Flipped Classroom Case Learning vs Traditional Lecture-Based Learning in Medical School Ophthalmology Education: A Randomized Trial.

PURPOSE: To address the problem of teaching noncore specialties, for which there is often limited teaching time and low student engagement, a flipped classroom case learning (FCCL) module was designed and implemented in a compulsory 5-day ophthalmology rotation for undergraduate medical students. The module consisted of a flipped classroom, online gamified clinical cases, and case-based learning. METHOD: Final-year medical students in a 5-day ophthalmology rotation were randomized to the FCCL or a traditional lecture-based (TLB) module. The outcomes of subjective assessments (student-rated anonymous Likert scale questionnaire, scale 1 to 5, and course and teaching evaluation, scale 1 to 6) and objective assessments (end-of-rotation and post-MBChB multiple-choice questions, scale 0 to 60) were compared between the 2 groups. RESULTS: Between May 2021 and June 2022, 216 students (108 in each group) completed the study. Compared with the TLB students, the students in the FCCL group rated various aspects of the course statistically significantly higher, including feeling more enthusiastic and engaged by the course and more encouraged to ask questions and participate in discussions (all P < .001). They also gave higher ratings for the instructional methods, course assignments, course outcomes, and course workload ( P < .001). They gave higher course and teaching evaluation scores to the tutors (5.7 ± 0.6 vs 5.0 ± 1.0, P < .001). The FCCL group scored higher than the TLB group on the end-of-rotation multiple-choice questions (53.6 ± 3.1 vs 51.8 ± 2.8, P < .001). When 32 FCCL students and 36 TLB students were reassessed approximately 20 weeks after the rotation, the FCCL group scored higher (40.3 ± 9.1) than the TLB group (34.3 ± 10.9, P = .018). CONCLUSIONS: Applying the FCCL module in ophthalmology teaching enhanced medical students' satisfaction, examination performance, and knowledge retention. A similar model may be suitable for other specialties.

Efficacy and safety of cilostazol in decreasing progression of cerebral white matter hyperintensities-A randomized controlled trial.

Introduction: Cerebral small vessel disease (SVD) is an important cause of dementia that lacks effective treatment. We evaluated the efficacy and safety of cilostazol, an antiplatelet agent with potential neurovascular protective effects, in slowing the progression of white matter hyperintensities (WMHs) in stroke- and dementia-free subjects harboring confluent WMH on magnetic resonance imaging (MRI). Methods: In this single-center, randomized, double-blind, placebo-controlled study, we randomized stroke- and dementia-free subjects with confluent WMHs to receive cilostazol or placebo for 2 years in a 1:1 ratio. The primary outcome was change in WMH volume over 2 years. Secondary outcomes were changes in brain volumes, lacunes, cerebral microbleeds, perivascular space, and alterations in white matter microstructural integrity, cognition, motor function, and mood. Results: We recruited 120 subjects from October 27, 2014, to January 21, 2019. A total of 55 subjects in the cilostazol group and 54 subjects in the control group were included for intention-to-treat analysis. At 2-year follow-up, the changes in WMH volume were not statistically different between cilostazol treatment and placebo (0.3±1.0 mL vs -0.1±0.8 mL, p = 0.167). Secondary outcomes, bleeding and vascular events, were also not statistically different between the two groups. Discussion: In this trial with stroke- and dementia-free subjects with confluent WMHs, cilostazol did not impact WMH progression but demonstrated an acceptable safety profile. Future studies should address the treatment effects of cilostazol on subjects at different clinical stages of SVD.

Temporal trend of opioid and nonopioid pain medications: results from a national in-home survey, 2001 to 2018.

Introduction: The opioid epidemic persists in the United States. The use of opioid medications is often assessed by claims data but potentially underestimated. Objectives: We evaluated the temporal trend in the use of opioid and nonopioid pain medications from a national survey. Methods: Using data from the 2001 to 2018 National Health and Nutrition Examination Survey (NHANES), we examined the current use of prescription analgesics in the past 30 days among 50,201 respondents aged 20 years or older. Joinpoint regressions were used to test statistically meaningful trends of opioid vs nonopioid analgesics. Results: The mean percentage of people who had pain medications in the past 30 days was 6.4% (5.3%-7.1%) for opioid and 11.3% (9.0%-14.8%) for nonopioid analgesics. The availability of opioid and nonopioid prescriptions at home has remained stable, except for the slight decline of opioids among cancer-free patients in 2005 to 2018. The most frequently used opioid analgesic medications included hydrocodone/acetaminophen, tramadol, and hydrocodone. Conclusion: We uniquely measured the proportion of people who had opioid and nonopioid pain medications at home in the United States and supplemented the previous knowledge of prescription rates mainly obtained from claims data.

Efficacy and safety comparing prasugrel/ticagrelor and clopidogrel in Hong Kong post-acute coronary syndrome patients-A 10-year cohort study.

BACKGROUND: Clinical evidence of prasugrel/ticagrelor in dual antiplatelet therapy (DAPT) in Asian acute coronary syndrome (ACS) population remains inconclusive. We aimed to compare the clinical efficacy and safety of prasugrel/ticagrelor compared to clopidogrel as part of DAPT in Hong Kong ACS population for 10 years. HYPOTHESIS: Prasugrel/ticagrelor, compared to clopidogrel, reduces risk of major adverse cardiovascular event (MACE) in Hong Kong ACS population. METHODS: The retrospective observational cohort study included patients admitted to seven institutions under Hospital Authority Hong Kong with diagnosis of ACS during 2008-2017. Risk of MACE, defined as composite of cardiovascular (CV) death, non-fatal myocardial infarction (MI) and non-fatal stroke, and risk of any bleeding leading to hospitalization were examined. Baseline characteristics difference was adjusted by propensity score (PS) matching. Adjusted Cox regression model was used to estimate hazard ratio of interested outcome. RESULTS: In PS matched cohort including 944 patients in each group, MACE risk reduction of 40% from 1 year to 5 years after index ACS event was observed in prasugrel/ticagrelor group (HR 0.60, 95% CI 0.39-0.91, p = .015). The risk reduction was highly driven by MI reduction (HR 0.54, 95% CI 0.33-0.91, p = .019). Lower bleeding risk was observed in prasugrel/ticagrelor group compared to clopidogrel from 1 year to 5 years (HR 0.46, 95% CI 0.21-1.00, p = .051). CONCLUSIONS: Prasugrel/ticagrelor showed MACE risk reduction over clopidogrel as part of DAPT up to 5 years after index event, while prasugrel/ticagrelor was not associated with increased bleeding risk.

Burden of smoking in Asia-Pacific countries.

INTRODUCTION: Smoking is a modifiable risk factor for many diseases. The public should recognize the impact of smoking on their health and their wealth. The current study aimed to evaluate the cost burden of smoking to target Asia-Pacific countries. METHODS: The current study estimated the annual spending and lifetime spending of smokers in the target Asia-Pacific countries (Hong Kong, Malaysia, Thailand, South Korea, Singapore, and Australia) on purchasing cigarettes, as well as predicted the revenue that could be generated if smokers spent the money on investment instead of buying cigarettes. Smokers' spending on cigarettes and the potential revenue generated from investment were estimated based on the selling prices of cigarettes, Standards & Poor's 500 Index, and life expectancies of smokers. Data were extracted from reports released by the World Health Organization or government authorities. RESULTS: The annual expenses (in US$) on purchasing one pack of cigarettes, in decreasing order, were: Australia ($5628.30), Singapore ($3777.75), Hong Kong ($2799.55), Malaysia ($1529.35), South Korea ($1467.30), and Thailand ($657.00). The lifetime spending on purchasing one pack of cigarettes each day were: Australia ($308993.67), Singapore ($207398.48), Hong Kong ($151735.61 for male and $166853.18 for female), South Korea ($80261.31), Malaysia ($72338.26), and Thailand ($31207.50). CONCLUSIONS: The cost burden of smoking is high from a smoker's perspective. Smokers should recognize the high economic burden and quit smoking to enjoy better health and wealth.

Pharmacologic Evidence of Green Tea in Targeting Tyrosine Kinases.

BACKGROUND: Green tea has been extensively studied for its potential health benefits against diseases, such as cancers, cognitive degenerative diseases, and cardiovascular diseases. METHODS: The authors undertook a structured search of peer-reviewed research articles from three databases including PubMed, Embase, and Ovid MEDLINE. Recent and up-to-date studies relevant to the topic were included. RESULTS: Green tea extract exerts its functions by interacting with multiple signalling pathways in human cells. Protein tyrosine kinase is one of the examples. Abnormal activation of tyrosine kinase is observed in some tumour cells. Green tea extract inhibits phosphorylation, reduces expression, or attenuates downstream signalling of epidermal growth factor receptor, insulin-like growth factor receptor, vascular endothelial growth factor receptor, and non-receptor tyrosine kinase. Combination of green tea extract with tyrosine kinase inhibitors may provide synergistic effects by overcoming acquired resistance. CONCLUSION: Green tea extract can affect multiple receptor targets. In the current review, we discuss the pharmacological mechanisms of green tea on tyrosine kinases and their implications on common diseases.

Anti-tumor necrosis factor biosimilars and intended copies in rheumatology: Perspective from the Asia Pacific region.

Although anti-tumor necrosis factor (TNF) agents have greatly improved the management of rheumatic diseases, their cost limits access to many patients throughout the world. As a result, patients and clinicians have turned to biosimilars to provide similar efficacy at a lower cost. Many of the regulatory guidelines in the Asia Pacific region are largely based on those of the European Medicines Agency and the World Health Organization; however, there are variations between countries. Additionally, in some countries, intended copies are available that were approved prior to the development of guidelines and have not fulfilled the requirements of a biosimilar. We review the various regulatory requirements for biosimilars in the Asia Pacific region, the anti-TNF biosimilars and intended copies approved in the region, and whether clinical data are available for these agents. We discuss concerns about the need for additional regulations and education, and we provide recommendations for a multidisciplinary pharmacovigilance approach that closely monitors the safety of biosimilar use.

Real-world evidence of improved healthcare utilization in patients with schizophrenia or schizoaffective disorder after early treatment of paliperidone palmitate once-monthly treatment in Hong Kong.

BACKGROUND: Very few data are available to demonstrate the economic benefit of early paliperidone palmitate once-monthly long-acting injectable (PP1M) treatment in patients with schizophrenia or schizoaffective disorder. METHODS AND MATERIALS: This study has retrospectively compared the healthcare utilization and associated costs of pre- and post-PPIM treatment in 413 patients with schizophrenia or schizoaffective disorder recruited from three major public hospitals providing psychiatric services in Hong Kong. Patients were categorized into early treatment (≤3 years since diagnosis) and chronic (>3 years) groups, and also whether they were receiving polypharmacy (POP). RESULTS: It was found that patients who were started on early therapy with no POP had the most favourable outcomes. Overall results of the entire cohort, including both early and late treatments, indicate that there was a slight increase in annual in-patient days (IP) per patient and outpatient visit (OP) by 3.18 and 1.87, respectively, and a decrease in emergency room visit (ER) of 0.9 (p < 0.05). For non-polypharmacy (NP) patients receiving early PP1M therapy, there was a significant decrease in IP and ER of 21.56 (p < 0.05) and 1.15 (p < 0.05), respectively, but an increase in OP of 1.88 (p < 0.05). For patients with POP, there was an all-across increase in IP and all-across decrease in OP and ER. In monetary terms, a NP patient receiving early therapy may have an overall saving of HKD40,878 (USD5,241, 1USD = 7.8HKD) per year compared to HKD6,224 (USD798) in patients where therapy was given after 3 years. For patients with POP, there was an all-across increase in overall spending despite reductions in OP and ER. CONCLUSIONS: From the 413 patients studied, potential annual savings is higher by early administration of PPIM in patients with NP. Analysis using multivariate linear regression based on generalized estimating equations and sensitivity analysis using a linear mixed model supported the findings.

Screening for Atrial Fibrillation: A Report of the AF-SCREEN International Collaboration.

Approximately 10% of ischemic strokes are associated with atrial fibrillation (AF) first diagnosed at the time of stroke. Detecting asymptomatic AF would provide an opportunity to prevent these strokes by instituting appropriate anticoagulation. The AF-SCREEN international collaboration was formed in September 2015 to promote discussion and research about AF screening as a strategy to reduce stroke and death and to provide advocacy for implementation of country-specific AF screening programs. During 2016, 60 expert members of AF-SCREEN, including physicians, nurses, allied health professionals, health economists, and patient advocates, were invited to prepare sections of a draft document. In August 2016, 51 members met in Rome to discuss the draft document and consider the key points arising from it using a Delphi process. These key points emphasize that screen-detected AF found at a single timepoint or by intermittent ECG recordings over 2 weeks is not a benign condition and, with additional stroke factors, carries sufficient risk of stroke to justify consideration of anticoagulation. With regard to the methods of mass screening, handheld ECG devices have the advantage of providing a verifiable ECG trace that guidelines require for AF diagnosis and would therefore be preferred as screening tools. Certain patient groups, such as those with recent embolic stroke of uncertain source (ESUS), require more intensive monitoring for AF. Settings for screening include various venues in both the community and the clinic, but they must be linked to a pathway for appropriate diagnosis and management for screening to be effective. It is recognized that health resources vary widely between countries and health systems, so the setting for AF screening should be both country- and health system-specific. Based on current knowledge, this white paper provides a strong case for AF screening now while recognizing that large randomized outcomes studies would be helpful to strengthen the evidence base.

Challenges for drug discovery and development in China.

INTRODUCTION: The drug development industry is restructuring worldwide in terms of the research and development process. As with pharmaceuticals in the west, China faces major challenges for drug discovery and development. Areas covered: In this review, the authors discuss anti-cancer, anti-allergy, anti-infectious, and proprietary Chinese Medicines (pCM) for various chronic diseases (such as the allergic diseases: eczema, asthma and allergic rhinitis), which remain the contemporary therapeutic strategies that are being explored and developed. Drug transporters, disease specific biomarkers, pharmacophores, bioactive natural products and pharmacogenetics are some aspects of research technologies. Proprietary Chinese medicine remains one of the most popular strategies. There is however the issue of good research documentation of efficacy versus adverse effects. China has a complex healthcare system involving a large patient pool. Expert opinion: Various factors can impact drug development in China including the concurrent use of both western and Chinese medicines, pharmacogenetic variances, lack of multidisciplinary team impact on disease management and drug safety. China may adopt the current development of big data analysis in other countries such as UK and US to build and centralize a nationwide database for better monitoring and clinical evaluation to provide more efficient care at a lower cost.

Outpatient Medication Use in Chinese Geriatric Patients Admitted for Falls: A Case-Control Study at an Acute Hospital in Hong Kong.

The study objective was to investigate the association of polypharmacy and medications with patient falls resulting in hip fractures among community-living geriatric patients. A case-control study was conducted at an acute public hospital in Hong Kong. The study population was community-living Chinese patients aged 65 years and above who were admitted for falls resulting in hip fractures during an 18-month study period. Each of these patients was matched to a control patient with the same age and sex, but without falls and fractures. Data were collected from electronic patient record. Data of 170 cases and 170 controls were eventually collected. The following variables associated with increased risk of falls resulting in hip fractures remained statistically significant after multivariate logistic regression, including benign prostatic hyperplasia [odds ratio (OR) = 2.654; 95% confidence interval (CI), 1.105-6.378; P = 0.029], first-generation antihistamines (OR = 3.176; 95% CI, 1.044-9.664; P = 0.042), antiparkinson medications (OR = 3.754; 95% CI, 1.158-12.169; P = 0.027), osteoporosis (OR = 3.159; 95% CI, 1.167-8.552; P = 0.024), and use of walking aids (OR = 2.543; 95% CI, 1.544-4.188; P < 0.001). In conclusion, this study identified various medications and comorbidities, rather than polypharmacy based on the number of medications, as predictors associated with increased risk of falls resulting in hip fractures for local geriatric patients. The findings provided insights into the potential medication-related fall prevention strategies, including clinical medication review, adverse drug event monitoring, and drug optimization.

Effects of intravenous and oral esomeprazole in the prevention of recurrent bleeding from peptic ulcers after endoscopic therapy.

OBJECTIVES: The use of intravenous proton-pump inhibitors (PPIs) has shown to reduce recurrent bleeding and improve patient outcome after endoscopic hemostasis on patients with peptic ulcer. However, the efficacy of oral PPI is uncertain. Studies from Asia indicated that even oral PPI can achieve the same therapeutic effect. This study is designed to compare the efficacy of high-dose intravenous PPI to oral PPI in preventing recurrent bleeding after endoscopic hemostasis. METHODS: This is a single-center, randomized-controlled, double-blind, and double-dummy study. Patients had Forrest IA/IB or IIA/IIB peptic ulcer bleeding and received endoscopic hemostasis before recruitment into the study. They were randomized to receive either (i) esomeprazole IV bolus at a dose of 80 mg plus infusion at 8 mg/h for 72 h and oral placebo every 12 h (IVP group), or (ii) IV placebo bolus plus infusion for 72 h and high-dose oral esomeprazole at a dose of 40 mg every 12 h (ORP group). Patients were followed up for 30 days after index bleeding. The primary end point was defined as the 30-day recurrent bleeding after successful endoscopic hemostasis. RESULTS: A total of 118 patients were randomized to the IVP group and 126 to the ORP group in this study. In all, 39.8% in the IVP and 42.9% in the ORP group used non-steroidal anti-inflammatory drug and/or aspirin before bleeding. In the IVP group (vs. ORP), Forrest IA represented 1.7% (5.6%), IB 41.5% (38.1%), IIA 52.5% (50.8%), and IIB 4.2% (5.6%). Recurrent bleeding in 30 days was reported in 7.7% of patients in the IVP group and 6.4% of patients in the ORP group, and the difference of recurrent bleeding was -1.3% (95% CI: -7.7%, 5.1%). There was no difference in blood transfusion, repeated endoscopic therapy, and hospital stay between the two groups. CONCLUSIONS: High-dose oral esomeprazole at 40 mg BID may be considered as a useful alternative to IV bolus plus infusion of esomeprazole in the management of ulcer bleeding in patients who are not candidates for high-dose IV infusion. However, as this study was stopped prematurely and was not designed as an equivalency trial, a much larger study would be necessary to document whether there is equivalency or non-inferiority of the two treatments in a heterogeneous patient population.

Effectiveness and cost-effectiveness of erlotinib versus gefitinib in first-line treatment of epidermal growth factor receptor-activating mutation-positive non-small-cell lung cancer patients in Hong Kong.

OBJECTIVE: To compare the effectiveness and cost-effectiveness of erlotinib versus gefitinib as first-line treatment of epidermal growth factor receptor-activating mutation-positive non-small-cell lung cancer patients. DESIGN. Indirect treatment comparison and a cost-effectiveness assessment. SETTING: Hong Kong. PATIENTS: Those having epidermal growth factor receptor-activating mutation-positive non-small-cell lung cancer. INTERVENTIONS: Erlotinib versus gefitinib use was compared on the basis of four relevant Asian phase-III randomised controlled trials: one for erlotinib (OPTIMAL) and three for gefitinib (IPASS; NEJGSG; WJTOG). The cost-effectiveness assessment model simulates the transition between the health states: progression-free survival, progression, and death over a lifetime horizon. The World Health Organization criterion (incremental cost-effectiveness ratio <3 times of gross domestic product/capita:

Medication adherence: is it a hidden drug-related problem in hidden elderly?

AIM: The present study aimed to identify the health needs of the hidden elderly in Hong Kong, and to investigate the impacts of pharmacist and nursing interventions on medication management and well-being in hidden elderly. METHODS: Participants were recruited by social workers if they were aged 65 years or older; did not have normal social life and network; did not have family support; and were not linked to the existing network of community support. Pharmacists identified drug-related problems. The health needs of participants were assessed by observations and interviews. Outcome measurements were scores of Morisky 8-item Medication Adherence Scale and EuroQoL (Quality of Life) 5-D Questionnaire. RESULTS: A total of 93 participants were recruited and 86 participants completed the study. The mean age was 81.46 ± 5.70 years, the mean number of chronic disease was 3.29 ± 1.45 and the mean number of chronic medications was 6.36 ± 2.96. The most commonly observed chronic diseases were hypertension, cardiac problems, diabetes, hyperlipidemia and arthritis. Drug non-adherence and storage problems were found in 61.63% and 69.77% of participants. The mean total EuroQoL score increased by 1.05 (P ≤ 0.001). The mean Morisky score decreased by 0.61, signifying improvement of medication adherence (P< 0.001). Female sex (P = 0.045), polypharmacy with more than nine concurrent medications (P = 0.013), arthritis (P = 0.006) and drug storage problems (P = 0.002) were identified as factors associated with poor medication adherence. CONCLUSIONS: The majority of hidden elderly suffered from multiple chronic diseases, and the prevalence of drug-related problems was high. Pharmacist and nursing interventions improved drug-related problems, drug compliance and quality of life in hidden elderly.

Adiponectin is required for PPARγ-mediated improvement of endothelial function in diabetic mice.

Rosiglitazone is a PPARγ agonist commonly used to treat diabetes. In addition to improving insulin sensitivity, rosiglitazone restores normal vascular function by a mechanism that remains poorly understood. Here we show that adiponectin is required to mediate the PPARγ effect on vascular endothelium of diabetic mice. In db/db and diet-induced obese mice, PPARγ activation by rosiglitazone restores endothelium-dependent relaxation of aortae, whereas diabetic mice lacking adiponectin or treated with an anti-adiponectin antibody do not respond. Rosiglitazone stimulates adiponectin release from fat explants, and subcutaneous fat transplantation from rosiglitazone-treated mice recapitulates vasodilatation in untreated db/db recipients. Mechanistically, adiponectin activates AMPK/eNOS and cAMP/PKA signaling pathways in aortae, which increase NO bioavailability and reduce oxidative stress. Taken together, these results demonstrate that adipocyte-derived adiponectin is required for PPARγ-mediated improvement of endothelial function in diabetes. Thus, the adipose tissue represents a promising target for treating diabetic vasculopathy.

A cost-minimisation analysis comparing different antibiotic regimens used in treating all-cause bacterial pneumonia in Hong Kong.

BACKGROUND: To find out the antibiotic treatment regimens with the lowest cost for all-cause bacterial pneumonia, a study to compare the costs of different antibiotic regimens in the treatment of patients diagnosed with all-cause bacterial pneumonia who required hospitalisation was carried out. METHODOLOGY: This was a multicentre, retrospective study of patient medical records. The primary aim was to examine whether the initial choice of antibiotic had affected the total cost of treatment, while the secondary aim was to find out whether the initial choice of antibiotic had affected the initial treatment failure rates and death rates. A cost-minimisation analysis (CMA) from a public hospital perspective was employed. RESULTS: A total of 333 patient medical case notes were reviewed. The most commonly prescribed antibiotic regimen was amoxycillin-clavulanate (AC) followed by amoxycillin-clavulanate plus macrolide (ACM) and quinolone (Q). In the study population, no statistical significance could be detected between the mean cost of the three regimens. In the subgroup analysis of patients with a history of chronic obstructive pulmonary disease (COPD) and patients with a history of smoking, the Q regimen appeared to be the least expensive. CONCLUSION: In the study population, no significant difference could be identified between the mean cost of the three antibiotic regimens. In a special populations such as patients with a history of COPD and patients with a history of smoking, the Q regimen appeared to be superior. Further studies in these areas are needed.

In vivo assessment of herb-drug interactions: possible utility of a pharmacogenetic approach?

Herbal medicines are frequently used in combination with conventional drugs and interactions are likely to be more common than those which manifest clinically. Pharmacokinetic interactions mediated by drug-metabolizing enzymes or transporters are involved in many herb-drug interactions. Polymorphisms in the genes for these enzymes and transporters may influence the interactions mediated through these pathways. Herb-drug interactions can be identified in vivo using the herbs with individual probe drugs or drugs with a narrow therapeutic index. A probe drug cocktail approach offers a more efficient screening procedure. If potential interactions are studied in subject groups with different genotypes, more definitive information can be obtained. The selection of genotype groups to study should depend not only on the major enzymes or transporters involved in the disposition of a drug, but also on alternate pathways which may become more important in subjects with reduced activity in the primary pathway, and the pathways for pharmacodynamic effects should also be considered for some drugs. Some genotypes may only be found in certain ethnic groups. Currently, the pharmacogenetic approach has been used mainly to study drug-drug interactions so there is considerable potential to extend this to the study of herb-drug interactions in vivo.

Attenuation of phospholipid signaling provides a novel mechanism for the action of valproic acid.

Valproic acid (VPA) is used to treat epilepsy and bipolar disorder and to prevent migraine. It is also undergoing trials for cancer therapy. However, the biochemical and molecular biological actions of VPA are poorly understood. Using the social amoeba Dictyostelium discoideum, we show that an acute effect of VPA is the inhibition of chemotactic cell movement, a process partially dependent upon phospholipid signaling. Analysis of this process shows that VPA attenuates the signal-induced translocation of PH(Crac)-green fluorescent protein from cytosol to membrane, suggesting the inhibition of phosphatidylinositol-(3,4,5)-trisphosphate (PIP(3)) production. Direct labeling of lipids in vivo also shows a reduction in PIP and PIP(2) phosphorylation following VPA treatment. We further show that VPA acutely reduces endocytosis and exocytosis-processes previously shown to be dependent upon PIP(3) production. These results suggest that in Dictyostelium, VPA rapidly attenuates phospholipid signaling to reduce endocytic trafficking. To examine this effect in a mammalian model, we also tested depolarization-dependent neurotransmitter release in rat nerve terminals, and we show that this process is also suppressed upon application of VPA and an inhibitor of phosphatidylinositol 3-kinase. Although a more comprehensive analysis of the effect of VPA on lipid signaling will be necessary in mammalian systems, these results suggest that VPA may function to reduce phospholipid signaling processes and thus may provide a novel therapeutic effect for this drug.

Omeprazole before endoscopy in patients with gastrointestinal bleeding.

BACKGROUND: A neutral gastric pH is critical for the stability of clots over bleeding arteries. We investigated the effect of preemptive infusion of omeprazole before endoscopy on the need for endoscopic therapy. METHODS: Consecutive patients admitted with upper gastrointestinal bleeding underwent stabilization and were then randomly assigned to receive either omeprazole or placebo (each as an 80-mg intravenous bolus followed by an 8-mg infusion per hour) before endoscopy the next morning. RESULTS: Over a 17-month period, 638 patients were enrolled and randomly assigned to omeprazole or placebo (319 in each group). The need for endoscopic treatment was lower in the omeprazole group than in the placebo group (60 of the 314 patients included in the analysis [19.1%] vs. 90 of 317 patients [28.4%], P=0.007). There were no significant differences between the omeprazole group and the placebo group in the mean amount of blood transfused (1.54 and 1.88 units, respectively; P=0.12) or the number of patients who had recurrent bleeding (11 and 8, P=0.49), who underwent emergency surgery (3 and 4, P=1.00), or who died within 30 days (8 and 7, P=0.78). The hospital stay was less than 3 days in 60.5% of patients in the omeprazole group, as compared with 49.2% in the placebo group (P=0.005). On endoscopy, fewer patients in the omeprazole group had actively bleeding ulcers (12 of 187, vs. 28 of 190 in the placebo group; P=0.01) and more omeprazole-treated patients had ulcers with clean bases (120 vs. 90, P=0.001). CONCLUSIONS: Infusion of high-dose omeprazole before endoscopy accelerated the resolution of signs of bleeding in ulcers and reduced the need for endoscopic therapy. (ClinicalTrials.gov number, NCT00164866 [ClinicalTrials.gov] .).

Non-invasive serological detection of Helicobacter pylori antigens in adult Hong Kong Chinese non-ulcer dyspepsia patients.

OBJECTIVE: The aim of our study was to evaluate the accuracy of the serology test kit (Signify H. pylori test), an office-based serological test and to compare relative performances with endoscopy, including biopsy urease tests (Clotest), histology, and culture when applied to dyspeptic adult patients in Hong Kong Chinese. METHODS: Prospective clinical trial was conducted at the Alice Ho Miu ling Nethersole Hospital (AHNH) outpatient endoscopy center from June to December 2004 and included adult Chinese patients who attended the endoscopy center. A research nurse interviewed consenting patients and whole blood samples were obtained via simple fingerstick were then and transferred to Signify test kits. The results were read after 5 minutes. The presence of two distinct lines within the result-reading window was treated as a positive result; a single distinct line was treated as a negative result. All patients underwent upper gastroduodenal endoscopy, and antral/antrum gastric biopsy specimens were taken and then processed for microbiological cultures. RESULTS: A total of 384 patients were recruited in the study and 131 (34.7%) patients were tested positive for H. pylori. Among them, 62 patients (47.3%) were detected by the Signify H. pylori test. The Signify serology test kit was 52.7% sensitive, 87.9% specific, and 75.7% accurate, respectively in the current study. CONCLUSION: The Signify H. pylori test showed a sub-optimal correlation between the presence of H. pylori infection and the serological test results in a Hong Kong Chinese population.