Ronald L. Koretz

Does enteral 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:The objective was to assess the effect of EN or volitional nutrition support (VNS) in individual disease states from available RCTs.DESIGN:We conducted a systematic review. RCTs comparing EN or VNS with untreated controls, or comparing EN with PN, were identified and separated according to the underlying disease state. Meta-analysis was performed when at least three RCTs provided data. The evidence from the RCTs was summarized into one of five grades. A or B, respectively, 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 nonhospitalized 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 with controls not receiving any type of artificial nutrition or had to compare recipients of EN with recipients of PN.OUTCOME MEASURES:These were 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 nonsignificant 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, nonstroke neurologic conditions, AIDS; EN in acute pancreatitis, chronic obstructive pulmonary disease, nonmalnourished geriatric patients; VNS in inflammatory bowel disease, arthritis, cardiac disease, pregnancy, allergic patients, preoperative bowel preparation. D: EN or VNS in patients receiving nonsurgical cancer treatment or in patients with hip fractures; EN in patients with inflammatory bowel disease; VNS in patients with chronic obstructive pulmonary disease. EN in the first week in dysphagic, or VNS at any time in nondysphagic, 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 nondysphagic, 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.

Non-A, Non-B Posttransfusion Hepatitis—A Decade Later

We have followed up 69 patients who developed non-A, non-B posttransfusion hepatitis in 1972-1978. Chronic hepatitis, defined by biochemical criteria, was observed in 46 patients (67%), the majority of whom subsequently failed to resolve the abnormalities. Chronic hepatitis was a sequela of non-A, non-B posttransfusion hepatitis less often after the blood bank changed to a policy of all volunteer donors. (However, this association may be explained by other coexistent factors.) The alanine aminotransferase level was more likely to be abnormal than the aspartate aminotransferase level during the chronic phase of non-A, non-B posttransfusion hepatitis. By actuarial means it was calculated that the probability of developing normal enzymes after 6-10 yr was 0.47. However, in spite of this high incidence of biochemical disease, virtually all of the patients have remained asymptomatic. Histologic evidence of cirrhosis has been obtained in 4 of these patients, but in only 2 patients at most has clinical evidence of hepatic failure supervened.

Chronic active hepatitis. Who meets treatment criteria

In order to ascertain the proportion of patients with biopsy-proven chronic active hepatitis who meet currently accepted criteria for immunosuppressive treatment, an analysis of 86 patients seen between 1973 and 1978 carrying this diagnosis was undertaken. Only 66 could be confirmed to have this lesion on blind histologic review. Nine of these 66 were on concomitant immunosuppressive therapy, four had inadequate documentation of chronicity, five consumed more than two ounces of alcohol daily, five had concurrent malignancy, two were prepubertal, and one had oxyphenisatin-induced disease. None of the remaining 40 patients met the biochemical criteria for disease activity. The disease was predominantly seen in asymptomatic middle-aged males and was of viral etiology. A small subgroup of elderly female patients was also identified whose disease was apparently nonviral. In conclusion, the vast majority of chronic active hepatitis seen at a large university center occurs in individuals for whom treatment guidelines have not been established.

Nutrition Society Symposium on 'End points in clinical nutrition trials' death, morbidity and economics are the only end points for trials

In order to determine whether surrogate markers predict clinical outcome, randomized controlled trials (RCT) of nutrition support v. no nutrition support that have reported at least one clinical outcome (mortality, infections, total complications, or duration of hospitalization) and at least one nutritional outcome (energy or protein intake, weight gain, N balance, albumin, prealbumin, transferrin, three anthropometric measures, skin testing, lymphocyte count) were assessed for concordance. If changes in nutritional markers predict clinical outcome, changes in both outcomes should go in the same direction. Concordance is defined as both outcomes changing in the same direction or both outcomes showing no difference. Discordance is defined as one outcome changing and the other not (partial) or both outcomes changing in opposite directions (complete). Ninety-nine RCT were identified, of which most were underpowered to see statistically significant changes, especially in clinical outcomes. Thus, the results were analysed only in relation to the direction of the respective changes in outcomes. Forty-eight comparisons (4 x 12) were made. The rates of concordance were < or =50% in forty-one of forty-eight comparisons; the rate was never >75%. A complete discordance rate of > or =25% was present in forty-three (> or =50% in thirteen) of the forty-eight comparisons. The discordance was usually a result of the nutritional outcome being better than the clinical outcome. Changes in nutritional markers do not predict clinical outcomes. Before adopting any surrogate marker as an end point for a clinical trial, it has to be known that improving it will result in patient benefit.

What supports nutritional support

Historique et revue des traitements par alimentation enterale et parenterale pour des affections digestives et autres

Is widespread screening for hepatitis C justified

Several organisations have recommended greatly expanded screening for hepatitis C infection. Ronald Koretz and colleagues are concerned that no study has tested whether this will lead to net clinical benefit or harm in screened populations

The Pursuit of Hepatitis in Dialysis Units

Chronic hemodialysis patients were prospectively followed at monthly intervals with hepatitis B serologic (HBsAg, anti-HBs, and anti-HBc) and aminotransferase determinations. Over this 1 year, 53/176 (30%) had two or more abnormal aminotransferase values. In at least 34 of these 53 patients, viral liver disease appeared to be the responsible factor. Although patients with anti-HBc were more likely to have abnormal aminotransferases, it is probable that most viral hepatitis in dialysis units is due to non-A, non-B hepatitis. After a further 2 1/2 years of follow-up, no clinical evidence of hepatic failure was seen in any of the patients with hepatitis. The ultimate course of this disease, however, is not yet established.

Failure of endoscopic transmission of hepatitis B

Emergency endoscopy was performed on two patients subsequently found to be hepatitis B surface antigen carriers. Before their carrier state was determined, nine other patients underwent endoscopy using the same instruments, which had been routinely cleaned between procedures. These patients were all notified within five days of the incident, given standard gamma globulin, and prospectively followed for the development of hepatitis. After one of the endoscopes was gas sterilized, the next three patients undergoing endoscopy were also followed. One of the hepatitis B surface antigen carriers was positive for antibody to e antigen; the other carrier had neither e antigen nor antibody. None of these individuals developed signs or symptoms of hepatitis, abnormal serum glutamic pyruvate transaminase elevations, or serologic evidence of hepatitis B exposure. From these data, and other recorded experiences, it appears that routine cleansing of endoscopy equipment is sufficient in preventing the transmission of hepatitis B.

Rapid Development of Cirrhosis Secondary to Squamous Cell Carcinoma of the Common Bile Duct

SummaryA 68-year-old male underwent cholecystectomy with a normal operative wedge liver biopsy. Five months later he presented with secondary biliary cirrhosis and signs of portal hypertension and hepatocellular failure. At autopsy, a squamous cell carcinoma of the bile duct was found. This case represents an unusually rapid development of cirrhosis secondary to extrahepatic biliary obstruction with documentation of normal liver histology five months prior to his last admission.

Post-Transfusion Hepatitis: The Role of Hepatitis B Antibody

Aliquots from units of blood previously transfused as part of a prospective post-transfusion hepatitis (PTH) study were rescreened for the presence of hepatitis B antibody (anti-HBS) to determine the effect of transfusion of such material. Anti-HBS was more commin in commercial blood. Infusion of anti-HBS was not associated with an increased or decreased risk of PTH, hepatitis B, or hepatitis B (HB) exposure. Receipt of anti-HBS did not modify the hepatitis which occurred. Receipt of large amounts of anti-HBS may be associated with an increased incidence of HB events. Preexisting anti-HBS was not only not protective against PTH, but more PTH (67% versus 40%) and hepatitis B (47% versus 12%) were seen in those patients with it.