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A15heterogeneity should be conducted, and approaches illustrated here can be useful to explore heterogeneity. Further evaluation of the value of patient-level as opposed to summary-level data in heterogeneity assessment is needed.

Sildenafil citrate, a widely-used oral therapy for erectile dysfunction, is a cytochrome P3A4 (CYP3A4) enzyme substrate. Studies have reported that this substrate has an inhibitory effect on CYP3A4 enzymes in long-term cigarette and cannabis smokers, which predominantly mediate the hepatic elimination of sildenafil. Cigarette and/or cannabis smoking could therefore alter the exposure of sildenafil. The aim of this study was to examine the effect of smoking cigarettes and/or cannabis on the pharmacokinetics, pharmacodynamics, safety and tolerability of sildenafil. Thirty-six healthy human subjects were equally divided into three groups: non-smokers, cigarette smokers and cannabis smokers. Each group was administered a single dose of sildenafil (50 mg tablets). The primary outcome measures included the maximum concentration of sildenafil in plasma (Cmax), the elimination half-life (t1/2) and the area under the plasma concentration time curve from zero to time (AUC0–t). The pharmacodynamics were assessed by the International Index of Erectile Function (IIEF-5). The exposure of sildenafil (AUC0–t) showed a statistically significant increase in cigarette smokers (1156 ± 542 ng·h/mL) of 61% (p < 0.05) while in cannabis smokers (967 ± 262 ng·h/mL), a non-significant increase in AUC0–t of 35% (p > 0.05) was observed relative to non-smokers (717 ± 311 ng·h/mL). Moreover, the Cmax of sildenafil increased by 63% (p < 0.05) and 22% (p > 0.05) in cigarette smokers and cannabis smokers, respectively. Cigarette smoking increases the exposure of sildenafil to a statistically significant level with no effect on its pharmacodynamics, safety and tolerability.

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Objectives: This study evaluated the effect of 20% amorphous calcium phosphate nanoparticles loaded in chlorhexidine as an intra-canal medicament, on root canal dentin microhardness. Methods: A total of 30 human permanent single rooted teeth were used in this study. Teeth were decoronated and roots were split longitudinally into two equal halves, the better one half was kept and the other was discarded (30 specimens). The specimens were randomly divided into 3 groups according to the medicament used: 20% amorphous calcium phosphate nanoparticles in chlorhexidine (NACP+CHX), 2% chlorhexidine (CHX) and calcium hydroxide (Ca(OH)2). Each medicament was applied for two weeks immediately after initial baseline microhardness determination. The initial baseline microhardness determination utilized Vickers indenter under a 200-g load and a 15-second dwell time. Post treatment microhardness values were obtained utilizing the same settings. The change in radicular microhardness was calculated as a percentage. Data were statistically analyzed utilizing 1-way analysis of variance (P=.05) and post hoc Tukey test for the multiple comparisons at the same level of significance. The difference between the pre-treatment and the post-treatment microhardness values were statistically analyzed utilizing t-test with a P < .05. Results: 20% amorphous calcium phosphate nanoparticles in chlorhexidine was the only medicament to result in a statistically significant increase in radicular dentin microhardness, while both 2% chlorhexidine and calcium hydroxide resulted in a statistically significant decrease, with calcium hydroxide having the most detrimental effect. Conclusion: On the contrary of 2% chlorhexidine and calcium hydroxide, 20% amorphous calcium phosphate nanoparticles in chlorhexidine demonstrated a reinforcing effect on radicular dentin microhardness.