Cost-effectiveness of cholecystectomy compared to conservative management in people presenting with uncomplicated symptomatic gallstones or cholecystitis in India.

OBJECTIVES: Gallstone diseases impose a significant economic burden on the health care system; thus, determining cost-effective management for gallstones is essential. We aim to estimate the cost-effectiveness of cholecystectomy compared with conservative management in individuals with uncomplicated symptomatic gallstones or cholecystitis in India. METHODS: A decision-analytic Markov model was used to compare the costs and QALY of early laparoscopic cholecystectomy (ELC), delayed laparoscopic cholecystectomy (DLC), and conservative management (CM) in patients with symptomatic uncomplicated gallstone/cholecystitis from an Indian health system perspective. Incremental cost-effectiveness ratio (ICER) was calculated. One-way and probabilistic sensitivity analyses were performed to test parameter uncertainties. RESULTS: ELC and DLC, compared to CM, incurred an incremental cost of -₹10,948 ($146) and ₹1,054 ($14) for the 0.032 QALYs gained. The ICER was -₹3,42,758 ($4577) for ELC vs. CM, and ₹33,183 ($443) for DLC vs. CM, suggesting ELC and DLC are cost-effective. ELC saved ₹12,001 ($160) for 0.0002 QALYs gained compared to DLC, resulting in an ICER of -₹6,43,89,441 ($8,59,733). The results were robust to changes in the input parameters in sensitivity analyses. CONCLUSION: ELC is dominant compared to both DLC and CM, and DLC is more cost-effective than CM. Thus, ELC may be preferable to other gallstone disease managements.

Systematic review and meta-analysis of gallstone disease treatment outcomes in early cholecystectomy versus conservative management/delayed cholecystectomy.

BACKGROUND: The effectiveness of early cholecystectomy for gallstone diseases treatment is uncertain compared with conservative management/delayed cholecystectomy. AIMS: To synthesise treatment outcomes of early cholecystectomy versus conservative management/delayed cholecystectomy in terms of its safety and effectiveness. DESIGN: We systematically searched randomised control trials investigating the effectiveness of early cholecystectomy compared with conservative management/delayed cholecystectomy. We pooled the risk ratios with a 95% CI, also estimated adjusted number needed to treat to harm. RESULTS: Of the 40 included studies for systematic review, 39 studies with 4483 patients are included in meta-analysis. Among the risk ratios of gallstone complications, pain (0.38, 0.20 to 0.74), cholangitis (0.52, 0.28 to 0.97) and total biliary complications (0.33, 0.20 to 0.55) are significantly lower with early cholecystectomy. Adjusted number needed to treat to harm of early cholecystectomy compared with conservative management/delayed cholecystectomy are, for pain 12.5 (8.3 to 33.3), biliary pancreatitis >1000 (50-100), common bile duct stones 100 (33.3 to 100), cholangitis (100 (25-100), total biliary complications 5.9 (4.3 to 9.1) and mortality >1000 (100 to100 000). CONCLUSIONS: Early cholecystectomy may result in fewer biliary complications and a reduction in reported abdominal pain than conservative management. PROSPERO REGISTRATION NUMBER: 2020 CRD42020192612.

Fluorinated 2'-hydroxychalcones as garcinol analogs with enhanced antioxidant and anticancer activities.

Chalcones are involved in the synthesis of flavonoids and are themselves known to exhibit multiple pharmacological properties. However, compared to other structurally similar phytochemicals like garcinol and curcumin, the therapeutic use of chalcones is limited because of their lower bioavailability and rapid metabolic clearance from biological system. In the present work, we have attempted to overcome these limitations in case of 2'-hydroxychalcones through bioisosteric substitution of fluoro groups in place of phenolic hydroxyls. The fluorinated chalcones were found to be more potent antioxidant and anti-proliferative compounds than their hydroxyl counterparts indicating the influence of metabolically stable C-F bonds towards bioavailability. The difluoro derivatives were found to be most effective against human pancreatic BxPC-3 cancer cells which possess up-regulated COX-2 expression and also showed activity against human breast cancer BT-20 cells with triple negative phenotype, suggesting that these compounds will have broader application in the future.

Emerging role of Garcinol, the antioxidant chalcone from Garcinia indica Choisy and its synthetic analogs.

Garcinol, harvested from Garcinia indica, has traditionally been used in tropical regions and appreciated for centuries; however its biological properties are only beginning to be elucidated. There is ample data to suggest potent antioxidant properties of this compound which have been used to explain most of its observed biological activities. However, emerging evidence suggests that garcinol could be useful as an anti-cancer agent, and it is increasingly being realized that garcinol is a pleiotropic agent capable of modulating key regulatory cell signaling pathways. Here we have summarized the progress of our current research knowledge on garcinol and its observed biological activities. We have also provided an explanation of observed properties based on its chemical structure and provided an insight into the structure and properties of chalcones, the precursors of garcinol. The available data is promising but more detailed investigations into the various properties of this compound, particularly its anti-cancer activity are urgently needed, and it is our hope that this review will stimulate further research for elucidating and appreciating the value of this nature's wonder agent.