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The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.
USPSTF recommendations for colorectal cancer screening (July 2016)
The United States Preventive Services Task Force (USPSTF) issued new guidelines for colorectal cancer screening in average risk adults . The guidelines make a strong recommendation for screening, starting at age 50 years and continuing to age 75 for most patients, but in a departure from prior recommendations do not give preference for any one of seven screening test strategies over another. Options for screening are shown in a table (table 1). We agree with this screening test strategy based on shared decision making. Incorporating patient personal preferences may increase the likelihood that ongoing screening will occur. (See "Screening for colorectal cancer: Strategies in patients at average risk", section on 'USPSTF guidelines'.)
Colonoscopy preparation and sessile-serrated polyp detection rates (September 2016)
Previous studies have not demonstrated an association between split-dose colonoscopy preparation (ie, one half the evening prior to the colonoscopy and the second half the morning of) and improvement in sessile-serrated polyp detection rates. In a randomized trial, 341 patients were assigned to 2 liters of polyethylene glycol electrolyte lavage solution with ascorbic acid either as single-dose or split-dose regimen . Split-dose lavage resulted in significantly lower duration and intensity of bowel movements, less disruption of sleep, and better quality of bowel preparation. There were no differences in adenoma detection rates between the two groups; however, split-dose lavage resulted in significantly higher sessile-serrated polyp detection rates (10 versus 2 percent). These data support current recommendations that colonoscopy preparations be administered as split-dose rather than being given entirely the evening prior to the colonoscopy. (See "Bowel preparation for colonoscopy and flexible sigmoidoscopy in adults", section on 'Split-dose lavage'.)
ESOPHAGEAL AND GASTRIC DISEASE
Unclear role of montelukast in eosinophilic esophagitis (October 2016)
Initial experience suggested that montelukast may be helpful for symptom reduction in patients with eosinophilic esophagitis, but subsequent experience has been mixed. In a small randomized trial, patients with eosinophilic esophagitis were assigned to maintenance treatment with montelukast or placebo for 26 weeks following steroid-induced symptomatic remission . There were no significant differences in the proportion of patients that remained in remission between the two groups. Thus, the role of montelukast in eosinophilic esophagitis, if any, remains unclear. (See "Treatment of eosinophilic esophagitis", section on 'Montelukast'.)
Tenofovir alafenamide for the treatment of chronic hepatitis B virus infection (December 2016)
Tenofovir disoproxil fumarate is a first-line therapy for chronic hepatitis B virus (HBV) infection. A newer formulation of tenofovir, tenofovir alafenamide, was approved by the US Food and Drug Administration in November 2016 for the treatment of chronic HBV in patients with compensated liver disease . In two large randomized noninferiority trials among patients with chronic HBV infection (both treatment-naive and experienced, and including patients positive or negative for HBV e antigen), tenofovir alafenamide resulted in similar rates of HBV suppression and fewer adverse effects on renal function and bone density at 48 weeks compared with tenofovir disoproxil fumarate [5,6]. Given these findings, tenofovir alafenamide is our preferred formulation for patients with chronic HBV who initiate therapy with tenofovir. We also favor switching those initially started on tenofovir disoproxil fumarate to tenofovir alafenamide. Given limited available safety data, we do not currently use tenofovir alafenamide in pregnant women. (See "Hepatitis B virus: Overview of management", section on 'Nucleos(t)ide analogues'.)
Prevention of graft reinfection in HCV-infected patients undergoing liver transplantation (December 2016)
In the absence of viral suppression or clearance of chronic hepatitis C virus (HCV) in patients who undergo liver transplantation, the new liver is almost always reinfected. In an open-label study, 16 HCV genotype 1-infected patients undergoing their first liver transplantation from an uninfected donor received a single dose of ledipasvir-sofosbuvir the day they arrived at the hospital for transplantation and once daily for four weeks postoperatively . The sustained virologic response rate 12 weeks after completion of treatment was 88 percent, suggesting that an abbreviated perioperative course of direct-acting antiviral (DAA) treatment can prevent reinfection of the graft. Additional studies are warranted to confirm the efficacy and safety of this approach in other HCV-infected populations and with other DAA regimens. (See "Recurrence of hepatitis C virus infection following liver transplantation", section on 'Perioperative therapy'.)
HBV reactivation during HCV antiviral therapy (October 2016)
Reactivation of hepatitis B virus (HBV) infection, including cases with fatal fulminant hepatitis, has been reported in several patients receiving direct-acting antiviral therapy for hepatitis C virus (HCV) infection . Patients should be tested for HBV coinfection prior to initiation of HCV therapy, with HBV treatment initiated for those who meet criteria (table 2). HBV surface antigen (HBsAg) positive patients who do not initially meet HBV treatment criteria should be monitored with HBV DNA testing during HCV treatment. In patients with a positive HBV core antibody (HBcAb) but negative HBsAg, we check liver enzymes during HCV treatment and perform reflex HBsAg and HBV DNA testing for unexplained elevations. (See "Patient evaluation and selection for antiviral therapy for chronic hepatitis C virus infection", section on 'HBV coinfection' and "Overview of the management of chronic hepatitis C virus infection", section on 'Other laboratory testing'.)
Sofosbuvir-velpatasvir for all genotypes of chronic HCV infection (July 2016)
All-oral, direct-acting antiviral regimens for chronic hepatitis C virus (HCV) infection have proliferated over the past two years. Sofosbuvir-velpatasvir, a coformulated combination of an NS5B and an NS5A inhibitor, is the first such regimen that has high, well-established efficacy for all genotypes, even in patients with cirrhosis or prior treatment failure with interferon-based regimens [9-11]. This agent was approved by the US Food and Drug Administration in June 2016 and is now our preferred or one of our preferred regimens for adults with chronic HCV infection of any genotype because of its efficacy, simplicity of administration, and limited drug interactions (algorithm 1 and algorithm 2 and algorithm 3 and algorithm 4). Sofosbuvir-velpatasvir is given for 12 weeks for all genotypes. For genotype 3 infection, the addition of ribavirin may be warranted, depending on the presence of cirrhosis, the prior treatment history, and the presence of mutations associated with NS5A resistance. (See "Treatment regimens for chronic hepatitis C virus genotype 1 infection in adults", section on 'Selection of treatment regimens' and "Treatment regimens for chronic hepatitis C virus genotypes 2 and 3 infection in adults", section on 'Selection of treatment regimen' and "Treatment regimens for chronic hepatitis C virus genotypes 4, 5, and 6 infection in adults", section on 'Selection of treatment regimens'.)
Declining use of feeding tubes in advanced dementia (August 2016)
Patients with advanced dementia commonly have eating problems in the final stages of illness, and caregivers are faced with decisions about whether to continue oral feeding by hand or place a long-term feeding tube. The available evidence fails to demonstrate any health benefits of tube feeding over ongoing hand feeding, and an increasing number of consensus-based guidelines advocate against feeding tube placement in this setting. In keeping with these recommendations, a recent study in the United States found that the proportion of nursing home residents with advanced dementia who received a feeding tube within one year of the onset of feeding problems decreased by approximately 50 percent between the years 2000 and 2014 . Advance care planning is critical in the management of patients with dementia and should include preparatory discussions about eating problems and other common complications encountered in the advanced stages of the disease. (See "Palliative care of patients with advanced dementia", section on 'Oral versus tube feeding'.)
SMALL BOWEL AND COLONIC DISEASE
Donor fecal microbiota transplant for recurrent Clostridium difficile infection (December 2016)
Strong evidence to support fecal microbiota transplant (FMT) in patients with recurrent Clostridium difficile infection (CDI) has been lacking. In a randomized trial, patients with three or more recurrences of CDI who had received vancomycin for their most recent acute episode were assigned to FMT administered by colonoscopy with donor stool or their own stool (as a control) . Patients who received donor FMT achieved higher clinical cure rates (92 versus 63 percent). These data support our recommendations to treat patients with recurrent CDI despite multiple courses of antibiotic therapy with donor FMT. (See "Fecal microbiota transplantation in the treatment of recurrent Clostridium difficile infection", section on 'Colonoscope'.)
Ustekinumab for anti-TNF refractory Crohn disease (November 2016)
Ustekinumab is approved for use in adult patients with moderate to severely active Crohn disease who have failed conventional therapy, but efficacy in inducing clinical remission in patients with disease refractory to anti-tumor necrosis factor (anti-TNF) therapy had not been previously established. In two randomized induction trials, approximately 1300 patients with Crohn disease and nonresponse or intolerable side effects to anti-TNF therapy were assigned to eight weeks of intravenous ustekinumab or placebo . Those who responded to ustekinumab were assigned to 44 weeks of subcutaneous maintenance with ustekinumab or placebo. Patients assigned to ustekinumab had significantly higher clinical response rates at week six and rates of remission at week 44 as compared with placebo, demonstrating a role for ustekinumab in patients who have failed anti-TNF therapy. (See "Overview of the medical management of severe or refractory Crohn disease in adults", section on 'Ustekinumab'.)
Biosimilars for tumor necrosis factor inhibitors (August 2016)
Copies of biologic agents, termed biosimilars, including several of the tumor necrosis factor (TNF) inhibitors and other medications, have been marketed or are under development for use in the rheumatic diseases. A recent systematic review of 19 observational studies and clinical trials compared biosimilar TNF-alpha inhibitors with their reference biologic products, including infliximab, etanercept, and adalimumab, with testing done in healthy volunteers and in patients with rheumatoid arthritis, inflammatory bowel disease, and ankylosing spondylitis . Pharmacokinetic measurements were within defined equivalence margins, and similar clinical responses and adverse events were found for the tested products and their reference drugs. Additionally, similar efficacy and safety were observed in four cohort studies in which patients were switched from the reference product to a biosimilar medication. Limitations for many of the studies included small sample size and short trial duration, but collectively these data illustrate the potential utility of these agents. (See "Overview of biologic agents and kinase inhibitors in the rheumatic diseases", section on 'Biosimilars for biologic agents'.)
Investigational stem cell therapy for complex perianal fistulas in Crohn disease (August 2016)
Complex fistulas in Crohn disease are often refractory to medical therapy. In a randomized trial, 212 patients with treatment-refractory, draining complex perianal fistulas were assigned to a single intralesional injection of allogeneic, expanded, adipose-derived mesenchymal stem cells (Cx601) or saline solution in addition to their concomitant baseline treatment . Rates of combined remission at 24 weeks were significantly higher in patients treated with Cx601 compared with placebo. The incidence of anal abscess and proctalgia, the most frequent serious treatment-related adverse events, were slightly higher in the placebo group. Additional studies with long-term follow-up are needed to assess the safety and efficacy of this therapy and its mechanism of action. (See "Investigational therapies in the medical management of Crohn disease", section on 'Stem cell therapy'.)
AAP guidance on use of biologic response modifiers (July 2016)
Biologic response modifiers (BRMs) are immunosuppressive agents that are used to treat autoimmune disorders such as juvenile idiopathic arthritis and inflammatory bowel disease. Patients receiving BRMs have an increased risk of infection, particularly mycobacterial, viral, and fungal infections. Thus, the American Academy of Pediatrics has published guidance for clinicians using these agents . A thorough history is recommended to help determine infectious risk, with performance of screening tests as indicated depending upon the history and biologic agent chosen. Administration of routine immunizations at least two weeks prior to starting a BRM is advised for inactivated or subunit vaccines and at least four weeks prior for live vaccines, if treatment can be safely delayed. Administration of live vaccines is not recommended during treatment with BRMs. An infectious disease specialist should be consulted if a live vaccine is deemed necessary while a patient is on biologic therapy. Inactivated and subunit vaccines can be given while on therapy, and an annual inactivated influenza vaccine is recommended. (See "Systemic juvenile idiopathic arthritis: Treatment", section on 'Biologic therapy'.)
- US Preventive Services Task Force, Bibbins-Domingo K, Grossman DC, et al. Screening for Colorectal Cancer: US Preventive Services Task Force Recommendation Statement. JAMA 2016; 315:2564.
- Horton N, Garber A, Hasson H, et al. Impact of Single- vs. Split-Dose Low-Volume Bowel Preparations on Bowel Movement Kinetics, Patient Inconvenience, and Polyp Detection: A Prospective Trial. Am J Gastroenterol 2016; 111:1330.
- Alexander JA, Ravi K, Enders FT, et al. Montelukast Does not Maintain Symptom Remission After Topical Steroid Therapy for Eosinophilic Esophagitis. Clin Gastroenterol Hepatol 2016.
- U.S. Food and Drug Administration Approves Gilead’s Vemlidy (Tenofovir Alafenamide) for the Treatment of Chronic Hepatitis B Virus Infection. http://www.gilead.com/news/press-releases/2016/11/us-food-and-drug-administration-approves-gileads-vemlidy-tenofovir-alafenamide-for-the-treatment-of-chronic-hepatitis-b-virus-infection (Accessed on November 28, 2016).
- Chan HL, Fung S, Seto WK, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of HBeAg-positive chronic hepatitis B virus infection: A randomised, double-blind, phase 3, non-inferiority trial. Lancet Gastroenterol Hepatol 2016; 1:185.
- Buti M, Gane E, Seto WK, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of HBeAg-negative chronic hepatitis B virus infection: A randomised, double-blind, phase 3, non-inferiority trial. Lancet Gastroenterol Hepatol 2016; 1:196.
- Levitsky J, Verna EC, O'Leary JG, et al. Perioperative Ledipasvir-Sofosbuvir for HCV in Liver-Transplant Recipients. N Engl J Med 2016; 375:2106.
- FDA Drug Safety Communication: FDA warns about the risk of hepatitis B reactivating in some patients treated with direct-acting antivirals for hepatitis C http://www.fda.gov/Drugs/DrugSafety/ucm522932.htm (Accessed on October 05, 2016).
- Feld JJ, Jacobson IM, Hézode C, et al. Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection. N Engl J Med 2015; 373:2599.
- Everson GT, Towner WJ, Davis MN, et al. Sofosbuvir With Velpatasvir in Treatment-Naive Noncirrhotic Patients With Genotype 1 to 6 Hepatitis C Virus Infection: A Randomized Trial. Ann Intern Med 2015; 163:818.
- Pianko S, Flamm SL, Shiffman ML, et al. Sofosbuvir Plus Velpatasvir Combination Therapy for Treatment-Experienced Patients With Genotype 1 or 3 Hepatitis C Virus Infection: A Randomized Trial. Ann Intern Med 2015; 163:809.
- Mitchell SL, Mor V, Gozalo PL, et al. Tube Feeding in US Nursing Home Residents With Advanced Dementia, 2000-2014. JAMA 2016; 316:769.
- Kelly CR, Khoruts A, Staley C, et al. Effect of Fecal Microbiota Transplantation on Recurrence in Multiply Recurrent Clostridium difficile Infection: A Randomized Trial. Ann Intern Med 2016; 165:609.
- Feagan BG, Sandborn WJ, Gasink C, et al. Ustekinumab as Induction and Maintenance Therapy for Crohn's Disease. N Engl J Med 2016; 375:1946.
- Chingcuanco F, Segal JB, Kim SC, Alexander GC. Bioequivalence of Biosimilar Tumor Necrosis Factor-α Inhibitors Compared With Their Reference Biologics: A Systematic Review. Ann Intern Med 2016; 165:565.
- Panés J, García-Olmo D, Van Assche G, et al. Expanded allogeneic adipose-derived mesenchymal stem cells (Cx601) for complex perianal fistulas in Crohn's disease: a phase 3 randomised, double-blind controlled trial. Lancet 2016; 388:1281.
- American Acedemy of Pediatrics Clinical Report: Infectious complications with the use of biologic response modifiers in infants and children. http://pediatrics.aappublications.org/content/pediatrics/early/2016/07/14/peds.2016-1209.full.pdf (Accessed on July 19, 2016).