Does enternal nutrition affect clinical outcome? A systematic review of the randomized trials

Background: Both parenteral nutrition (PN) and enteral nutrition (EN) are widely advocated as adjunctive care in patients with various diseases. A systematic review of 82 randomized controlled trials (RCTs) of PN published in 2001 found little, if any, effect on mortality, morbidity, or duration of hospital stay; in some situations, PN increased infectious complication rates. Objective: To assess the effect of EN or volitional nutrition support (VNS) in individual disease states from available randomized controlled trials (RCTs). Design: We conducted a systematic review. RCTs comparing EN or VNS to untreated controls, or comparing EN to PN, were identified and separated according to the underlying disease state. Meta-analysis was performed when at least 3 RCTs provided data. The evidence from the RCTs was summarized into one of five grades. A or B indicated the presence of strong or weak (low quality RCTs) evidence supporting the use of the intervention. C indicated a lack of adequate evidence to make any decision about efficacy. D indicated that limited data could not support the intervention. E indicated either that strong data found no effect, or that either strong or weak data suggested that the intervention caused harm. Patients and settings: RCTs could include either hospitalized or non-hospitalized patients. The EN or VNS had to be provided as part of a treatment plan for an underlying disease process. Interventions: The RCT had to compare recipients of either EN or VNS to controls not receiving any type of artificial nutrition or had to compare recipients of EN with recipients of PN. Outcome measures: Mortality, morbidity (disease-specific), duration of hospitalization, cost, or interventional complications. Summary of grading: A – No indication was identified. B – EN or VNS in the perioperative patient or in patients with chronic liver disease; EN in critically ill patients or low birth weight infants (trophic feeding); VNS in malnourished geriatric patients. (The low quality trials found a significant difference in survival favoring the VNS recipients in the malnourished geriatric patient trials; two high quality trials found non-significant differences that favored VNS as well.) C – EN or VNS in liver transplantation, cystic fibrosis, renal failure, pediatric conditions other than low birth weight infants, well-nourished geriatric patients, non-stroke neurologic conditions, AIDS; EN in acute pancreatitis, chronic obstructive pulmonary disease, non-malnourished geriatric patients; VNS in inflammatory bowel disease, arthritis, cardiac disease, pregnancy, allergic patients, preoperative bowel preparation D – EN or VNS in patients receiving non-surgical cancer treatment or in patients with hip fractures; EN in patients with inflammatory bowel disease; VNS in patients with chronic obstructive pulmonary disease E – EN in the first week in dysphagic, or VNS at any time in non-dysphagic, stroke patients who are not malnourished; dysphagia persisting for weeks will presumably ultimately require EN. Conclusions: There is strong evidence for not using EN in the first week in dysphagic, and not using VNS at all in non-dysphagic, stroke patients who are not malnourished. There is reasonable evidence for using VNS in malnourished geriatric patients. The recommendations to consider EN/VNS in perioperative/liver/critically ill/low birth weight patients are limited by the low quality of the RCTs. No evidence could be identified to justify the use of EN/VNS in other disease states

Is Sustained Virological Response a Marker of Treatment Efficacy in Patients with Chronic Hepatitis C Viral Infection with No Response or Relapse to Previous Antiviral Intervention?

Background: Randomised clinical trials (RCTs) of antiviral interventions in patients with chronic hepatitis C virus (HCV) infection use sustained virological response (SVR) as the main outcome. There is sparse information on long-term mortality from RCTs.  Methods: We created a decision tree model based on a Cochrane systematic review on interferon retreatment for patients who did not respond to initial therapy or who relapsed following SVR. Extrapolating data to 20 years, we modelled the outcome from three scenarios: (1) observed medium-term (5 year) annual mortality rates continue to the long term (20 years); (2) long-term annual mortality in retreatment responders falls to that of the general population while retreatment non-responders continue at the medium-term mortality; (3) long-term annual mortality in retreatment non-responders is the same as control group non-responders (i.e., the increased treatment-related medium mortality “wears off”).  Results: The mean differences in life expectancy over 20 years with interferon versus control in the first, second, and third scenarios were -0.34 years (95% confidence interval (CI) -0.71 to 0.03), -0.23 years (95% CI -0.69 to 0.24), and -0.01 (95% CI -0.3 to 0.27), respectively. The life expectancy was always lower in the interferon group than in the control group in scenario 1. In scenario 3, the interferon group had a longer life expectancy than the control group only when more than 7% in the interferon group achieved SVR.  Conclusions: SVR may be a good prognostic marker but does not seem to be a valid surrogate marker for assessing HCV treatment efficacy of interferon retreatment. The SVR threshold at which retreatment increases life expectancy may be different for different drugs depending upon the adverse event profile and treatment efficacy. This has to be determined for each drug by RCTs and appropriate modelling before SVR can be accepted as a surrogate marker