The Effect of Roux-en-Y Gastric Bypass Surgery in Morbidly Obese Patients on Pharmacokinetics of (Acetyl)Salicylic Acid and Omeprazole: the ERY-PAO Study

Background

Data on the absorption of orally administered drugs following Roux-en-Y gastric bypass (RYGB) surgery in obese patients are limited and inconclusive. As it is difficult to predict changes in absorption, studies on frequently used drugs in this population are necessary. Acetylsalicylic acid (ASA) and omeprazole are two commonly prescribed drugs in obese patients.

Methods

In this repeated measures study, omeprazole and salicylic acid (SA) serum concentrations were measured before and after RYGB in 34 morbidly obese subjects. Time to maximum concentration (Tmax), lag time (Tlag), maximum concentration (Cmax), and area under the serum concentration versus time curve (AUC) were calculated for both drugs to determine possible differences in drug absorption after the procedure.

Results

For SA, Tmax significantly decreased after RYGB, while both Cmax and AUC_0–24 significantly increased. For omeprazole, both Tmax and Tlag significantly decreased after RYGB, while Cmax significantly increased. Mean AUC_0–12 significantly decreased post-surgery. The difference in AUC_0–12 before and after surgery varied between subjects.

Conclusions

Our study shows a faster absorption of both ASA and omeprazole after RYGB. The exposure to ASA is higher post-surgery, but the standard dose of 80 mg does not need to be modified, considering its range in effective dose. The exposure to omeprazole is, on average, decreased after surgery. Clinicians should be aware to increase the dose of omeprazole if symptoms suggest inadequate response.

     

General and Ethnic-Biased Bullying Among Latino Students: Exploring Risks of Depression,Suicidal Ideation,and Substance Use

Using a cross-sectional sample of 534 Latino students from middle and high schools in a large North Carolina school district, we examined the relation of general and ethnic-biased bullying to depression and the indirect pathways through depression to suicidal ideation and substance use outcomes. A structural equation model tested the direct and indirect paths. The final model fit was excellent, χ²(90)?=?127.6, p?=?.0056, RMSEA?=?0.028, CFI?=?0.974, TLI?=?0.961. Ethnic-biased and verbal or relational bullying had a direct effect on depression, but general and physical bullying did not. Indirect effects through depression were found for ethnic-biased and verbal or relational bullying in relation to suicidal ideation, alcohol, and illicit drug use. Child nativity was marginally associated with ethnic-biased bullying, indicating foreign-born students may experience greater ethnic-biased bullying. Implications for future research and bullying prevention are discussed.     

Behavioral therapies trials: a case example

BACKGROUND: Behavior change is integral to the prevention and treatment of many disorders associated with deleterious lifestyles. Rigorous scientific testing of behavior change interventions is an important goal for nursing research. APPROACH: The stage model for behavioral therapy development is recommended as a useful framework for evaluating behavior change strategies. The NIH model specifies three stages from initial testing of novel behavioral therapies to their dissemination in community settings. Definitions of each step in a Stage I trial and a case example of Mindfulness-Based Stress Reduction (MBSR) in therapeutic community treatment are provided. RESULTS: It is feasible to adapt a behavioral therapy such as MBSR using the stage model framework. Steps in the process include: (a) determining pilot study design and describing the population; (b) modifying the intervention and developing the manual; (c) training the teachers; (d) implementing a pilot study; and (e) monitoring treatment integrity. DISCUSSION: The development of behavior therapies requires the same scientific rigor used in pharmacotherapy research. Stage I of the model enables consideration of the "dose" of a behavioral intervention necessary to achieve behavior change in a defined population. The stage model offers an excellent approach to achieving rigor in a variety of potentially useful therapies of interest to nurse researchers.     

Rab geranylgeranyl transferase alpha mutation in the gunmetal mouse reduces Rab prenylation and platelet synthesis

Few molecular events important to platelet biogenesis have been identified. Mice homozygous for the spontaneous, recessive mutation gunmetal (gm) have prolonged bleeding, thrombocytopenia, and reduced platelet alpha- and delta-granule contents. Here we show by positional cloning that gm results from a G-->A substitution mutation in a splice acceptor site within the alpha-subunit of Rab geranylgeranyl transferase (Rabggta), an enzyme that attaches geranylgeranyl groups to Rab proteins. Most Rabggta mRNAs from gm tissues skipped exon 1 and lacked a start codon. Rabggta protein and Rab geranylgeranyl transferase (GGTase) activity were reduced 4-fold in gm platelets. Geranylgeranylation and membrane association of Rab27, a Rab GGTase substrate, were significantly decreased in gm platelets. These findings indicate that geranylgeranylation of Rab GTPases is critical for hemostasis. Rab GGTase inhibition may represent a new treatment for thrombocytosis and clotting disorders.