to the typical disease phenotype. Some APC mutations are associated with a milder form of the disease known as attenuated FAP. Virtually all mutations that have been described in the APC gene result in the formation of a premature stop codon and very little is known about missense mutations apart from a common Ashkenazi Jewish mutation (1307 K) and a British E1317Q missense change. The incidence of missense mutations in the APC gene has been underreported since the APC gene lends itself to analysis using an artificial transcription and translation assay known as the Protein Truncation Test (PTT) or the In Vitro Synthetic Protein assay (IVSP)

Utility of coronary artery calcium in refining 10-year ASCVD risk prediction using a Thai CV risk score

BackgroundCoronary artery calcium (CAC) scanning is a valuable additional tool for calculating the risk of cardiovascular (CV) events. We aimed to determine if a CAC score could improve performance of a Thai CV risk score in prediction of 10-year atherosclerotic cardiovascular disease (ASCVD) risk for asymptomatic patients with CV risk factors.MethodsThis was a retrospective cohort study that enrolled asymptomatic patients with CV risk factors who underwent CAC scans between 2005 and 2013. The patients were classified as low-, intermediate-, or high-risk (&lt;10%, 10%–&lt;20%, and ≥20%, respectively) of having ASCVD within 10-years based on a Thai CV risk score. In each patient, CAC score was considered as a categorical variable (0, 1–99, and ≥100) and natural-log variable to assess the risk of developing CV events (CV death, non-fatal MI, or non-fatal stroke). The C statistic and the net reclassification improvement (NRI) index were applied to assess whether CAC improved ASCVD risk prediction.ResultsA total of 6,964 patients were analyzed (mean age: 59.0 ± 8.4 years; 63.3% women). The majority of patients were classified as low- or intermediate-risk (75.3% and 20.5%, respectively), whereas only 4.2% were classified as high-risk. Nearly half (49.7%) of patients had a CAC score of zero (no calcifications detected), while 32.0% had scores of 1–99, and 18.3% of ≥100. In the low- and intermediate-risk groups, patients with a CAC ≥100 experienced higher rates of CV events, with hazard ratios (95% CI) of 1.95 (1.35, 2.81) and 3.04 (2.26, 4.10), respectively. Incorporation of ln(CAC + 1) into their Thai CV risk scores improved the C statistic from 0.703 (0.68, 0.72) to 0.716 (0.69, 0.74), and resulted in an NRI index of 0.06 (0.02, 0.10). To enhance the performance of the Thai CV risk score, a revision of the CV risk model was performed, incorporating ln(CAC + 1), which further increased the C statistic to 0.771 (0.755, 0.788).ConclusionThe addition of CAC to traditional risk factors improved CV risk stratification and ASCVD prediction. Whether this adjustment leads to a reduction in CV events and is cost-effective will require further assessment