Nonspecific Adverse Events in Knee Osteoarthritis Clinical Trials: A Systematic Review

<div><p>Background</p><p>Adverse events (AEs) derived from nonspecific activity of treatments can impair the validity of trials, and even make it difficult to identify specific AEs associated with treatments. To better understand these nonspecific AEs, we investigated the AEs in placebo groups by using knee osteoarthritis clinical trials.</p><p>Methods</p><p>Randomized, placebo-controlled, knee osteoarthritis trials were identified by searching electronic databases. We determined the rate of patients with AEs and the rate of dropouts caused by AEs in the active and placebo groups. Furthermore, we calculated the rate of patients for individual AEs in the placebo groups. Finally, we performed secondary analyses to identify the factors associated with these rates.</p><p>Results</p><p>Overall, 272 papers reporting 281 trials were included in the analysis. The rates of patients with AEs were 31.8% in the active groups and 27.4% in the placebo groups. The rate of the placebo groups accounted for 86.2% of the rate of the active groups. The rates of dropouts caused by AEs were 5.2% in the active groups and 4.8% in the placebo groups. The rate of the placebo groups accounted for 92.3% of the rate of the active groups. AEs in the placebo groups included a number of clinical conditions, with elevated alanine aminotransferase (0.59%; 95% CI: 0.46 to 0.77) being the most common objective outcome and headache (4.48%; 95% CI: 4.20 to 4.79) being the most frequent subjective outcome. The rate of patients with AEs and the rate of dropouts caused by AEs were associated with the treatment type, delivery route, and study design.</p><p>Conclusions</p><p>The nonspecific AEs substantially accounted for the development of AEs in the active groups and included conditions involving the entire body.</p></div

Rates of nonspecific adverse events.

<p>n, number of patients reporting adverse events; N, total sample size; ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, gamma-glutamyltransferase.</p

Results of the meta-regression analysis.

<p>CI, confidence interval.</p><p>The coefficients are values after logit transformation.</p><p>*For binary outcomes, “no/unclear” and “yes” were coded as 1 and 2, respectively.</p><p>Results of the meta-regression analysis.</p

Characteristics of the included trials.

<p>No., number.</p><p>*Six studies administered treatments using mixed methods.</p><p>Characteristics of the included trials.</p

Funnel plots including an Egger's regression line.

<p>Funnel plots including an Egger's regression line.</p

Rates for treatment type and delivery route.

<p>Rates for treatment type and delivery route.</p

Iridoids from the Roots of <i>Patrinia scabra</i> and Their Inhibitory Potential on LPS-Induced Nitric Oxide Production

An activity-guided fractionation procedure of the 70% aqueous EtOH extract from the roots of <i>Patrinia scabra</i> led to the isolation and characterization of five new iridoids, patriscabrins A–E (<b>1</b>–<b>5</b>), along with 13 known compounds. The structures of <b>1</b>–<b>5</b> were determined by interpretation of spectroscopic data, particularly by 1D and 2D NMR, ECD, and VCD studies. Thereafter, isolates were evaluated for their inhibitory effects on lipopolysaccharide-induced nitric oxide production in RAW 264.7 cells. Of these, the new iridoids <b>2</b> and <b>5</b> and the known lignan patrineolignan B (<b>6</b>) exhibited IC₅₀ values of 14.7 to 17.8 μM

New Flavonol Glucuronides from the Flower Buds of <i>Syzygium aromaticum</i> (Clove)

Repeated chromatography of the EtOAc-soluble fraction from the 70% EtOH extract of the flower buds of <i>Syzygium aromaticum</i> (clove) led to the isolation and characterization of four new flavonol glucuronides, rhamnetin-3-<i>O</i>-β-d-glucuronide (<b>1</b>), rhamnazin-3-<i>O</i>-β-d-glucuronide (<b>2</b>), rhamnazin-3-<i>O</i>-β-d-glucuronide-6″-methyl ester (<b>3</b>), and rhamnocitrin-3-<i>O</i>-β-d-glucuronide-6″-methyl ester (<b>4</b>), together with 15 flavonoids (<b>5</b>–<b>19</b>) having previously known chemical structures. The structures of the new compounds <b>1</b>–<b>4</b> were determined by interpretation of spectroscopic data, particularly by 1D- and 2D-NMR studies. Six flavonoids (<b>6</b>, <b>7</b>, <b>9</b>, <b>14</b>, <b>18</b>, and <b>19</b>) were isolated from the flower buds of <i>S. aromaticum</i> for the first time in this study. The flavonoids were examined for their cytotoxicity against human ovarian cancer cells (A2780) using MTT assays. Among the isolates, pachypodol (<b>19</b>) showed the most potent cytotoxicity on A2780 cells with an IC₅₀ value of 8.02 μM