Development of a Controlled Continuous Low-Dose Feeding Process.

This paper proposes a feed rate control strategy for a novel volumetric micro-feeder, which can accomplish low-dose feeding of pharmaceutical raw materials with significantly different powder properties. The developed feed-forward control strategy enables a constant feed rate with a minimum deviation from the set-point, even for materials that are typically difficult to accurately feed (e.g., due to high cohesion or low density) using conventional continuous feeders. Density variations observed during the feeding process were characterized via a displacement feed factor profile for each powder. The characterized effective displacement density profile was applied in the micro-feeder system to proactively control the feed rate by manipulating the powder displacement rate (i.e., computing the feed rate from the powder displacement rate). Based on the displacement feed factor profile, the feed rate can be predicted during the feeding process and at any feed rate set-point. Three pharmaceutically relevant materials were used for the micro-feeder evaluation: di-calcium phosphate (large-particle system, high density), croscarmellose sodium (small-particle system, medium density), and barium sulfate (very small-particle <10 µm, high density). A significant improvement in the feeding performance was achieved for all investigated materials. The feed rate deviation from the set-point and its relative standard deviation were minimal compared to operations without the control strategy.

Changes in layers of laboratory vermicomposting using spent mushroom substrate of Agaricus subrufescens P.

World mushroom production in 2018 was approximately 8.99 million tonnes. The most commonly cultivated species in the Czech Republic are Agaricus spp., which are sold fresh or canned. In 2017, 2018 mushroom production in the Czech Republic was approximately 540 tonnes. Vermicomposting is an easy and less ecologically harmful way to process the spent mushroom substrate. Earthworms, which are referred to as the engine of the process of vermicomposting, and microorganisms, help convert organic waste into fertilizer. This study is concerned with laboratory vermicomposting in a system of continuous feeding of earthworms Eisenia andrei. It compares the differences between variants with and without earthworms. The dry matter percentage was approximately 20% or more in both variants. The variant with earthworms showed a significant decrease in electrical conductivity. The C/N ratio was very low in both variants. The highest total P was recorded in the variant with earthworms, but the highest values of K and Mg were found in the control. Both variants recorded higher content of bacteria than fungi. All values of microorganism contents were higher in the vermicomposter without earthworms, but the bacterial/fungal ratio was higher in the variant with earthworms. The highest content in both variants shows the bacteria especially G-bacteria, on the other side, the lowest content shows the actinobacteria. The highest activity of ß-D-glucosidase and acid phosphatase was measured in the vermicomposter with earthworms, but the activity of other enzymes was higher in the control. In both vermicomposters laccase activity was below the detection limit. The method of classical vermicomposting can be used for processing the spent mushroom substrate. However, in terms of higher content of total and available nutrients, there seems to be a better method of processing the substrate without earthworms.

Performance Evaluation of a High-Precision Low-Dose Powder Feeder.

Highly potent active pharmaceutical ingredients (APIs) and low-dose excipients, or excipients with very low density, are notoriously hard to feed with currently available commercial technology. The micro-feeder system presented in this work is capable of feeding low-dose rates of powders with different particle sizes and flow properties. Two different grades of lactose, di-calcium phosphate, croscarmellose sodium, silicon dioxide, a spray-dried intermediate, and an active ingredient were studied to vary material properties to test performance of the system. The current micro-feeder system is a volumetric feeder combined with a weighing balance at the outlet that measures feeder output rates. Feeding results are shown as a so-called "displacement-feed factor" curve for each material. Since the powder mass and volume are known in the micro-feeder system, in this work, we characterized an observed density variation during processing via a "displacement-feed factor" profile for each of the fed powders. This curve can be later used for calibrating the system to ensure an accurate, constant feed rate and in addition predicting feeding performance for that material at any feed rate. There is a relation between powder properties and feeding performance. Powders with finer particles and higher compressibility show densification during their feeding process. However, powders with larger particles and lower compressibility show both "densification" and "powder bed expansion," which is the manifestation of dilation and elastic recovery of particles during the micro-feeding process. Through the application of the displacement-feed factor, it is possible to provide precise feeding accuracy of low-dose materials.

Change of the parameters of layers in a large-scale grape marc vermicomposting system with continuous feeding.

The main by-product of wine-making is grape marc. With proper treatment, grape marc may return to the vineyard as a fertiliser. This study deals with the vermicomposting of grape marc in a continuous feeding system in outdoor conditions for more than 12 months. The N-NH4+, dissolved organic carbon (DOC), and N-NH4+/N-NO3- contents were greater in the top layers. The pH value was about 8 in all the layers. The electrical conductivity was the greatest in the bottom layer. The ion-exchange capacity did not modify significantly during vermicomposting. The microbial biomass was the greatest in the upper layer, as well as the number and the biomass of the earthworms. The process of vermicomposting seems to be an ideal way of processing residues from the winemaking industry. This vermicompost has very good properties for use as a fertiliser, and for returning the nutrients and organic matter to the soil, for example, in a vineyard.

Dynamics of a vertical-flow windrow vermicomposting system.

Large-scale vermicomposting under outdoor conditions may differ from small-scale procedures in the laboratory. The present study evaluated changes in selected properties of a large-scale vertical-flow windrow vermicomposting system with continuous feeding with household biowaste. The windrow profile was divided into five layers of differing thickness and age after more than 12 months of vermicomposting. The top layer (0-30 cm, age <3 months) was characterised by partially decomposed organic matter with a high pH value and an elevated carbon/nitrogen (C/N) ratio. The earthworm biomass was 15 g kg-1 with a population density of 125 earthworms per kilogram predominantly found in clusters. The greatest amount of fungi (3.5 µg g-1 dw) and bacteria (62 µg g-1 dw) (expressed as phospholipid fatty acid analysis) was found in this layer. Thus, the top layer could be used for an additional cycle of windrow vermicomposting and for the preparation of aqueous extracts to protect plants against diseases. The lower layers (graduated by 30 cm and by 3 months of age) were mature as reflected by the low content of ammonia nitrogen, ratio of ammonia to nitrate nitrogen and dissolved organic carbon, and high ion-exchange capacity and its ratio to carbon. These layers were characterised by elevated values for electrical conductivity, total content of nutrients, available magnesium content, and a relatively large bacterial/fungal ratio. On the basis of the observed properties, the bottom layers were predetermined as effective fertilisers.

High efficiency production of 5-hydroxyectoine Zusing metabolically engineered Escherichia coli.

The 5-hydroxyectoine is a natural protective agent with long-lasting moisturising and radiation resistance properties. It can be naturally synthesized by some extremophiles using the "bacterial milking" process, but this can corrode bioreactors and downstream purification may cause environmental pollution. In this study, an engineered Escherichia coli (E. coli) strain was constructed for the 5-hydroxyectoine production. First, three ectoine hydroxylases were characterised and the enzyme from Halomonas elongata was the most effective. The L-2,4-diaminobutyrate transaminase mutant was introduced into the engineered strain, which could accumulate 2.8 g/L 5-hydroxyectoine in shake flasks. By activating the glyoxylate cycle and balancing the α-ketoglutarate distribution, the 5-hydroxyectoine titer was further increased to 3.4 g/L. Finally, the optimized strain synthesized 58 g/L 5-hydroxyectoine via a semi-continuous feeding process in a NaCl-free medium. Overall, this study reported the highest titer of 5-hydroxyectoine synthesized by E. coli and established a low-salt fermentation process through the aforementioned efforts.

A continuous micro-feeder for cohesive pharmaceutical materials.

Over the past decade, continuous manufacturing has garnered significant attention in the pharmaceutical industry. Still, numerous continuous unit operations need developments, such as powder blending and feeding at low and high throughputs. Especially the continuous and consistent feeding of solid drug substances and excipients at low feed rates remains challenging. This study demonstrates a micro-feeder capable of feeding poorly-flowing pharmaceutical powders at low feed rates. The system performance was investigated using three grades of pharmaceutical powder: croscarmellose sodium (cohesive), magnesium stearate (very cohesive), and an active ingredient, paracetamol (non-flowing). The results show that the micro-feeder can continuously and consistently feed powders at low flow rates (<20 g/h) with low variability (<10 % for non-flowing materials and < 5 % for cohesive materials). Notably, the micro-feeder achieves these results without any feedback control and remains unaffected by refilling, making it a truly versatile and industry-relevant solution. The study's results demonstrate that this micro-feeder system effectively tackles the challenge of consistent and accurate powder feeding at low rates.

A multicenter randomized controlled trial comparing three-times-a-day intermittent enteral postural feeding to continuous enteral feeding among mechanically ventilated patients in intensive care.

BACKGROUND AND AIMS: Previous randomized controlled trials (RCTs) comparing intermittent feeding versus continuous feeding used different methods, employed shorter fasting intervals, ignored patients' posture in bed during feeds, and showed mixed results. Prolonged fasting intervals are hypothesized to have several benefits. Additionally, there is evidence for more efficient gastric emptying in the right lateral position. In this multicenter RCT, we aimed to compare the effects of three-times-a-day gastric feeding while in the right lateral tilt position (intermittent postural feeding) versus standard continuous gastric feeding (standard feeding) on gastrointestinal intolerance and mortality among mechanically ventilated patients in ICU. METHODS: Adult ICU patients with gastric feeding tube in-situ and requiring invasive mechanical ventilation were randomized to either intermittent postural feeding group or to the standard feeding group. The feeding formula, target daily feed volume and posture turns were determined as per standard practice for all patients. Primary outcome was an incidence rate per 100 patient-days of gastrointestinal intolerance, a composite outcome of vomiting, diarrhea or constipation. Secondary outcomes were all-cause hospital mortality, gastrointestinal intolerance-free days, ventilator-free days, episodes of vomiting or diarrhea per patient, and mean diet volume ratio (diet received/diet prescribed). RESULTS: At five multidisciplinary ICUs, 120 mechanically ventilated, adult ICU patients (median age 65 years, 60% males) were randomly allocated to intermittent postural feeding (n = 61) and standard feeding (n = 59). The primary outcome did not differ between intermittent feeding arm versus standard arm (8.5, 95% confidence interval (CI): 5.9-11.8, versus 6.2, 95% CI: 4.1-9.1 per 100 patient-days; p = 0.23). Gastrointestinal intolerance-free days until day 14 were similar (6 [2-8] versus 5 [2-10]; p = 0.68) in both groups. Number of episodes per patient of vomiting, diarrhea, or constipation also did not differ in between groups. All-cause hospital mortality between intermittent feeding arm versus standard arm was 20% versus 31% (p = 0.17). There were no significant between-group differences in any of the other secondary outcomes. CONCLUSIONS: Intermittent gastric feeds delivered three-times-a-day while in the right lateral tilt position among mechanically ventilated patients was as well tolerated as the continuous enteral feeding. A definitive RCT to assess other clinically important outcomes is justified. TRIAL REGISTRATION: ACTRN12616000212459 https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=365526&isReview=true.

Protocol for a systematic review and meta-analysis investigating the impact of continuous versus intermittent enteral feeding in critically ill patients.

INTRODUCTION: Enteral nutrition (EN) is the recommended nutritional support in most critically ill populations. When given by feeding tube, EN may be administered either continuously or intermittently. It is unclear which approach is superior in reducing gastrointestinal complications-such as diarrhea-and meeting nutritional targets. The main objectives of this systematic review and meta-analysis are to (1) determine whether continuous or intermittent enteral nutrition is associated with higher incidence of adverse gastrointestinal outcomes, including diarrhea, and (2) determine which feeding modality is associated with reaching nutritional goals. METHODS AND ANALYSIS: This systematic review protocol is reported in accordance with guidelines from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement. We will search MEDLINE, Embase, the Cochrane Library, and the World Health Organization (WHO) International Clinical Trials Registry (ICTRP) search portal for studies comparing continuous EN and intermittent EN in critically ill patients with no date or language restrictions. Studies will be screened, selected, and extracted independently and in duplicate. We will assess the risk-of-bias assessment using the Cochrane Collaboration's Risk of Bias (RoB) 2 tool. The primary outcome will include the incidence of diarrhea; secondary outcomes include other adverse GI outcomes (nausea, vomiting, abdominal pain, and constipation), as well as reaching nutritional goals, and length of ICU and hospital stay and mortality. We will pool data using a random-effects model and assess the certainty of the evidence for each outcome using Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methodology. ETHICS AND DISSEMINATION: Ethics approval is not required for this study as no original data will be collected. We will disseminate results through peer-reviewed publication and conference presentations. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022330118.

Development and implementation of a pneumatic micro-feeder for poorly-flowing solid pharmaceutical materials.

Consistent powder micro-feeding (<100 g/h) is a significant challenge in manufacturing solid oral dosage forms. The low dose feeding can well control the content consistency of the dosage forms, which improves drug efficiency and reduces manufacturing waste. Current commercial micro-feeders are limited in their ability to feed < 20 g/h of cohesive (i.e. powders of poor flowability) active pharmaceutical ingredients (API) and excipients (e.g. lubricants) with low fluctuation. To breach this gap, this study presents an advanced micro-feeder design capable of feeding a range of pharmaceutical-grade powders consistently at flow rates as low as 0.7 g/h with <20 % flow rate variation. This was possible due to a novel powder conveying concept utilising particle re-entrainment to minimise flow rate variations. This work details the design of this pneumatic micro-feeder and its excellent micro-feeding performance even for cohesive powders. The experimental studies investigated the influence of the process parameters (air pressure and air flow rate) and equipment configurations (insert size and plug position) on the feeding performance of different pharmaceutical-relevant powders, i.e., microcrystalline cellulose (MCC), croscarmellose sodium (CCS), crospovidone (XPVP) and paracetamol (APAP). It was shown that the system is capable of delivering consistent powder flow rates with good repeatability and stability.

The effect of intermittent versus continuous enteral feeding for critically ill patients: a meta-analysis of randomized controlled trials.

Objectives: The appropriate strategy for enteral feeding in critically ill patients still remains controversial. Therefore, we conducted this meta-analysis to compare the effect of intermittent versus continuous enteral feeding method for critically ill patients. Methods: Electronic databases including PubMed, Embase, Scopus, and Cochrane Library were searched up to April 10th, 2023 for randomized controlled trials evaluating the effect of intermittent versus continuous enteral feeding for critically ill patients. The primary outcomes were feeding intolerances, including diarrhea, vomiting, distension, constipation, gastric retention, and aspiration pneumonia. The secondary outcomes were mortality in intensive care unit (ICU), length of stay in ICU, and achievement of nutritional goal. Results: Thirteen studies with a total of 884 patients were analyzed in this meta-analysis. Overall, the use of intermittent enteral feeding was associated with higher incidence of diarrhea (OR 1.66, 95%CI 1.13 to 2.43, I2 = 16%) and distension (OR 2.29, 95%CI 1.16 to 4.51, I2 = 0%), lower incidence of constipation (OR 0.58, 95%CI 0.37 to 0.90, I2 = 0%), and longer length of ICU stay (MD 1.09, 95%CI 0.53 to 1.64, I2 = 0%). Moreover, no significant difference was identified for other outcome measures. Conclusion: In critically ill patients, the implementation of intermittent enteral feeding was associated with higher incidence of diarrhea and distension, longer length of ICU stay, but lower occurrence of constipation. Nevertheless, the absence of sufficient high-quality randomized controlled clinical trials precludes any definitive conclusions regarding the optimal approach to enteral feeding in this population. There is an imperative need for more studies to further assess the efficacy of the two enteral feeding strategies.

Flowsheet modelling of a powder continuous feeder-mixer system.

In this study, an integrated flowsheet model of the continuous feeder-mixer system was calibrated, simulated and compared against experimental data. The feeding process was first investigated using two major components (ibuprofen and microcrystalline cellulose (MCC)), in a formulation comprised of: 30 wt% of ibuprofen, 67.5 wt% MCC, 2 wt% of sodium starch glycolate and 0.5 wt% of magnesium stearate. The impact of a refill on feeder performance was experimentally evaluated for different operating conditions. Results showed that it had no influence on feeder performance. While simulations with the feeder model fairly reproduced the material behaviour observed in the feeder, unintended disturbances were underpredicted due to the model's low complexity. Experimentally, mixer's efficiency was assessed based on ibuprofen residence time distribution. Mean residence time pointed to a higher mixer's efficiency at lower flow rates. Blend homogeneity results showed that for the entire set of experiments, ibuprofen RSD < 5%, irrespective of process variables. A feeder-mixer flowsheet model was calibrated, after regressing the axial model coefficients. The regression curves exhibited a R2 above 0.96, whereas the RMSE varied from 1.58x10-4 to 1.06x10-3 s-1 across all fitted curves. Simulations confirmed that flowsheet model captured the powder dynamics inside the mixer and qualitatively predicted the mixer's filtering ability against feeding composition fluctuations, as well as ibuprofen RSD in blend, in line with real experiments.

Intermittent bolus versus continuous feeding in children receiving an enteral formula with food derived ingredients: A national multicentre retrospective study.

BACKGROUND AND AIM: A perceived factor believed to have an impact on feed tolerance relates to the mode in which nutrition is delivered regarding intermittent bolus or continuous feeding. Enteral formulas with food derived ingredients have been developed to help address some of the many feeding issues experienced by children who are tube fed. This study aimed to evaluate the tolerance of different feeding modes in children who are fed with an enteral formula with food derived ingredients. METHODS: Data was collected by paediatric dietitians from dietetic records over a month period on children who had switched to an enteral formula with food derived ingredients. Data was inputted to a Microsoft form to capture the impact of varying modes of feeding (intermittent bolus/continuous/combination) on gastrointestinal and anthropometric outcomes. RESULTS: Forty-three children were recruited between March 2021 to July 2021 across four National Health Service Trusts. Children who were continuously fed saw the greatest reported improvement in retching, abdominal pain and loose stools. Children who were fed intermittent bolus reported the greatest increase in weight (p-value 0.003). Over 90% of dietitians reported nutritional goals were achieved after switching formula; children who were fed continuously reported the highest achievement to meet dietitian's nutritional goals. CONCLUSION: Enteral formulas with food derived ingredients are well tolerated and effective in achieving weight gain and meeting dietetic goals whether delivered continuously or as intermittent bolus feed. The clinical situation will determine the most appropriate and effective feeding mode and should be guided by the dietitian and medical team.

Prospective randomised trial of bolus vs. continuous regime of jejunostomy feed.

Enteral alimentation can be administered continuously, cyclically, intermittently, or by a bolus technique. Current literature does not suggest superiority of any one regime. Most studies have used nasogastric feeds, little is known about the outcome of jejunal feeding.This study compares the efficiency and safety of bolus and continuous jejunostomy feeding. 46 adults undergoing a feeding jejunostomy for nutritional support or as an adjunct to a major upper GI surgery, were randomised to bolus feeding (BF group, n = 24) and continuous feeding (CF group, n = 22). Demographic, anthropometric, and laboratory parameters were measured preoperatively and on post-operative days (POD) 3, 7, 15, and 30. These parameters; as well as nutritional and functional outcomes, and complications at POD 30; were comparable in both groups. Both groups tolerated jejunal feeds well. Bolus feeding is simple, inexpensive, and permits daily physical activities. Hence it may be preferred over continuous jejunostomy feeding for enteral alimentation.

Efficient and advanced nitrogen removal from mature landfill leachate via combining nitritation and denitritation with Anammox in a single sequencing batch biofilm reactor.

A novel combined partial nitrification-Anammox and partial denitrification-Anammox (PnA/PdA) single sequencing batch biofilm reactor (SBBR) was established to realize efficient and advanced nitrogen removal from mature landfill leachate with low biodegradability. Nitrogen removal rate and nitrogen removal efficiency were increased to 2.83 ± 0.06 kgN/(m3∙d) and 98.6 ± 0.2% by stepwise increase of dissolved oxygen (DO, from 0.5 to 3.5 mg/L) and continuous carbon source feeding. Comparable activities of ammonia oxidation bacteria and Anammox bacteria were realized during aerobic period. More organic carbon was redirected from complete denitrification to partial denitrification during anoxic period. The main pathway PnA jointly synergized with PdA, which contributed to 76.04% and 19.44% nitrogen removal, respectively. Nitrosomonas, Thauera, and Kuenenia dominated in floc sludge (0.78%, 5.38%, and 1.14%, respectively) and biofilm (0.34%, 5.18%, and 0.98%, respectively). Overall, this study provides new insight into the high-efficiency treatment of landfill leachate at full-scale landfill sites.

Factors Influencing Breast Milk Fat Loss during Administration in the Neonatal Intensive Care Unit.

The objective of this study was to investigate factors influencing fat loss during tube feeding of breast milk to preterm infants. An experimental study with 81 feeding simulations was performed, with nine continuous infusions in each of six modalities: Horizontal Higher, Horizontal Matched, Horizontal Lower, Tilted Higher, Tilted Matched, and Tilted Lower, and for comparison, 27 bolus feedings: nine flushed with air, nine with water, and nine that were not flushed, done at matched height. Each simulation utilized 16 mL of breast milk given over four hours. Continuous infusions were given with a flow rate of 4 mL/h. Bolus was given as 8 mL over the course of 15-20 min every other hour. Analysis for fat, true protein, carbohydrate, total solids, and energy was performed before and after each simulation. The percent of macronutrient loss was compared between all simulations. Continuous infusion resulted in an average fat loss of 40%. Bolus feedings resulted in an average fat loss of 11% (p ≤ 0.001). Considerable fat loss is seen during continuous tube feeding. Neither height in relation to the infant nor tilting of the pump reduce fat loss. To limit fat loss, the bolus feeding method should be utilized.

The Effect of Intermittent and Continuous Feeding on Growth and Discharge Time in Very Low Birth Weight Preterm Infants.

OBJECTIVES: The aim of this study was to determine the effect of intermittent bolus feeding and continuous feeding models on early growth and discharge time in very low birth weight infants. METHODS: The study was designed as a prospective, randomized, and controlled study. Infants born in our hospital with birth weight below 1500 g within a 1 year period were included in the study. The number of samples was determined by power analysis. Babies were randomized according to birth weight and fed with intermittent bolus feeding and continuous feeding models. Demographic characteristics, clinical findings, diagnosis, nutritional status, and length of hospital stay were compared. RESULTS: The study was conducted with 80 preterm infants, which consisted of continuous feeding (n=41) and intermittent bolus feeding (n=39). There was no significant difference in gender, gestational week, birth weight, height, and head circumference distribution of the babies between groups. The difference between the reach time to birth weight and maximum weight loss rates, parenteral feeding time, transition time to full enteral feeding, transition time to oral feeding, development of feeding intolerance, mechanical ventilation time, and hospitalization time in intensive care unit were not statistically significant. Necrotizing enterocolitis (NEC) Stage I and II developed in 34.1% of babies fed with continuous feeding model and 28.2% of babies fed intermittently; NEC was detected to start in 4.5±2.8 days in the continuous feeding group and in 2.8±5.2 days in the intermittent group. These differences were found to be insignificant between the two groups (p=0.634 and p=0.266, respectively). CONCLUSION: There was no difference between growth parameters and discharge time of preterm babies who were applied continuous and intermittent bolus feeding model. Although there was no statistically significant difference on the development of NEC, it was determined that NEC developed earlier in the intermittent bolus feeding model.

Continuous Feeding Reduces the Generation of Metabolic Byproducts and Increases Antibodies Expression in Chinese Hamster Ovary-K1 Cells.

Chinese hamster ovary (CHO) cells are the most important host system used for monoclonal antibody (mAb) expression. Moreover, the fed-batch culture mode is the most widely used method to increase mAb expression in CHO cells by increasing the amount of feed. However, a high amount of culture feed results in the production of metabolic byproducts. In this work, we used a continuous feeding strategy to reduce metabolic byproducts and improve mouse-human chimeric anti-epidermal growth factor receptor vIII (EGFRvIII) antibody C12 expression in Chinese hamster ovary-K1 cells. Moreover, the effects of the feeding strategy on the cell culture and monoclonal antibody production were evaluated in chemically defined suspension cultures of recombinant CHO-K1 cells. Compared with bolus feeding methods, the continuous feeding method did not have any advantages when the feeding amount was low, but with a high feeding amount, the continuous feeding method significantly reduced the concentrations of lactate and NH4+ in the later culture stage. At the end of the culture stage, compared with bolus feeding methods, the lactate and NH4+ concentrations under the continuous feeding mode were reduced by approximately 45% and 80%, respectively. In addition, the antibody C12 expression level was also increased by almost 10%. Compared to the bolus feeding method, the antibody C12 produced by the continuous feeding method had a lower content of high-mannose glycoforms. Further analysis found that the osmolality of the continuous feeding method was lower than that of the typical fed-batch bolus feeding method. Conclusively, these results indicate that the continuous feeding method is very useful for reducing metabolic byproducts and achieving higher levels of mAb production.

Intermittent versus continuous enteral nutrition on feeding intolerance in critically ill adults: A meta-analysis of randomized controlled trials.

OBJECTIVES: Enteral formula delivery strategy is an important part of enteral nutrition. We aimed to synthesize up-to-date studies to clarify the effects of intermittent versus continuous feeding on feeding intolerance during enteral nutrition in critically ill adults. DESIGN: A meta-analysis of randomized controlled trials. DATA SOURCES: Embase, PubMed, Information Sciences Institute Web of Science, CINAHL EBSCO, Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature Database, China National Knowledge Infrastructure databases were searched from inception to 17th of June 2020. REVIEW METHODS: The Cochrane "risk of bias" tool was used to assess the quality of individual studies, and the quality of each outcome was assessed by GRADE approach. Fixed or random effect meta-analysis was used pending the presence of heterogeneity. Dichotomous data synthesis was presented as risk ratio and 95% confidence interval, and quantitative data synthesis was shown as mean difference and 95% confidence interval. RESULTS: Fourteen trials with 1025 critically ill adults were included in the meta-analysis. We found that intermittent feeding could significantly increase the occurrence of feeding intolerance (risk ratio = 1.64, 95% confidence interval = 1.23 to 2.18, P < 0.001) compared with continuous feeding, as well as the incidence of high gastric volume (risk ratio = 3.62, 95% confidence interval = 1.43-9.12, P = 0.006) and aspiration (risk ratio = 3.29, 95% confidence interval = 1.18-9.16, P = 0.02) in > 1-week trial duration, while constipation rate was reduced in intermittent feeding group (risk ratio = 0.66, 95% confidence interval = 0.45-0.98, P = 0.04). Patients in intermittent feeding group received more calories compared with continuous feeding group (mean difference = 184.81, 95% confidence interval = 56.61-313.01, P = 0.005). The quality of all evidence synthesis was "low" or "very low". CONCLUSIONS: In critically ill adults, continuous feeding was associated with lower overall incidence of feeding intolerance, especially in high gastric volume and aspiration. However, decreased constipation incidence and more calorie intake were observed in intermittent feeding group. Because quality of the synthesized evidence was "low" or "very low", there is considerable uncertainty about this estimate.

Gastric Volume Changes in Preterm Neonates during Intermittent and Continuous Feeding-GRV and Feeding Mode in Preterm Neonates.

Background: We aimed to evaluate gastric volume changes during intermittent milk feeds (IMF) and continuous milk feeds (CMF) in very premature neonates (VPN), with gastric residual volume (GRV) based on antral cross-sectional area (ACSA) measurements and to examine if there were differences in GRV between the two feeding methods. Methods: A randomized prospective clinical trial with crossover design was conducted in 31 preterm neonates (gestational age < 30 weeks). Gastric volume was assessed twice in each neonate (during IMF and CMF feeding), at 7 specific time points during a 2-h observation period by measuring ACSA changes via the ultrasound (U/S) method. Results: There was a significantly different pattern of gastric volume changes between the two feeding methods. GRV, expressed as the median percentage of ACSA measurement at 120 min relative to the higher ACSA measurement during IMF, was found to be 3% (range 0-25%) for IMF and 50% (range 15-80%) for CMF. Neonates fed with IMF had a shorter mean gastric emptying time compared to those fed with CMF (p = 0.0032). No signs of feeding intolerance were recorded in either group during the period of observation. Conclusions: Our results showed that gastric volume changes and gastric emptying time in VPN, based on ACSA measurement changes, depend on the milk feeding method. No gastrointestinal complications/adverse events were noted with GRV up to 80% with CMF.