Topological models for prediction of physico-chemical, pharmacokinetic and toxicological properties of antihistaminic drugs using decision tree and moving average analysis.

Various topostructural and topochemical indices were used to encode the structureal features of antihistaminic drugs. The values of 18 indices for each drug comprising the dataset were computed using an in-house computer program. In the present study, decision tree and moving average analysis were used to predict physico-chemical (log P), pharmacokinetic (T(max)) and toxicological properties (LD(50)) of antihistaminic drugs. A decision tree was constructed for each property to determine the importance of Topological Indices (TIs). Single topological index based models were developed using moving average analysis. The tree learned the information from the input data with an accuracy of >94% and predicted the cross-validated (10-fold) data with an accuracy of upto 71%. Moving average analysis resulted in single index based models with an accuracy upto 80%.

Minimally invasive surgery fellows would perform a wider variety of cases in their "ideal" fellowship.

BACKGROUND: With the increase in minimally invasive surgery (MIS) fellowships, the concept of the ideal and standardized training curriculum is emerging in importance. The authors hypothesize that the procedure mix in current MIS training is different from what current MIS fellows would expect for their "ideal" fellowship. METHODS: An anonymous survey of current MIS fellows examined their perceptions of the case diversity and volume they expect to perform in their fellowships as compared with an ideal fellowship. Differences between expected and ideal case volume were analyzed using Wilcoxon tests. RESULTS: A total of 32 questionnaires were returned. Current MIS fellows believe their expected training will exceed the ideal volume of laparoscopic cholecystectomies (p = 0.002). They believe their expected training is equivalent to ideal training in laparoscopic gastric bypass, ventral herniorraphy, inguinal herniorraphy, antireflux procedures, appendectomy, and diagnostic endoscopy (nonsignificant difference). However, current expected training falls short of their "ideal" case volume in laparoscopic gastric banding, colectomy, common bile duct exploration, gastrectomy, esophagectomy, splenectomy, adrenalectomy, hepatectomy, nephrectomy, and pancreatectomy (p < 0.05). The current MIS fellows also expect that their thoracoscopic, therapeutic endoscopy, and robotic procedure volume will be less than "ideal" (p < 0.05). CONCLUSION: In 13 of 20 procedure types, current MIS fellows expect to perform a smaller case volume than in an "ideal" fellowship. The ideal case volume in the MIS fellowship curriculum needs to be defined better.

In vitro metabolism of indiplon and an assessment of its drug interaction potential.

This study was designed to study the in vitro metabolism of indiplon, a novel hypnotic agent, and to assess its potential to cause drug interactions. In incubations with pooled human liver microsomes, indiplon was converted to two major, pharmacologically inactive metabolites, N-desmethyl-indiplon and N-desacetyl-indiplon. The N-deacetylation reaction did not require NADPH, and appeared to be catalyzed by organophosphate-sensitive microsomal carboxylesterases. The N-demethylation of indiplon was catalyzed by CYP3A4/5 based on the following observations: (1) the sample-to-sample variation in N-demethylation of indiplon ([S] = 100 microM) in a bank of human liver microsomes was strongly correlated with testosterone 6beta-hydroxylase (CYP3A4/5) activity (r(2) = 0.98), but not with any other CYP enzyme; (2) recombinant CYP1A1, CYP1A2, CYP3A4, CYP3A5 and CYP3A7 had the ability to catalyze this reaction; (3) the N-demethylation of indiplon was inhibited by CYP3A4/5 inhibitors (ketoconazole and troleandomycin), but not by a CYP1A2 inhibitor (furafylline). In pooled human liver microsomes, indiplon exhibited a weak capacity to inhibit CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2D6, CYP2E1, CYP3A4/5 and carboxylesterase (p-nitrophenylacetate hydrolysis) activities (IC50 >/= 20 microM). Clinical data available on indiplon support the conclusions of this paper that the in vitro metabolism of indiplon is catalyzed by multiple enzymes, and indiplon is a weak inhibitor of human CYP enzymes.

A research agenda for gastrointestinal and endoscopic surgery.

BACKGROUND: Development of a research agenda may help to inform researchers and research-granting agencies about the key research gaps in an area of research and clinical care. The authors sought to develop a list of research questions for which further research was likely to have a major impact on clinical care in the area of gastrointestinal and endoscopic surgery. METHODS: A formal group process was used to conduct an iterative, anonymous Web-based survey of an expert panel including the general membership of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES). In round 1, research questions were solicited, which were categorized, collapsed, and rewritten in a common format. In round 2, the expert panel rated all the questions using a priority scale ranging from 1 (lowest) to 5 (highest). In round 3, the panel re-rated the 40 questions with the highest mean priority score in round 2. RESULTS: A total of 241 respondents to round 1 submitted 382 questions, which were reduced by a review panel to 106 unique questions encompassing 33 topics in gastrointestinal and endoscopic surgery. In the two successive rounds, respectively, 397 and 385 respondents ranked the questions by priority, then re-ranked the 40 questions with the highest mean priority score. High-priority questions related to antireflux surgery, the oncologic and immune effects of minimally invasive surgery, and morbid obesity. The question with the highest mean priority ranking was: "What is the best treatment (antireflux surgery, endoluminal therapy, or medication) for GERD?" The second highest-ranked question was: "Does minimally invasive surgery improve oncologic outcomes as compared with open surgery?" Other questions covered a broad range of research areas including clinical research, basic science research, education and evaluation, outcomes measurement, and health technology assessment. CONCLUSIONS: An iterative, anonymous group survey process was used to develop a research agenda for gastrointestinal and endoscopic surgery consisting of the 40 most important research questions in the field. This research agenda can be used by researchers and research-granting agencies to focus research activity in the areas most likely to have an impact on clinical care, and to appraise the relevance of scientific contributions.

Establishing a laparoscopic bariatric program in a safety net hospital.

BACKGROUND: Most laparoscopic bariatric programs are situated in a community- or university-based hospital. The authors have recently initiated a program at a safety net hospital. This investigation hypothesizes that a laparoscopic bariatric program can be established at a safety net hospital with good clinical and financial results. METHODS: A laparoscopic bariatric program was initiated December 2002 at a safety net hospital. The program included a dedicated operative suite, an operative team, a bariatric unit, and a clinical pathway. The data for all the patients who underwent laparoscopic gastric bypasses up to June 2003 were analyzed. The patients were analyzed by type of insurance: government-sponsored insurance (G) or commercial insurance (C). RESULTS: There were 104 patients during this period. Their mean age was 40 years (range, 18-63 years), and their mean body mass index was 48 (range, 38-62). The median length of hospital stay was 2 days (mean, 3.9 days). Hypertension and diabetes were resolved for more than 80% of the patients. The average percentage of excess body weight loss was 73% after 1 year. There were no significant clinical differences between payor groups. The payor mix was 31% G and 69% C. The mean collection rates for hospital charges were 10% for G versus 53% for C (p < 0.0001). CONCLUSIONS: A laparoscopic bariatric program can be established in a safety net hospital with good clinical results. Findings showed that 1-year weight loss and comorbidity improvement/resolution compares favorably with those of other programs. Despite the overall poor payor mix of many safety net hospitals, a bariatric program can be established and can attract a high rate of commercially insured patients.

Despite high satisfaction, majority of gastro-oesophageal reflux disease patients continue to use proton pump inhibitors after antireflux surgery.

BACKGROUND: While antireflux surgery is effective in controlling symptoms of gastro-oesophageal reflux, its role in eliminating the use of antireflux medicines after surgery and as such its long-term cost-effectiveness remains controversial. AIM: To assess the patient satisfaction and the continued medication use following laparoscopic Nissen fundoplication at a tertiary level community hospital. METHODS: Adult patients who underwent laparoscopic Nissen fundoplication at our institution over a period of over 3 years were asked to complete a questionnaire recording their demographic information, date and reason for the surgery, preprocedure and postprocedure symptoms, smoking and alcohol use, and medication use preoperatively and post-operatively. Patients were also asked about their satisfaction with surgery. RESULTS: One hundred patients participated in the study. Overall, 90% patients experienced satisfaction with their surgery. Eighty percentage patients were willing to undergo surgery again, if needed. Over two-thirds (67%) patients had decrease in the severity of their symptoms. None of the patients had worsening of symptoms post-operatively. However, 80% patients were still taking antireflux medications including proton pump inhibitors (53%). CONCLUSIONS: Most patients continue to use antireflux medications including after laparoscopic Nissen fundoplication despite high satisfaction with surgery.

Ageism in medical students' treatment recommendations: the example of breast-conserving procedures.

PURPOSE: Age bias may play a role in physicians' discussions of equivalent therapeutic options with patients, especially in respect to breast-conservation therapy. This study investigated bias based on age (ageism) among physicians-in-training in their treatment recommendations for breast-conserving procedures. METHOD: Second-year medical students responded to a questionnaire concerning recommendations they would make for breast conservation or mastectomies with or without breast reconstruction for eight patients with similar-stage breast cancer. The patients differed by age (older were > or =59 years, younger < or =31 years), race, and marital status. A total of 116 students made 1,146 recommendations. Percentages of the students' recommendations for breast-conservation therapy (BCT) were calculated for the two patient age groups and for the recommendations for breast reconstruction after the patient had already chosen modified radical mastectomy (MRM). Chi-square tests were used for statistical analysis. RESULTS: The students recommended BCT for a significantly higher percentage of younger patients than older patients (86% versus 66%; p<.001). They recommended MRM to 34% of older patients versus 14% of younger patients (p<.001). Furthermore, the students recommended breast reconstruction after MRM to a significantly higher percentage of younger patients than older patients (95% versus 65%; p<.001). CONCLUSIONS: Medical students' recommendations of breast conservation and breast reconstruction showed age bias. Educational efforts should be instituted during the medical school to decrease ageism in students' treatment recommendations.

Comparison of simulated patient and didactic methods of teaching HIV risk assessment to medical residents.

INTRODUCTION: Physicians need to be well trained in HIV risk assessment interview skills. Little has been written in the literature concerning training methods for this specialized interview. METHODS: One model to teach the HIV risk assessment interview has been developed and has been used to teach third-year medical students. We compared this interactive model, which uses simulated patients to teach HIV Risk Assessment, to a didactic one. Twelve medical residents were taken through either the interactive session or the didactic session. Pre-post changes from questionnaires were calculated to determine any differences in sessions. Also, Objective Structured Clinical Examinations (OSCEs) were used to grade all residents 2 weeks after their sessions. RESULTS: All pre-post changes were calculated and no statistically significant differences were seen (P > 0.50). OSCE interpersonal skills scores and content scores were calculated. The interactive group had statistically significantly higher scores (P < 0.05). CONCLUSION: The data supports the conclusion that an interactive method is more effective to use to train HIV risk assessment interview skills to medical residents when compared to the didactic method.