Economic and health outcomes of capsule endoscopy: Opportunities for improved management of the diagnostic process for obscure gastrointestinal bleeding

The estimated annual incidence of gastrointestinal bleeding in the United States is approximately 100 episodes per 100,000 persons, resulting in 300,000 hospitalizations annually. Diagnostic tools such as radiologic studies and endoscopic examination often fail to identify a source of bleeding, resulting in a cycle of repetitive testing over months or even years. Costs associated with the diagnostic process, and with interim treatment for anemia and other symptoms, can be significant. The diagnostic process also takes a toll on the patient, in terms of worry, pain, and discomfort. Capsule endoscopy, a technology that received FDA clearance in August, 2001, consists of a video capsule that is ingested by the patient, and that transmits images to a wireless data recorder worn on the belt. The recorded stream of approximately 50,000 images can be reviewed on a computer workstation by a physician to identify nature and location of potential sources of bleeding. This paper presents a framework for economic analysis of this new technology. First, we present a review of the literature on the current diagnostic methods. Next, we present a conceptual model for examining contributors to costs in diagnosing obscure intestinal bleeds. We conclude by exploring the potential economic impact of the technology. Analysis of data from the first U.S. clinical trial of capsule endoscopy demonstrates its high diagnostic yield, and patient satisfaction. While further study is required, this analysis indicates that capsule endoscopy may reduce total medical utilization and costs and improve patient quality of life, when used for appropriate indications

Persistent risk for new, subsequent new and recurrent hepatocellular carcinoma despite successful anti-hepatitis B virus therapy and tumor ablation: The need for hepatitis B virus cure.

Hepatitis B virus (HBV) is one of the most significant hepatocarcinogens. The ultimate goal of anti-HBV treatment is to prevent the development of hepatocellular carcinoma (HCC). During the last two decades, with the use of currently available anti-HBV therapies (lamivudine, entecavir and tenofovir disoproxil fumatate), there has been a decrease in the incidence of HBV-associated HCC (HBV-HCC). Furthermore, several studies have demonstrated a reduction in recurrent or new HCC development after initial HCC tumor ablation. However, during an observation period spanning 10 to 20 years, several case reports have demonstrated the development of new, subsequent new and recurrent HCC even in patients with undetectable serum HBV DNA. The persistent risk for HCC is attributed to the presence of covalently closed circular DNA (cccDNA) in the hepatocyte nucleus which continues to work as a template for HBV replication. While a functional cure (loss of hepatitis B surface antigen and undetectable viral DNA) can be attained with nucleos(t)ide analogues, these therapies do not eliminate cccDNA. Of utmost importance is successful eradication of the transcriptionally active HBV cccDNA from hepatocyte nuclei which would be considered a complete cure. The unpredictable nature of HCC development in patients with chronic HBV infection shows the need for a complete cure. Continued support and encouragement for research efforts aimed at developing curative therapies is imperative. The aims of this minireview are to highlight these observations and emphasize the need for a cure for HBV

An old problem with a new therapy: gastrointestinal bleeding in ventricular assist device patients and deep overtube-assisted enteroscopy.

Conventional algorithms for diagnosis and treatment of gastrointestinal bleeding (GIB) in patients with nonpulsatile ventricular assist devices (VADs) may take days to perform while patients require transfusions. We developed a new algorithm based on deep overtube-assisted enteroscopy (DOAE) to facilitate a rapid diagnosis and treatment. From 2004 to 2012, 84 patients who underwent VAD placement in our institution, were evaluated for episodes of GIB. Our new algorithm for the management of GIB using DOAE was evaluated by dividing the episodes into three groups: group A (traditional management without enteroscopy), group B (traditional management with enteroscopy performed \u3e24 hours after presentation), and group C (new management algorithm with enteroscopy performedpresentation). Gastrointestinal bleeding was observed in 14 (17%) of our study patients for a total of 45 individual episodes of which 28 met our criteria for subanalysis. Forty-one (84%) lesions were confined to the upper gastrointestinal tract with more than 91% of these lesions being arteriovenous malformations. Average number of transfusions in groups A, B, and C were 4.1, 6.3, and 1.3, respectively (p = 0.001). The number of days to treatment was significantly shorter in group C than group B (0.4 vs. 5.3 days, p = 0.0002). Our new algorithm for the management of GIB using DOAE targets the most common locations of bleeding found in this patient population. When performed early, DOAE has the potential to decrease the need for transfusions and allow for an early diagnosis of GIB in VAD recipients

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio