An indirect comparison of efficacy including histologic assessment and safety in biologic therapy in ulcerative colitis: Systemic review and network meta-analysis.

BACKGROUNDS AND AIMS: There are currently no studies comparing histologic remission of FDA-approved biologics for moderate to severe ulcerative colitis (UC), except for one head-to-head VARSITY trial. The current study employs a network meta-analysis to compare the efficacy, including histologic remission and safety of biologic agents for UC. METHODS: Using four electronic databases, including Pubmed, EMBASE, The Cochrane Library, and ClinicalTrials.gov, a search was conducted of all literature published until September 2022. Included were studies of randomized controlled trials with adult patients with moderate to severe UC using biologics approved by the FDA. An odd ratio with a 95 percent credible interval and ranking information was calculated for each endpoint. RESULTS: The results of the network meta-analysis did not reveal statistically significant differences among biological agents. However, the ranking information for each biological agent exhibited the following patterns. Vedolizumab was ranked first for overall efficacy endpoints in the maintenance phase, including histologic remission. Except for histologic remission, Ustekinumab was identified as the top-ranked drug for induction phase efficacy endpoints other than histologic remission. Adalimumab was identified as the top-ranked drug for maintenance phase corticosteroid-free remission. Vedolizumab was identified as the top-ranked drug in the induction phase for Treatment Emergent Adverse Events (TEAE). Adalimumab was identified as the top-ranked drug in the induction phase for infection. For TEAE and infection in the maintenance phase and Treatment Emergent Severe Adverse Events (TESAE) in both the induction and maintenance phases, Ustekinumab was determined to be the top-ranked medication. CONCLUSIONS: Including histologic remission, for the overall efficacy endpoints in the maintenance phase, VDZ was identified as the first rank drug, but there was no statistically significant difference between biologics. Therefore, the generalization of the results of this study is bounded due to the intrinsic limitations of the study provided.

Effect of Low FODMAPs Diet on Irritable Bowel Syndromes: A Systematic Review and Meta-Analysis of Clinical Trials.

We conducted a meta-analysis exploring the effect of a low fermentable oligo-, di-, monosaccharides, and polyols diet (LFD) on the overall symptoms, quality of life, and stool habits of irritable bowel syndrome (IBS) patients. The meta-analysis was performed using a random-effects method. The effect size was presented as weighted standardized mean difference (SMD) and 95% confidence interval (CI). Subgroup analyses were conducted to determine the potential effects of covariates on the outcome. Twenty-two papers were included. The LFD group showed a moderate reduction in symptom severity and a slight improvement in quality of life compared to the control group (SMD, -0.53 and 0.24; 95% CI, -0.68, -0.38 and 0.02, 0.47, respectively). IBS symptom improvement was consistent between subgroups stratified according to proportions of female patients, study durations, IBS subtypes, assessment methods, and control interventions. Three studies regarding stool habits change in IBS-D patients showed a significant decrease in stool frequency (mean differences [MD], -5.56/week; 95% CI, -7.40, -3.72) and a significant improvement in stool consistency (MD, -0.86; 95% CI, -1.52, -0.19) in the LFD group compared to the control group. This is the most updated meta-analysis including studies that adopted diverse control interventions such as dietary interventions, supplementation, habitual diets, and lifestyle changes.

Application of a drug-interaction detection method to the Korean National Health Insurance claims database.

Drug interactions (DIs) constitute a serious problem and are considered to contribute to 6-30% of all adverse events (AEs). The use of existing data, including claims data, is expected to be helpful in detecting unknown DIs by complementing conventional spontaneous reporting systems. In the present study, an 'Ω shrinkage measure' was applied to the Korean National Health claims database to test the potential of the claims database as a DI surveillance resource. A well-known DI between non-steroidal anti-inflammatory drugs (NSAIDs) and diuretics was analyzed using the model. International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) codes related to DIs were assigned to the AEs of the DIs: I50, I50.0, I50.1, I50.9, R60, R60.1, R60.9, and J81. An elevated occurrence of AEs versus the expected level was observed using a two-sided 95% lower credibility interval limit above zero, Ω025=0.245, which was the screening limit. The result was consistent with the actual DI between the two drugs. The finding indicates that the claims data have the potential to be used as a DI surveillance resource and that the Ω shrinkage measure may be a promising tool for detecting DIs in claims data.

Protective effects of vitamin E on chemotherapy-induced peripheral neuropathy: a meta-analysis of randomized controlled trials.

PURPOSE: This study aimed to investigate the neuroprotective effects of vitamin E for preventing chemotherapy-induced peripheral neuropathy (CIPN). METHODS: A comprehensive search from 1973 through July 2011 identified randomized controlled trials (RCTs) that reported the preventive effects of vitamin E on CIPN. The relative risk (RR) of CIPN with vitamin E supplementation, compared with placebo, was assessed with the Bayesian random effect model and expressed as RR with a 95 % credible-interval (CrI). Bayesian outcome probabilities were calculated as the probability (P) of RR < 1. RESULTS: Five RCTs, involving 319 patients, were identified. Upon pooling these RCTs, vitamin E supplementation (300 - 600 mg/day) had a significant effect on CIPN prevention (RR 0.43; 95 % CrI 0.10 - 1.00, P = 97.5 %). Subgroup analysis by chemotherapeutic agent type was only available for cisplatin and showed that vitamin E supplementation significantly reduced the incidence of CIPN (RR 0.26; 95 % CrI 0.06 - 0.89, P = 98.1 %). Furthermore, there were no adverse effects caused by vitamin E supplementation in any of the RCTs. CONCLUSION: Available data included in this meta-analysis show that vitamin E supplementation might significantly prevent CIPN. Currently, however, the data are insufficient to confidently conclude the true value. Large-scale, rigorously designed RCTs are needed to confirm the role of vitamin E supplementation in CIPN prevention.

Protective effects of Haematococcus astaxanthin on oxidative stress in healthy smokers.

Free radicals induced by cigarette smoking have been strongly linked to increased oxidative stress in vivo, contributing to the pathobiology of various diseases. This study was performed to investigate the effects of Haematococcus astaxanthin (ASX), which has been known to be a potent antioxidant, on oxidative stress in smokers. Thirty-nine heavy smokers (≥20 cigarettes/day) and 39 non-smokers were enrolled in this study. Smokers were randomly divided into three dosage groups to receive ASX at doses of 5, 20, or 40 mg (n=13, each) once daily for 3 weeks. Oxidative stress biomarkers such as malondialdehyde, isoprostane, superoxide dismutase, and total antioxidant capacity, and ASX levels in plasma were measured at baseline and after 1, 2, and 3 weeks of treatment. Compared with baseline, the plasma malondialdehyde and isoprostane levels decreased, whereas superoxide dismutase level and total antioxidant capacity increased in all ASX intervention groups over the 3-week period. In particular, isoprostane levels showed a significant dose-dependent decrease after ASX intake. The results suggest that ASX supplementation might prevent oxidative damage in smokers by suppressing lipid peroxidation and stimulating the activity of the antioxidant system in smokers.

Effects of astaxanthin on oxidative stress in overweight and obese adults.

Oxidative stress is caused by an imbalance between the antioxidant and the reactive oxygen species, which results in damage to cells or tissues. Recent studies have reported that oxidative stress is involved in obesity, in addition to many other human diseases and aging. A prospective, randomized, double-blind study was performed to investigate the effect of astaxanthin (ASX), which is known to be a potent antioxidant, on oxidative stress in overweight and obese adults in Korea. Twenty-three adults with BMI > 25.0 kg/m(2) enrolled in this study and were randomly assigned to two dose groups: ASX 5 mg and 20 mg once daily for 3 weeks. Malondialdehyde (MDA), isoprostane (ISP), superoxide dismutase (SOD) and total antioxidant capacity (TAC), as oxidative stress biomarkers, were measured at baseline and 1, 2 and 3 weeks after ASX administration. Compared with baseline, the MDA (by 34.6% and 35.2%) and ISP (by 64.9% and 64.7%) levels were significantly lowered, whereas SOD (by 193% and 194%) and TAC (by 121% and 125%) levels were significantly increased in two dose groups after the 3 week intervention. This study revealed that supplemental ASX for 3 weeks improved oxidative stress biomarkers by suppressing lipid peroxidation and stimulating the activity of the antioxidant defense system.

Lignans from the Fruits of Forsythia suspensa (Thunb.) Vahl Protect High-Density Lipoprotein during Oxidative Stress.

The objective of the present study was to investigate the beneficial properties lignan compounds obtained from the fruits of Forsythia suspensa (Thunb.) Vahl (Oleaceae) for protecting human high-density lipoprotein (HDL) against lipid peroxidation. The isolated compounds (1-8) inhibited the generation of thiobarbituric acid-reactive substances (TBARS) in a dose-dependent manner with IC50 values from 8.5 to 18.7 microM, since HDL oxidation mediated by catalytic Cu2+. They also exerted an inhibitory effect against thermo-labile radical initiator (AAPH)-induced lipid peroxidation of HDL with IC50 values from 12.1 to 51.1 microM. Compounds 1 and 5 exerted inhibitory effects against the Cu2+-induced lipid peroxidation of HDL, as shown by an extended lag time prolongation at the concentration of 3.0 microM. These results suggest that the antioxidative effects of F. suspensa are due to its lignans and that these constituents may be useful for preventing the oxidation of HDL.

Triterpenoids and a sterol from the stem-bark of Styrax japonica and their protein tyrosine phosphatase 1B inhibitory activities.

Five pentacyclic triterpenoids (1-5) and a sterol (6) were isolated from the stem-bark of Styrax japonica. The six compounds, 1-6, were determined to be 3beta-acetoxy-28-hydroxyolean-12-ene (1), 3beta-acetoxyolean-12-en-28-acid (2), 3beta-acetoxyolean-12-en-28-aldehyde (3), 3beta-acetoxy-17beta-hydroxy-28-norolean-12-ene (4), taraxerol (5) and stigmasterol (6), respectively, by spectroscopic means, including the 2D-NMR technique. Compound 4 is a newly discovered natural compound. The protein tyrosine phosphatase 1B (PTP1B) inhibitory activities of the isolated compounds (1-6) were determined in vitro. Among the isolated compounds, 3beta-acetoxyolean-12-en-28-acid (2) and 3beta-acetoxyolean-12-en-28-aldehyde (3) had the most potent inhibitory PTP1B activity, with IC50 values of 7.8 and 9.3 microm, respectively.

Anticomplementary activity of triterpenoids from the whole plant of Aceriphyllum rossii against the classical pathway.

To provide a better understanding of the anti-complement activity of triterpenoids, seven unusual pentacyclic triterpenoids bearing a carboxyl group at C-27 were evaluated for their anticomplement activities against the classical pathway of the complement system. The triterpenoids were isolated from the whole plant of Aceriphyllum rossii of the family Saxifragaceae and were determined to be 3alpha,23-isopropylidenedioxyolean-12-en-27-oic acid (1), 3-oxoolean-12-en-27-oic acid (2), 3alpha-hydroxyolean-12-en-27-oic acid (3), beta-peltoboykinolic acid (4), 3alpha,23-diacetoxyolean-12-en-27-oic acid (5), 23-hydroxy-3-oxoolean-12-en-27-oic acid (6) and aceriphyllic acid A ( 7). Among them, compounds 2, 3, and 5 showed significant anticomplement activity on the classical pathway with IC (50) values of 71.4, 98.5, and 180.7 microM, respectively, whereas compounds 1, 4, 6, and 7 were inactive. Our findings suggest that both the ketone at C-3 and the methyl at C-23 in the oleanane triterpenoids with a carboxyl group at C-27 are important for the anticomplement activity against the classical pathway.

Cytotoxic lignans from the stem bark of Magnolia officinalis.

Three new lignans, 4'-methoxymagndialdehyde ( 1), 4'-methoxymagnaldehyde B ( 2), and 4'-methoxymagnaldehyde E ( 3), were isolated from hexane- and EtOAc-soluble fractions of the stem bark of Magnolia officinalis, together with eight known compounds ( 4- 11). The structures of compounds 1- 3 were determined on the basis of spectroscopic and physicochemical data analysis. Compounds 1- 11 were tested in vitro for their cytotoxic activity against the K562, HeLa, and A549 cancer cell lines. Among the compounds tested, compound 1 showed the most potent cytotoxic activity against these cancer cell lines, with IC50 values of 3.9, 1.5, and 3.7 microg/mL, respectively.