Sofosbuvir and simeprevir in hepatitis C genotype 1-patients with end-stage renal disease on haemodialysis or GFR <30 ml/min.

BACKGROUND & AIMS: Treating chronic hepatitis C (CHC) in patients with end-stage renal disease (ESRD) has suboptimal tolerability and cure rates. Safety and efficacy of sofosbuvir plus simeprevir regimen in CHC-infected patients with ESRD on haemodialysis (HD) or glomerular filtration rate (GFR) <30 ml/min is unknown. We evaluated the safety and efficacy of sofosbuvir and simeprevir in this special patient population. METHODS: All (n = 17) patients in the analysis had ESRD on HD or GFR <30 ml/min. All received sofosbuvir 400 mg daily and simeprevir 150 mg daily, without ribavirin for 12 weeks. Safety and efficacy data were collected; including SVR4 and SVR12 data for all patients after completing therapy. RESULTS: In this 17 patient cohort, eight (47%) were cirrhotic, four (24%) had stage three liver fibrosis and 13 (76%) were genotype 1A. All 17 have completed 12 weeks of therapy. Treatment was overall well tolerated with no treatment discontinuations reported. Four (24%) patients reported mild adverse events (AE). These AEs were insomnia (n = 2), headache (n = 1), nausea (n = 1) and worsening anaemia requiring blood transfusion (n = 1). All 17 patients reached post-treatment week-12 follow-up, and achieved SVR12 or virological cure (100% SVR12). CONCLUSIONS: Daily, full dose of sofosbuvir plus simeprevir for 12 weeks of therapy appears to be well tolerated in patients with ESRD on HD or GFR <30 ml/min. Most common AEs resembled those of healthier CHC patients without significant renal impairment. The cure rates obtained in this cohort treated with sofosbuvir and simeprevir are dramatically superior to any previous treatment regimen studied & published in this special patient population.

Safety and efficacy of simeprevir plus sofosbuvir with or without ribavirin in patients with decompensated genotype 1 hepatitis C cirrhosis.

Combination antiviral therapy involving sofosbuvir (SOF) and simeprevir (SIM) is a treatment option in patients with genotype 1 chronic hepatitis C; however, the safety of this regimen in patients with decompensated cirrhosis is not established. Data from a combined treatment cohort of 2 large hepatology referral centers were evaluated to assess for safety and efficacy of SIM plus SOF with or without ribavirin (RBV) in patients with Child B or C cirrhosis. All (n = 42) patients included in the analysis had Child B (n = 35) or C (n = 7) cirrhosis and received 400 mg daily of SOF plus 150 mg daily of SIM, with (n = 7) or without (n = 35) RBV, for 12 weeks. Of the 42 patients in this cohort, 31 (74%) were male, 22 (52%) had failed prior treatments, and 28 (67%) were genotype 1a. Prior decompensating events included encephalopathy (57%), fluid overload (88%), or variceal hemorrhage (24%). Median Model for End-Stage Liver Disease score was 12 (range, 6-25). Treatment was well tolerated overall with more than one-half (57%) reporting no adverse events. In those reporting adverse events, the most common were fatigue (n = 6), insomnia (n = 4), headache (n = 5), nausea (n = 4), and grade 1 rash (n = 1). One patient developed chemical pancreatitis that did not require treatment discontinuation. Three of 7 patients who received RBV developed anemia, with 2 requiring blood transfusions and 1 requiring a dose reduction. No episodes of decompensation requiring hospitalization or deaths occurred on treatment. Of 42 patients, 38 (90%) patients had negative viral load at end of treatment (EOT), and 31 of 42 patients (74%) achieved sustained virological response 12 weeks after EOT; 10 of 10 patients (100%) with HCV genotype 1b achieved sustained virological response for 12 weeks (SVR12). In conclusion, SOF plus SIM was very well tolerated in patients with advanced Child B/C decompensated cirrhosis. Overall, 74% of patients achieved SVR12; 100% of patients with genotype 1b decompensated cirrhosis achieved SVR12.

A partnered approach for structured observation to assess the environment of a neighborhood with high diabetes rates.

BACKGROUND: The Communities IMPACT Diabetes Center uses partnered methods to address diabetes-related conditions among African Americans and Latinos in East Harlem, New York. OBJECTIVES: To describe a novel, partnered approach that integrates simultaneous structured observation by community and academic partners with "on-the-spot" resolution of differences to collect baseline data regarding the built and food environments in a two census tract area of East Harlem and present select findings. METHODS: We designed an environmental assessment to explore characteristics of the environment related to walking and eating. We paired community and academic partners to assess each block, resolve any differences, and report results. Nearly one year later, we surveyed the data collectors and analyzed responses using standard qualitative methods. RESULTS: Key themes included connection to and characteristics of the community; interactions with partners; surprises and learning, and aspects of data collection. All but the first were common to academic and community partners. Relationships between partners were generally amiable. Both community-"I think it was very helpful, we made sure neither of us made mistakes, and helped each other when we could"-and academic-"I really enjoyed it . . . I learned a lot about the areas I surveyed"-partners were complimentary. Community partners' strengths included local knowledge of the community, whereas academic partners' focus on adherence to the specifications was critical. Structured observation identified many sidewalks in disrepair or obstructed, few benches, and highly variable times allocated for pedestrians to cross at cross walks. CONCLUSIONS: The partnered data collection was both successful and formative, building additional relationships and further capacity for ongoing partnership. Community partners saw their community in a new way, seeing, "little things that are important but people don't pay attention to." Structured observations added to our understanding of how an environment may contribute to diabetes.

Reduction in low-density lipoprotein cholesterol levels during statin therapy is associated with a reduced incidence of advanced colon polyps.

BACKGROUND: Elevated serum cholesterol levels may stimulate proliferation in adenomatous polyps (AP). Our aim was to determine how a reduction of low-density lipoprotein (LDL) cholesterol levels in patients taking statins influences the incidence of APs. METHODS: We performed a retrospective study of patients taking statins who were found to have > or =1 APs on an index colonoscopy, and who also had a follow-up colonoscopy within 3 to 5 years. Patients were divided into 2 groups: (1) those with > or =30% reduction in LDL levels and (2) those with < 30% reduction in LDL levels during the interval between colonoscopies. Univariate and multivariate analysis were evaluated for their association with advanced APs. RESULTS: We identified 231 patients. Univariate analysis showed that patients with > or =30% LDL reduction had fewer mean total numbers of APs (2.6 versus 3.3, P = 0.02), fewer advanced APs (14% versus 26%, P = 0.04), and smaller APs (5 mm versus 6.1 mm, P = 0.01) than those with <30% reduction in LDL. Multiple logistic regression analysis confirmed that > or =30% LDL reduction was associated with smaller APs (P < 0.01). Subjects with > or =30% LDL reduction also had a 53% reduced incidence of advanced APs (OR, 0.47; CI, 0.22-0.96; P < 0.05). These findings remained significant even when adjusted for nonsteroidal antiinflammatory drug use, age, family history of APs, and body mass index. CONCLUSIONS: A reduction in LDL levels of > or=30% during a 3- to 5-year period of statin therapy was associated with a 53% reduction in the incidence of advanced APs, even after adjustment for other known polyp risk factors.

For patients with colorectal cancer, the long-term use of statins is associated with better clinical outcomes.

Statins have been found to suppress tumor cell growth and to limit the ability of tumor cells to metastasize in studies involving cell lines and animals. To explore how the long-term use of statins influences the presentation and survival of patients with colorectal cancer (CRC), we conducted a retrospective case-control study of male patients with a new diagnosis of CRC who we categorized as: (1) Statin Users who used statins continuously >/=3 years prior to the diagnosis of CRC and (2) Statin Non-Users who did not use statins. Clinical factors were analyzed by simple Chi-square and multivariate regression analysis to identify independent predictors for advanced CRC. We identified 1,309 male patients with a new diagnosis of CRC (mean age 69 +/- 1.1 (SE) years; 326 Statin Users, 983 Statin Non-Users). Compared to Statin Non-Users, Statin Users had a less advanced tumor stage (2.2 vs. 2.6; P < 0.01), a lower prevalence of metastases (OR = 0.7 [0.4-0.9, 95% CI]; P < 0.01), and a higher frequency of right-sided tumors (OR = 1.6 [1.3-2.1], 95%CI]; P < 0.01). Overall 5-year survival for Statin Users was 37% compared to 33% in Statin Non-Users (OR = 0.7 [0.6-0.9], 95%CI]; P = 0.03). In patients who present to the hospital with CRC, the long-term use of statins is associated with a less advanced tumor stage, a higher prevalence of right-sided tumors, a lower frequency of distant metastases, and a better survival rate.

Obesity is associated with an increased prevalence of advanced adenomatous colon polyps in a male veteran population.

Obesity has been associated with an increased risk for colonic adenomatous polyps (APs) and colorectal cancers, but the influence of obesity on the development of advanced APs is not clear. The purpose of this study is to determine the influence of obesity on the prevalence of advanced APs in a male veteran population. We performed a retrospective study of patients (n = 2,903) with histologically confirmed APs on an index colonoscopy. APs were evaluated for advanced features (size > or = 1 cm in diameter and/or a villous component and/or high grade dysplasia). Patients were categorized as: normal weight (BMI > 18.5 and < 25), overweight (BMI > or = 25 and < 30), and obese (BMI > or = 30). An association between clinical factors and advanced APs was sought by Kruskal-Wallis test and Pearson Chi-square. Multiple logistic regression analysis was used to determine independent predictors for advanced APs. We identified 2,903 male patients with APs (mean age 64 + 1.1(SE) years; 770 (27%) normal weight, 1,029 (35%) overweight, 1,104 (38%) obese. By univariate analysis, obese patients had a greater prevalence of advanced APs than the overweight and normal weight patients (28 vs. 23 vs. 24%, p = 0.025). Multiple logistic regression analysis confirmed the association of obesity and advanced APs (OR = 1.01, CI = 1-1.02, p = 0.04). For every one-unit increase in BMI above 30, there was a corresponding 1% increase in the frequency of finding advanced APs. Obesity in male veteran patients is associated with the finding of advanced APs on colonoscopy. We speculate that obesity may increase the risk for CRC by promoting the development of advanced APs.

The long-term use of statins is associated with a decreased incidence of adenomatous colon polyps.

BACKGROUND/AIMS: Studies have suggested that statins may protect against colorectal cancer (CRC), but it is not clear whether that protection results from effects on established adenomatous polyps (APs) or from preventing the development of new APs. We have conducted a retrospective, cohort study to explore how the long-term use of statins influences the development of new APs. METHODS: We reviewed endoscopy and pathology databases to identify patients with histologically verified APs, all of which were removed during an index colonoscopy, and who had a follow-up colonoscopy 3-5 years later. Patients were categorized as users or nonusers of statins by review of their medical and pharmacy records, and the characteristics of APs found on follow-up colonoscopy in the 2 groups was compared. RESULTS: We identified 2,626 patients (84% men, mean age 62.2 years) with APs removed during an index colonoscopy. Of 1,688 patients (35%) who used statins continuously, 583 had an AP found on follow-up colonoscopy, compared to 477 of 938 patients (51%) who did not use statins continuously [odds ratio (OR) 0.51, 95% confidence interval (CI) 0.43-0.60; p < 0.01]. Statin use was associated with a smaller mean number of polyps (2.6 vs. 3.1; p = 0.002), a smaller mean polyp size (7.1 vs. 7.9 mm; p = 0.03) and a significant reduction in the incidence of advanced APs (OR 0.74, 95% CI 0.52-0.96; p = 0.03). CONCLUSIONS: In patients with APs removed colonoscopically, long-term statin usage is associated with a decreased incidence of new and advanced APs. This suggests that statins may protect against CRC by reducing the development of new APs.

Safety and efficacy of metallic stents in the management of colorectal obstruction.

BACKGROUND: The use of self-expandable metallic stents in the management of obstructing colorectal cancer has been described with increasing frequency in the literature. Our goal was to evaluate the efficacy and associated morbidity of the use of self-expandable metallic stents to relieve colorectal obstruction at our institution. METHODS: A retrospective chart review of patients who underwent colorectal stent placement between December 2001 and December 2003 in a tertiary referral center was performed. RESULTS: Stents were placed successfully in 17 of 21 patients (81%) with colorectal obstruction. Placement was achieved endoscopically in 13 patients and radiologically in 4. Ten self-expandable metallic stents were used as a bridge to surgery, and 7 were used for palliation. The obstructions were located in the sigmoid colon (11 patients), the rectosigmoid (3), the splenic flexure, the hepatic flexure, and the rectum. Malignant obstruction was noted in 14 patients. One patient with malignancy experienced a sigmoid perforation, and 2 patients with benign disease had complications (1 stent migration and 1 re-obstruction). Stent patency in obstruction secondary to colonic adenocarcinoma was 100% in our follow-up period (range, 5 to 15 months). CONCLUSIONS: The use of stents as a bridge to surgery is associated with low morbidity, allows for bowel preparation, and thus avoids the need for a temporary colostomy. Long-term patency suggests that stents may allow for the avoidance of an operation in patients with metastatic disease and further defines their role in the palliation of malignant obstruction. Further prospective randomized studies are necessary to fully elucidate the use of stents in the management of colorectal cancer.