A multifaceted approach to addressing feeding intolerance in the preterm infant

In 2013, 11.4% of births in the United States occurred preterm.1 Due to the immaturity of the gastrointestinal tract, these infants are at increased risk of feeding intolerance and necrotizing enterocolitis (NEC). NEC is the most common surgical emergency among infants and proves fatal for 25-33% those diagnosed.2,3 Effective early detection of these conditions,4 combined with targeted therapies to promote intestinal adaptation and weaning from parenteral nutrition (PN), represent an important opportunity to improve infant outcomes. To this end, the following studies were conducted. 1. The safety and efficacy of teduglutide, an analog of human glucagon-like peptide-2 (GLP-2) approved for use only in adults, in reducing PN requirements was assessed via a systematic review.5 Fourteen reports met the inclusion criteria. Teduglutide reduced PN requirements vs. placebo regardless of PN dependence duration, whereas adverse event incidence was similar between groups (number needed to treat to benefit [NNTB] = 3-4; number needed to treat to harm [NNTH] = 24-187). 2. Teduglutide-stimulated intestinal adaptation, potential synergies with partial enteral nutrition (PEN), and distinct temporal markers of adaptation were investigated in a neonatal piglet model of short bowel syndrome (SBS). Teduglutide improved (P < 0.05) mucosal surface area (villus height: duodenum, jejunum, ileum; crypt depth: ileum, colon; proliferation: duodenum, jejunum, ileum, colon; apoptosis: jejunum, ileum, colon) and acute nutrient processing capacity (glucose: duodenum, jejunum, ileum; glutamine: duodenum, jejunum). PEN complimented and synergistically enhanced these effects. Structural adaptation preceded functional adaptation, but crypt depth was a strong indicator of adaptation, regardless of time. 3. A novel feeding intolerance and NEC risk scoring tool was implemented in the University of Illinois-affiliated Carle Foundation Hospital (CFH) level III neonatal intensive care unit (NICU). During the study period, 499 tools were completed on the 133 enrolled infants. Indices of feeding intolerance included days with emesis, abdominal distention, or gastric residuals > 50% of previous feeding volume, and NEC. Anonymous surveys (n = 42) indicated nurses’ positive attitudes toward the tool (ease of use of 6.9 [SD 1.9] on 10-point scale). Estimated tool completion time was 4.2 minutes (range 1-10). Error rate (9.2%), Cronbach’s alpha (0.71), the intraclass correlation coefficient (ICC; 0.99), and Fleiss’ kappa (1.00) were in acceptable ranges. Gestational age at birth, hypoxia/asphyxia at birth, red blood cell (RBC) transfusion, and congenital heart disease/patent ductus arteriosis (PDA) were significantly associated with all four outcome measures. Total optimized tool score was also associated with all four outcome measures, with area under the ROC curve (AUC) and diagnostic odds ratio (OR) estimates [95% CI] of: emesis, AUC = 0.69 and OR = 1.14 [1.06, 1.23]; abdominal distention, AUC = 0.82 and OR = 1.28 [1.18, 1.41]; gastric residuals > 50% of previous feeding volume, AUC = 0.64 and OR = 1.11 [1.04, 1.20]; NEC, AUC = 0.90 and OR = 1.29 [1.12, 1.56]. Scores of infants who did and did not develop each of the four outcome measures were significantly (P < 0.05) different, and an “at-risk” threshold of 9 points was established. The tool represents a clinically feasible means to discriminate infants at risk of feeding intolerance and NEC. Further refinement will improve its clinical utility and identify infants who may benefit from targeted therapies, including teduglutide and/or PEN, to promote gastrointestinal maturation and improve feeding tolerance.   REFERENCES 1. Martin J, Hamilton B, Osterman M, Curtin S, Mathews T. Births: final data for 2013. Natl Vital Stat Rep 2015;64(1):1-65. 2. Henry M, Moss R. Current issues in the management of necrotizing enterocolitis. Semin Perinatol 2004;28:221-233. 3. Lin P, Stoll B. Necrotising enterocolitis. Lancet 2006;368:1271-1283. 4. Neu J, Walker W. Necrotizing enterocolitis. N Engl J Med 2011;364:255-264. 5. Higgins J, Green S (eds). Cochrane Handbook for Systematic Reviews of Interventions, version 5.1.0. The Cochrane Collaboration 2011

Prognostication in advanced cancer: update and directions for future research

The objective of this review is to provide an update on prognostication in patients with advanced cancer and to discuss future directions for research in this field. Accurate prognostication of survival for patients with advanced cancer is vital, as patient life expectancy informs many important personal and clinical decisions. The most common prognostic approach is clinician prediction of survival (CPS) using temporal, surprise, or probabilistic questions. The surprise and probabilistic questions may be more accurate than the temporal approach, partly by limiting the time frame of prediction. Prognostic models such as the Glasgow Prognostic Score (GPS), Palliative Performance Scale (PPS), Palliative Prognostic Score (PaP), Palliative Prognostic Index (PPI), or Prognosis in Palliative Care Study (PiPS) predictor model may augment CPS. However, care must be taken to select the appropriate tool since prognostic accuracy varies by patient population, setting, and time frame of prediction. In addition to life expectancy, patients and caregivers often desire that expected treatment outcomes and bodily changes be communicated to them in a sensible manner at an appropriate time. We propose the following 10 major themes for future prognostication research: (1) enhancing prognostic accuracy, (2) improving reliability and reproducibility of prognosis, (3) identifying the appropriate prognostic tool for a given setting, (4) predicting the risks and benefits of cancer therapies, (5) predicting survival for pediatric populations, (6) translating prognostic knowledge into practice, (7) understanding the impact of prognostic uncertainty, (8) communicating prognosis, (9) clarifying outcomes associated with delivery of prognostic information, and (10) standardizing prognostic terminology