Oral etoposide for patients with metastatic gastric adenocarcinoma

PURPOSE: Oral administration of etoposide represents a pharmacokinetic advantage over the traditional intermittent intravenous usage of this drug. This phase II trial was undertaken to determine its activity against gastric adenocarcinoma in chemotherapy-naive patients. PATIENTS AND METHODS: Patients with measurable, unresectable, metastatic gastric carcinoma with performance status < or = 2 by Zubrod scale were eligible. Patients had to have normal liver, renal, and bone marrow functions. Written informed consent was obtained from all patients. The starting dose of etoposide was 50 mg/m2/day, given orally daily for 21 days, followed by a 7-day rest period. Oral etoposide was repeated every 28 days. Response was evaluated after two courses. RESULTS: Twenty-eight patients were registered. The median number of courses was two (range, 1 to 12; total, 69 courses). Twenty-six patients were evaluable for response and toxicity. Five patients (19%; 95% confidence interval, 3% to 35%) achieved a partial response. The median duration of response was 3.5 months. There was no treatment-related death. Toxic effects were mild to moderate. CONCLUSIONS: Oral etoposide is modestly active against gastric carcinoma. It is well tolerated by patients. Further studies in combination with other active agents against gastric carcinoma may be warranted.     

Prevalence of appropriate colorectal cancer screening and preferences for receiving screening advice among people attending outpatient clinics

Objective: To examine among people attending outpatient clinics aged 50–74 at average risk of colorectal cancer (CRC): 1) The proportion who report: a) faecal occult blood test (FOBT) within the past two years; and b) colonoscopy within the past five years, including the reasons for undergoing colonoscopy; 2) characteristics associated with under‐screening; 3) For those who are under‐screened, the proportion who are: a) willing to receive help and the acceptability of different methods of receiving help, and; b) unwilling to receive help and reasons for this. Methods: Cross‐sectional survey of 197 participants attending a major regional hospital in New South Wales, Australia. Multivariable logistic regression was used to determine correlates of under‐screening. Results: A total of 59% reported either FOBT in the past two years or colonoscopy in the past five years. Of those reporting colonoscopy in the past five years, 21% were potentially over‐screened. Males were more likely than females to be under‐screened. Of those under‐screened (41%), fewer than half were willing to receive screening advice. Conclusions and implications for public health: A significant proportion of people attending outpatient clinics are under‐screened for CRC, with some people also over‐screened. There is a need to explore strategies to overcome both under‐ and over‐screening.     

Posttraumatic Stress Disorder and Incident Heart Failure Among a Community-Based Sample of US Veterans

Objectives. We investigated the association between posttraumatic stress disorder (PTSD) and incident heart failure in a community-based sample of veterans.Methods. We examined Veterans Affairs Pacific Islands Health Care System outpatient medical records for 8248 veterans between 2005 and 2012. We used multivariable Cox regression to estimate hazard ratios and 95% confidence intervals for the development of heart failure by PTSD status.Results. Over a mean follow-up of 7.2 years, veterans with PTSD were at increased risk for developing heart failure (hazard ratio [HR] = 1.47; 95% confidence interval [CI] = 1.13, 1.92) compared with veterans without PTSD after adjustment for age, gender, diabetes, hyperlipidemia, hypertension, body mass index, combat service, and military service period. Additional predictors for heart failure included age (HR = 1.05; 95% CI = 1.03, 1.07), diabetes (HR = 2.54; 95% CI = 2.02, 3.20), hypertension (HR = 1.87; 95% CI = 1.42, 2.46), overweight (HR = 1.72; 95% CI = 1.25, 2.36), obesity (HR = 3.43; 95% CI = 2.50, 4.70), and combat service (HR = 4.99; 95% CI = 1.29, 19.38).Conclusions. Ours is the first large-scale longitudinal study to report an association between PTSD and incident heart failure in an outpatient sample of US veterans. Prevention and treatment efforts for heart failure and its associated risk factors should be expanded among US veterans with PTSD.Posttraumatic stress disorder (PTSD) is a psychiatric illness that affects approximately 7.7 million Americans aged older than 18 years.1 PTSD typically results after the experience of severe trauma, and veterans are at elevated risk for the disorder. The National Vietnam Veterans Readjustment Study reported the prevalence of PTSD among veterans who served in Vietnam as 15.2% among men and 8.1% among women.2 In fiscal year 2009, nearly 446 045 Veterans Administration (VA) patients had a primary diagnosis of PTSD, a threefold increase since 1999.3 PTSD is of growing clinical concern as evidence continues to link psychiatric illnesses to conditions such as arthritis,4 liver disease,5 digestive disease,6 and cancer.6 When the postwar health status of Vietnam veterans was examined, those with PTSD had higher rates of diseases of the circulatory, nervous, digestive, musculoskeletal, and respiratory systems.7The evidence linking PTSD to coronary heart disease (CHD) is substantial.8–10 Veterans with PTSD are significantly more likely to have abnormal electrocardiograph results, myocardial infarctions, and atrioventricular conduction deficits than are veterans without PTSD.11 In a study of 605 male veterans of World War II and the Korean War, CHD was more common among veterans with PTSD than among those without PTSD.12 Worldwide, adults exposed to the disaster at Chernobyl experienced increased rates of CHD up to 10 years after the event,13 and studies of stressors resulting from the civil war in Lebanon found elevated CHD mortality.14,15Although the exact biological mechanism by which PTSD contributes to CHD remains unclear, several hypotheses have been suggested, including autonomic nervous system dysfunction,16 inflammation,17 hypercoagulability,18 cardiac hyperreactivity,19 altered neurochemistry,20 and co-occurring metabolic syndrome.16 One of the hallmark symptoms of PTSD is hyperarousal,21 and the neurobiological changes brought on from sustained sympathetic nervous system activation affect the release of neurotransmitters and endocrine function.22 These changes have negative effects on the cardiovascular system, including increased blood pressure, heart rate, and cardiac output.22,23Most extant literature to date examining cardiovascular sequelae has shown a positive association between PTSD and coronary artery disease.8–10 Coronary artery disease is well documented as one of the most significant risk factors for future development of heart failure.24 Despite burgeoning evidence for the role of PTSD in the development of coronary artery disease, there are few studies specifically exploring the relationship between PTSD and heart failure. Limited data suggest that PTSD imparts roughly a threefold increase in the odds of developing heart failure in both the general population5 and in a sample of the elderly.25 These investigations, however, have been limited by cross-sectional study design, a small proportion of participants with PTSD, and reliance on self-reported measures for both PTSD and heart failure.5,25 Heart failure is a uniquely large public health issue, as nearly 5 million patients in the United States are affected and there are approximately 500 000 new cases each year.26 Identifying predictors of heart failure can aid in early detection efforts while simultaneously increasing understanding of the mechanism behind development of heart failure.To mitigate the limitations of previous investigations, we undertook a large-scale prospective study to further elucidate the role of prevalent PTSD and development of incident heart failure among veterans, while controlling for service-related and clinical covariates. Many studies investigating heart failure have relied on inpatient records; we leveraged outpatient records to more accurately reflect the community burden of disease.     

Acid and stretch, but not capsaicin, are effective stimuli for ATP release in the porcine bladder mucosa: Are ASIC and TRPV1 receptors involved?

Stretch-evoked ATP release from the bladder mucosa is a key event in signaling bladder fullness. Our aim was to examine whether acid and capsaicin can also release ATP and to determine the receptors involved, using agonists and antagonists at TRPV1 and acid-sensing ion channels (ASICs). Strips of porcine bladder mucosa were exposed to acid, capsaicin or stretch. Strip tension was monitored. Bath fluid was collected for ATP measurement. Gene expression of ASICs and TRPV1 in porcine bladders was quantified using quantitative real-time PCR (qRT-PCR). Stretch stimulus (150% of original length) repeatedly and significantly increased ATP release to approximately 45 times basal release. Acid (pH 6.5, 6.0, 5.6) contracted mucosal strips and also increased ATP release up to 30-fold, without evidence of desensitization. Amiloride (0.3 μM) reduced the acid-evoked ATP release by approximately 70%, while capsazepine (10 μM) reduced acid-evoked ATP release at pH 6.0 and pH 5.6 (by 68% and 61%, respectively). Capsaicin (0.1-10 μM) was ineffective in causing ATP release, and also failed to contract porcine mucosal or detrusor strips. Gene expression for ASIC1, ASIC2, ASIC3 and TRPV1 was seen in the lateral wall, dome, trigone and neck of both detrusor and mucosa. In conclusion, stretch and acid induce ATP release in the porcine bladder mucosa, but capsaicin is ineffective. The pig bladder is a well-known model for the human bladder, however these data suggest that it should be used with caution, particularly for TRPV1 related studies.     

PCV16 Smoking Related Costs in the United States

Smoking is a high-risk behavior that affects the health and economic welfare of society. Thus, it is important to quantify the economic burden smoking places on social institutions in the United States.
OBJECTIVE: The purpose of this review paper is to analyze smoking cost studies and to provide estimates that represent the economic costs of smoking from different perspectives of society, and as a whole.
METHODS: Current Contents (1996–), Health Star (1970–), and Medline (1966–) databases were searched through the use of pertinent subject headings and key words: tobacco use, smoking, cost, and economics. The internet was utilized to identify potential sources of epidemiological and cost information on smoking. Recent cost-of-illness studies using different methodologies: human capital, incidence, and prevalence were chosen for review based on their relevance.
RESULTS: Preliminary results indicate that the published cost studies available underestimate the "true" costs of smoking. The most current articles approximate annual direct medical costs to health care payers of $50 billion (1993); inflating to 1997 equals $59 billion or $1,200 per smoker. Although the latest cost studies do not attempt to estimate indirect costs, past studies have found indirect costs to be 1.5–2 times the direct costs. Therefore, using direct and indirect costs we estimate total smoking costs to be $150 billion (1993); inflating to 1997 equals $176 billion or $3,500 per smoker.
CONCLUSION: Quantifying the cost of smoking is a difficult task due to tobacco use infiltrating many aspects of life and the dependency of cost on perspective. Cost-of-illness studies provide cost estimation data which can be useful in aiding decision-makers who are allocating health care resources.     

A high dietary concentration of inulin is necessary to reduce the incidence of swine dysentery in pigs experimentally challenged with Brachyspira hyodysenteriae

A total of sixty surgically castrated male pigs (Large White?×?Landrace) weighing 31·2 (sd 4·3)?kg were used in a randomised block experiment to examine the effect of added dietary inulin (0, 20, 40 and 80?g/kg) on the occurrence of swine dysentery (SD) and on fermentation characteristics in the large intestine after experimental challenge with the causative spirochaete Brachyspira hyodysenteriae. The pigs were allowed to adapt to the diets for 2 weeks before each pig was challenged orally four times with a broth culture containing B. hyodysenteriae on consecutive days. Increasing dietary levels of inulin linearly (P?=?0·001) reduced the risk of pigs developing SD; however, eight out of fifteen pigs fed the diet with 80?g/kg inulin still developed the disease. The pH values in the caecum (P?=?0·072) tended to decrease, and in the upper colon, the pH values did decrease (P?=?0·047) linearly with increasing inulin levels in the diets, most probably due to a linear increase in the concentration of total volatile fatty acids in the caecum (P?=?0·018), upper colon (P?=?0·001) and lower colon (P?=?0·013). In addition, there was a linear reduction in the proportion of the branched-chain fatty acids isobutyric acid and isovaleric acid in the caecum (P?=?0·015 and 0·026) and upper colon (P?=?0·011 and 0·013) with increasing levels of dietary inulin. In conclusion, the present study showed that a diet supplemented with a high level of inulin (80?g/kg) but not lower levels reduced the risk of pigs developing SD, possibly acting through a modification of the microbial fermentation patterns in the large intestine.     

Review article: smoking cessation as primary therapy to modify the course of Crohn's disease

This article aims to offer an updated review of the effects of smoking on inflammatory bowel disease, and provide a review of the methods of achieving smoking cessation. A systematic review of Embase and Medline databases was conducted. Smoking causes opposing effects on ulcerative colitis and Crohn's disease. The odds ratio of developing ulcerative colitis for smokers compared with lifetime non-smokers is 0.41. Conversely, smokers with Crohn's disease have a more aggressive disease requiring more therapeutic intervention. Smoking cessation is associated with a 65% reduction in the risk of a relapse as compared with continued smokers, a similar magnitude to that obtained with immunosuppressive therapy. Although difficult to achieve smoking cessation can best be encouraged by accessing appropriate counselling services, nicotine replacement therapy and bupropion. Using a combination of these treatments there is an improved chance of success of up to 20% compared with an unassisted quit attempt. Smoking cessation unequivocally improves the course of Crohn's disease and should be a primary therapeutic aim in smokers with Crohn's disease.