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Omega-3 fatty acid-containing parenteral nutrition in ICU patients: systematic review with meta-analysis and cost-effectiveness analysis

Pradelli, Lorenzo; Klek, Stanislaw; Mayer, Konstantin; Omar Alsaleh, Abdul Jabbar; Rosenthal, Martin D; Heller, Axel R; Muscaritoli, Maurizio
BACKGROUND:Omega-3 (ω-3) fatty acid (FA)-containing parenteral nutrition (PN) is associated with significant improvements in patient outcomes compared with standard PN regimens without ω-3 FA lipid emulsions. Here, we evaluate the impact of ω-3 FA-containing PN versus standard PN on clinical outcomes and costs in adult intensive care unit (ICU) patients using a meta-analysis and subsequent cost-effectiveness analysis from the perspective of a hospital operating in five European countries (France, Germany, Italy, Spain, UK) and the US. METHODS:We present a pharmacoeconomic simulation based on a systematic literature review with meta-analysis. Clinical outcomes and costs comparing ω-3 FA-containing PN with standard PN were evaluated in adult ICU patients eligible to receive PN covering at least 70% of their total energy requirements and in the subgroup of critically ill ICU patients (mean ICU stay > 48 h). The meta-analysis with the co-primary outcomes of infection rate and mortality rate was based on randomized controlled trial data retrieved via a systematic literature review; resulting efficacy data were subsequently employed in country-specific cost-effectiveness analyses. RESULTS:In adult ICU patients, ω-3 FA-containing PN versus standard PN was associated with significant reductions in the relative risk (RR) of infection (RR 0.62; 95% CI 0.45, 0.86; p = 0.004), hospital length of stay (HLOS) (- 3.05 days; 95% CI - 5.03, - 1.07; p = 0.003) and ICU length of stay (LOS) (- 1.89 days; 95% CI - 3.33, - 0.45; p = 0.01). In critically ill ICU patients, ω-3 FA-containing PN was associated with similar reductions in infection rates (RR 0.65; 95% CI 0.46, 0.94; p = 0.02), HLOS (- 3.98 days; 95% CI - 6.90, - 1.06; p = 0.008) and ICU LOS (- 2.14 days; 95% CI - 3.89, - 0.40; p = 0.02). Overall hospital episode costs were reduced in all six countries using ω-3 FA-containing PN compared to standard PN, ranging from €-3156 ± 1404 in Spain to €-9586 ± 4157 in the US. CONCLUSION:These analyses demonstrate that ω-3 FA-containing PN is associated with statistically and clinically significant improvement in patient outcomes. Its use is also predicted to yield cost savings compared to standard PN, rendering ω-3 FA-containing PN an attractive cost-saving alternative across different health care systems. STUDY REGISTRATION:PROSPERO CRD42019129311.
PMCID:7607851
PMID: 33143750
ISSN: 1466-609x
CID: 5411672

Acute intestinal failure: International multicenter point-of-prevalence study

Reintam Blaser, Annika; Ploegmakers, Ilse; Benoit, Michael; Holst, Mette; Rasmussen, Henrik Hojgaard; Burgos, Rosa; Forbes, Alastair; Shaffer, Jon; Gabe, Simon; Irtun, Oivind; Thibault, Ronan; Klek, Stanislaw; Olde Damink, Steven Wm; van de Poll, Marcel; Panisic-Sekeljic, Marina; Wanten, Geert; Pironi, Loris
BACKGROUND & AIMS:Intestinal failure (IF) is defined from a requirement or intravenous supplementation due to failing capacity to absorb nutrients and fluids. Acute IF is an acute, potentially reversible form of IF. We aimed to identify the prevalence, underlying causes and outcomes of acute IF. METHODS:This point-of-prevalence study included all adult patients hospitalized in acute care hospitals and receiving parenteral nutrition (PN) on a study day. The reason for PN and the mechanism of IF (if present) were documented by local investigators and reviewed by an expert panel. RESULTS:Twenty-three hospitals (19 university, 4 regional) with a total capacity of 16,356 acute care beds and 1237 intensive care unit (ICU) beds participated in this study. On the study day, 338 patients received PN (21 patients/1000 acute care beds) and 206 (13/1000) were categorized as acute IF. The categorization of reason for PN was revised in 64 cases (18.9% of total) in consensus between the expert panel and investigators. Hospital mortality of all study patients was 21.5%; the median hospital stay was 36 days. Patients with acute IF had a hospital mortality of 20.5% and median hospital stay of 38 days (P > 0.05 for both outcomes). Disordered gut motility (e.g. ileus) was the most common mechanism of acute IF, and 71.5% of patients with acute IF had undergone abdominal surgery. Duration of PN of ≥42 days was identified as being the best cut-off predicting hospital mortality within 90 days. PN ≥ 42 days, age, sepsis and ICU admission were independently associated with 90-day hospital mortality. CONCLUSIONS:Around 2% of adult patients in acute care hospitals received PN, 60% of them due to acute IF. High 90-day hospital mortality and long hospital stay were observed in patients receiving PN, whereas presence of acute IF did not additionally influence these outcomes. Duration of PN was associated with increased 90-day hospital mortality.
PMID: 30683610
ISSN: 1532-1983
CID: 5411392

Use of Catheter Lock Solutions in Patients Receiving Home Parenteral Nutrition: A Systematic Review and Individual-Patient Data Meta-Analysis

Wouters, Yannick; Causevic, Erna; Klek, Stanislaw; Groenewoud, Hans; Wanten, Geert J A
BACKGROUND:Use of catheter lock solutions (CLSs) as a strategy to prevent catheter-related bloodstream infections (CRBSIs) has been evaluated in recent clinical trials. Our aim was to identify the most effective CLS formulation in patients receiving home parenteral nutrition (HPN). METHODS:We conducted a systematic review and individual-patient data meta-analysis (IPDMA). Prospective randomized clinical trials in adult HPN patients using CLS were identified from PubMed, EMBASE, Web of Science, CINAHL, Cochrane library, and ClinicalTrials.gov. Primary outcome was the number of CRBSIs per 1000 catheter days for each CLS. Other outcomes included time to CRBSI and identification of patients with a higher risk for CRBSIs. RESULTS:In total, 1107 studies were screened for eligibility, of which three studies comprising 162 HPN patients and 45,695 catheter days were included in the IPDMA. CRBSI rates were significantly decreased in patients using taurolidine (rate 0.13; 95% confidence interval [CI], 0.05-0.32) when compared with saline (rate 0.74; 95% CI, 0.31-1.74; P = .002) or heparin (rate 2.01; 95% CI, 1.03-3.91; P < .001). The cumulative proportion of CRBSI-free patients using taurolidine, saline, and heparin after 1 year was 88%, 56%, and 14%, respectively. Three risk factors for CRBSIs were identified: type of CLS, intestinal dysmotility as underlying condition, and use of central venous catheters. CONCLUSIONS:Taurolidine was the most effective CLS formulation in HPN patients for the prevention of CRBSIs. We suggest discussing with patients the benefits and risks when starting taurolidine, especially in patients who are considered to have a higher risk for CRBSIs.
PMCID:7540581
PMID: 31985068
ISSN: 1941-2444
CID: 5411472

ω-3 Fatty-Acid Enriched Parenteral Nutrition in Hospitalized Patients: Systematic Review With Meta-Analysis and Trial Sequential Analysis

Pradelli, Lorenzo; Mayer, Konstantin; Klek, Stanislaw; Omar Alsaleh, Abdul Jabbar; Clark, Richard A C; Rosenthal, Martin D; Heller, Axel R; Muscaritoli, Maurizio
This systematic review and meta-analysis investigated ω-3 fatty-acid enriched parenteral nutrition (PN) vs standard (non-ω-3 fatty-acid enriched) PN in adult hospitalized patients (PROSPERO 2018 CRD42018110179). We included 49 randomized controlled trials (RCTs) with intervention and control groups given ω-3 fatty acids and standard lipid emulsions, respectively, as part of PN covering ≥70% energy provision. The relative risk (RR) of infection (primary outcome; 24 RCTs) was 40% lower with ω-3 fatty-acid enriched PN than standard PN (RR 0.60, 95% confidence interval [CI] 0.49-0.72; P < 0.00001). Patients given ω-3 fatty-acid enriched PN had reduced mean length of intensive care unit (ICU) stay (10 RCTs; 1.95 days, 95% CI 0.42-3.49; P = 0.01) and reduced length of hospital stay (26 RCTs; 2.14 days, 95% CI 1.36-2.93; P < 0.00001). Risk of sepsis (9 RCTs) was reduced by 56% in those given ω-3 fatty-acid enriched PN (RR 0.44, 95% CI 0.28-0.70; P = 0.0004). Mortality rate (co-primary outcome; 20 RCTs) showed a nonsignificant 16% reduction (RR 0.84, 95% CI 0.65-1.07; P = 0.15) for the ω-3 fatty-acid enriched group. In summary, ω-3 fatty-acid enriched PN is beneficial, reducing risk of infection and sepsis by 40% and 56%, respectively, and length of both ICU and hospital stay by about 2 days. Provision of ω-3-enriched lipid emulsions should be preferred over standard lipid emulsions in patients with an indication for PN.
PMCID:7003746
PMID: 31250474
ISSN: 1941-2444
CID: 5411442

The fragility of statistically significant results from clinical nutrition randomized controlled trials

Pędziwiatr, Michał; Mizera, Magdalena; Wysocki, Michał; Małczak, Piotr; Stefura, Tomasz; Gajewska, Natalia; Torbicz, Grzegorz; Droś, Jakub; Kacprzyk, Artur; Major, Piotr; Kłęk, Stanisław; Bała, Małgorzata
BACKGROUND & AIMS:Recently, a parameter called "Fragility index" (FI) has been proposed, which measures how many events the statistical significance relies on. The lower the FI the more "fragile" the results, and thus more care should be taken when interpreting the results. Our aim in this study was to check FI of nutritional trials. METHODS:We conducted a systematic review of human clinical nutrition RCTs that report statistically significant dichotomous primary outcomes. We searched the EMBASE, MEDLINE, and Scopus databases. The FI of primary outcomes using the Fisher exact test was calculated and checked the correlations of FI with the number of randomised trials, the p-value of primary outcomes, the publication date, the journal impact factor and the number of patients lost to follow-up. RESULTS:The initial database search revealed 5790 articles, 37 of which were included in qualitative synthesis. The median (IQR) FI for all studies was 1 (1-3). 28 studies (75.7%) had an FI lower or equal to 2, and in 12 (32.43%) articles, the FI was lower than the number of patients lost to follow-up. No correlations were found between FI and the study characteristics (number of randomized patients, p value of primary outcome, event ratio in experimental group, event ratio in control group, publication date, journal impact factor, lost to follow-up). CONCLUSION:The results of RCTs in nutritional research often rely on a small number of events or patients. The number of patients lost to follow-up is frequently higher than the FI calculation. Formulating recommendations based on RCTs should be done with caution and FI may be used as auxiliary parameter when assessing the robustness of their findings.
PMID: 31221372
ISSN: 1532-1983
CID: 5411432

THYROTOXIC PERIODIC PARALYSIS IN A COMPETITIVE BODYBUILDER WITH THYROTOXICOSIS FACTITIA [Case Report]

Patel, Amy J; Tejera, Stephanie; Klek, Stanislaw P; Rothberger, Gary D
Objective/UNASSIGNED:We report a case of thyrotoxic periodic paralysis (TPP) in a bodybuilder who developed paralysis secondary to thyrotoxicosis factitia after taking a supplement containing thyroid hormone. Interestingly, the patient had no intrinsic thyroid disease. Prompt recognition of thyrotoxicosis is critical to avoid progression of paralysis and subsequent complications. Methods/UNASSIGNED:We discuss a 27-year-old body builder who presented after a 3-day bodybuilding competition with sudden upper and lower extremity paralysis. He admitted to taking anabolic steroids, a supplement containing an unknown amount of thyroid hormone for 2 weeks, and furosemide 40 mg twice daily with near-complete fluid restriction for 3 days. Results/UNASSIGNED:Laboratory results showed a thyroid-stimulating hormone (TSH) level of <0.010 μIU/mL (normal, 0.3 to 5.8 μIU/mL), normal total triiodothyronine level, elevated free thyroxine level of 3.6 ng/dL (normal, 0.8 to 1.9 ng/dL), and potassium level of 1.9 mEq/L (normal, 3.7 to 5.2 mEq/L). Thyroid peroxidase antibody, thyroid-stimulating immunoglobulin, and thyroglobulin antibody levels were normal. Thyroid uptake was 1% (normal, 8 to 25%) after administration of I-123 and thyroglobulin level was 9 ng/mL (normal, 1.4 to 29.2 ng/mL). The patient was treated with normal saline infusion, magnesium supplementation and a total of 230 mEq of potassium within 12 hours of hospitalization. Muscle weakness resolved within this time period and potassium level normalized. By the third day of hospitalization free thyroxine level also normalized and TSH improved to 0.1 mIU/L. Conclusion/UNASSIGNED:TPP is a rare complication of thyrotoxicosis that should be considered in bodybuilders who are presenting with acute muscle weakness.
PMCID:7511107
PMID: 32984532
ISSN: 2376-0605
CID: 4981142

SAFETY AND EFFICACY OF GLUCOSTABILIZER IN THE MANAGEMENT OF DIABETIC KETOACIDOSIS

Groysman, Anna Y; Peragallo-Dittko, Virginia; Islam, Shahidul; Klek, Stanislaw
Objective: To evaluate the safety and efficacy of GlucoStabilizer software intravenous insulin (IV) dosing in comparison to American Diabetes Association (ADA) protocol-directed provider-guided insulin dose adjustment (PGIA). Methods: GlucoStabilizer calculates the dose of IV insulin required to reach a prescribed target glucose range. GlucoStabilizer has not been fully studied in DKA. This retrospective study compared outcomes in patients with DKA before and after implementation of GlucoStabilizer. Insulin doses were administered based on GlucoStabilizer calculations or PGIA. The analysis evaluated before-after changes in amount of insulin used, time to target, hypoglycemia or hypokalemia events, and time to DKA resolution. Results: We studied 77 patients with insulin doses calculated by GlucoStabilizer and 69 patients with PGIA dosing. GlucoStabilizer was superior to PGIA. Patients treated with GlucoStabilizer-calculated doses did not experience hypoglycemia (N= 0 vs. N= 10; p<0.001). The 10 unique PGIA patients had a total of 18 episodes with 17 between 55 to 69 mg/dL; 1 <54 mg/dL, and no episodes <40 mg/dL. The GlucoStabilizer group required less insulin to reach DKA resolution (59.2 vs. 101.2 units; p<0.001). Time to glycemic target and DKA resolution were similar (6.7 vs. 4.6 hours; p= 0.132) and (9.8 vs. 9.9 hours; p= 0.803), respectively. No difference in incidence of hypokalemia was seen (N= 9 vs. N= 11; p= 0.48).
PMID: 31968186
ISSN: 1530-891x
CID: 4294882

Evaluation of Y-site compatibility of home total parenteral nutrition and intravenous loop diuretics

Watrobska-Swietlikowska, Dorota; Pietka, Magdalena; Klek, Stanislaw
In chronic kidney disease (CKD), the design of the parenteral nutrition (PN) regimen becomes more challenging where only individualized PN is appropriate, coupled with the increased risk of unintended interactions with diuretic therapy. In an effort to ensure safe therapy in the home, we assessed the physical stability of bespoke PN formulations intended for use in CKD in the simultaneous presence of Y-site compatibility of furosemide and torasemide. The patient's daily needs were determined based on both metabolic demands as well as the demand for fluids.Complete admixtures were subjected to physical stability analysis consisting of visual inspection, a validated light microscope method, pH measurement, zeta potential measurement, and characterization of oily globule size distribution. Y-site compatibility of furosemide and torasemide with the formulated admixtures was also performed.The total parenteral admixture was stable over 7 days at +4°C and 24 h at +25°C and compatible via the Y-line together with furosemide and torasemide over 12 h at +25°C.The stability assessment guarantees the safety and efficiency of home PN with loop diuretics therapy in CKD patients. This means that these patients do not need long hospitalization and they can be safely treated at home. Furthermore, this study proved that torasemide is the same safety diuretic as furosemide, which has a great impact on clinical practice.
PMCID:6571370
PMID: 31124957
ISSN: 1536-5964
CID: 5411422

An international study of the quality of life of adult patients treated with home parenteral nutrition

Baxter, Janet P; Fayers, Peter M; Bozzetti, Federico; Kelly, Darlene; Joly, Francisca; Wanten, Geert; Jonkers, Cora; Cuerda, Cristina; van Gossum, Andre; Klek, Stanislaw; Boudreault, Marie-France; Gilbert, Alain; Jobin, Manon; Staun, Michael; Gillanders, Lyn; Forbes, Alastair; O'Callaghan, Margie; Faedo, Ceferino Martínez; Brunelli, Cinzia; Mariani, Luigi; Pironi, Loris
BACKGROUND & AIMS:in a multinational sample of adult patients; to provide a description of QOL dimensions by short and long HPN treatment duration; to explore clinical factors potentially associated to QOL scores. METHODS:. The questionnaires were analysed to evaluate data completeness, convergent/discriminant validity and internal-consistency reliability. The association of overall QOL and HPN treatment duration as well as other clinical factors were investigated using multivariable linear regression models. RESULTS:in the different English, French and Italian language patient sub-groups confirmed psychometric equivalence of the three questionnaire versions. The results of the multivariable linear regression showed that QOL scores were significantly associated with HPN duration (better in long-term), underlying disease (better in Crohn's disease and mesenteric ischaemia) and living status (worse in living alone) and, after adjusting for the other factors, with the number of days of HPN infusion per week. CONCLUSIONS:, is a valid tool for measurement of QOL in patients on HPN, to be used in the clinical practice as well as in research.
PMID: 30115461
ISSN: 1532-1983
CID: 5411362

Investigating Risk Factors for Complications after Ileostomy Reversal in Low Anterior Rectal Resection Patients: An Observational Study

Rubinkiewicz, Mateusz; Witowski, Jan; Wysocki, Michał; Pisarska, Magdalena; Kłęk, Stanisław; Budzyński, Andrzej; Pędziwiatr, Michał
PMCID:6832752
PMID: 31581485
ISSN: 2077-0383
CID: 5411452