Ultrasound elastography for fibrosis surveillance is cost effective in patients with chronic hepatitis C virus in the UK.

BACKGROUND: Chronic hepatitis C (HCV) is a significant risk factor for cirrhosis and subsequently hepatocellular carcinoma (HCC). HCV patients with cirrhosis are screened for HCC every 6 months. Surveillance for progression to cirrhosis and consequently access to HCC screening is not standardized. Liver biopsy, the usual test to determine cirrhosis, carries a significant risk of morbidity and associated mortality. Transient ultrasound elastography (fibroscan) is a non-invasive test for cirrhosis. PURPOSE: This study assesses the cost effectiveness of annual surveillance for cirrhosis in patients with chronic HCV and the effect of replacing biopsy with fibroscan to diagnose cirrhosis. METHOD: A Markov decision analytic model simulated a hypothetical cohort of 10,000 patients with chronic HCV initially without fibrosis over their lifetime. The cirrhosis surveillance strategies assessed were: no surveillance; current practice; fibroscan in current practice with biopsy to confirm cirrhosis; fibroscan completely replacing biopsy in current practice (definitive); annual biopsy; annual fibroscan with biopsy to confirm cirrhosis; annual definitive fibroscan. RESULTS: Our results demonstrate that annual definitive fibroscan is the optimal strategy to diagnose cirrhosis. In our study, it diagnosed 20 % more cirrhosis cases than the current strategy, with 549 extra patients per 10,000 accessing screening over a lifetime and, consequently, 76 additional HCC cases diagnosed. The lifetime cost is £98.78 extra per patient compared to the current strategy for 1.72 additional unadjusted life years. Annual fibroscan surveillance of 132 patients results in the diagnosis one additional HCC case over a lifetime. The incremental cost-effectiveness ratio for an annual definitive fibroscan is £6,557.06/quality-adjusted life years gained. CONCLUSION: Annual definitive fibroscan may be a cost-effective surveillance strategy to identify cirrhosis in patients with chronic HCV, thereby allowing access of these patients to HCC screening.

Unraveling the sequence dynamics of the formation of genus-specific satellite DNAs in the family solanaceae.

Tandemly repeated DNAs, referred to as satellite DNAs, often occur in a genome in a genus-specific manner. However, the mechanisms for generation and evolution for these sequences are largely unknown because of the uncertain origins of the satellite DNAs. We found highly divergent genus-specific satellite DNAs that showed sequence similarity with genus-specific intergenic spacers (IGSs) in the family Solanaceae, which includes the genera Nicotiana, Solanum and Capsicum. The conserved position of the IGS between 25S and 18S rDNA facilitates comparison of IGS sequences across genera, even in the presence of very low sequence similarity. Sequence comparison of IGS may elucidate the procedure of the genesis of complex monomer units of the satellite DNAs. Within the IGS of Capsicum species, base substitutions and copy number variation of subrepeat monomers were causes of monomer divergence in IGS sequences. At the level of inter-generic IGS sequences of the family Solanaceae, however, genus-specific motif selection, motif shuffling between subrepeats and differential amplification among motifs were involved in formation of genus-specific IGS. Therefore, the genus-specific satellite DNAs in Solanaceae plants can be generated from differentially organized repeat monomers of the IGS rather than by accumulation of mutations from pre-existent satellite DNAs.

The prevalence of Barrett's esophagus in the US: estimates from a simulation model confirmed by SEER data.

Barrett's esophagus (BE) is the precursor and the biggest risk factor for esophageal adenocarcinoma (EAC), the solid cancer with the fastest rising incidence in the US and western world. Current strategies to decrease morbidity and mortality from EAC have focused on identifying and surveying patients with BE using upper endoscopy. An accurate estimate of the number of patients with BE in the population is important to inform public health policy and to prioritize resources for potential screening and management programs. However, the true prevalence of BE is difficult to ascertain because the condition frequently is symptomatically silent, and the numerous clinical studies that have analyzed BE prevalence have produced a wide range of estimates. The aim of this study was to use a computer simulation disease model of EAC to determine the estimates for BE prevalence that best align with US Surveillance Epidemiology and End Results (SEER) cancer registry data. A previously developed mathematical model of EAC was modified to perform this analysis. The model consists of six health states: normal, gastroesophageal reflux disease (GERD), BE, undetected cancer, detected cancer, and death. Published literature regarding the transition rates between these states were used to provide boundaries. During the one million computer simulations that were performed, these transition rates were systematically varied, producing differing prevalences for the numerous health states. Two filters were sequentially applied to select out superior simulations that were most consistent with clinical data. First, among these million simulations, the 1000 that best reproduced SEER cancer incidence data were selected. Next, of those 1000 best simulations, the 100 with an overall calculated BE to Detected Cancer rates closest to published estimates were selected. Finally, the prevalence of BE in the final set of best 100 simulations was analyzed. We present histogram data depicting BE prevalences for all one million simulations, the 1000 simulations that best approximate SEER data, and the final set of 100 simulations. Using the best 100 simulations, we estimate the prevalence of BE to be 5.6% (5.49-5.70%). Using our model, an estimated prevalence for BE in the general population of 5.6% (5.49-5.70%) accurately predicts incidence rates for EAC reported to the US SEER cancer registry. Future clinical studies are needed to confirm our estimate.

Systematic review: cost-effectiveness of direct-acting antivirals for treatment of hepatitis C genotypes 2-6.

BACKGROUND: The availability of direct-acting antivirals (DAAs) has dramatically changed the landscape of hepatitis C virus (HCV) therapy; however, the cost and budget requirements for DAA treatment have been widely debated. AIMS: To systematically review published studies evaluating the cost-effectiveness of DAAs for HCV genotype 2-6 infections, and synthesise and re-evaluate results with updated drug prices. METHODS: We conducted a systematic search of various electronic databases, including Medline, EMBASE, Cochrane library and EconLit for cost-effectiveness studies published from 2011 to 2016. Studies evaluating DAAs for genotypes 2-6 were included. Reported costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) were abstracted. We re-estimated ICERs by varying the price of DAAs from $20 000 to $100 000, and estimated the threshold price at which DAA regimens would be deemed cost-effective (ICER≤$100 000/QALY). RESULTS: A total of 92 ICERs for 7 different DAA regimens from 10 published articles were included. Among the abstracted 92 ICERs, 20 were for genotype 2, 40 for genotype 3, 30 for genotype 4, 2 for genotype 5 and none for genotype 6; therefore, only genotypes 2-5 were analysed. At the discounted price of $40 000, 87.0% analyses found DAA regiments to be cost-effective, and 7.6% found to be cost-saving. The median threshold price below which DAAs would be deemed cost-effective was between $144 400 and $225 000, and cost-saving between $17 300 and $25 400. CONCLUSIONS: HCV treatment with DAAs is highly cost-effective in patients with HCV genotypes 2-5 at a $100 000/QALY threshold. Timely HCV treatment would be an optimal strategy from both a public health and economic perspective.

The prevalence and radiological findings in 1347 elderly patients with scoliosis.

In order to determine the epidemiology of adult scoliosis in the elderly and to analyse the radiological parameters and symptoms related to adult scoliosis, we carried out a prospective cross-sectional radiological study on 1347 adult volunteers. There were 615 men and 732 women with a mean age of 73.3 years (60 to 94), and a mean Cobb angle of 7.55 degrees (sd 5.95). In our study, 478 subjects met the definition of scoliosis (Cobb angle > or = 10 degrees ) showing a prevalence of 35.5%. There was a significant difference in the epidemiological distribution and prevalence between the age and gender groups. The older adults showed a larger prevalence and more severe scoliosis, more prominent in women (p = 0.004). Women were more affected by adult scoliosis and showed more linear correlation with age (p < 0.001). Symptoms were more severe in those with scoliosis than in the normal group, but were similar between the mild, moderate and severe scoliosis groups (p = 0.224) and between men and women (p = 0.231). Adult scoliosis showed a significant relationship with lateral listhesis, vertebral rotation, lumbar hypolordosis, sagittal imbalance and a high level of the L4-5 disc (p < 0.0001, p < 0.0001, p = 0.002, p = 0.002, p < 0.0001 respectively). Lateral listhesis, lumbar hypolordosis and sagittal imbalance were related to symptoms (p < 0.0001, p = 0.001, p < 0.0001 respectively).

Pancreatic cystic lesions: clinical predictors of malignancy in patients undergoing surgery.

BACKGROUND: Despite advances in cross-sectional imaging and the use of molecular markers, distinguishing between benign and malignant cysts remains a clinical challenge. AIMS: To identify both preoperative clinical and cyst characteristics at the time of EUS that predict malignancy. METHODS: A retrospective analysis was performed on consecutive patients with pancreatic cysts who underwent endoscopic ultrasound (EUS) and surgical resection from May 1996 to December 2007 at a tertiary centre. Clinical history, EUS characteristics, cytology, tumour markers and surgical histology were collected. Predictors of malignancy were determined by univariate and multivariate analysis using logistic regression. RESULTS: A total of 153 patients underwent a EUS and subsequent surgical intervention.Of the 153 patients, 57 (37%) had a histological diagnosis of malignancy. On univariate analysis, older age (P < 0.001), male gender (P = 0.010), jaundice (P = 0.039), history of other malignancy (P = 0.036), associated mass in cyst (P = 0.004) and malignant cytology (P < 0.001) were found to be associated with malignancy. History of pancreatitis (P = 0.008) and endoscopist impression of pseudocyst (P = 0.001) were found to be associated with benign cysts. Multivariate analysis found that only older age [Odds ratio (OR), 1.04; 95% confidence interval (CI), 1.01-1.08], male gender (OR, 2.26; 95% CI, 1.08-4.73) and malignant cytology (OR, 6.60; 95% CI, 2.02-21.58) were independent predictors of malignancy. CONCLUSIONS: Older age, male gender and malignant cytology from EUS predict malignancy at surgical resection. These characteristics may be used to estimate the probability of malignancy in a cyst and aid in management.

Arthrodesis of the knee using cannulated screws.

We retrospectively evaluated eight patients who underwent arthrodesis of the knee using cannulated screws. There were six women and two men, with a mean age of 53 years. The indications for arthrodesis were failed total knee arthroplasty, septic arthritis, tuberculosis, and recurrent persistent infection. Solid union was achieved in all patients at a mean of 6.1 months. One patient required autogenous bone graft for delayed union. One suffered skin necrosis which was treated with skin grafting. The mean limb-length discrepancy was 3.1 cm. On a visual analogue scale, the mean pain score improved from 7.9 to 3.3. According to the Knee Injury and Osteoarthritis Outcome score quality of life items, the mean score improved from 38.3 pre-operatively to 76.6 at follow-up. Cannulated screws provide a high rate of union in arthrodesis of the knee with minimal complications, patient convenience, and a simple surgical technique.

Infliximab dose escalation vs. initiation of adalimumab for loss of response in Crohn's disease: a cost-effectiveness analysis.

BACKGROUND: Crohn's disease patients who have lost response to 5 mg/kg of infliximab may regain response by increasing the dose of infliximab to 10 mg/kg. Alternatively, adalimumab can be used as a rescue therapy. AIM: To determine whether dose escalation of infliximab was a cost-effective strategy compared with adalimumab initiation after loss of response to 5 mg/kg of infliximab. METHODS: A decision-analysis model simulated two cohorts of Crohn's patients: (i) infliximab dose was escalated to 10 mg/kg and (ii) infliximab was discontinued and patients were started on adalimumab. The time horizon was 1 year. One- and two-way sensitivity analyses were performed. RESULTS: The infliximab dose escalation strategy yielded more quality-adjusted life years (0.79) compared with the adalimumab strategy (0.76). The incremental cost-effectiveness ratio was $332,032/quality-adjusted life year. Sensitivity analysis demonstrated that the model findings were robust. The most significant variables were the cost of infliximab and that of adalimumab, such that a reduction in the cost of infliximab by 1/3 resulted in an incremental cost-effectiveness ratio below $80,000/quality-adjusted life year. CONCLUSION: After a Crohn's patient has lost response to 5 mg/kg of infliximab, dose escalation will yield more quality-adjusted life-year compared with switching to adaliumamb; however, the cost was considerable.

Determination of Panthenol, Cholecalciferol and Tocopherol in Cosmetic Products by Gas Chromatography-Mass Spectrometry in SIM Mode.

A novel simple method to detect vitamins in cosmetic products by gas chromatography-mass spectrometry (GC-MS) has been developed. Three vitamins (panthenol, cholecalciferol and tocopherol) were used for this study. Vitamins were prepared by dissolving in tetrahydrofuran (ThF), and silylated with bis-trimethylsilyltri-fluoroacetamide- trichloromethylsilane (BSTFA). Silylated vitamins were separated on a fused-silica capillary column coated with DB-5. The identification of each vitamin was accomplished by retention time and mass spectrum library search with a computer, and the quantitation was made in the selected-ion monitoring (SIM) mode of GC-MS. SIM mode had given sensitivity to determine 50 pg of panthenol, 285 pg of cholecalciferol and 130 pg of tocopherol. Linearity was maintained over the range 0.005-0.20% for each vitamin. Each cosmetic product (i.e. hair tonic and lotion) was found to contain amounts of the vitamins. This method was sensitive and gave 77.5-99.9% recovery of each vitamin from these cosmetic products. From these results, we concluded that silylation with BSTFA followed by GC-MS analysis allows the simple, convenient and exact determination of panthenol, cholecalciferol and tocopherol.

Discovery of genes for ginsenoside biosynthesis by analysis of ginseng expressed sequence tags.

Expressed sequence tags (ESTs) provide a valuable tool that can be used to identify genes in secondary metabolite biosynthesis. Ginseng (Panax ginseng C.A Meyer) is a medicinal plant that accumulates ginsenosides in roots. We sequenced 11,636 ESTs from five ginseng libraries in order to create a gene resource for biosynthesis of ginsenosides, which are thought to be the major active component in roots. Only 59% of the ginseng ESTs exhibited significant homology to previously known polypeptide sequences. Stress- and pathogen-response proteins were most abundant in 4-year-old ginseng roots. ESTs involved in ginsenoside biosynthesis were identified by a keyword search of BLASTX results and a domain search of ginseng ESTs. We identified 4 oxidosqualene cyclase candidates involved in the cyclization reaction of 2,3-oxidosqualene, 9 nine cytochrome P450 and 12 glycosyltransferse candidates, which may be involved in modification of the triterpene backbone.