Accounting for effects of system dynamics to improve accuracy of emissions reported in e-cig vaping machines.

Laboratory emissions testing of electronic cigarettes continues to be a focus in the tobacco research community. In particular, to inform policy regarding appropriate test protocols to regulate the manufacture, marketing and sale of tobacco products. This study aims to enhance current understanding of the way laboratory systems used to generate topography profiles and capture resultant emissions from inhaled tobacco products may interact with the device under test. A programmable emission system (vaping machine) is introduced and characterized. The operating envelope of this system is presented. This study demonstrates that the performance of an emissions system may be influenced by various factors, resulting in discrepancies between command puff parameter inputs and the observed puffs generated. The study findings conclude that any emissions system should be characterized with the desired test device to determine the effective operating range of the system under "Load" conditions. Furthermore, reporting emissions from electronic cigarettes as a function of "command" puff flow rate and cumulative volume result in under-estimation bias and may give rise to incorrect conclusions regarding the impact of product characteristics on emissions. Conversely, reporting emissions in terms of "observed" puff flow rate and cumulative volume reduces bias errors and limits opportunity for intentional misrepresentation of results.

Effect of e-liquid flavor on electronic cigarette topography and consumption behavior in a 2-week natural environment switching study.

Electronic Nicotine Delivery Systems (ENDS) offer an alternate means to consume nicotine in a variety of flavored aerosols. Data are needed to better understand the impact of flavors on use behavior. A natural environment observational study was conducted on experienced ENDS users to measure the effect of e-liquid flavor on topography and consumption behavior. The RIT wPUMTM monitor was used to record to record the date and time and puff topography (flow rate, volume, duration) for every puff taken by N = 34 participants over the course of two weeks. All participants used tobacco flavor for one week, and either berry or menthol flavor for one week. Results provide strong evidence that flavor affects the topography behaviors of mean puff flow rate and mean puff volume, and there is insufficient evidence to support an influence of flavor on mean puff duration and mean puff interval. There was insufficient evidence, due to the low power associated with the limited number of observation days, to establish a relationship between flavor and cumulative consumption behavior. While the results indicate that an effect may be evident, additional observation days are required to establish significance.

Week Long Topography Study of Young Adults Using Electronic Cigarettes in Their Natural Environment.

Results of an observational, descriptive study quantifying topography characteristics of twenty first generation electronic nicotine delivery system users in their natural environment for a one week observation period are presented. The study quantifies inter-participant variation in puffing topography between users and the intra-participant variation for each user observed during one week of use in their natural environment. Puff topography characteristics presented for each user include mean puff duration, flow rate and volume for each participant, along with descriptive statistics of each quantity. Exposure characteristics including the number of vaping sessions, total number of puffs and cumulative volume of aerosol generated from ENDS use (e-liquid aerosol) are reported for each participant for a one week exposure period and an effective daily average exposure. Significant inter-participant and intra-participant variation in puff topography was observed. The observed range of natural use environment characteristics is used to propose a set of topography protocols for use as command inputs to drive machine-puffed electronic nicotine delivery systems in a controlled laboratory environment.

Electronic Cigarette Topography in the Natural Environment.

This paper presents the results of a clinical, observational, descriptive study to quantify the use patterns of electronic cigarette users in their natural environment. Previously published work regarding puff topography has been widely indirect in nature, and qualitative rather than quantitative, with the exception of three studies conducted in a laboratory environment for limited amounts of time. The current study quantifies the variation in puffing behaviors among users as well as the variation for a given user throughout the course of a day. Puff topography characteristics computed for each puffing session by each subject include the number of subject puffs per puffing session, the mean puff duration per session, the mean puff flow rate per session, the mean puff volume per session, and the cumulative puff volume per session. The same puff topography characteristics are computed across all puffing sessions by each single subject and across all subjects in the study cohort. Results indicate significant inter-subject variability with regard to puffing topography, suggesting that a range of representative puffing topography patterns should be used to drive machine-puffed electronic cigarette aerosol evaluation systems.

The differential effects of statins on the risk of developing pancreatic cancer: a case-control study in two centres in the United Kingdom.

INTRODUCTION: There are plausible biological mechanisms for how statins may prevent pancreatic cancer, although the evidence from epidemiological studies in the general population is conflicting. This study aims to clarify whether statins exert their effects in specific sub-groups, namely, gender, smoking status and diabetes. METHODS: A matched case-control study was conducted in patients diagnosed with pancreatic cancer, and a group of dermatology patients of similar ages and gender, diagnosed with basal cell carcinoma. Participants' medical records were reviewed for information on statin use prior to diagnosis. Odds ratios and 95 % CIs for the development of pancreatic cancer were estimated using conditional logistic regression. Subgroup analysis was performed in men, women, smokers and those with type 2 diabetes. RESULTS: Two hundred fifty-two cases (median age 71 years, range 48-73 years, 51 % women) and 504 controls were identified, of which 23 % of cases were regular statin users versus 21 % of controls. In the general study population there was no association between pancreatic cancer and regular statin use (OR 0.82, 95 % CI 0.53-1.23, p = 0.33). However, in male smokers, regular statin use was associated with significantly reduced odds of pancreatic cancer compared to male smokers not prescribed a statin (OR 0.11, 95 % CI 0.01-0.96, p = 0.05). In patients with type 2 diabetes statins use was not associated with reduced odds (OR 0.92, 95 % CI 0.35-2.45, p = 0.80), with no gender effects. CONCLUSIONS: In male smokers, statins may reduce the odds of pancreatic cancer. Statin use should be measured in aetiological studies of pancreatic cancer but analysed in specific sub-groups. Future work should investigate statins as chemopreventative agents in this high risk sub-group.

Combined percutaneous-endoscopic stenting of malignant biliary obstruction: results from 106 consecutive procedures and identification of factors associated with adverse outcome.

BACKGROUND: In patients in whom attempted endoscopic stenting of malignant biliary obstruction fails, combined percutaneous-endoscopic stenting and percutaneous stenting using expandable metallic endoprostheses offer alternative approaches to biliary drainage. Despite the popularity of the percutaneous route, there is no available evidence to support its superiority over combined stenting in this patient group. The objective of this study was to present the short- and long-term results of a large series of combined percutaneous-endoscopic stenting procedures and identify factors associated with adverse outcome. METHODS: Data were retrospectively collected on patients undergoing combined percutaneous-endoscopic biliary stenting for malignant biliary obstruction between January 2002 and December 2006. Short- and long-term outcomes were recorded, and pre-procedure variables correlated with adverse outcome. RESULTS: Combined biliary stenting was technically successful in 102 (96.2%) of 106 patients. Procedure-associated mortality rate was 0%. In-hospital morbidity and mortality rates were 24.5% and 16.7%, respectively, with the majority of deaths resulting from biliary sepsis. Median survival was 100 days, with a 13.7% stent occlusion rate. On multivariable analysis, baseline American Society of Anaesthesiologists (ASA) grade, decreasing serum albumin and increasing leucocyte count were independently associated with in-hospital mortality following combined stenting. CONCLUSION: Combined biliary stenting is associated with short- and long-term outcomes equal to those reported in recent series of percutaneous transhepatic stenting. Randomised control trials, including cost-effectiveness analyses, are required to further compare these techniques. Outcomes following combined stenting may be further improved by early recognition and treatment of sepsis and scrupulous management of co-morbid disease.

Meta analysis: Cancer risk in Barrett's oesophagus.

BACKGROUND: Risk of cancer in Barrett's oesophagus is reported to vary between studies and also between countries, where the studies were conducted as per several systematic reviews. Cancer incidence has implications on surveillance strategies. AIM: To perform a meta-analysis to determine the incidence of oesophageal cancer in Barrett's oesophagus. METHODS: Articles retrieved by MEDLINE search (English language, 1966-2004). Studies had to necessarily include verified Barrett's oesophagus surveillance patients, documented follow-up and cancer identified as the outcome measure. A random effects model of meta-analysis was chosen and results were expressed as mean (95% CI). RESULTS: Forty-one articles selected for conventional Barrett's oesophagus (length >3 cm); eight included short segment Barrett's oesophagus (one additional article including only short segment Barrett's oesophagus). Cancer incidence was 7/1000 (6-9) person-years duration of follow-up (pyd), with no detectable geographical variation [UK 7/1000 (4-12) pyd, USA 7/1000 (5-9) pyd and Europe 8/1000 (5-12) pyd]. Cancer incidence in the UK was 10/1000 (7-14), when two large studies were excluded. Cancer incidence in SSBO was 6/1000 (3-12) pyd. When short segment Barrett's oesophagus compared to conventional Barrett's oesophagus, there was a trend towards reduced cancer risk [OR 0.55, (95% CI: 0.19-1.6), P = 0.25]. CONCLUSION: We found no geographical variations in Barrett's oesophagus cancer risk, but observed a trend towards reduced cancer risk in short segment Barrett's oesophagus. There is a time trend of decreasing cancer incidence.

Meta-analysis: cancer risk of low-grade dysplasia in chronic ulcerative colitis.

BACKGROUND: The cancer risk of low-grade dysplasia (LGD) in chronic ulcerative colitis is variable and its management remain contentious. AIM: To determine the risk of cancer or any advanced lesion once LGD is diagnosed. METHODS: A MEDLINE, EMBASE and Pub Med search was conducted using the key words 'surveillance', 'colorectal cancer', 'low-grade dysplasia' and 'ulcerative colitis'. A random effects model of meta-analysis was used. RESULTS: Twenty surveillance studies had 508 flat LGD or LGD with dysplasia-associated lesion or mass. An average of 4.3 colonoscopies was performed/patient post-LGD diagnosis (range: 3-7.6). An average of 18 biopsies taken per colonoscopy (range: 9-24) detected 73 advanced lesions (cancer or high-grade dysplasia) pre-operatively. The cancer incidence was 14 of 1000 (95% CI: 5.0-34) person years duration (pyd) and the incidence of any advanced lesion was 30 of 1000 pyd (95% CI: 12-76). When LGD is detected on surveillance there is a ninefold risk of developing cancer (OR: 9.0, 95% CI: 4.0-20.5) and 12-fold risk of developing any advanced lesion (OR: 11.9, 95% CI: 5.2-27). CONCLUSIONS: The risk of developing cancer in patients with LGD is high. These estimates are valuable for decision-making when LGD is encountered on surveillance.

High-grade dysplasia in Barrett's oesophagus: natural history and review of clinical practice.

BACKGROUND: Management of high-grade dysplasia in Barrett's oesophagus is controversial: surgery carries an appreciable morbidity/mortality, high-grade dysplasia may not progress to cancer and endoscopic ablation is an emerging option. AIM: To review Barrett's oesophagus-related high-grade dysplasia management and outcome over a 10-year period. METHODS: This was a retrospective case note review of 36 patients identified from a pathology database. RESULTS: There were 31 men of mean age 67 years. Endoscopic surveillance identified nine. Median follow-up was 21 months. Seven patients had no further intervention because of age/comorbidity. The other 29 had repeat endoscopic biopsies, nine showing cancer (six oesophagectomized). Of the 20 remaining patients with persisting high-grade dysplasia, eight had surgery (histology showed cancer in six), seven continued endoscopic surveillance (high-grade dysplasia regressed in four) and five had 'curative' argon ablation. An intensive biopsy protocol was not followed in 55% of endoscopies. Prevalent cancers occurred in 44% with an annual incidence of 5% over 5 years. All cause mortality was 39% (14 of 36, eight of 14 from cancer). CONCLUSIONS: Management of high-grade dysplasia was not uniform. Unsuspected cancer was common in high-grade dysplasia patients undergoing surgery but 13% regressed under surveillance. High-grade dysplasia patients have a high mortality but 43% did not die from cancer.

Osteoporosis and exercise.

Osteoporosis is a common medical problem. Lifestyle measures to prevent or help treat existing osteoporosis often only receive lip service. The evidence for the role of exercise in the prevention and treatment of osteoporosis is reviewed.

Respiratory symptoms in patients with treated hypothyroidism and inflammatory bowel disease.

BACKGROUND: Patients with idiopathic chronic cough and unexplained airflow obstruction in non-smokers have been shown to have an increased prevalence of hypothyroidism and other organ specific autoimmune disorders. Whether patients with hypothyroidism have an increased prevalence of respiratory symptoms is unknown. METHODS: The prevalence of respiratory symptoms was assessed in 124 patients with treated hypothyroidism recruited from primary and secondary care, 64 outpatients with inflammatory bowel disease, and 1346 control adults recruited randomly from the electoral register in a case-control study. Respiratory symptoms and smoking history were assessed by a respiratory symptom questionnaire. RESULTS: After adjustment for age, sex and smoking, symptoms of breathlessness and sputum production were more prevalent in both patient populations than in controls (odds ratios for hypothyroidism and inflammatory bowel disease; breathlessness: 3.1 (95% CI 2.1 to 4.6) and 3.4 (95% CI 2.0 to 6.0), respectively; sputum production: 2.7 (95% CI 1.6 to 4.5) and 2.5 (95% CI 1.2 to 5.0), respectively). Cough during the day and night was significantly more prevalent in patients with hypothyroidism (1.8 (95% CI 1.2 to 2.9)) and approached significance in those with inflammatory bowel disease (1.8 (95% CI 1.0 to 3.4)). Wheeze and nocturnal cough were no more prevalent in either disease population than in controls. CONCLUSION: There is a significantly increased prevalence of respiratory symptoms in patients with hypothyroidism or inflammatory bowel disease compared with controls recruited from the general population. Further work is required to determine whether similar differences are seen in comparison with hospital based controls. These findings support the hypothesis that there is a link between autoimmune hypothyroidism and respiratory disease.

Indications and efficacy of botulinum toxin in disorders of the gastrointestinal tract.

In recent years, botulinum toxin type A (BT) has been found to be effective in the treatment of various spastic disorders of smooth muscle in the upper and lower gastrointestinal tract. The short-term efficacy of intrasphincteric injection of BT in achalasia is now well established, however, because of the chronic nature of the disease, patients will require repeated injections at regular intervals. In contrast, after a single injection into the anal sphincter, BT has impressively high healing rate with minimal side effects. BT remains a novel therapeutic approach in a range of other gastrointestinal motility disorders including diffuse oesophageal spasm, sphincter of Oddi dysfunction and anismus, and the list of its indications is increasing. BT seems to be safe but as its long-term effects remain unestablished, it should be used with caution in younger patients. In this review we discuss the mechanism of action, indications, efficacy and side-effects of BT with its use in various areas of gastrointestinal tract.

Production and evaluation of guidelines for the management of inflammatory bowel disease: the Leicester experience.

Consensus guidelines for the management of patients with inflammatory bowel disease were produced by gastroenterologists, gastrointestinal surgeons and a cross-section of general practitioners (GPs) from Leicestershire in order to develop a seamless pattern of care with a common approach to diagnosis and treatment. It was hoped that the guidelines would encourage a movement towards care in the community for many patients with stable disease and so speed up new consultation rates. The study then assessed the impact of these guidelines on the referral letters of GPs to hospital consultants, the prediction of disease and adherence to them on re-referring patients after discharge. The guidelines were distributed to all 487 GPs in the Leicester Health Authority area and the gastroenterology teams within the hospitals. The value of the guidelines was assessed by an audit of referral letters, the length of time from referral letter to out-patient appointment, both before and after the launch of the guidelines, adherence to the guidelines on re-referral, and monitoring the outcome of the discharged patients. Whilst the guidelines may have helped GPs to manage stable patients in the community, the content of referral letters and the diagnostic abilities of GPs were not seen to improve since the launch of the guidelines. However, only 5% of stable patients who were discharged from one clinic were re-referred for inflammatory bowel disease.

Osteoporosis and determinants of bone density in patients with Crohn's disease.

Low bone mineral density (BMD) is common in patients with Crohn's disease; however, the pathogenesis of bone loss and risk factors for osteoporosis are not established. Our aim was to evaluate the clinical, dietary, and nutritional determinants of BMD in Crohn's disease. A cross-sectional analysis of 117 patients with Crohn's disease was undertaken. All patients underwent a clinical and dietary evaluation including assessment of nutritional state and life-style. BMD was measured at the hip and lumbar spine by dual-energy x-ray absorptiometry; and z scores obtained by comparison with age- and sex-matched normal values for the healthy UK population. Multiple regression analysis was used to assess associations between BMD and potential risk factors, allowing for possible confounding variables. Thirteen (11%) patients had osteoporosis (z score < -2), with osteopenia (z score < -1, > -2) in a further 34 (29%). Patients with jejunal disease had significantly lower BMD at the spine (P = 0.03) and femoral neck (P = 0.02) than those with disease at other sites. Mean BMD was significantly lower at the hip of patients with previous bowel resection (diff in means = 0.53, 95% CI -0.97, -0.08, P = 0.02), but type of surgery was not significant. Active disease, menstrual history, diet, level of physical activity, and smoking were not associated with low bone mass. At the lumbar spine, body weight (P < 0.0001), male sex (P < 0.0001), and current prednisolone use (P < 0.02) were independently predictive of low bone mass. Body weight (P < 0.0001), male sex (P < 0.0001), and cumulative steroid dose (P = 0.02) were predictive at the femoral neck. The major determinants of BMD in Crohn's disease are body weight, current steroid use, and cumulative steroid dose. Men with Crohn's disease are at greatest risk of osteoporosis, with jejunal involvement and previous bowel resection also contributing to the low bone mineral density.

Increased bone resorption in patients with Crohn's disease.

BACKGROUND: Patients with Crohn's disease are at risk of osteoporosis and premature fracture. However, the pathophysiology underlying bone loss remains poorly understood and the optimum treatment has not been established. AIM: To investigate mechanisms of bone loss in Crohn's disease using biochemical markers of bone turnover. METHODS: Bone mineral density was measured at the hip and spine using dual-energy X-ray absorptiometry in 117 patients (48 male) with Crohn's disease. Bone turnover was assessed by measuring serum osteocalcin (BGP), pro-collagen carboxy-terminal propeptide (PICP), bone specific alkaline phosphatase (BALP) and urinary deoxypyridinoline (DPD); and compared to age-matched healthy controls (n = 28). RESULTS: Bone mineral density was reduced (z-score < -1) in 48 (41%) patients with Crohn's disease. Mean values for bone formation markers in patients with Crohn's disease were all within the normal reference range (BGP 8.92 (+/- 3.23) ng/mL (normal range 3.4-10.0), BALP 17.6 (+/- 12.6) U/L (normal range 11.6-43.3), PICP 95.1 (+/- 46.5) ng/mL (normal range 69-163)) and were not significantly different to the control population. However, mean urinary DPD was significantly higher in patients with Crohn's disease compared to healthy controls (10.97 (+/- 9.22) nM DPD/mM creatinine vs. 5.02 (+/- 1.03) nM DPD/mM creatinine, difference in means = 5.95, 95% CI: -9.6 to -2.3, P = 0.00001) and compared to the UK reference range DPD levels were increased in 74 (63%) patients. CONCLUSIONS: Bone resorption as evidenced by urinary DPD was frequently increased in patients with Crohn's disease and was significantly higher than in an age-matched control population. The high levels of urinary DPD suggest increased bone collagen degradation may contribute to osteoporosis in patients with Crohn's disease. These results suggest anti-resorptive agents such as the bisphosphonates may be effective treatment for osteoporosis in Crohn's disease.

Sex hormone status and bone metabolism in men with Crohn's disease.

BACKGROUND: Men with Crohn's disease (CD) are at risk of osteoporosis, but the factors contributing to low bone mineral density and its optimum treatment have not been established. AIM: To investigate the sex hormone status of men with CD, and to establish the influence of sex hormones on their bone metabolism. METHODS: Bone density was measured by dual energy X-ray absorptiometry at the hip and lumbar spine in 48 men with CD. Total serum testosterone and gonadotrophins were measured in all subjects and the free androgen index calculated in men with low or borderline total testosterone. Serum osteocalcin, pro-collagen carboxy-terminal peptide, bone specific alkaline phosphatase and urinary deoxypyridinoline were measured as markers of bone turnover. RESULTS: Eight (17%) men had osteoporosis, and a further 14 (29%) had osteopenia. Three (6%) men had a low free androgen index and normal gonadotrophins consistent with secondary hypogonadism, two of whom had osteopenia of the hip and spine. Age (P = 0.002) and small bowel Crohn's disease (P = 0.02) were the only independent predictors of serum testosterone. There was a significant association between total testosterone and osteocalcin (r = 0.53, 95%, CI: 0.29-0.71, P = 0.0001) which was independent of age and current steroid use (P = 0.0001). CONCLUSIONS: Previously undiagnosed hypogonadism is an uncommon cause of low bone density in men with CD. The independent association between testosterone and the bone formation marker osteocalcin suggests sex hormone status influences bone metabolism in men with CD. The results suggest testosterone replacement might be effective treatment for some men with osteoporosis and Crohn's disease.

Effect of a low-impact exercise program on bone mineral density in Crohn's disease: a randomized controlled trial.

BACKGROUND & AIMS: Physical exercise increases bone mineral density (BMD) in healthy young adults and slows the rate of bone loss in later life. The aim of this randomized controlled trial was to investigate the effect of exercise on BMD in patients with Crohn's disease. METHODS: A total of 117 patients with Crohn's disease were randomized to a control group or a low-impact exercise program of increasing intensity. BMD (g/cm2) was measured at baseline and 12 months at the hip and spine (L2-L4) by dual energy x-ray absorptiometry. RESULTS: Nonsignificant gains in BMD occurred at the hip and spine in the exercise group compared with controls (P > 0.05). In fully compliant patients, BMD increased by 3.54% (7.95%) at the femoral neck, 2.97% (7.7%) at the spine, 4.1% (10.26%) at Ward's triangle, and 7.77% (8.2%) at the greater trochanter. Compared with controls, gain in BMD at the greater trochanter was statistically significant (difference in means, 4.67; 95% confidence interval, 0.86-8.48; P = 0.02). Increases in BMD were significantly related to the number of exercise sessions completed (femoral neck; r = 0.28; 95% confidence interval, 0.10-0.45; P = 0.04). CONCLUSIONS: Progressive low-impact exercise is a potentially effective method of increasing BMD in Crohn's disease. If sustained, the increases in BMD may reduce the risk of osteoporotic fracture.

Screening for osteoporosis in Crohn's disease. A detailed evaluation of calcaneal ultrasound.

OBJECTIVES: To compare calcaneal broadband ultrasonic attenuation (BUA) and velocity of sound (VOS) in patients with Crohn's disease with an age-matched control population. The validity of BUA as a screening tool for osteoporosis was evaluated and the relationship between BUA and previous fracture studied. DESIGN: Cross-sectional study. BACKGROUND: Since patients with Crohn's disease are at risk of osteoporosis and premature fracture, routine assessment of bone mineral density (BMD) is recommended. Quantitative ultrasound of the calcaneum is an inexpensive and radiation-free means of assessing bone density which also provides information on bone microstructure. METHODS: BUA (dB/MHz) and VOS (m/s) were measured at the calcaneum (CUBAclinical, McCue Ultrasonics, Winchester, UK) and compared with bone mineral density at the hip and lumbar spine measured by dual-energy X-ray absorptiometry (DEXA); 100 patients (42 men) with Crohn's disease and 52 age-matched healthy controls (23 men) were studied. RESULTS: BUA was significantly reduced in patients with Crohn's disease compared with age-matched controls [76.53 dB/MHz (+/-17.3) vs 87.29 dB/MHz (+/-17.9), difference in means = 10.76, 95% CI -16.67, -4.85, P = 0.0004] and was significantly associated with BMD at the spine (r = 0.49, 95% CI 0.32, 0.63, P< 0.0001) and femoral neck (r = 0.54, 95% CI 0.38, 0.67, P < 0.0001). In the diagnosis of osteoporosis (t score <-2.5) BUA had a sensitivity of 66.7% at the femoral neck, with a specificity of 85.6%; sensitivity of BUA at the spine was 75% with specificity 89%. CONCLUSION: Patients with Crohn's disease have reduced BUA compared with an age-matched control population. Calcaneal BUA is significantly associated with BMD at the hip and spine but the correlation is insufficient to recommend ultrasound as a screening tool for DEXA.