February 2016 E-Journal Club

Greetings,

February in Charlottesville is typically full of extremes, with teases of daffodil blossoms and warm breezes followed immediately by record cold and snow, then a deluge of rain (rinse, repeat). This year is no exception, but now by the end of February we generally feel that winter is near spent, although the wise among us know that winter is not really over in Charlottesville until the dogwoods bloom.

February Citation:

Deutz NE, Matheson EM, Matarese LE, et al. Readmission and mortality in malnourished, older, hospitalized adults treated with a specialized oral nutritional supplement: A randomized clinical trial. Clin Nutr. 2016 Feb;35(1):18-26.

Summary: 

This was a multicenter, prospective, randomized, double-blind, placebo-controlled, parallel-group study that investigated the effects of an oral liquid nutrition supplement enriched with beta-hydroxy-beta-methylbutyrate (HMB) on hospital readmission and mortality in older, hospitalized, malnourished patients. The study compared 2 servings/day of a nutrient-dense (350 kcals/8 oz), high-protein (20 gm/8 oz) vitamin-mineral containing oral supplement enriched with 1.5 gm HMB with a low-calorie, low-protein placebo supplement that provided 12 gm CHO, 48 kcals, 10 mg vitamin C and no other macro or micronutrients. Patients received either the nutrition supplement or placebo 2X/day in addition to their hospital diet, and were instructed to continue to drink 2 servings/day for 90 days after discharge.  Assessment of functional and nutrition status, supplement compliance, quality-of-life indices, adverse events and morbidities were conducted at 30, 60 and 90 days.  Additionally calls or home visits were conducted weekly to encourage compliance, collect information regarding outcomes.

The primary outcome was the combined incidence of non-elective readmission or death within 90 days. Secondary outcomes included non-elective admission at 30 and 60 days, initial length of hospitalization, activities of daily living, nutrition status indices, morbid events,

Inclusion and Exclusion Criteria:

Inclusion criteria:

Age ≥65 years, hospitalized within 72 h of study entry, with a primary diagnosis of CHF, AMI, PNA, or COPD, Subjective Global Assessment (SGA) class of B (moderate or suspected malnutrition) or C (severe malnutrition), functionally ambulatory during the immediate 30 days prior to admission.

Exclusion criteria:

Diabetes mellitus, dementia, current active or treated cancer, impaired renal or liver function, active tuberculosis, HIV+ with CD4<350, GI disorder with impaired absorption, autoimmune disorder requiring immunosuppression.

Major Results:

A total of 42,799 patients were assessed, with 652 patients (1.5% of those assessed) randomized from 78 sites (328 HP-HMB and 324 placebo). Data from 30 randomized patients who had missing information or who did not receive the intervention was excluded from the analysis, so that ultimately data from 313 supplement and 309 placebo patients was utilized. Prior to the 90-day visit, 121 of the supplement group (38.7%) and 126 of the placebo group (40.8%) exited the study. The most common reason for discontinuation was patient’s request, (66 supplement and 61 placebo).

While in the hospital, patients consumed an average of 73% of the nutrition supplement/placebo, but over the entire study period only 36.2% of the placebo group and 32.9% of the supplement group reported consuming ≥75% of the study product.

There was no significant difference between groups for the primary endpoint of non-elective readmission/death at 90 days. The 30, 60 and 90-day readmission rates were not significantly different between groups. However, the mortality rates were significantly less in the supplement group compared to the placebo group at 30 days (2.9% vs. 6.2%; p = 0.049), 60 days (4.2% vs. 8.7%; p = 0.020) and at 90 days (4.8% vs. 9.7%; p = 0.018).

There were no statistical differences between groups in hospital length of stay, ADL’s, or SGA status up through day 60. At day 90 SGA scores indicated a significantly higher odds ratio of patients in the supplement group achieving a better nutritional status relative to placebo (odds ratio = 2.04, 95% CI, 1.28 to 3.25; p = 0.009).

Serum 25-OH vitamin D was significantly higher in the supplement group compared with placebo at days 30 and 60 (p = 0.035 and p = 0.008, respectively). There was no significant difference in adverse events or study withdrawal between groups.

 

Author’s Conclusions:

“…a specialized, nutrient-dense ONS containing high protein and HMB did not alter the primary composite endpoint of hospital readmission rates and mortality in this specific population of malnourished, older adults hospitalized for CHF, AMI, PNA, or COPD. However, early administration (within 72 h of hospitalization) of HP-HMB in addition to the current nutritional care was associated with decreased postdischarge mortality and improved nutritional status.”

Evaluation:

This was a multi-center, placebo controlled, double blind study with a reasonably large number of patients (to study re-admissions). However, there are a number of factors that significantly limit the validity of this research.

The first study limitation is the use of a low-calorie drink with no protein and minimal micronutrients as a placebo supplement, which introduces bias into this study. Consuming 2 drinks/day that provide minimal nutrition with low-nutrient density (“empty calories”) could displace other foods and make it more difficult for older, malnourished, hospitalized patients to take in adequate nutrition. Unlike a sugar-pill placebo used in drug studies that has no effect, the placebo used in this study would have potential negative effects on nutrition status. It is possible that the results of this study simply demonstrate the negative effects of giving low-calorie, low nutrient-dense drinks to older, malnourished, hospitalized patients.

This study was also funded by the company that makes nutrition supplements, and a number of the authors are employed by the supplement company. Normally, funding source alone should not diminish the validity of well-conducted research.  However, considering the composition of the placebo and the fact that the nutrition supplement contains HMB, we had concerns about this study being used to promote the sale of HMB containing supplements.  Products with “pharmaco-nutrients” generally cost more per calorie than standard products, and there should be a comparison to iso-caloric, iso-nitrogenous standard products before encouraging people to purchase specialized supplements, especially if they cost more per calorie.

Another limitation of this study is the fact that the study population may not represent our typical patient since only 1.5% of all evaluated patients met all inclusion/exclusion criteria. The number of exclusion criteria is helpful to allow a more homogenous study group and limit the “noise” from other co-morbidities that influence outcomes, but then we are not sure what our results will be in our “typical” patient.

In terms of the mortality differences reported during the study, this study enrolled too few patients to make any strong conclusions regarding mortality. The calculations for the number of patients needed for statistical power were based on a baseline readmission rate of 29%. Considering that the baseline event-rate for mortality at 90 days was likely much less frequent than readmission (actual mortality approx. 5-10%), there would need to be many more patients enrolled before we could have some confidence that the mortality difference between groups was not occurring by chance alone.

Compliance with the nutrition supplement was good during admission and up to day 30, with patients averaging between 1.4-1.7 servings/day of the study product during this time. It would be remarkable indeed if 500-600 kcals (30-35 gm protein)/day for 1 month had such a powerful effect on survival from 30-90 days post-hospitalization. Compliance declined by day-90 with only about 1/3 of patients reported that they consumed ≥ 75% of the study product throughout the entire study.

Our Take Home Message(s)

1. Encouraging older, malnourished hospitalized patients to consume a low-calorie, low-protein, low nutrient-dense “supplement” may have negative effects on nutrition status compared to a high-calorie, high-protein supplement.
2. This study enrolled too few patients to reliably study mortality.
3. Specialized supplements with pharmaco-nutrients should be compared with standard oral supplements before being used in routine practice.

Other News on the UVAHS GI Nutrition Website: (www.ginutrition.virginia.edu):

Having trouble seeing any of the resources on our page? Retype www.GInutrition.virginia.edu into your browser to reach our newly updated page

Upcoming Webinars 2016:

March 23: Peri-Operative Nutrition

April 12: Severe Hypoglycemia Following Gastric Bypass Surgery: A Rare but Debilitating Problem

May 24: Meeting Calorie Needs in the ICU—Should We?

Latest Practical Gastroenterology article:

Solorzano, GE, Guha, R. Wernicke’s Encephalopathy: Under Our Radar More Than It Should Be?. Practical Gastroenterology 2016;XXXX(2):30.

 

Joe Krenitsky MS, RDN

PS – Please feel free to forward on to friends and colleagues.