Physical Compatibility and Chemical Stability of Injectable and Oral Ranitidine Solutions.

Objectives: The physical compatibility and chemical stability of ranitidine hydrochloride injectable solutions and oral syrup were studied to define beyond-use dates (BUDs). Methods: Ranitidine hydrochloride injectable solutions of 25 mg/mL packaged in glass vials and 5 mg/mL in polypropylene (PP) syringes were prepared in triplicate. Samples were refrigerated and protected from light (PFL) or stored at 25°C and either exposed to light (ETL) or PFL. Ranitidine hydrochloride oral syrup 15 mg/mL in unit-dose amber PP syringes were prepared in triplicate and then kept at 25°C. Samples were collected at days 0, 7, 14, 28, 56, and 91. Additional samples were collected at 6 months and at 6, 9, and 12 months for the 25 mg/mL solution and oral syrup, respectively. Physical parameters of pH, clarity, and color were obtained at each collection time. A validated stability-indicating high-performance liquid chromatography (HPLC) method was used to determine the chemical stability. Results: Formulations had no significant change in pH or clarity. Although some samples yellowed, this was not associated with a decrease in concentration. The 25 mg/mL solution remained above 98.6% for 6 months, whereas the 5 mg/mL solution remained above 93.5% for 91 days under all storage conditions. At 25°C, the oral syrup retained greater than 98.8% for 12 months. Conclusions: The ranitidine hydrochloride injectable solutions were stable for 6 months and 91 days under the 3 storage conditions, respectively, for the 25 mg/mL solution in glass vials and 5 mg/mL solution in PP syringes. The 15 mg/mL oral syrup in unit-dose amber PP syringes was stable for 12 months at 25°C and PFL.

New Approach for Investigating Reaction Dynamics and Rates with Ab Initio Calculations.

Herein, we demonstrate a convenient approach to systematically investigate chemical reaction dynamics using the metadynamics (MetaD) family of enhanced sampling methods. Using a symmetric SN2 reaction as a model system, we applied infrequent metadynamics, a theoretical framework based on acceleration factors, to quantitatively estimate the rate of reaction from biased and unbiased simulations. A systematic study of the algorithm and its application to chemical reactions was performed by sampling over 5000 independent reaction events. Additionally, we quantitatively reweighed exhaustive free-energy calculations to obtain the reaction potential-energy surface and showed that infrequent metadynamics works to effectively determine Arrhenius-like activation energies. Exact agreement with unbiased high-temperature kinetics is also shown. The feasibility of using the approach on actual ab initio molecular dynamics calculations is then presented by using Car-Parrinello MD+MetaD to sample the same reaction using only 10-20 calculations of the rare event. Owing to the ease of use and comparatively low-cost of computation, the approach has extensive potential applications for catalysis, combustion, pyrolysis, and enzymology.

Characterizing the catalyzed hydrolysis of ß-1,4 glycosidic bonds using density functional theory.

Unraveling the mechanistic details of biomass deconstruction at ambient conditions has remained a challenge for many years. In this study we examine a crucial step in the pretreatment of biomass: the hydrolytic cleavage of the glycosidic bond present in many forms of biomass and other oligomeric saccharides. We present the detailed mechanistic steps found using density functional theory and transition state calculations on the acid catalyzed hydrolysis of a pyranose dimer linked by a ß-1,4 glycosidic bond in a vacuum and various continuum solvation models. The order that the bonds in the double displacement reaction form and break was revealed along with the transition state energies and an overall intrinsic reaction pathway for the two-step mechanism. The uncatalyzed hydrolysis reaction, mediated by a single water splitting event, was also determined with DFT calculations and a detailed comparison to the two-step catalyzed reaction was performed. The effects of the surrounding solvent on the reaction energetics were studied by systematically changing the dielectric strength and polarity of the solvent model. For acidic solvents, a trend was observed that related the transition state energy barrier to the inverse of the dielectric constant whereas solvents that varied slightly in dielectric strength but strongly in polarity (e.g., alcohols) did not significantly change the reaction energetics. The effects of the substituents on the model sugar were also studied by changing from a model pyranose dimer to xylobiose and cellobiose. Irrespective of the solvent choice or model sugar characteristics we observed identical ordering of all bond breaking/forming in both transition states in the double displacement mechanism.

Patient-provider discussions about colorectal cancer screening: who initiates elements of informed decision making?

BACKGROUND: Colorectal cancer (CRC) screening rates remain low among low-income minority populations. OBJECTIVE: To evaluate informed decision making (IDM) elements about CRC screening among low-income minority patients. DESIGN: Observational data were collected as part of a patient-level randomized controlled trial to improve CRC screening rates. Medical visits (November 2007 to May 2010) were audio-taped and coded for IDM elements about CRC screening. Near the end of the study one provider refused recording of patients' visits (33 of 270 patients). Among all patients in the trial, agreement to be audio taped was 43.5 % (103/237). Evaluable patient (n = 100) visits were assessed for CRC screening discussion occurrence, IDM elements, and who initiated discussion of each IDM element. PARTICIPANTS: Patients were African American (72.2 %), female (63.7 %), with annual household incomes <$20,000 (60.7 %), without health insurance (57.0 %), and limited health literacy (53.7 %). KEY RESULTS: Although CRC screening was mentioned during 48 (48 %) visits, no further discussion about screening occurred in 23 visits (19 times mentioned by the participant with no response from providers). During any visit, the maximum number of IDM elements was five; however, only two visits included five elements. The most common IDM element discussed in addition to the nature of the decision was the assessment of the patient's understanding in 16 (33.3 %) of the visits that included a CRC discussion. CONCLUSIONS: A patient activation intervention initiated CRC screening discussions with health care providers; however, limited IDM occurred about CRC screening during medical visits of minority and low-income patients.

Patient activation increases colorectal cancer screening rates: a randomized trial among low-income minority patients.

BACKGROUND: Colorectal cancer (CRC) screening rates remain low among low-income and minority populations. The purpose of this study was to determine whether providing patients with screening information, activating them to ask for a screening test, and telephone barriers counseling improves CRC screening rates compared with providing screening information only. METHODS: Patients were randomized to CRC screening information plus patient activation and barriers counseling (n = 138) or CRC screening information (n = 132). Barriers counseling was attempted among activated patients if screening was not completed after one month. CRC screening test completion was determined by medical record review at two months after the medical visit. Logistic regression was used to determine whether activated patients were more likely to complete CRC screening, after adjustment for confounding factors (e.g., demographic characteristics and CRC knowledge). RESULTS: Patients were African American (72.2%), female (63.7%), had annual household incomes less than $20,000 (60.7%), no health insurance (57.0%), and limited health literacy skills (53.7%). In adjusted analyses, more patients randomized to the activation group completed a screening test (19.6% vs. 9.9%; OR = 2.35, 95% CI: 1.14-5.56; P = 0.020). In addition, more activated patients reported discussing screening with their provider (54.4% vs. 27.5%, OR = 3.29, 95% CI: 1.95-5.56; P < 0.001) and had more screening tests ordered (39.1% vs. 17.6%; OR = 3.40, 95% CI: 1.88-6.15; P < 0.001) compared with those in the control group. CONCLUSION: Patient activation increased CRC screening rates among low-income minority patients. IMPACT: Innovative strategies are still needed to increase CRC screening discussions, motivate providers to recommend screening to patients, as well as assist patients to complete ordered screening tests.

Ileal impaction in 245 horses: 1995-2007.

The objective of this study was to identify parameters that would assist in determining the probability of a successful outcome with medical management versus surgical intervention in horses with ileal impaction. Medical records of 245 horses admitted for ileal impaction were reviewed and placed into 2 groups: medical (med) and surgical (sx) treatment. Persistence of abdominal pain, gastric reflux, frequency of analgesic administration, and 1-year survival were evaluated. There were no differences in signalment, abdominal pain, or heart rate among groups; however, significantly more sx horses had peritoneal fluid abnormalities (51%) and produced gastric reflux (62%) than did med horses (38% and 15%, respectively). Eighty-nine percent of med horses required repeated analgesic administration for successful resolution. One-year survival was 91% for sx horses and 92% for med horses. Horses with ileal impaction responsive to analgesic therapy with minimal gastric reflux are likely to be managed successfully with medical treatment. Horses with persistent abdominal pain and gastric reflux are candidates for surgery.