Ivo C. Ditah

Clostridium difficile-associated diarrhea and proton pump inhibitor therapy: a meta-analysis.

OBJECTIVES:Clostridium difficile-associated diarrhea (CDAD) is a major cause of morbidity and increasing health-care costs among hospitalized patients. Although exposure to antibiotics remains the most documented risk factor for CDAD, attention has recently been directed toward a plausible link with proton pump inhibitors (PPIs). However, the results of studies on the association between CDAD and PPIs remain controversial. We have conducted a meta-analysis to summarize the association between PPIs and CDAD among hospitalized patients.METHODS:A systematic search of published literature on studies that investigated the association between PPIs and CDAD from 1990 to 2010 was conducted on Medline and PubMed. The identified articles were reviewed for additional references. The most adjusted risk estimates were extracted by two authors and summarized using random effects meta-analysis. We also conducted a subgroup analysis by study design. Publication bias was evaluated using the Begg and Egger tests. A sensitivity analysis using the Duval and Tweedie “trim-and-fill” method has also been performed.RESULTS:Twenty-three studies including close to 300,000 patients met the inclusion criteria. There was a 65% (summary risk estimate 1.69 with a 95% confidence interval (CI) from 1.395 to 1.974; P<0.000) increase in the incidence of CDAD among patients on PPIs. By study design, whether case–control study (17) or cohort study (6), there was still a significant increase in the incidence of CDAD among PPI users. The risk estimates were 2.31 (95% CI from 1.72 to 3.10; P<0.001) and 1.48 (95% CI from 1.25 to 1.75; P<0.001) for cohort and case–control studies, respectively.CONCLUSIONS:There is sufficient evidence to suggest that PPIs increase the incidence of CDAD. Our meta-analysis shows a 65% increase in the incidence of CDAD among PPI users. We recommend that the routine use of PPIs for gastric ulcer prophylaxis should be more prudent. Establishing a guideline for the use of PPI may help in the future with the judicious use of PPIs. Further studies, preferably prospective, are needed to fully explore the association between PPIs and CDAD.

Emerging Trends in Hepatocellular Carcinoma Incidence and Mortality

The rise in incidence of hepatocellular carcinoma (HCC) in the United States has been well documented. The purpose of this analysis was to examine temporal trends in HCC incidence, mortality, and survival within the U.S. population. The Surveillance, Epidemiology, and End Results data were used to examine incidence and incidence‐based (IB) mortality in HCC from 1973 to 2011. Secular trends in age‐adjusted incidence and IB mortality by sex and cancer stage were characterized using the Joinpoint Regression program. In 1973, HCC incidence was 1.51 cases per 100,000, whereas in 2011, HCC incidence was 6.20 cases per 100,000. Although HCC incidence continues to increase, a slowing of the rate of increase occurs around 2006. In a sensitivity analysis, there was no significant increase in incidence and IB mortality from 2009 to 2011. There was a significant increase in overall median survival from the 1970s to 2000s (2 vs. 8 months; P < 0.001). On multivariable Coxs regression analysis, age, sex, race, tumor grade, stage at diagnosis, lymph/vascular invasion, number of primary tumors, tumor size, and liver transplant were independently associated with mortality. Conclusion: Our results indicate a deceleration in the incidence of HCC around 2006. Since 2009 and for the first time in four decades, there is no increase in IB mortality and incidence rates for HCC in the U.S. population. The nonsignificant increase in incidence and IB mortality in recent years suggest that the peak of the HCC epidemic may be near. A significant survival improvement in HCC was also noted from 1973 to 2010, which seems to be driven by earlier detection of HCC at a curative stage and greater utilization of curative modalities (especially transplant). (Hepatology 2015;61:191–199)

The changing epidemiology of hepatitis C virus infection in the United States: National health and nutrition examination survey 2001 through 2010

BACKGROUND & AIMS In light of the dramatically changing hepatitis C therapeutic landscape, knowledge of the current burden of HCV infection in the general population of the United States is critical. METHODS The National Health and Nutrition Examination survey collects nationally representative data on HCV infection in the civilian population of the United States. Data from 2001 to 2010 were combined for this study. HCV testing was completed in 38,025 participants. RESULTS The prevalence of anti-HCV in the United Sates decreased from 1.9% (95% CI 1.5%-2.5%) in 2001-2002 to 1.3% (95% CI 0.9%-1.8%) in 2005-2006, and remained stable up to 2010. About 67% of all infected persons were positive for HCV RNA, indicating 2.3 million people with chronic HCV infection, of whom 68% have genotype 1. Seventy percent of infected persons were born between 1945 and 1965, with prevalence of 3.5% (95% CI 2.2%-4.8%). The stable rate since 2006 is mostly related to prevalent cases and foreign born persons migrating into US. Other important risk factors include less education and low economic status. Race, HIV status, number of sexual partners, and blood transfusions are no longer associated with HCV infection. CONCLUSIONS As of 2010, approximately 2.3 million persons were chronically infected with Hepatitis C in the US. Most of those infected are prevalent, rather than incident cases. The prevalence of HCV was on the decline, but has stabilized since 2006. Future studies should explore reasons for no decline in HCV prevalence since 2006.

Prevalence, Trends, and Risk Factors for Fecal Incontinence in United States Adults, 2005-2010

BACKGROUND & AIMS We investigated the prevalence of and trends and risk factors for fecal incontinence (FI) in the United States among non-institutionalized adults from 2005 to 2010. METHODS We analyzed data from 14,759 participants in the U.S. National Health and Nutrition Examination Survey (49% women, 20 years or older) from 2005 to 2010 (the FI Severity Index was added in 2005-2006). FI was defined as accidental leakage of solid or liquid stool or mucus at least once in preceding month. Sampling weights were used to obtain estimates for the national population. Logistic regression was used to identify risk factors for FI. RESULTS The prevalence of FI among non-institutionalized U.S. adults was 8.39% (95% confidence interval, 7.76-9.05). It was stable throughout the study period: 8.26% in 2005-2006, 8.48% in 2007-2008, and 8.41% in 2009-2010. FI resulted in release of liquid stool in most cases (6.16%). Prevalence increased with age from 2.91% among 20- to 29-year-old participants to 16.16% (14.15%-18.39%) among participants 70 years and older. Independent risk factors for FI included older age, diabetes mellitus, urinary incontinence, frequent and loose stools, and multiple chronic illnesses. FI was more common among women only when they had urinary incontinence. CONCLUSIONS FI is a common problem among non-institutionalized U.S. adults. Its prevalence remained stable from 2005-2010. Diabetes mellitus and chronic diarrhea are modifiable risk factors. Future studies on risk factors for FI should assess for presence of urinary incontinence.

Current epidemiology of hepatitis E virus infection in the United States: Low seroprevalence in the National Health and Nutrition Evaluation Survey

Analysis of the National Health and Nutrition Evaluation Survey (NHANES) 1988‐1994 dataset found a relatively high seroprevalence (21%) of hepatitis E virus (HEV) infection in the U.S. general population. Using data obtained within the NHANES 2009‐2010 survey, where a high performance assay for HEV was used, we estimated the weighted seroprevalence of HEV infection among U.S. individuals 6 years and older. We also evaluated factors associated with HEV seropositivity. A total of 8,814 individuals were included in the analysis. The median age of study participants was 37 years (interquartile range [IQR] 17‐58 years), with 51.2% being female. The weighted national seroprevalence of HEV was 6% (95% confidence interval [CI] 5.1%‐6.9%). About 0.5% of those with HEV had evidence of recent exposure (immunoglobulin M‐positive). In the univariate analyses, factors associated with HEV seropositivity were increasing age (P‐trend < 0.001), birth outside of the U.S., Hispanic race, and “meat” consumption (>10 times/month). No significant association was observed with low socioeconomic status, water source, or level of education. In the multivariate analysis, only older age remained predictive of HEV seropositivity. Conclusion: The weighted national seroprevalence of HEV in the U.S. is much less than previously reported. Using data obtained with a high performance assay, the seroprevalence of HEV was estimated at 6.0% in the U.S. Based on these results, the seroprevalence of HEV is only one‐third as high as previously reported. (Hepatology 2014;60:815–822)

Trends and racial/ethnic disparities in gluten-sensitive problems in the United States: Findings from the national health and nutrition examination surveys from 1988 to 2012

Objectives:Racial disparities in the prevalence of celiac disease (CD) and the number of people without CD avoiding gluten (PWAG) in the United States are unknown. We aimed to describe racial differences in the prevalence of CD and PWAG, and evaluate the trends of CD in the noninstitutionalized civilian adult population of the US between 1988 and 2012.Methods:A population-based cross-sectional study was conducted using data from the National Health and Nutrition Examination Surveys (NHANES) from 1988 to 1994, 1999 to 2004, and 2009 to 2012. Serum samples from the NHANES participants were tested for CD serology, which included IgA tissue transglutaminase (tTG IgA) and, if findings were abnormal, for IgA endomysial antibodies. Information about adherence to a gluten-free diet was obtained by means of an interviewer-administered questionnaire.Results:In NHANES 2009–2012, the adjusted prevalence of CD was significantly higher (P<0.0001) among non-Hispanic whites (1.0%) than among non-Hispanic blacks (0.2%) and Hispanics (0.3%), whereas the adjusted prevalence of PWAG was significantly higher (P=0.01) in blacks (1.2%) as compared with Hispanics (0.5%) and whites (0.7%). The seroprevalence of CD in adults aged 50 years and older increased from 0.17% (95% confidence interval (CI) 0.03–0.33) in 1988–1994 to 0.44% (95% CI 0.24–0.81) in 2009–2012 (P<0.05).Conclusions:The overall prevalence of CD increased between 1988 and 2012 and is significantly more common in whites. In addition, a higher proportion of individuals maintaining a gluten-free diet in the absence of a diagnosis of CD are blacks.

Temporal Trends in the Incidence and Natural History of Diverticulitis: A Population-Based Study

OBJECTIVES:Data on the incidence and natural history of diverticulitis are largely hospital-based and exclude the majority of diverticulitis patients, who are treated in an outpatient setting for uncomplicated diverticulitis. We assessed temporal trends in the epidemiology of diverticulitis in the general population.METHODS:Through the Rochester Epidemiology Project we reviewed the records of all individuals with a diagnosis of diverticulitis from 1980 to 2007 in Olmsted County, Minnesota, USA.RESULTS:In 1980–1989, the incidence of diverticulitis was 115/100,000 person-years, which increased to 188/100,000 in 2000–2007 (P<0.001). Incidence increased with age (P<0.001); however, the temporal increase was greater in younger people (P<0.001). Ten years after the index and second diverticulitis episodes, 22% and 55% had a recurrence, respectively. This recurrence rate was greater in younger people (hazard ratio (HR) per decade 0.63; 95% confidence interval (CI), 0.59–0.66) and women (HR 0.68; 95% CI, 0.58–0.80). Complications were seen in 12%; this rate did not change over time. Recurrent diverticulitis was associated with a decreased risk of complications (P<0.001). Age was associated with increased risk of local (odds ratio (OR) 1.27 per decade; 95% CI, 1.04–1.57) and systemic (OR 1.83; 95% CI, 1.20–2.80) complications. Survival after diverticulitis was lower in older people (P<0.001) and men (P<0.001) and worsened over time (P<0.001). The incidence of surgery for diverticulitis did not change from 1980 to 2007.CONCLUSIONS:The incidence of diverticulitis has increased by 50% in 2000–2007 compared with 1990–1999, and more so in younger people. Complications are relatively uncommon. Recurrent diverticulitis is frequent but typically uncomplicated. Younger people with diverticulitis have less severe disease, more recurrence, and better survival.

C-reactive protein in arrhythmogenic right ventricular dysplasia/cardiomyopathy and relationship with ventricular tachycardia.

Background. The relationship between C-reactive protein (CRP) elevation and ventricular tachycardia (VT) in arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is unclear. Methods and Results. In 91 consecutive patients with either ARVD/C with or without VT (cases) or idiopathic right ventricular outflow tract (RVOT) tachycardia (controls), blood sampling were taken to determine CRP levels. In ARVD/C patients with VT, we analyzed the association between VT occurrences and CRP level. Sixty patients had ARVD/C, and 31 had idiopathic RVOT VT. Patients with ARVD/C had a significant higher level of CRP compared to those with RVOT VT (3.5 ± 4.9 versus 1.1 ± 1.2 mg/l, P = .0004). In ARVD/C group, 77%, (n = 46) patients experienced VT. Of these, 37% (n = 17) underwent blood testing for CRP within 24 h after the onset of VT and the remaining 63% (n = 29) after 24 h of VT reduction. CRP level was similar in ARVD/C patients with or without documented VT (3.6 ± 5.1 mg/l versus 3.1 ± 4.1 mg/l, P = .372). However, in patients with ARVD/C and documented VT, CRP was significantly higher when measured within 24 hours following VT in comparison to that level when measured after 24 h (4.9 ± 6.2 mg/l versus 3.0 ± 4.4 mg/l, P = .049). Conclusion. Inflammatory state is an active process in patients with ARVD/C. Moreover, there is a higher level of CRP in patients soon after ventricular tachycardia, and this probably tends to decrease after the event.

Lack of Health Insurance Limits the Benefits of Hepatitis C Virus Screening: Insights from the National Health and Nutrition Examination Hepatitis C Follow-Up Study

Objectives:Identifying barriers to access to hepatitis C virus (HCV) treatment among screen detected subjects is critical for any public health strategy aimed at controlling HCV infection in the general population.Methods:Data from the National Health and Nutrition Examination Survey HCV Follow-up study from 2001 to 2010 were used. Participants who tested positive for HCV were sent a letter informing them of their test results and advised to pursue further evaluation. Information on HCV transmission and its potential complications was also provided to all positive participants. These subjects were recontacted 6 months after notification to determine what action they had taken regarding the positive result.Results:Of 38,025 participants, 502 tested positive for HCV infection, giving a prevalence of 1.3% (95% confidence interval (CI) 0.8%, 1.8%). A total of 205 subjects participated in the 6-month follow-up interview. Those who could not be reached were more likely to be less educated, injecting drugs, and not to have health insurance. Half (50.2%) of the positive individuals were not aware of their status before notification. A total of 166 (81%) had pursued further evaluation. Only 18 (26.9%) received therapy. The main reason for not receiving treatment was high cost (19.4%). In adjusted analysis, the only barrier to pursuing downstream HCV care was the lack of health insurance (2.76, 95% CI 1.54, 7.69; P=0.007).Conclusions:This study suggests that the lack of health insurance may attenuate the theoretical benefits of a screening program that identifies asymptomatic HCV-infected individuals who are less likely to pursue downstream care.

Transjugular intrahepatic portosystemic stent shunt for medically refractory hepatic hydrothorax: A systematic review and cumulative meta-analysis

AIM To assess the effectiveness of transjugular intrahepatic portosystemic stent shunt (TIPSS) in refractory hepatic hydrothorax (RHH) in a systematic review and cumulative meta-analysis. METHODS A comprehensive literature search was conducted on MEDLINE, EMBASE, and PubMed covering the period from January 1970 to August 2014. Two authors independently selected and abstracted data from eligible studies. Data were summarized using a random-effects model. Heterogeneity was assessed using the I (2) test. RESULTS Six studies involving a total of 198 patients were included in the analysis. The mean (SD) age of patients was 56 (1.8) years. Most patients (56.9%) had Child-Turcott-Pugh class C disease. The mean duration of follow-up was 10 mo (range, 5.7-16 mo). Response to TIPSS was complete in 55.8% (95%CI: 44.7%-66.9%), partial in 17.6% (95%CI: 10.9%-24.2%), and absent in 21.2% (95%CI: 14.2%-28.3%). The mean change in hepatic venous pressure gradient post-TIPSS was 12.7 mmHg. The incidence of TIPSS-related encephalopathy was 11.7% (95%CI: 6.3%-17.2%), and the 45-d mortality was 17.7% (95%CI: 11.34%-24.13%). CONCLUSION TIPSS is associated with a clinically relevant response in RHH. TIPSS should be considered early in these patients, given its poor prognosis.