Concurrence of inflammatory bowel disease with multiple sclerosis or Hodgkin lymphoma.

BACKGROUND AND AIMS: Epidemiologic evidence suggests that Hodgkin lymphoma (HL) and multiple sclerosis (MS) share a common set of risk factors with Crohn's disease (CD) and ulcerative colitis (UC). It was hypothesized that such shared risk factors would lead to clustering of the 4 diagnoses in the same patients. METHODS: All patients with HL, MS, CD, or UC were identified in the veterans population from 2016-2020 and the Medicare population from 1986 to 1989. In a case-control study, the observed concurrences amongst these 4 diagnoses were compared with their expected frequencies in the overall veterans or Medicare population during the same time period by calculating odds ratios (OR) with their 95% confidence intervals (CI). RESULTS: The study included 6 million veterans and 35 million Medicare patients. In the veterans population, inflammatory bowel disease (IBD) was significantly associated with a concurrent diagnosis of HL (OR: 1.40, 95% CI: 1.15-1.71) and MS (1.34, 1.19-1.50). In the Medicare population, IBD was also significantly associated with HL (1.84, 1.07-3.17) and MS (2.31, 1.59-3.35). Similar trends were observed in CD or UC when analyzed separately in both datasets. In the veterans population, adjustment for the potentially confounding influence of ethnicity, sex, and age left all OR values largely unaffected and statistically significant. CONCLUSION: The concurrence of IBD with HL or MS could reflect on a common pathway in the etiology or pathogenesis of these 4 diseases.

Clinical care in hepatocellular carcinoma: A mixed methods assessment of experiences and challenges of oncology professionals.

INTRODUCTION: Healthcare providers (HCPs) may face numerous dilemmas in optimally screening, diagnosing, and treating patients with, and/or at risk for, hepatocellular carcinoma (HCC). This study aimed to achieve a greater understanding of the challenges in HCC care which in turn could delineate HCP educational opportunities within this oncologic sub-specialty. METHODS: A mixed-methods approach was used to identify practice gaps and clinical barriers experienced by US-based medical oncologists, hepatologists, oncology physician assistants, oncology nurse practitioners, and interventional radiologists involved in HCC care. The qualitative (semi-structured interview) and quantitative (survey) data collection approaches were deployed sequentially with findings subsequently triangulated. RESULTS: A total of 214 HCPs participated in this study. Analysis revealed challenges related to screening and diagnosing HCC, specifically in applying appropriate screening guidelines, and the optimal use and decisions related to diagnostic imaging and biopsy. Issues related to treatment selection included the application of existing HCC guidelines in treatment decision-making, weighing risk/benefit ratios of various antineoplastics regimens (i.e., tyrosine kinase inhibitors-TKIs, immunotherapy agents, chemotherapy), sequencing therapies, potential toxicity management, and optimally educating patients about their HCC. CONCLUSION: These findings highlight the educational needs of those involved in HCC care and provide a starting point for clinicians to both reflect on their practice and identify opportunities to enhance communication within the HCC team and between provider and patient. There is an opportunity to optimize continuing professional development interventions that address the identified gaps in clinical practice specifically related to teamwork and interdisciplinary communication.

A Novel Biomarker Panel for the Early Detection and Risk Assessment of Hepatocellular Carcinoma in Patients with Cirrhosis.

Novel biomarkers for hepatocellular carcinoma (HCC) surveillance in patients with cirrhosis are urgently needed. We previously identified osteopontin (OPN) as a promising biomarker for the early detection of HCC. This study is to further validate the performance of OPN and identify fatty acids (FA) that could improve OPN's performance in HCC risk assessment in patients with cirrhosis. To that end, we selected 103 patients with cirrhosis under surveillance. Among them, 40 patients developed HCC during follow-up. We investigated in these 103 patients, the association between HCC incidence and prediagnostic serum levels of AFP, OPN, and 46 FAs. OPN performance was higher than AFP in detecting prediagnosis HCCs and the combination with AFP further improved OPN's performance. For patients with a diagnosis of HCC within 18 months of follow-up (HCC < 18 months), AUC for OPN + AFP was 0.77. Abundance of 11 FAs [four long-chain saturated FAs (SFA), four n-3 poly-unsaturated FAs (PUFA), and three n-6 PUFAs] were statistically different between patients who developed HCC and those who did not. Abundance changes correlated with time to diagnosis for the PUFAs, but not for the SFAs. Adding arachidic acid (20:0) and n-3 docosapentaenoic acid (22:5n3) to OPN and AFP improved the discriminatory performance (AUC = 0.83). AUC for this panel reached 0.87 for HCC < 18 months (82% sensitivity at 81% specificity). In conclusion, we identified a panel of 4 markers with strong performances that could have significant utility in HCC early detection in patients with cirrhosis under surveillance. PREVENTION RELEVANCE: This study identified a panel of 4 biomarkers that identifies with high performance patients with cirrhosis at high risk for HCC. This panel could have utility in HCC early detection in patients with cirrhosis under surveillance.

Predictors of five-year survival among patients with hepatocellular carcinoma in the United States: an analysis of SEER-Medicare.

BACKGROUND: Most patients with hepatocellular carcinoma (HCC) are ≥ 65 years old at diagnosis and ~ 20% present with disease amenable to curative intent surgical therapy. The aim of this study was to examine whether treatment, the demographic variables, and clinical factors could predict 5-year survival among HCC patients. METHODS: We included patients, 66 years or older, diagnosed with a first primary HCC from 1994 through 2007 in the SEER-Medicare database, and followed up until death or 31 December 2012. Curative intent treatment was defined as liver transplantation, surgery resection, or ablation. We estimated odds ratios (OR) and 95% confidence intervals (CI) for associations with 5-year survival using logistic regression. RESULTS: We identified 10,826 patients with HCC with mean age 75.3 (standard deviation, 6.4) years. Most were male (62.2%) and non-Hispanic white (59.7%). Overall, only 8.1% of patients were alive 5 years post-HCC diagnosis date. Among all patients that survived ≥ 5 years, 69.8% received potentially curative treatment. Conversely, patients who received potentially curative treatment represented only 15.7% of patients who survived < 5 years. Curative intent treatment was the strongest predictor for surviving ≥ 5 years (vs. none/palliative treatment; adjusted OR 8.12, 95% CI 6.90-9.64). While stage at diagnosis and comorbidities were also independently associated with ≥ 5-year survival in HCC patients, these factors did not improve discrimination between short- and long-term survivors. CONCLUSIONS: Curative intent treatment was the strongest predictor for survival ≥ 5 years among HCC patients. Given the limited availability of liver transplant and limited eligibility for surgical resection, finding curative intent HCC therapies remain critically important.

Sex and Race Disparities in the Incidence of Hepatocellular Carcinoma in the United States Examined through Age-Period-Cohort Analysis.

BACKGROUND: Incidence rates for hepatocellular carcinoma (HCC) vary considerably by age, sex, and race/ethnicity. We assessed whether the underlying reasons for variations in HCC among subgroups of the population by age, sex, race/ethnicity, and birth cohort are uniform or whether they interact with one another or have changed over time. METHODS: Data were from the U.S. Cancer Statistics registry. We assessed annual trends within population subgroups and examined for secular trends in the male-to-female ratio for HCC incidence. We used joinpoint regression to compute annual percent change and average annual percent change (AAPC) and corresponding 95% confidence intervals (CI). We also used age-period-cohort models to disentangle period and cohort effects. RESULTS: Between 2001 and 2015, HCC rates increased in men and women ≥50 years, remained stable among women ages 40 to 49 years, but decreased among males ages 40 to 44 years (AAPC = -2.47%; 95% CI, -3.15% to -1.80%) and 45 to 49 years (AAPC = -3.49%; 95% CI, -4.78% to -2.17%). As a result, the male-to-female incidence rate ratio (IRR) among persons aged <50 years decreased from 4.63 in 2001 to 2.42 in 2015 but remained stable over time among persons aged ≥50 years. HCC rates were lower among successive cohorts of males born after circa 1956, whereas HCC rates among females born circa 1991 were higher than those among females born circa 1956 (IRR = 1.67; 95% CI, 1.05-2.65). CONCLUSIONS: As a result of decreasing incidence among males aged <50 years and strong cohort effect, the epidemiology of HCC is changing from a disease with striking male predominance to one with less male predominance. IMPACT: The sex and racial disparities and strong birth cohort effect on HCC risk identified in this study have important implications for population-based HCC prevention efforts.

Epidemiology and Management of Hepatocellular Carcinoma.

The major risk factors for hepatocellular carcinoma (HCC) in contemporary clinical practice are becoming increasingly related to sustained virological response after hepatitis C, suppressed hepatitis B virus during treatment, and alcoholic and nonalcoholic fatty liver disease. We review the emerging data on the risk and determinants of HCC in these conditions and the implications of HCC surveillance. However, from a public health perspective, active hepatitis C and B continue to drive most of the global burden of HCC. In United States, the age-adjusted incidence rates of HCC in Hispanics have surpassed those of HCC in Asians. Prognosis in HCC is complex because of the competing risk imposed by underlying cirrhosis and presence of malignancy. In addition to tumor burden, liver function and performance status; additional parameters including tumor biopsy, serum markers, and subclassification of current staging systems; and taking into account patterns of tumor progression may improve patient selection for therapy. Advancements in the treatment of HCC have included identification of patients who are most likely to derive a clinically significant benefit from the available therapeutic options. Additionally, the combination strategies of locoregional therapies and/or systemic therapy are being investigated.

Global epidemiology and burden of HCV infection and HCV-related disease.

Chronic HCV infection is a global health problem that affects >184 million people worldwide. HCV is associated with several hepatic and extrahepatic disorders, including several malignancies. The burden of HCV-related disorders is influenced by the number of new and existing cases, number of existing cases and the natural history of the infection. The natural history of HCV is affected by several demographic, virological, clinical and lifestyle factors. Major variations exist in the burden of HCV among different populations and geographical regions, as well as over time. With the advent of new and efficacious antiviral treatments, it is important to learn the determinants of HCV burden to design appropriate strategies for detection, prognostication and treatment. Furthermore, with the expected growth of patients cured of HCV, it is essential to learn about the possible change in natural history and burden of disease in these patients. In this Review, we will discuss the global epidemiology and burden of HCV and its complications, as well as the natural history and clinical course of chronic and cured HCV infection.

Determinants of Healthcare Utilization Among Veterans with Inflammatory Bowel Disease.

BACKGROUND: Identifying patient-level and disease-specific predictors of healthcare utilization in inflammatory bowel disease (IBD) may allow targeted interventions to reduce costs and improve outcomes. AIM: To identify demographic and clinical predictors of healthcare utilization among veterans with IBD. METHODS: We conducted a single-center cross-sectional study of veterans with IBD from 1998 to 2010. Demographics and disease characteristics were abstracted by manual chart review. Annual number of IBD-related visits was estimated by dividing total number of IBD-related inpatient and outpatient encounters by duration of IBD care. Associations between predictors of utilization were determined using stepwise multivariable linear regression. RESULTS: Overall, 676 patients (56% ulcerative colitis (UC), 42% Crohn's disease (CD), and 2% IBD unclassified (IBDU)) had mean 3.08 IBD-related encounters annually. CD patients had 3.59 encounters compared to 2.73 in UC (p < 0.01). In the multivariable model, Hispanics had less visits compared to Caucasians and African-Americans (2.09 vs. 3.09 vs. 3.42), current smokers had more visits than never smokers (3.54 vs. 2.43, p = 0.05), and first IBD visit at age <40 had more visits than age >65 (3.84 vs. 1.75, p = 0.04). UC pancolitis was associated with more visits than proctitis (3.47 vs. 2.15, p = 0.04). CD penetrating phenotype was associated with more encounters than inflammatory type (4.68 vs. 4.15, p = 0.04). CONCLUSIONS: We found that current tobacco use, age <40 at first IBD visit, UC pancolitis, and CD fistuilizing phenotype in addition to Caucasian and African-American race were independent predictors of increased healthcare utilization. Interventions should be targeted at these groups to decrease healthcare utilization and costs.

Assessment of disease specific knowledge and health-related quality of life among United States military veterans with inflammatory bowel disease.

AIM: To evaluate the association between patient disease knowledge of inflammatory bowel disease (IBD) and health related quality of life (HRQoL) and identify patient and disease related predictors of patient knowledge of IBD. METHODS: We performed a cross-sectional study of IBD patients with an established diagnosis of IBD longer than 3 mo prior to enrollment. The Crohn's and colitis knowledge score (CCKNOW) and short inflammatory bowel disease questionnaire (SIBDQ) were self-administered to assess patient knowledge of IBD and HRQoL, respectively. Demographic and disease characteristics were abstracted from the electronic medical record. The correlation between CCKNOW and SIBDQ scores was assessed by a linear regression model. Associations of patient knowledge and the variables of interest were calculated using ANOVA. RESULTS: A total of 101 patients were recruited. Caucasian race, younger age at diagnosis, and having a college or post-graduate degree were significantly associated with higher CCKNOW scores. Patients with CD had higher CCKNOW scores compared to patients with ulcerative colitis and inflammatory bowel disease type unclassified, P < 0.01. There was no significant correlation between overall CCKNOW and SIBDQ scores (r (2) = 0.34, P = 0.13). The knowledge sub-domain of diet in CCKNOW was negatively correlated with HRQoL (r (2) = 0.69, P < 0.01). CONCLUSION: IBD diagnosis at a younger age in addition to Caucasian race and higher education were significantly associated with higher knowledge about IBD. However, patient knowledge of IBD was not correlated with HRQoL. Further studies are required to study the effect of patient knowledge of IBD on other clinical outcomes.

Cost-effectiveness and diagnostic effectiveness analyses of multiple algorithms for the diagnosis of Lynch syndrome.

BACKGROUND AND AIMS: The optimal algorithm to identify Lynch syndrome (LS) among patients with colorectal cancer (CRC) is unclear. The definitive test for LS, germline testing, is too expensive to be applied in all cases. Initial screening with the revised Bethesda Guidelines (RBG) cannot be applied in a considerable number of cases due to missing information. METHODS: We developed a model to evaluate the cost-effectiveness of 10 strategies for diagnosing LS. Three main issues are addressed: modeling estimates (20-40%) of RBG applicability; comparing sequential or parallel use of microsatellite instability (MSI) and immunohistochemistry (IHC); and a threshold analysis of the charge value below which universal germline testing becomes the most cost-effective strategy. RESULTS: LS detection rates in RBG-based strategies decreased to 64.1-70.6% with 20% inapplicable RBG. The strategy that uses MSI alone had lower yield, but also lower cost than strategies that use MSI sequentially or in parallel with IHC. The use of MSI and IHC in parallel was less affected by variations in the sensitivity and specificity of these tests. Universal germline testing had the highest yield and the highest cost of all strategies. The model estimated that if charges for germline testing drop to $633-1,518, universal testing of all newly diagnosed CRC cases becomes the most cost-effective strategy. CONCLUSIONS: The low applicability of RBG makes strategies employing initial laboratory-based testing more cost-effective. Of these strategies, parallel testing with MSI and IHC offers the most robust yield. With a considerable drop in cost, universal germline testing may become the most cost-effective strategy for the diagnosis of LS.

Bundling in medicare patients undergoing bidirectional endoscopy: how often does it happen?

BACKGROUND & AIMS: In patients with appropriate indications, performance of both colonoscopy and esophagogastroduodenoscopy (EGD) at the same time (bundling) is convenient for patients, efficient for providers, and cost saving for the health care system. However, Medicare reimbursement for bundled procedures is at a rate that is less than the sum of the 2 procedures when charged separately, and this may create a disincentive to bundle. The practice patterns of bundling are unknown at a US population-based level. METHODS: We examined Medicare claims from 2007 to 2009 from the Carrier file in a national, random sample of fee-for-service beneficiaries aged 66 and older. We identified patients who had both a colonoscopy and EGD performed within 180 days of each other and calculated the proportions of patients with both procedures bundled on the same date, within 1 to 30 days, and within 31 to 180 days of each other. We compared patients in these 3 groups for demographics and clinical indications for the procedures (bleeding, lower or upper gastrointestinal symptoms, surveillance, and screening). RESULTS: We identified 12,982 Medicare-enrolled individuals who had a colonoscopy and an EGD performed within 180 days of each other. Approximately 35% of procedures were not bundled on the same day, and, of these, 2359 (18%) were performed within 30 days of each other, and 2219 (17%) were performed within 31 to 180 days of each other. There were marked geographic differences in the percentage of bundling, with the lowest occurrence in the Northeast and the highest in the West. Patients with bundled procedures were more likely to have gastrointestinal bleeding and less likely to have screening or surveillance indications. CONCLUSIONS: Although same-day bundling of endoscopic procedures offers a number of advantages, it is not practiced in more than one-third of cases in a national sample of Medicare beneficiaries.

Limited life expectancy among a subgroup of medicare beneficiaries receiving screening colonoscopies.

BACKGROUND & AIMS: Life expectancy is an important consideration when assessing appropriateness of preventive programs for older individuals. Most studies on this subject have used age cutoffs as a proxy for life expectancy. We analyzed patterns of utilization of screening colonoscopy in Medicare enrollees by using estimated life expectancy. METHODS: We used a 5% random national sample of Medicare claims data to identify average-risk patients who underwent screening colonoscopies from 2008 to 2010. Colonoscopies were considered to be screening colonoscopies in the absence of diagnoses for nonscreening indications, which were based on either colonoscopies or any claims in the preceding 3 months. We estimated life expectancies by using a model that combined age, sex, and comorbidity. Among patients who underwent screening colonoscopies, we calculated the percentage of those with life expectancies <10 years. RESULTS: Among the 57,597 Medicare beneficiaries 66 years old or older who received at least 1 screening colonoscopy, 24.8% had an estimated life expectancy of <10 years. There was a significant positive association between total Medicare per capita costs in hospital referral regions and the proportion of patients with limited life expectancies (<10 years) at the time of screening colonoscopy (R = 0.25; P < .001, Pearson correlation test). In a multivariable analysis, men were substantially more likely than women to have limited life expectancy at the time of screening colonoscopy (odds ratio, 2.25; 95% confidence interval, 2.16-2.34). CONCLUSIONS: Nearly 25% of Medicare beneficiaries, especially men, had life expectancies <10 years at the time of screening colonoscopies. Life expectancy should therefore be incorporated in decision-making for preventive services.

Association between facility characteristics and the process of care delivered to patients with hepatitis C virus infection.

BACKGROUND: Available data suggest problems in the process of care provided to patients with chronic hepatitis C (HCV). However, the solutions to these problems are less obvious. Healthcare facility factors are potentially modifiable and may enhance process quality in HCV treatment. METHODS: We evaluated the relationship between the process of HCV care and facility factors including number of weekly half-day HCV clinics per 1,000 HCV patients, HCV-specific quality-improvement initiatives, and administrative service of the HCV clinic (gastroenterology, infectious disease, primary care) for a cohort of 34,258 patients who sought care in 126 Veterans Affairs facilities during 2003-2006. We measured HCV care on the basis of 23 HCV-specific process measures capturing pretreatment (seven measures), preventive and/or comorbid (seven measures), and treatment and treatment monitoring care (nine measures). RESULTS: Patients seen at a facility with >8 half-day clinics were 52 % more likely to receive overall indicated care (OR 1.52, 95 % CI 1.13-2.05). Patients seen at a facility with >3 HCV quality improvement initiatives were more likely to receive better preventive and/or comorbid care (OR 1.32, 95 % CI 1.00-1.74). Compared with patients in facilities with no dedicated HCV clinic, patients at facilities with gastroenterology-based clinics received better pretreatment care (OR 1.36, 95 % CI 1.01-1.85) and more antiviral treatment (OR 1.45, 95 % CI 1.06-1.97) whereas those at facilities with infectious disease-based or primary care-based clinics received better preventive and/or comorbid care (OR 1.59, 95 % CI 1.06-2.39 and 1.84, 95 % CI 1.21-2.79 respectively). CONCLUSION: Several facility factors affected the process of HCV care. These factors may serve as targets for quality-improvement efforts.

Population-attributable fractions of risk factors for hepatocellular carcinoma in the United States.

OBJECTIVES: Risk factors for hepatocellular carcinoma (HCC) include hepatitis B and C viruses (HBV, HCV), excessive alcohol consumption, rare genetic disorders and diabetes/obesity. The population attributable fractions (PAF) of these factors, however, have not been investigated in population-based studies in the United States. METHODS: Persons ≥68 years diagnosed with HCC (n=6,991) between 1994 and 2007 were identified in the SEER-Medicare database. A 5% random sample (n=255,702) of persons residing in SEER locations were selected for comparison. For each risk factor, odds ratios (ORs), 95% confidence intervals (95% CI) and PAFs were calculated. RESULTS: As anticipated, the risk of HCC was increased in relationship to each factor: HCV (OR 39.89, 95% CI: 36.29-43.84), HBV (OR 11.17, 95% CI: 9.18-13.59), alcohol-related disorders (OR 4.06, 95% CI: 3.82-4.32), rare metabolic disorders (OR 3.45, 95% CI: 2.97-4.02), and diabetes and/or obesity (OR 2.47, 95% CI: 2.34-2.61). The PAF of all factors combined was 64.5% (males 65.6%; females 62.2%). The PAF was highest among Asians (70.1%) and lowest among black persons (52.4%). Among individual factors, diabetes/obesity had the greatest PAF (36.6%), followed by alcohol-related disorders (23.5%), HCV (22.4%), HBV (6.3%) and rare genetic disorders (3.2%). While diabetes/obesity had the greatest PAF among both males (36.4%) and females (36.7%), alcohol-related disorders had the second greatest PAF among males (27.8%) and HCV the second greatest among females (28.1%). Diabetes/obesity had the greatest PAF among whites (38.9%) and Hispanics (38.1%), while HCV had the greatest PAF among Asians (35.4%) and blacks (34.9%). The second greatest PAF was alcohol-related disorders in whites (25.6%), Hispanics (30.1%) and blacks (and 18.5%) and HBV in Asians (28.5%). CONCLUSIONS: The dominant risk factors for HCC in the United States among persons ≥68 years differ by sex and race/ethnicity. Overall, eliminating diabetes/obesity could reduce the incidence of HCC more than the elimination of any other factor.

Patient-centered, comparative effectiveness of esophageal cancer screening: protocol for a comparative effectiveness research study to inform guidelines for evidence-based approach to screening and surveillance endoscopy.

BACKGROUND: The comparative effectiveness (CE) of endoscopic screening (versus no screening) for Barrett's esophagus (BE) in patients with GERD symptoms, or among different endoscopic surveillance strategies in patients with BE, for the early detection of esophageal adenocarcinoma (EA) is unknown. Furthermore, it is unclear if patients or providers have or will adopt any of these strategies (screening only, screening and surveillance, vs. none), irrespective of their effectiveness. Endoscopic screening and surveillance is expensive and can be risky. Therefore, it is imperative to establish the CE and acceptability about the risks and outcomes related to these practices to better inform expert recommendations and provider-patient decisions. METHODS/RESULTS: We propose a mixed methods study which will involve: (1) an analysis of secondary databases (VA and VA-Medicare linked datasets for 2004-09) to examine CE of endoscopic screening and surveillance in an observational study cohort (an estimated 680,000 patients with GERD; 25,000-30,000 with BE; and 3,000 with EA); (2) a structured electronic medical record (EMR) review on a national sample of patients using VA EMRs to verify all EA cases, identify cancer stage, cancer-targeted therapy, and validate the screening and surveillance endoscopy; and (3) qualitative in depth interviews with patients and providers to elicit preferences, norms, and behaviors to explain clinical contexts of these findings and address gaps arising from the CE study. CONCLUSION: This study will compare clinical strategies for detecting and monitoring BE, a pre-cancerous lesion. Additionally, by eliciting acceptability of these strategies for patients and providers, we will be able to propose effective and feasible strategies that are likely to be implemented in routine use. Findings will inform recommendations for clinical practice guidelines. Our innovative approach is consistent with the methodological standards of patient-centered outcomes research, and our findings will offer a significant contribution to the literature on cancer surveillance.

Epidemiology of viral hepatitis and hepatocellular carcinoma.

Most cases of hepatocellular carcinoma (HCC) are associated with cirrhosis related to chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Changes in the time trends of HCC and most variations in its age-, sex-, and race-specific rates among different regions are likely to be related to differences in hepatitis viruses that are most prevalent in a population, the timing of their spread, and the ages of the individuals the viruses infect. Environmental, host genetic, and viral factors can affect the risk of HCC in individuals with HBV or HCV infection. This review summarizes the risk factors for HCC among HBV- or HCV-infected individuals, based on findings from epidemiologic studies and meta-analyses, as well as determinants of patient outcome and the HCC disease burden, globally and in the United States.

Functional Dyspepsia Treatment Trial (FDTT): a double-blind, randomized, placebo-controlled trial of antidepressants in functional dyspepsia, evaluating symptoms, psychopathology, pathophysiology and pharmacogenetics.

BACKGROUND: Functional dyspepsia (FD) is a common problem affecting up to 10-25% of individuals. FD accounts for significant health care costs and affects quality of life but has no definitive treatment. OBJECTIVES: The Functional Dyspepsia Treatment Trial (FDTT) aims to test whether treatment with an antidepressant (amitriptyline or escitalopram) leads to improvement of symptoms in patients with moderate to severe FD. DESIGN: The FDTT is an international multicenter, parallel group, randomized, double-blind, placebo-controlled trial to evaluate whether 12 weeks of treatment with escitalopram or amitriptyline improves FD symptoms compared to treatment with placebo. Secondly, it is hypothesized that acceleration of solid gastric emptying, reduction of postprandial satiation, and enhanced gastric volume change with a meal will be significant positive predictors of short- and long-term outcomes for those on antidepressants vs. placebo. The third aim is to examine whether polymorphisms of GNß3 and serotonin reuptake transporter influence treatment outcomes in FD patients receiving a tricyclic antidepressant, selective serotonin reuptake inhibitor therapy, or placebo. METHODS: The FDTT enrollment began in 2006 and is scheduled to randomize 400 patients by the end of 2012 to receive an antidepressant or placebo for 12 weeks, with a 6-month post-treatment follow-up. The study incorporates multiple validated questionnaires, physiological testing, and specific genetic evaluations. The protocol was approved by participating centers' Institutional Review Boards and an independent Data Safety Monitoring Board was established for monitoring to ensure patient safety and a single interim review of the data in December 2010 (ClinicalTrials.gov number NCT00248651).

Utilization and outcomes of palliative therapy for hepatocellular carcinoma: a population-based study in the United States.

GOALS: To evaluate the utilization and determinants of receiving palliative treatment for hepatocellular carcinoma (HCC), and its effect on survival. BACKGROUND: Palliative treatment for HCC, including transarterial chemoembolization (TACE) and systemic chemotherapy, is available for patients who do not receive potentially curative therapy. The utilization and outcomes of these therapies in clinical practice are unknown. STUDY: We conducted a population-based cohort study using the Surveillance, Epidemiology, and End-Results Registry data linked to Medicare claims of HCC patients aged above 65 years diagnosed during 2000 to 2005 who did not receive liver transplant, resection, or ablation. The proportions of patients who received TACE or systemic chemotherapy were calculated by tumor stage, liver disease status, and non-HCC comorbidity. Determinants of receiving palliative therapy were examined in logistic regression models and propensity scores were calculated. Cox proportional hazards models were used to evaluate mortality risk. RESULTS: We identified 3163 HCC patients (median age, 75 y; 67% men) who did not receive potentially curative treatment. Approximately 12.5% of patients received TACE and 11.0% received chemotherapy. In patients with early or intermediate stage HCC, no liver decompensation, and little or no comorbidity, only 22.8% received TACE and 13.8% received chemotherapy. Median survival was significantly higher among patients who received TACE (14.0 mo) compared with who received chemotherapy (5.0 mo) or no therapy (2.0 mo). A significant reduction in overall mortality was observed for TACE (54%) and chemotherapy (33%). CONCLUSIONS: Utilization of palliative treatment for HCC is low, which could not be explained by clinical features. However, misclassification could have occurred due to the data source. Receipt of TACE or systemic chemotherapy was associated with a reduction in mortality.