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Challenges of a simplified opt-out consent process in a neonatal randomised controlled trial: qualitative study of parents' and health professionals' views and experiences.
McLeish, J, Alderdice, F, Robberts, H, Cole, C, Dorling, J, Gale, C, ,
Archives of disease in childhood. Fetal and neonatal edition. 2021;(3):244-250
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Abstract
BACKGROUND More effective recruitment strategies like alternative approaches to consent are needed to facilitate adequately powered trials. Witholding Enteral feeds Around Transfusion was a multicentre, randomised, pilot trial that compared withholding and continuing feeds around transfusion. The primary clinical outcome was necrotising enterocolitis. The trial used simplified opt-out consent with concise parent information and no consent form. OBJECTIVE To explore the views and experiences of parents and health professionals on the acceptability and feasibility of opt-out consent in randomised comparative effectiveness trials. METHODS A qualitative, descriptive interview-based study nested within a randomised trial. Semistructured interview transcripts were analysed using inductive thematic analysis. SETTING Eleven neonatal units in England. PARTICIPANTS Eleven parents and ten health professionals with experience of simplified consent. RESULTS Five themes emerged: 'opt-out consent operationalised as verbal opt-in consent', 'opt-out consent normalises participation while preserving parental choice', 'opt-out consent as an ongoing process of informed choice', 'consent without a consent form' and 'choosing to opt out of a comparative effectiveness trial', with two subthemes: 'wanting "normal care"' and 'a belief that feeding is better'. CONCLUSION Introducing a novel form of consent proved challenging in practice. The principle of a simplified, opt-out approach to consent was generally considered feasible and acceptable by health professionals for a neonatal comparative effectiveness trial. The priority for parents was having the right to decide about trial participation, and they did not see opt-out consent as undermining this. Describing a study as 'opt-out' can help to normalise participation and emphasise that parents can withdraw consent.
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Efficacy and Safety of Enteral Recombinant Human Insulin for Reduction of Time-to-Full Enteral Feeding in Preterm Infants: A Randomized, Double-blind, Placebo-Controlled Trial.
Shehadeh, N, Simmonds, A, Zangen, S, Riskin, A, Shamir, R
The Israel Medical Association journal : IMAJ. 2021;(9):563-568
Abstract
BACKGROUND Infants born very prematurely have functionally and structurally immature gastrointestinal tracts. OBJECTIVES To assess the safety and tolerability of administration of enteral recombinant human (rh) insulin on formula fed preterm infants and to assess whether enteral administration of rh-insulin enhances gastrointestinal tract maturation by reducing the time to reach full enteral feeding. METHODS A phase 2, multicenter, double-blind, placebo-controlled, randomized study was conducted. Premature infants (26-33 weeks gestation) were randomized 1:1 to receive insulin 400 μU/ml mixed with enteral feeding or placebo added to their formula. The primary efficacy outcome measure was the number of days required to achieve full enteral feeding. Safety outcomes included adverse events and blood glucose levels. RESULTS The study consisted of 33 infants randomized for the safety population and 31 for efficacy analysis. The mean time to full enteral feeding was 6.37 days (95% confidence interval [95%CI] 4.59-8.15) in the enteral rh-insulin treatment group (n=16) and 8.00 days (95%CI 6.20-9.80) in the placebo group (n=15), which represents a statistically significant reduction of 1.63 days (95%CI 0.29-2.97; P = 0.023). There was no difference in blood glucose levels between the groups and none of the participants experienced hypoglycemia. Adverse events occurred in 9/17 (53%) infants in the enteral rh-insulin group and 12/16 (75%) in the placebo group. CONCLUSIONS Our trial demonstrated that administration of enteral rh-insulin as supplement to enteral nutrition significantly reduced time to achieve full enteral feeding in preterm infants with a gestational age of 26-33 weeks.
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Achieving enteral nutrition during the acute phase in critically ill children: Associations with patient characteristics and clinical outcome.
Eveleens, RD, Hulst, JM, de Koning, BAE, van Brakel, J, Rizopoulos, D, Garcia Guerra, G, Vanhorebeek, I, Van den Berghe, G, Joosten, KFM, Verbruggen, SCAT
Clinical nutrition (Edinburgh, Scotland). 2021;(4):1911-1919
Abstract
BACKGROUND & AIMS In the absence of methodologically sound randomized controlled trials (RCTs), current recommendations for timing and amount of enteral nutrition (EN) in critically ill children are based on observational studies. These studies have associated achievement of a higher EN intake in critically ill children with improved outcome. Inherent to the observational design of these underlying studies, thorough insight in possible confounding factors to correct for is essential. We evaluated the associations between EN intake and 1) patient and daily clinical characteristics and 2) clinical outcomes adjusted for these patient and clinical characteristics during the first week of critical illness with a multivariable mixed model. METHODS This secondary analysis of the multicentre PEPaNIC RCT investigated a subgroup of critically ill children with daily prospectively recorded gastrointestinal symptoms and EN intake during the first week with multivariable analyses using two-part mixed effect models, including multiple testing corrections using Holm's method. These models combined a mixed-effects logistic regression for the dichotomous outcome EN versus no EN, and a linear mixed-effects model for the patients who received any EN intake. EN intake per patient was expressed as mean daily EN as % of predicted resting energy expenditure (% of EN/REE). Model 1 included 40 fixed effect baseline patient characteristics, and daily parameters of illness severity, feeding, medication and gastrointestinal symptoms. Model 2 included these patient and daily variables as well as clinical outcomes. RESULTS Complete data were available for 690 children. EN was provided in 503 (73%) patients with a start after a median of 2 (IQR 2-3) days and a median % of EN/REE of 38.8 (IQR 14.1-79.5) over the first week. Multivariable mixed model analyses including all patients showed that admission after gastrointestinal surgery (-49%EN/REE; p = 0.002), gastric feeding (-31% EN/REE; p < 0.001), treatment with inotropic agents (-22%EN/REE; p = 0.026) and large gastric residual volume (-64%EN/REE; p < 0.001) were independently associated with a low mean EN intake. In univariable analysis, low mean EN intake was associated with new acquired infections, hypoglycaemia, duration of PICU and hospital stay and duration of mechanical ventilation. However, after adjustment for confounders, these associations were no longer present, except for low EN and hypoglycaemia (-39%EN/REE; p = 0.018). CONCLUSIONS Several patient and clinical characteristics during the first week of critical illness were associated with EN intake. No independent associations were found between EN intake and clinical outcomes such as mortality, new acquired infection and duration of stay. These data emphasize the necessity of adequate multivariable adjustment in nutritional support research and the need for future RCTs investigating optimal EN intake.
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A multicenter randomized clinical trial of pharmacological vitamin B1 administration to critically ill patients who develop hypophosphatemia during enteral nutrition (The THIAMINE 4 HYPOPHOSPHATEMIA trial).
Deane, AM, Jiang, A, Tascone, B, Clancy, A, Finnis, ME, Collie, JT, Greaves, R, Byrne, KM, Fujii, T, Douglas, JS, et al
Clinical nutrition (Edinburgh, Scotland). 2021;(8):5047-5052
Abstract
BACKGROUND Hypophosphatemia may be a useful biomarker to identify thiamine deficiency in critically ill enterally-fed patients. The objective was to determine whether intravenous thiamine affects blood lactate, biochemical and clinical outcomes in this group. METHOD This randomized clinical trial was conducted across 5 Intensive Care Units. Ninety critically ill adult patients with a serum phosphate ≤0.65 mmol/L within 72 h of commencing enteral nutrition were randomized to intravenous thiamine (200 mg every 12 h for up to 14 doses) or usual care (control). The primary outcome was blood lactate over time and data are median [IQR] unless specified. RESULTS Baseline variables were well balanced (thiamine: lactate 1.2 [1.0, 1.6] mmol/L, phosphate 0.56 [0.44, 0.64] mmol/L vs. control: lactate 1.0 [0.8, 1.3], phosphate 0.54 [0.44, 0.61]). Patients randomized to the intervention received a median of 11 [7.5, 13.5] doses for a total of 2200 [1500, 2700] mg of thiamine. Blood lactate over the entire 7 days of treatment was similar between groups (mean difference = -0.1 (95 % CI -0.2 to 0.1) mmol/L; P = 0.55). The percentage change from lactate pre-randomization to T = 24 h was not statistically different (thiamine: -32 (-39, -26) vs. control: -24 (-31, -16) percent, P = 0.09). Clinical outcomes were not statistically different (days of vasopressor administration: thiamine 2 [1, 4] vs. control 2 [0, 5.5] days; P = 0.37, and deaths 9 (21 %) vs. 5 (11 %); P = 0.25). CONCLUSIONS In critically ill enterally-fed patients who developed hypophosphatemia, intravenous thiamine did not cause measurable differences in blood lactate or clinical outcomes. TRIAL REGISTRATION Australian and New Zealand Clinical Trials Registry (ACTRN12619000121167).
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Impact of an Oral Nutritional Protocol with Oligomeric Enteral Nutrition on the Quality of Life of Patients with Oncology Treatment-Related Diarrhea.
Sanz-Paris, A, Martinez-Trufero, J, Lambea-Sorrosal, J, Milà-Villarroel, R, Calvo-Gracia, F, On Behalf Of The Diapoeno Study,
Nutrients. 2020;(1)
Abstract
(1) Background: Nutritional status can influence the quality of life (QoL) of cancer patients. (2) Methods: This subanalysis evaluated the impact of an oral oligomeric enteral nutrition (OEN) protocol on the QoL of patients with oncology treatment-related diarrhea (OTRD) in a multicenter, observational, prospective study (DIAPOENO study). QoL was assessed with the Nottingham Health Profile (NHP) at baseline and after eight weeks of OEN treatment. (3) In the overall population, all the NHP categories significantly improved after eight weeks of OEN treatment: energy levels (p < 0.001), pain (p < 0.001), emotional reactions (p < 0.001), sleep (p < 0.001), social isolation (p = 0.023), and physical abilities (p = 0.001). QoL improvement was higher in patients with improved or maintained nutritional status and in those with improved consistency of stools with the OEN protocol. However, QoL did not significantly improve in patients with worse nutritional status and with worse or maintained stool consistency with the OEN protocol. QoL improved regardless of disease severity. Multivariate logistic regression analysis showed that weight change was significantly associated with improved QoL (OR 2.90-5.3), except for social isolation, in models unadjusted and adjusted to age, sex, oncology treatment, and stool consistency. (4) Conclusion: In this subanalysis, the OEN protocol was associated with improved QoL.
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Direct Oral Feeding Following Minimally Invasive Esophagectomy (NUTRIENT II trial): An International, Multicenter, Open-label Randomized Controlled Trial.
Berkelmans, GHK, Fransen, LFC, Dolmans-Zwartjes, ACP, Kouwenhoven, EA, van Det, MJ, Nilsson, M, Nieuwenhuijzen, GAP, Luyer, MDP
Annals of surgery. 2020;(1):41-47
Abstract
OBJECTIVE Patients undergoing an esophagectomy are often kept nil-by-mouth postoperatively out of fear for increasing anastomotic leakage and pulmonary complications. This study investigates the effect of direct start of oral feeding following minimally invasive esophagectomy (MIE) compared with standard of care. BACKGROUND Elements of enhanced recovery after surgery (ERAS) protocols have been successfully introduced in patients undergoing an esophagectomy. However, start of oral intake, which is an essential part of the ERAS protocols, remains a matter of debate. METHODS Patients in this multicenter, international randomized controlled trial were randomized to directly start oral feeding (intervention) after a MIE with intrathoracic anastomosis or to receive nil-by-mouth and tube feeding for 5 days postoperative (control group). Primary outcome was time to functional recovery. Secondary outcome parameters included anastomotic leakage, pneumonia rate, and other surgical complications scored by predefined definitions. RESULTS Baseline characteristics were similar in the intervention (n = 65) and control (n = 67) group. Functional recovery was 7 days for patients receiving direct oral feeding compared with 8 days in the control group (P = 0.436). Anastomotic leakage rate did not differ in the intervention (18.5%) and control group (16.4%, P = 0.757). Pneumonia rates were comparable between the intervention (24.6%) and control group (34.3%, P = 0.221). Other morbidity rates were similar, except for chyle leakage, which was more prevalent in the standard of care group (P = 0.032). CONCLUSION Direct oral feeding after an esophagectomy does not affect functional recovery and did not increase incidence or severity of postoperative complications.
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[Effect of an oral nutritional supplementation on nutritional status and quality of life in patients with colorectal cancer and postoperative adjuvant chemotherapy: A multi-center prospective randomized control trial].
Yang, X, Zhu, MW, Xiu, DR, Yang, Y, Yang, GX, Hu, WG, Wang, ZG, Cui, HY, Wei, JM
Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery. 2020;(6):566-571
Abstract
Objective: To evaluate the effect of oral nutritional supplementation (ONS) on the nutritional status and quality of life in patients with colorectal cancer and postoperative adjuvant chemotherapy. Methods: This study was registered in the Chinese Clinical Trial Registry (ChiCTR-TRC-13003798). A multi-center randomized controlled trial was conducted. Colorectal cancer patients who underwent radical surgery and postoperative adjuvant chemotherapy, and had nutritional risk (nutrition risk screening 2002 score ≥3) when discharge from hospital in six hospitals (Beijing Hospital, Peking University Third Hospital, Guangzhou Nanfang Hospital, Shanghai Xinhua Hospital, Shanghai Ruijin Hospital, and Shanghai The Sixth People's Hospital) from June 2013 to August 2015 were prospectively enrolled. These patients were randomly divided into the ONS group and control group. Patients in the ONS group received dietary guidance and oral nutritional supplements (2092 kJ/day, whole protein enteral nutrition) for 90 days after discharge from hospital, while patients in the control group only received dietary guidance. Anthropometric measurements (body weight, body mass index [BMI], upper arm circumference, gripping power of the dominant hand, triceps skin fold), nutrition-related laboratory tests (hemoglobin, albumin, prealbumin, total cholesterol, triglyceride), gastrointestinal function scores and quality of life (evaluated by EuroQol five dimensions questionnaire) were collected and compared at baseline (at discharge), and at 30-day, 60-day and 90-day after discharge. Results: A total of 90 patients were included into this multi-center study, of whom 5 patients dropped out, 43 patients were assigned to the ONS group and 42 patients to the control group. Compared with baseline, the body weight of patients in the ONS group increased by (1.523±0.525) kg at 60-day and (1.967±0.661) kg at 90-day, which were significantly higher than those of patients in the control group [60-day: (-0.325±0.518) kg, P=0.015; 90-day: (-0.224±0.705) kg, P=0.027, respectively]. A similar pattern was observed for BMI, the ONS group increased by (0.552±0.203) kg/m(2) at 60-day and (0.765±0.205) kg/m(2) at 90-day, which were significantly higher than those of patients in control group [60-day: (-0.067±0.202) kg/m(2), P=0.034; 90-day: (0.022±0.210) kg/m(2), P=0.013]. No significant differences of other anthropometric measurements and nutrition-related laboratory tests were found between the two groups (all P>0.05). Furthermore, there were no significant differences of improvement in gastrointestinal function and quality of life between two groups (all P>0.05). Conclusion: Oral nutritional supplements can improve the body weight and BMI of colorectal cancer patients with nutritional risk receiving postoperative adjuvant chemotherapy, though it does not improve the quality of life.
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Effects of oral/enteral nutrition alone versus plus pantoprazole on gastrointestinal bleeding in critically ill patients with low risk factor: a multicenter, randomized controlled trial.
Gündoğan, K, Karakoc, E, Teke, T, Zerman, A, Esmaoglu, A, Temel, Ş, Güven, M, Sungur, M
Turkish journal of medical sciences. 2020;(4):776-783
Abstract
BACKGROUND/AIM: Critically ill patients are at risk of developing gastrointestinal (GI) bleeding due to stress causing mucosal damage. Aim of the study was to determine the effect of oral/enteral nutrition with or without concomitant pantoprazole on upper GI bleeding in low risk critically ill patients. MATERIALS AND METHODS This was a prospective, randomized, open-label, multicenter study conducted with intensive care unit (ICU) patients receiving oral/enteral nutritional support. Patients were randomly assigned into two groups including intervention group (received oral/EN plus pantoprazole) and control group (received only oral/EN). RESULTS A total of 300 patients (intervention group: 152, control group: 148) participated in the study. Overall, 226 (75%) patients were fed by orally and 74 (25%) patients fed by enteral tube feeding. Median duration of nutritional support 4 (range: 2–33) days. Overt upper GI bleeding was noted only in one patient (0.65%) who was in the intervention group. The overall length of ICU stay of 4 (2–105) days, while ICU stay was significantly longer in the intervention group than in the control group (P = 0.006). CONCLUSIONS Our findings seems to indicate that in patients who are at low risk for GI bleeding and under oral/enteral nutritional support, the use of PPIs may not reduce the risk of bleeding, however these results are imprecise because of low event (GI bleeding) rate and limited power.
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Simo decoction versus domperidone suspension for post-pyloric spiral nasoenteric tube placement: A multicenter, randomized, non-inferiority trial.
Xiao, Y, He, Z, Long, Y, Chen, W, Chen, D, Chi, R, Ye, H, Deng, X, Lv, B, Sun, C, et al
Clinical nutrition (Edinburgh, Scotland). 2020;(8):2406-2412
Abstract
BACKGROUND & AIMS Leveraging prokinetics to facilitate trans-pyloric migration is a conventional strategy. However, due to restrictions on the use of domperidone suspension, oral prokinetics is relatively modest. The study aims to assess the effectiveness of simo decoction as an alternative to domperidone suspension in facilitating post-pyloric placement of spiral nasoenteric tubes. METHODS A prospective, open-label, parallel, and non-inferiority randomized controlled trial was performed involving critically ill adults in 6 university hospitals in China between September 2017 and May 2019. Patients were randomly assigned to receive either simo decoction 20 ml q8h, or domperidone suspension 20 mg/20 ml q6h for 24 h. The primary outcome was procedure success defined as post-pyloric placement (spiral nasoenteric tubes reached the first portion of the duodenum or beyond confirmed by abdominal X-ray 24 h after tube insertion). RESULTS Of 268 patients assessed for eligibility, 224 patients were enrolled and randomly assigned to the simo decoction group or the domperidone suspension group (n = 112 per group). The success rate of post-pyloric placement was 41.1% (46/112) in the simo decoction group, as compared with 47.3% (53/112) in the domperidone suspension group (a risk difference of -6.3%, 95% CI, -19.2% to 6.7%, adjusted risk difference -3.7%, 95% CI -16.3% to 9.0%), in the intention-to-treat analysis, crossing the prespecified margin of -10% for non-inferiority. There were no differences between groups in the success rates of post-D1 (reaching the second portion of the duodenum or beyond), post-D2 (reaching the third portion of the duodenum or beyond), post-D3 (reaching the fourth portion of the duodenum or beyond) and proximal jejunum placement, the incidences of any adverse events, length of ICU stay or mortality in ICU. CONCLUSIONS Non-inferiority of simo decoction to domperidone suspension was not confirmed in facilitating post-pyloric placement of spiral nasoenteric tubes. Registration: The trial was registered with the Chinese Clinical Trial Registry at http://www.chictr.org.cn (registration number ChiCTR-INR-17011311).
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Promotion of Regular Oesophageal Motility to Prevent Regurgitation and Enhance Nutrition Intake in Long-Stay ICU Patients. A Multicenter, Phase II, Sham-Controlled, Randomized Trial: The PROPEL Study.
Heyland, DK, Marquis, F, Lamontagne, F, Albert, M, Turgeon, AF, Khwaja, KA, Garland, A, Hall, R, Chapman, MG, Kutsiogannis, DJ, et al
Critical care medicine. 2020;(3):e219-e226
Abstract
OBJECTIVES To evaluate the effect of esophageal stimulation on nutritional adequacy in critically ill patients at risk for enteral feeding intolerance. DESIGN A multicenter randomized sham-controlled clinical trial. SETTING Twelve ICUs in Canada. PATIENTS We included mechanically ventilated ICU patients who were given moderate-to-high doses of opioids and expected to remain alive and ventilated for an additional 48 hours and who were receiving enteral nutrition or expected to start imminently. INTERVENTIONS Patients were randomly assigned 1:1 to esophageal stimulation via an esophageal stimulating catheter (E-Motion Tube; E-Motion Medical, Tel Aviv, Israel) or sham treatment. All patients were fed via these catheters using a standardized feeding protocol. MEASUREMENTS AND MAIN RESULTS The co-primary outcomes were proportion of caloric and protein prescription received enterally over the initial 7 days following randomization. Among 159 patients randomized, the modified intention-to-treat analysis included 155 patients: 73 patients in the active treatment group and 82 in the sham treatment group. Over the 7-day study period, the percent of prescribed caloric intake (± SE) received by the enteral route was 64% ± 2 in the active group and 65% ± 2 in sham patients for calories (difference, -1; 95% CI, -8 to 6; p = 0.74). For protein, it was 57% ± 3 in the active group and 60% ± 3 in the sham group (difference, -3; 95% CI, -10 to 3; p = 0.30). Compared to the sham group, there were more serious adverse events reported in the active treatment group (13 vs 6; p = 0.053). Clinically important arrhythmias were detected by Holter monitoring in 36 out of 70 (51%) in the active group versus 22 out of 76 (29%) in the sham group (p = 0.006). CONCLUSIONS Esophageal stimulation via a special feeding catheter did not improve nutritional adequacy and was associated with increase risk of harm in critically ill patients.