Real-world effectiveness of elbasvir/grazoprevir In HCV-infected patients in the US veterans affairs healthcare system.

Elbasvir/grazoprevir (EBR/GZR) is an all-oral direct-acting antiviral agent (DAA) with high sustained virologic response (SVR) in clinical trials. This study's primary objective was to evaluate effectiveness of EBR/GZR among HCV-infected patients in a real-world clinical setting. We conducted a nationwide retrospective observational cohort study of HCV-infected patients in the US Department of Veterans Affairs (VA) using the VA Corporate Data Warehouse. The study population included patients with positive HCV RNA who initiated EBR/GZR from February 1 to August 1, 2016. We calculated the 95% confidence interval for binomial proportions for SVR overall and by demographic subgroups. Clinical and demographic characteristics were also evaluated. We included 2436 patients in the study cohort. Most were male (96.5%), African American (57.5%), with mean age of 63.5 (SD = 5.9) and 95.4% infected with genotype (GT) 1 [GT1a (34.7%), GT1b (58.6%)]. Other comorbidities included diabetes (53.2%), depression (57.2%) and HIV (3.0%). More than 50% had history of drug or alcohol abuse (53.9% and 60.5%, respectively). 33.2% of the cohort had cirrhosis. A total of 95.6% (2,328/2,436; 95% CI: 94.7%-96.4%) achieved SVR. The SVR rates by subgroups were: male, 95.5% (2245/2350); female, 96.5% (83/86); GT1a, 93.4%, GT1b, 96.6%, GT4, 96.9%, African American, 95.9% (1,342/1,400); treatment-experienced, 96.3% (310/322); cirrhosis, 95.6% (732/766); stage 4-5 CKD, 96.3% (392/407); and HIV, 98.6% (73/74). SVR rates were high overall and across patient subgroups regardless of gender, race/ethnicity, cirrhosis, renal impairment or HIV. This study provided important data regarding the effectiveness of EBR/GZR in a large clinical setting.

Hepatitis C virus-related complications are increasing in women veterans: A national cohort study.

There are gender-specific variations in the epidemiology and clinical course of hepatitis C virus (HCV) infection. However, few long-term longitudinal studies have examined trends in the incidence and prevalence of serious liver complications among women compared with men with HCV infection. We used the Veterans Administration Corporate Data Warehouse to identify all veterans with positive HCV viraemia from January 2000 to December 2013. We calculated gender-specific annual incidence and prevalence rates of cirrhosis, decompensated cirrhosis and hepatocellular cancer (HCC) adjusting for age, diabetes, HIV and alcohol use. We also calculated the average annual per cent change (AAPC) for each outcome by gender using piecewise linear regression in the Joinpoint software. We identified 264 409 HCV-infected veterans during 2000-2013, of whom 7162 (2.7%) were women. There were statistically significant increases over time in the incidence rates of cirrhosis, decompensated cirrhosis and HCC for both men and women. The annual-adjusted incidence rates of cirrhosis, decompensated cirrhosis and HCC were higher in men than women for all study years. However, these complications increased at a similar rate in both groups. Specifically, the AAPC for cirrhosis was 13.1 and 15.2, while it was 15.6 and 16.9 for decompensated cirrhosis and 21.0 and 25.3 for HCC in men and women, respectively (all test of parallelism not significant). The results were similar in the prevalence analyses, although AAPCs were slightly smaller for each outcome. In conclusion, we found an ongoing upward trend in the incidence and prevalence of HCV complications in this cohort of HCV-infected women. This increase in cirrhosis complications in women with active HCV infection is similar to those in men. With cure from HCV now becoming a reality, most of the projected burden of HCV is potentially preventable. However, benefits of HCV treatment will need to extend to all patients in order to stem the rising tide of HCV complications.

Relative social standing and suicide ideation among Kenyan males: the interpersonal theory of suicide in context.

PURPOSE: The purpose of this study is to investigate the association between subjective social status and suicide ideation in a sample of young Kenyan men (age 18-34 years). Situating insights from the interpersonal theory of suicide within social determinants of health framework, we consider whether lower subjective social status predicts lower collective self-esteem (CSE), hopelessness, less meaning in life and more loneliness, and whether these characteristics mediate associations between subjective social status and suicide ideation. METHOD: A community-based, semi-rural sample (n = 532) of young men, aged 18-34 years, was collected using a standardized questionnaire. The survey questionnaire included the following validated scale items: the short form of the Social and Emotional Loneliness Scale for Adults, CSE, Herth Hope Index, the Meaning in Life Questionnaire, and the Modified Scale for Suicide Ideation. Regression and mediation analyses were used to test hypotheses. RESULTS: Nearly 12% of respondents reported suicide ideation. Suicide ideation was significantly more common among survey respondents who reported lower subjective social standing. In the first of two mediation models, we found that lower CSE and more loneliness mediate the association between lower subjective social status and suicide ideation. In the second model, we found that respondents with lower CSE and more loneliness expressed lower hope and meaning in life, which also mediated pathways to suicide ideation. CONCLUSIONS: Findings show a novel synthesis of social determinants literature with the interpersonal theory of suicide. Suicide ideation, along with other mental and social outcomes, may figure more prominently than previously appreciated in the benefits of socio-economic equality. Those who do not participate equally in socio-economic development may be at greater risk of engaging in suicide ideation and behaviors. Suicide prevention research and programmatic responses should adopt a health equity perspective to ensure that prevention is targeted where people are more likely to engage in suicide ideation.

Epidemiology and outcomes of hepatitis C infection in elderly US Veterans.

The chronic hepatitis C (CHC) cohort in the United States is getting older. Elderly patients with CHC may be at a high risk of cirrhosis and hepatocellular carcinoma (HCC), but also other nonhepatic comorbidities that negatively impact their likelihood of receiving or responding to antiviral treatment. There is little information on the clinical epidemiology or outcomes of CHC and its treatment in the elderly. We conducted a retrospective cohort study of 1 61 744 patients with a positive Hepatitis C virus RNA in the Veterans Health Administration Hepatitis C Clinical Case Registry to examine the association between age subgroups (20-49, 50-64, 65-85 years) and risk of cirrhosis, HCC or death using Cox proportional hazards models. We also examined the effect of treatment with a sustained viral response (SVR) on these outcomes in each age subgroup. The age distribution was 36.8% 20- to 49-year-olds, 57.6% 50- to 64-year-olds and 5.6% 65- to 85-year-olds (i.e. elderly). Risk of cirrhosis, HCC and death was significantly elevated in elderly patients [HR cirrhosis = 1.14 (1.00-1.29), HR HCC = 2.44 (1.99-2.99); HR death 2.09 (1.98-2.22)] compared with younger patients. The incidence of HCC was than 8.4 per 1000 PY in the elderly compared with 2.6 per 1000 PY and 5.7 per 1000 PY, among the 20-49 and 50-64 age groups, respectively. Elderly patients were significantly less likely to receive antiviral treatment (3.8% vs 14.8% and 19.1%, P < 0.0001), but among those who received treatment SVR was not different among the age groups (33.5% vs 33.2% and 32.1%). In an analysis limited to those who received treatment, SVR compared to treatment receipt with no SVR was associated with a reduction in risk of developing cirrhosis (HR = 0.34; 0.18-0.66) and HCC (HR = 0.60; 0.22-1.61) and all-cause mortality risk (HR = 0.52, 0.33-0.82). Elderly patients with CHC are more likely to develop HCC than younger patients but have traditionally received less antiviral treatment than younger patients. However, receipt of curative treatment is associated with a benefit in reducing cirrhosis, HCC and overall mortality, irrespective of age.

Physical activity and the risk of Barrett's esophagus.

Physical activity either directly or through influencing body fat may affect the risk of Barrett's esophagus (BE). However, the effect of physical activity on the risk of developing BE has not been examined. We conducted a case-control study among consecutive eligible patients either scheduled for elective endoscopy or recruited from primary care clinics to undergo a study endoscopy. Study participants completed the International Physical Activity Questionnaire (IPAQ) short form that measures physical activity during the past 7 days. We categorized level of physical activity by low, moderate, or high and estimated metabolic equivalent minutes per week (MET min/week). We calculated odds ratios (ORs) using logistic regression models and adjusted for age, sex, race, gastroesophageal reflux disease symptoms, Helicobacter pylori infection, body mass index, and waist-to-hip ratio. There were 307 cases with BE and 1724 controls (1262 from endoscopy and 462 from the primary care clinic) with IPAQ information. BE cases were more likely to be in the high-category physical activity category than controls (14.3% vs. 11.5% P = 0.08). However, there were no differences in the overall average MET min/week for walking between BE cases and controls (909 vs. 561; P = 0.16), with similar findings among those with moderate activity (1094 vs. 755, P = 0.18) or vigorous activity (784 vs. 826, P = 0.93). In multivariable logistic regression, physical activity level was not significantly associated with BE (OR = 1.19, 95% confidence interval: 0.82-1.73). Recent amount and intensity of physical activity are not associated with a reduction in the risk of BE. Studies are required to examine the long-term effects of physical activity.

Brief report: the length of newly diagnosed Barrett's esophagus may be decreasing.

Few studies have examined the temporal trends of length in newly diagnosed Barrett's esophagus (BE) and arrived at conflicting results. The aim of this study was to identify whether there has been a change over time in the length of BE at the time of diagnosis. This is a retrospective, single-center, observational study from Houston, Texas on newly diagnosed BE between 2008 and 2013. All cases were defined by the presence of endoscopically visible BE and histologic confirmation of intestinalized columnar epithelium with goblet cells. The length of BE was measured using the Prague classification. We examined temporal changes in 1-year intervals in the length of BE at the time of diagnosis. Both the frequency and mean length of BE at diagnosis seemed to decrease over time from February 2008 to July 2013. The proportion of patients diagnosed with BE ≥3 cm per year declined during the study period, while the proportion of patients with BE ≥1 and <3 cm increased, and those with <1 cm remained stable. The mean age and the gender of patients diagnosed with BE ≥3 cm did not differ significantly by BE length or year of diagnosis. The mean length of newly diagnosed BE may be decreasing as a result of a decline in BE ≥3 cm. These observations cannot be explained by changes in age and gender.

Personal and family history of cancer and the risk of Barrett's esophagus in men.

The association between Barrett's esophagus (BE) and a personal or family history of cancer other than gastroesophageal remains unknown. To evaluate the effect of personal and family history of certain cancers and cancer treatments on the risk of BE, we analyzed data from a Veterans Affairs case-control study that included 264 men with definitive BE (cases) and 1486 men without BE (controls). Patients with history of esophageal or gastric cancer were excluded. Patients underwent elective esophagogastroduodenoscopy or a study esophagogastroduodenoscopy concurrently with screening colonoscopy to determine BE status. Personal and family history of several types of cancer was obtained from self-reported questionnaires, supplemented and verified by electronic medical-record reviews. We estimated the association between personal and family history of cancer or radiation/chemotherapy, and BE. Personal history of oropharyngeal cancer (1.5% vs. 0.4%) or prostate cancer (7.2% vs. 4.4%) was more frequently present in cases than controls. The association between BE and prostate cancer persisted in multivariable analyses (adjusted odds ratio 1.90; 95% confidence interval 1.07-3.38, P = 0.028) while that with oropharyngeal cancer (adjusted odds ratio 3.63; 95% confidence interval 0.92-14.29, P = 0.066) was attenuated after adjusting for retained covariates of age, race, gastroesophageal reflux disease, hiatal hernia, and proton pump inhibitor use. Within the subset of patients with cancer, prior treatment with radiation or chemotherapy was not associated with BE. There were no significant differences between cases and controls in the proportions of subjects with several specific malignancies in first- or second-degree relatives. In conclusion, the risk of BE in men may be elevated with prior personal history of oropharyngeal or prostate cancer. However, prior cancer treatments and family history of cancer were not associated with increased risk of BE. Further studies are needed to elucidate if there is a causative relationship or shared risk factors between prostate cancer and BE.

Sleep duration and incidence of colorectal cancer in postmenopausal women.

BACKGROUND: Sleep duration is dependent on circadian rhythm that controls a variety of key cellular functions. Circadian disruption has been implicated in colorectal tumorigenesis in experimental studies. We prospectively examined the association between sleep duration and risk of colorectal cancer (CRC). METHODS: In the Women's Health Initiative Observational Study, 75 828 postmenopausal women reported habitual sleep duration at baseline 1993-1998. We used Cox proportional hazards regression model to estimate the hazard ratio (HR) of CRC and its associated 95% confidence interval (CI). RESULTS: We ascertained 851 incident cases of CRC through 2010, with an average 11.3 years of follow-up. Compared with 7 h of sleep, the HRs were 1.36 (95% CI 1.06-1.74) and 1.47 (95% CI 1.10-1.96) for short (≤5 h) and long (≥9 h) sleep duration, respectively, after adjusting for age, ethnicity, fatigue, hormone replacement therapy (HRT), physical activity, and waist to hip ratio. The association was modified by the use of HRT (P-interaction=0.03). CONCLUSION: Both extreme short and long sleep durations were associated with a moderate increase in the risk of CRC in postmenopausal women. Sleep duration may be a novel, independent, and potentially modifiable risk factor for CRC.

Esophageal eosinophilia after radiofrequency ablation for Barrett's esophagus.

Radiofrequency ablation (RFA) with HALO system has been developed as a new treatment option for Barrett's esophagus (BE). It had been observed that some patients had esophageal eosinophilia (EE) infiltration after RFA. The incidence and features of EE after RFA were systematically determined. From a prospectively compiled database, data on 148 patients who underwent RFA for BE were analyzed. Biopsies were taken pre- and post-RFA from the BE segment, and histological sections of the biopsy specimens were stained with hematoxylin and eosin, and examined by a gastrointestinal pathologist. The incidence of EE post-RFA was then determined. Of the 148 patients, 120 (81%) were men, 137 (92%) were white, 64 (43%) were overweight and 49 (33%) obese, and 128 (86%) were over 50 years of age or more. Four (2.7%) of the patients developed post-RFA EE, but none had symptoms of eosinophilic esophagitis. All patients except one had a history of seasonal allergies. All four were taking proton pump inhibitor before and after RFA. Two patients with EE drank alcohol, one of which was a smoker. EE is a potential adverse event of RFA for BE. The absence of esophageal dysfunction symptoms suggests a different clinicopathological entity from eosinophilic esophagitis. Further studies should be done to assess its clinical significance, if therapy is needed, or if it may eventually lead to eosinophilic esophagitis.

Human papillomavirus and the risk of Barrett's esophagus.

Human papillomavirus (HPV) is strongly associated with squamous esophageal cancer. The potential role of HPV in Barrett's esophagus (BE) has been examined but remains unclear. The aim of the study was to determine the prevalence of HPV in esophageal and gastric tissues obtained from patients with and without BE. We designed a cross-sectional study was conducted with prospective enrollment of eligible patients scheduled for esophagogastroduodenoscopy (EGD). All participants had biopsies of endoscopic BE, squamous-lined esophagus, and stomach. Immunohistochemistry (IHC) on formalin-fixed and paraffin-embedded tissue was conducted using monoclonal antibodies. Polymerase chain reaction (PCR) for HPV was performed on DNA extracted from esophageal biopsies snapped frozen within 30 minutes after endoscopic capture. The Roche HPV Linear Array Assay with PGMY primers that has high sensitivity for detecting 37 types of HPV was used. A total of 127 subjects were included: 39 with definitive BE had IHC done on samples from non-dysplastic BE, squamous esophagus, gastric cardia, and gastric body; and 88 control patients without BE had IHC done on squamous esophageal samples, gastric cardia, and gastric body. HPV was not detected in any of the samples in either group. For confirmation, HPV DNA PCR was performed on randomly selected samples from 66 patients (both esophagus and BE from 13 patients with BE, and 53 esophagus from patients without BE); no sample had HPV DNA detected via PCR in the presence of adequate quality control. HPV infection does not play a role in the formation of non-dysplastic Barrett's esophagus in men in the United States.

Patients' intuitive judgments about surveillance endoscopy in Barrett's esophagus: a review and application to models of decision-making.

Adherence to practice guidelines for endoscopic surveillance of Barrett's esophagus is equivocal with evidence of underutilization and overutilization. While physicians report strong agreement with and adherence to recommended surveillance endoscopy (esophagogastroduodenoscopy [EGD]) guidelines, less is known about modifiable barriers and facilitators shaping patients' adherence behaviors. The aim of this study is to conduct a structured literature review of studies exploring patients' perspectives regarding surveillance EGD and to place these results within a conceptual framework. A structured literature review of PubMed, Cochrane, and Google Scholar databases with qualitative thematic analysis was performed. Six studies met eligibility criteria. Analysis of results identified five distinct themes. First, patients' objective cancer risk estimates are consistent with subjective risk perceptions, but neither is associated with EGD surveillance. Second, patients have strong beliefs in the benefits of cancer screening and surveillance and trust in their doctors. Third, anxiety and depression symptoms are related to risk perceptions and outcome expectancies of surveillance. Fourth, endoscopic surveillance itself has affective and physical consequences. Finally, health services and system variables are related to risk perception and EGD surveillance. These themes coherently fit within an integrated model of intuitive decision-making and health behaviors. Studies meeting eligibility criteria were heterogeneous in terms of their study objectives and findings. Quantitative meta-analyses of study findings could not be performed. To improve adherence, endoscopic surveillance programs should consider how patients intuitively frame risks and benefits and patients' emotional reactions to the endoscopy procedure, and focus on how physicians communicate recommendations.

Gallstones and cholecystectomy in relation to risk of intra- and extrahepatic cholangiocarcinoma.

BACKGROUND: Cholangiocarcinomas are highly lethal tumours of the intrahepatic or extrahepatic biliary tract. The aetiology is largely unknown, and the potential roles of gallstones and gall bladder removal (cholecystectomy) need to be addressed in a large study with a long follow-up. METHODS: A population-based nationwide Swedish cohort study was carried out, in which patients hospitalised for gallstone diagnosis with or without gallbladder removal (cholecystectomy) between 1965 and 2008 were identified in the Swedish Patient Registry. The cohort was followed up for cancer in the Swedish Cancer Registry. The observed numbers of intra- and extrahepatic cholangiocarcinomas that developed after one year of follow-up were compared with the expected numbers, calculated from the corresponding background population, and the relative risks were estimated by standardised incidence ratios (SIRs) and 95% confidence intervals (CIs). RESULTS: Among the 192,960 non-cholecystectomised individuals with gallstones, there was a more than two-fold overall increased risk of both intra- and extra- hepatic cholangiocarcinomas, which remained stable over the follow-up period (SIR 2.77, 95% CI 2.17-3.49, and SIR 2.58, 95% CI 2.21-3.00, respectively). In the cholecystectomy cohort, including 345,251 people and 4,854,969 person-years, 325 incident cholangiocarcinomas were identified, of which 98 (30%) were intrahepatic and 227 (70%) were extrahepatic. Initially (1-4 years after surgery), the risk was increased for both intrahepatic cholangiocarcinoma (SIR 1.80, 95% CI 1.19-2.62) and extrahepatic cholangiocarcinoma (SIR 2.29, 95% CI 1.83-2.82), but no increase remained after 10 years of follow-up or more (SIR 1.10, 95% CI 0.79-1.48, and SIR 0.87, 95% CI 0.70-1.07, respectively). INTERPRETATION: Gallstones seem to increase the risk of both intra- and extrahepatic cholangiocarcinoma. However, this risk seems to decline to the level of the background population with time after cholecystectomy.

Risk profiles of prostate cancers identified from UK primary care using national referral guidelines.

OBJECTIVE: Prostate cancer in the United Kingdom is mainly diagnosed from primary care referrals based on national guidelines published by the Department of Health. Here we investigated the characteristics of cancers detected through the use of these guidelines. METHODS: A prospective two-centre study was established to assess men referred from the primary care based on the UK national guidelines. RESULTS: The overall cancer detection rate was 43% (169 out of 397) with 15% (26 out of 169) of all cancers metastatic at presentation. Amongst 50-69-year-old men these rates were 34% (68 out of 200) and 15% (10 out of 68). Only 21% (25 out of 123) of men with local cancers had low-risk disease. In comparison to a historical cohort from 2001 (n=137) we found no overall differences in rates of metastatic disease, locally advanced tumours, or risk categories. Amongst 50-69-year-old men with local disease, however, we observed an increase in detection of low-risk cancers in a contemporary cohort (P=0.04). This was primarily because of the increased detection of low-stage organ-confined tumours in this group (P=0.02). CONCLUSION: Use of the UK prostate cancer guidelines detects a high proportion of clinically significant cancers. Use of the guidelines does not seem to have led to an overall change in the clinical characteristics of presenting cancers. There may, however, be a specific benefit in detecting more low-risk disease in younger men.

Increased risk of hepatocellular carcinoma after cholecystectomy.

BACKGROUND: The association between gall bladder removal (cholecystectomy) and hepatocellular carcinoma warrants investigation. An increased intrahepatic bile duct pressure following cholecystectomy might cause chronic inflammation in the surrounding liver tissue, which might induce cancer development. METHODS: A nationwide Swedish population-based cohort study in 1965-2008 included 345,251 patients undergoing cholecystectomy because of gallstone. The number of observed hepatocellular carcinoma cases was divided by the expected number, calculated from the corresponding background Swedish population, thus providing standardised incidence ratios (SIRs) with 95% confidence intervals (CIs). RESULTS: During follow-up of 4,854,969 person-years, 333 new cases of hepatocellular carcinoma were identified, rendering an overall increased risk (SIR 1.24, 95% CI: 1.11-1.38). The risk increased with longer follow-up (P for trend=0.003). Among patients who underwent cholecystectomy 30-43 years earlier, SIR was 2.00 (95% CI: 1.32-2.87). The results were similar after exclusion of 15,634 patients with any recorded risk factor, that is, diabetes, obesity, hepatitis, liver cirrhosis, alcoholism, or blood transfusion. CONCLUSION: Cholecystectomy might be associated with a long-term increased risk of hepatocellular carcinoma.

Phase I and II enzyme polymorphisms as risk factors for Barrett's esophagus and esophageal adenocarcinoma: a systematic review and meta-analysis.

Although several studies have examined the association between phase I/II enzyme polymorphisms and esophageal adenocarcinoma (EAC) and/or Barrett's esophagus (BE), their overall findings remain unclear. We performed a systematic review and meta-analysis to determine whether phase I/II polymorphisms are independent risk factors for either BE or EAC. We employed keyword searches in multiple databases to identify studies published before October 1, 2007. Single-nucleotide polymorphisms (SNPs) examined in > or =3 studies were meta-analyzed to obtain a pooled estimate of effect. Meta-analysis suggested the minor allele for GSTP1 Val(105) conveys modest excess risk (odds ratio [OR](BE)= 1.50, 95% confidence interval [CI] 1.16-1.95; OR(EAC)= 1.20, 95% CI 0.94-1.54). No excess risk was observed with GSTM1 null (OR(BE)= 0.77, 95% CI: 0.56-1.08; OR(EAC)= 1.08, 95% CI: 0.79-1.48), GSTT1 null (OR(BE)= 1.35, 95% CI: 0.91-2.01; OR(EAC)= 0.84, 95% CI: 0.48-1.49), or CYP1A Val(462) (OR(EAC)= 0.89, 95% CI: 0.40-1.97). Insufficient data existed to meta-analyze remaining SNPs. Our review identified GSTP1(Ile105Val) as a possible risk factor for BE and EAC in Caucasian males. No excess risk was observed for other phase I/II polymorphisms with sufficient data to meta-analyze. Additional studies are needed to determine if GSTP1 conveys excess risk in females or non-Caucasians and to evaluate other phase I/II polymorphisms.

Epidemiology, screening, diagnosis and treatment of hepatocellular carcinoma.

Globally, over half a million people develop hepatocellular carcinoma (HCC) each year and an almost equal number die of it. Some aspects of HCC remain disappointingly unchanged. For example, hepatitis B infection, for which an effective safe vaccine has been developed, remains responsible for a substantial proportion of cases worldwide. Further, the overall survival of patients with HCC remains very low. Nevertheless, the past few years have witnessed several important advances in our understanding of risk factors, screening, as well as treatment of HCC; these advances may change some of the current realities for HCC. In this paper, we will review the epidemiology, screening, diagnosis, and treatment of HCC with special emphasis on recent developments such the role of fatty liver disease, obesity, and coffee may play in causing HCC, the recent guidelines in screening and diagnosis, and state-of-the-art treatment algorithms.

The association between gastro-oesophageal reflux disease and asthma: a systematic review.

BACKGROUND AND AIMS: Gastro-oesophageal reflux disease (GORD) has been linked to a number of extra-esophageal symptoms and disorders, primarily in the respiratory tract. This systematic review aimed to provide an estimate of the strength and direction of the association between GORD and asthma. METHODS: Studies that assessed the prevalence or incidence of GORD in individuals with asthma, or of asthma in individuals with GORD, were identified in Medline and EMBASE via a systematic search strategy. RESULTS: Twenty-eight studies met the selection criteria. The sample size weighted average prevalence of GORD symptoms in asthma patients was 59.2%, whereas in controls it was 38.1%. In patients with asthma, the average prevalence of abnormal oesophageal pH, oesophagitis and hiatal hernia was 50.9%, 37.3% and 51.2%, respectively. The average prevalence of asthma in individuals with GORD was 4.6%, whereas in controls it was 3.9%. Pooling the odds ratios gave an overall ratio of 5.5 (95% CI 1.9-15.8) for studies reporting the prevalence of GORD symptoms in individuals with asthma, and 2.3 (95% CI 1.8-2.8) for those studies measuring the prevalence of asthma in GORD. One longitudinal study showed a significant association between a diagnosis of asthma and a subsequent diagnosis of GORD (relative risk 1.5; 95% CI 1.2-1.8), whereas the two studies that assessed whether GORD precedes asthma gave inconsistent results. The severity-response relationship was examined in only nine studies, with inconsistent findings. CONCLUSIONS: This systematic review indicates that there is a significant association between GORD and asthma, but a paucity of data on the direction of causality.

Acid suppression medications reduce risk of oesophageal adenocarcinoma in Barrett's oesophagus: a nested case-control study in US male veterans.

BACKGROUND: Proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) may reduce the risk of oesophageal adenocarcinoma (OAC) in Barrett's oesophagus; however, current epidemiologic studies are inconclusive. AIM: To evaluate the independent effects of PPIs and H2RAs on risk of OAC in patients with Barrett's oesophagus. METHODS: We conducted a nested case-control study of male veterans diagnosed with Barrett's oesophagus. Cases with incident OAC were matched by incidence density sampling on birth year and Barrett's diagnosis date to controls with Barrett's oesophagus who did not develop OAC. We identified prescription medication usage 1 year prior to Barrett's oesophagus diagnosis to 3 months prior to the OAC diagnosis. Odds ratios (OR) and 95% CI were estimated using conditional logistic regression. RESULTS: Compared with 798 controls, the 300 cases were less likely to use PPIs (90.0% vs 94.5%, P = 0.01) and H2RAs (19.7% vs 25.7%, P = 0.04). In the multivariable model including the use of statins, H2RAs, aspirin and nonsteroidal anti-inflammatory drugs, PPI use was associated with 41% lower risk of OAC (OR 0.59, 95% CI 0.35-0.99). While risk reduction of OAC was stronger for high-dose PPIs (omeprazole daily dose >40 mg, adjusted OR 0.11, 95% 0.04-0.36), we did not find a dose-response relationship with PPI duration (P trend = 0.45). Likewise, H2RA use was independently associated with 30% lower risk of OAC (OR 0.70, 95% CI 0.50-0.99). CONCLUSION: Use of PPIs and H2RAs among patients with Barrett's oesophagus are associated with lower risk of OAC. Further clinical trials are needed to confirm this possible chemopreventive effect.

GI Epidemiology: databases for epidemiological studies.

BACKGROUND: Large databases are being increasingly used for examining the epidemiology and outcomes of digestive and liver disorders. The complexity and rigor of the methods used to conduct these studies are often underestimated. AIMS: For the most commonly used databases, we provide a brief description of the contents, highlight strengths and weakness, and provide links for more detailed information. We also present a systematic approach to utilizing large databases for addressing research questions, highlighting commonly encountered study design issues, as well as strategies for resolving these issues. CONCLUSIONS: 1. Research using large databases requires the same essential skills needed to conduct research studies using other data sources. These include a rigorous study design, expertise in analytic methods, and relevant research questions. 2. The completeness and accuracy of information contained in the database must be assessed. Methods for improving the quality and completeness of this information should be considered. 3. Despite similarities among large databases, gaining insight and experience into the structure and content of each database is essential. Key points *Large databases can be a powerful source of information to examine the clinical epidemiology and outcomes of digestive and liver disorders. * Research using large databases requires the same essential skills needed to conduct research studies using other data sources. These include a rigorous study design, expertise in analytic methods, and relevant research questions. * The completeness and accuracy of information contained in the database must be assessed. Methods for improving the quality and completeness of this information should be considered. * Despite similarities among large databases, gaining insight and experience into the structure and content of each database is essential. * Examples of commonly used large databases are presented with a synopsis of information contained in the database, as well as strengths and limitations of using the database for research.