Challenges of correlating pH change with relief of clinical symptoms in gastro esophageal reflux disease: a phase III, randomized study of Zegerid versus Losec.

BACKGROUND: Zegerid (on demand immediate-release omeprazole and sodium bicarbonate combination therapy) has demonstrated earlier absorption and more rapid pH change compared with Losec (standard enteric coated omeprazole), suggesting more rapid clinical relief of heartburn. This Phase III, multicenter, double-blind, double-dummy, randomized study assessed the clinical superiority of Zegerid versus Losec for rapid relief of heartburn associated with gastro-esophageal reflux disease (GERD). METHODS: Patients with a history of frequent (2 3 days/week) uncomplicated GERD, were randomized to receive Zegerid (20 mg) or Losec (20 mg) with corresponding placebo. Study medication was self-administered on the first episode of heartburn, and could be taken for up to 3 days within a 14 day study period. Heartburn severity was self assessed up to 180 minutes post dose (9 point Likert scale). Primary endpoint was median time to sustained response (≥3 point reduction in heartburn severity for ≥45 minutes). RESULTS: Of patients randomized to Zegerid (N=122) or Losec (N=117), 228/239 had recorded ≥1 evaluable heartburn episodes and were included in the modified intent-to-treat population. No significant between-group differences were observed for median time to sustained response (60.0 vs. 52.2 minutes, Zegerid [N=117] and Losec [N=111], respectively), sustained partial response (both, 37.5 minutes) and sustained total relief (both, 105 minutes). Significantly more patients treated with Zegerid reached sustained total relief within 0-30 minutes post dose in all analysis sets (p<0.05). Both treatments were well tolerated and did not raise any safety concerns. CONCLUSIONS: Superiority of Zegerid over Losec for rapid heartburn relief was not demonstrated; both treatments were equally effective however the rapid onset of action of Losec was unexpected. Factors, including aspects of study design may have contributed to this. This study supports previously reported difficulty in correlating intra-gastric pH change with clinical effect in GERD therapy, highlighting the significance of several technical considerations for studies of this type. TRIAL REGISTRATION: ClinicalTrials.gov NCT01493089.

Perceived sexual control, sex-related alcohol expectancies and behavior predict substance-related sexual revictimization.

OBJECTIVES: Although numerous studies have documented linkages between childhood sexual abuse (CSA) and later sexual revictimization, mechanisms underlying revictimization, particularly assaults occurring in the context of substance use, are not well-understood. Consistent with Traumagenic Dynamics theory, the present study tested a path model positing that lowered perceptions of sexual control resulting from CSA may be associated with increased sex-related alcohol expectancies and heightened likelihood of risky sexual behavior, which in turn, may predict adult substance-related rape. METHODS: Participants were 546 female college students who completed anonymous surveys regarding CSA and adult rape, perceptions of sexual control, sex-related alcohol expectancies, and likelihood of engaging in risky sexual behavior. RESULTS: The data fit the hypothesized model well and all hypothesized path coefficients were significant and in the expected directions. As expected, sex-related alcohol expectancies and likelihood of risky sexual behavior only predicted substance-related rape, not forcible rape. CONCLUSIONS: Findings suggested that low perceived sexual control stemming from CSA is associated with increased sex-related alcohol expectancies and a higher likelihood of engaging in sexual behavior in the context of alcohol use. In turn these proximal risk factors heighten vulnerability to substance-related rape. Programs which aim to reduce risk for substance-related rape could be improved by addressing expectancies and motivations for risky sexual behavior in the context of substance use. Implications and future directions are discussed.

Number of sexual partners and sexual assertiveness predict sexual victimization: do more partners equal more risk?

In previous studies, number of sexual partners and sexual assertiveness were examined as independent risk factors for sexual victimization among college women. Using a sample of 335 college women, this study examined the interaction of number of sexual partners and sexual assertiveness on verbal sexual coercion and rape. Approximately 32% of the sample reported unwanted sexual intercourse, 6.9% (n = 23) experienced verbal sexual coercion, 17.9% (n = 60) experienced rape, and 7.2% (n = 24) experienced both. As number of sexual partners increased, instances of verbal sexual coercion increased for women low in relational sexual assertiveness but not for women high in relational sexual assertiveness. A similar relationship was not found for rape. Among women who experienced both verbal sexual coercion and rape, increases in number of partners in the context of low refusal and relational assertiveness were associated with increases in verbal sexual coercion and rape. Findings suggest sexual assertiveness is related to fewer experiences of sexual coercion.

Depth profiling of water molecules at the liquid-liquid interface using a combined surface vibrational spectroscopy and molecular dynamics approach.

The studies presented here combine experimental and computational approaches to provide new insights into how water structures and penetrates into the organic phase at two different liquid-liquid systems: the interfaces of carbon tetrachloride-water (CCl4-H2O) and 1,2-dichloroethane-water (DCE-H2O). In particular, molecular dynamics simulations are performed to generate computational spectral intensities of the CCl4-H2O and DCE-H2O interfaces that are directly comparable with experimental measurements. These simulations are then applied toward the generation of spectral profiles, responses that vary as functions of both frequency and interfacial depth. These studies emphasize the similarities and differences in the structure, orientation, and bonding of interfacial water as a function of interfacial depth for these two liquid-liquid systems and demonstrate the differing behavior of water monomers that penetrate into the organic phase.

Understanding the population, coordination, and orientation of water species contributing to the nonlinear optical spectroscopy of the vapor-water interface through molecular dynamics simulations.

Molecular dynamics simulations are used to deconvolve the vibrational spectral features of the vapor-water interface based on molecular environment. A simple geometric description of hydrogen bonding is deployed to identify the OH stretch modes that comprise the vibrational sum-frequency spectrum of the vapor-water interface with direct comparison to our experimental results. The population densities of different species of water molecules are presented as functions of interfacial depth and orientation. It is found that surface water molecules that possess one proton donor bond and one proton acceptor bond make the dominant contribution to both the SSP- and SPS-polarized spectral responses and are located within an angstrom of the Gibbs dividing surface.