Two Hours of In Vivo Lung Perfusion Improves Lung Function in Sepsis-Induced Acute Respiratory Distress Syndrome.

Sepsis is the leading cause of acute respiratory distress syndrome (ARDS) in adults and carries a high mortality. Utilizing a previously validated porcine model of sepsis-induced ARDS, we sought to refine our novel therapeutic technique of in vivo lung perfusion (IVLP). We hypothesized that 2 hours of IVLP would provide non-inferior lung rehabilitation compared to 4 hours of treatment. Adult swine (n = 8) received lipopolysaccharide to develop ARDS and were placed on central venoarterial extracorporeal membrane oxygenation. Animals were randomized to 2 vs 4 hours of IVLP. The left pulmonary vessels were cannulated to IVLP using antegrade Steen solution. After IVLP treatment, the left lung was decannulated and reperfused for 4 hours. Total lung compliance and pulmonary venous gases from the right lung (control) and left lung (treatment) were sampled hourly. Biochemical analysis of tissue and bronchioalveolar lavage was performed along with tissue histologic assessment. Throughout IVLP and reperfusion, treated left lung PaO2/FiO2 ratio was significantly higher than the right lung control in the 2-hour group (332.2 ± 58.9 vs 264.4 ± 46.5, P = 0.01). In the 4-hour group, there was no difference between treatment and control lung PaO2/FiO2 ratio (258.5 ± 72.4 vs 253.2 ± 90.3, P = 0.58). Wet-to-dry weight ratios demonstrated reduced edema in the treated left lungs of the 2-hour group (6.23 ± 0.73 vs 7.28 ± 0.61, P = 0.03). Total lung compliance was also significantly improved in the 2-hour group. Two hours of IVLP demonstrated superior lung function in this preclinical model of sepsis-induced ARDS. Clinical translation of IVLP may shorten duration of mechanical support and improve outcomes.

Local Application of Magnesium Sulfate Solution Suppressed Cortical Spreading Ischemia and Reduced Brain Damage in a Rat Subarachnoid Hemorrhage-Mimicking Model.

OBJECTIVE: Cortical spreading depolarization (CSD), cortical spreading ischemia (CSI), and early brain injury are involved in the occurrence of delayed brain ischemia after subarachnoid hemorrhage (SAH). We tested whether local application of magnesium (Mg) sulfate solution suppressed CSD and CSI, and decreased brain damage in a rat SAH-mimicking model. METHODS: Nitric oxide synthase inhibitor L-NG-nitroarginine methyl ester (L-NAME) and high concentration potassium solution were topically applied to simulate the environment after SAH. We irrigated the parietal cortex with artificial cerebrospinal fluid (ACSF), containing L-NAME (1 mM), K+ (35 mM), and Mg2+ (5 mM). Forty-five rats were divided into 3 groups: sham surgery (sham group), L-NAME + [K+]ACSF (control group), and L-NAME + [K+]ACSF + [Mg2+] (Mg group). CSD was induced by topical application with 1 M KCl solution in 3 groups. The effects of Mg administration on CSD and cerebral blood flow were evaluated. Histological brain tissue damage, body weight, and neurological score were assessed at 2 days after insult. RESULTS: Mg solution significantly shortened the total depolarization time, and reduced CSI, histological brain damage, and brain edema compared with those of the control group (P < 0.05). Body weight loss was significantly suppressed in the Mg group (P < 0.05), but neurological score did not improve. CONCLUSIONS: Local application of Mg suppressed CSI and reduced brain damage in a rat SAH-mimicking model. Mg irrigation therapy may be beneficial to suppress brain damage due to CSI after SAH.

Identification and quantification of glucose degradation products in heat-sterilized glucose solutions for parenteral use by thin-layer chromatography.

During heat sterilization of glucose solutions, a variety of glucose degradation products (GDPs) may be formed. GDPs can cause cytotoxic effects after parenteral administration of these solutions. The aim of the current study therefore was to develop a simple and quick high-performance thin-layer chromatography (HPTLC) method by which the major GDPs can be identified and (summarily) quantified in glucose solutions for parenteral administration. All GDPs were derivatized with o-phenylenediamine (OPD). The resulting GDP derivatives (quinoxalines) were applied to an HPTLC plate. After 20 minutes of chamber saturation with the solvent, the HPTLC plate was developed in a mixture of 1,4-dioxane-toluene-glacial acetic acid (49:49:2, v/v/v), treated with thymol-sulfuric acid spray reagent, and heated at 130°C for 10 minutes. Finally, the GDPs were quantified by using a TLC scanner. For validation, the identities of the quinoxaline derivatives were confirmed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Glyoxal (GO)/methylglyoxal (MGO) and 3-deoxyglucosone (3-DG)/3-deoxygalactosone (3-DGal) could be identified and quantified in pairs, glucosone (2-KDG), 5-hydroxymethylfurfural (5-HMF), and 3,4-dideoxyglucosone-3-ene (3,4-DGE) each individually. For 2-KDG, the linearity of the method was demonstrated in the range of 1-50 µg/mL, for 5-HMF and 3,4-DGE 1-75 µg/mL, for GO/MGO 2-150 µg/mL, and for 3-DG/3-DGal 10-150 µg/mL. All GDPs achieved a limit of detection (LOD) of 2 µg/mL or less and a limit of quantification (LOQ) of 10 µg/mL or less. R2 was 0.982 for 3.4-DGE, 0.997 for 5-HMF, and 0.999 for 2-KDG, 3-DG/3-DGal, and GO/MGO. The intraday precision was between 0.4 and 14.2% and the accuracy, reported as % recovery, between 86.4 and 112.7%. The proposed HPTLC method appears to be an inexpensive, fast, and sufficiently sensitive approach for routine quantitative analysis of GDPs in heat-sterilized glucose solutions.

Metabolism and Mass Balance of the Novel Nonsteroidal Androgen Receptor Inhibitor Darolutamide in Humans.

The biotransformation and excretion of darolutamide were investigated in a phase I study. Six healthy male volunteers received a single dose of 300 mg 14C-darolutamide as an oral solution in the fasted state. Plasma, urine, and feces samples were analyzed for mass balance evaluation by liquid scintillation counting (LSC). Metabolite profiling and identification were determined using liquid chromatography mass-spectrometry with off-line radioactivity detection using LSC. Complete mass balance was achieved, with mean radioactivity recovery of 95.9% within 168 hours (63.4% in urine, 32.4% in feces). The administered 1:1 ratio of (S,R)- and (S,S)-darolutamide changed to approximately 1:5, respectively, in plasma. Darolutamide and the oxidation product, keto-darolutamide, were the only components quantifiable by LSC in plasma, accounting for 87.4% of total radioactivity, with a 2.1-fold higher plasma exposure for keto-darolutamide. Aside from darolutamide, the most prominent metabolites in urine were O-glucoronide (M-7a/b) and N-glucuronide (M-15a/b), as well as pyrazole sulfates (M-29, M-24) and glucuronides (M-21, M-22) resulting from oxidative cleavage of the parent. The darolutamide diastereomers were mainly detected in feces. In vitro assays showed that darolutamide metabolism involves a complex interplay between oxidation and reduction, as well as glucuronidation. Interconversion of the diastereomers involves oxidation to keto-darolutamide, primarily mediated by CYP3A4, followed by reduction predominantly catalyzed by cytosolic reductase(s), with aldo-keto reductase 1C3 playing the major role. The latter reaction showed stereoselectivity with preferential formation of (S,S)-darolutamide. SIGNIFICANCE STATEMENT: The metabolism and excretion of darolutamide in humans revealed that oxidation (CYP3A4) and glucuronidation (UGT1A9, UGT1A1) were the main metabolic routes of elimination. Direct excretion also contributed to overall clearance. The two pharmacologically equipotent diastereomers of darolutamide interconvert primarily via oxidation to the active metabolite keto-darolutamide, followed by reduction predominantly by cytosolic reductase(s). The latter reaction showed stereoselectivity with preferential formation of (S,S)-darolutamide. Data indicate a low drug-drug interaction potential of darolutamide with inducers or inhibitors of metabolizing enzymes.

Long-term outcome after perineural injection with 5% dextrose for carpal tunnel syndrome: a retrospective follow-up study.

OBJECTIVE: Perineural injection therapy with 5% dextrose water is progressively becoming a mainstream method for treating carpal tunnel syndrome. However, its long-term outcome is still unknown. Hence, the purpose of this retrospective study was to investigate the long-term outcome after perineural injection therapy using 5% dextrose water. METHODS: A total of 185 patients diagnosed with carpel tunnel syndrome at least 1 year post-therapy were enrolled. All the patients underwent ultrasound-guided perineural injection therapy using 10 ml of 5% dextrose water at the outpatient department. In a structured telephone interview, the patients were asked about the outcome post-therapy compared with pre-injection. A symptom relief ≥50% indicated effective outcome, and a symptom relief <50% was indicative of a poor outcome. RESULTS: In total, 88.6% patients reported an effective outcome, and 11.4% rated the outcome as poor, after a mean of 2.2 injections with a mean of 1-3 years' post-injection follow-up. The outcome was significantly related with severity level, and the patients that reported a poor outcome had a significantly higher incidence of severe grade compared with those who reported an effective outcome (52.4% vs 31.7%, P = 0.03). Patients with mild, moderate and severe grades, respectively, required an average of 1.7 (0.1), 2.4 (0.2) and 2.6 (0.3) injections to reach an effective outcome (P = 0.006) (severe vs mild, P = 0.008; moderate vs mild, P = 0.062). CONCLUSION: Perineural injection therapy is a novel approach for treatment of carpal tunnel syndrome with safe and outstanding long-term effects.

Feasibility of developing children's Pill School within a UK hospital.

OBJECTIVE: We assessed the feasibility of introducing an intervention (children's Pill School-PS) within a UK hospital to provide swallowing training for children, identified the proportion of children who can be switched from oral liquid medicines to pills and assessed children/parents' opinions about the PS training. METHODS: 30 inpatient children (aged 3-18 years; taking oral liquid medicines; their liquid medications assessed suitable for switching to pills; can (and their parents) speak/understand English were included. Training sessions were delivered using hard sweets of different sizes. RESULTS: 87% (26) of children successfully learnt how to swallow pills after one training session (mean duration 14.5 min), and 92% (24) were discharged on pills. 75 prescribed oral liquid medications were deemed suitable for switching to pills. Of these, 89% (67) were switched successfully. CONCLUSION: Children as young as 3 years were successful in swallowing pills after training. Providing children PS training session within hospital is feasible and acceptable to children and their parents.

Current situation of carboplatin desensitisation protocols in the hospitals of Spain.

Desensitisation protocols allow the continuation of treatment in patients who have presented hypersensitivity reactions. Carboplatin desensitisation solutions are usually prepared in the chemotherapy centralised units of hospital pharmacies and they are diluted under the established concentration limit to guarantee the stability of the preparation. An online survey was sent to hospital pharmacies, inquiring about local desensitisation protocols: reasons for use of desensitisation protocols, the protocols used and the stability given to carboplatin solutions. An important variability among the hospitals in carboplatin desensitisation practice was detected. Six different carboplatin desensitisation protocols were described and discordance with the storage period of the carboplatin solutions was observed. The lack of consensus on which protocol must be followed and data supporting the stability of the diluted product, contribute to distrust of carboplatin desensitisation protocols. Although the efficacy and safety of carboplatin desensitisation protocols has been widely demonstrated, many professionals still have concerns.

An UPLC-MS/MS Method for Simultaneous Quantification of the Components of Shenyanyihao Oral Solution in Rat Plasma.

OBJECTIVES: To study the quantification of the components in rat plasma after oral administration of Shenyanyihao oral solution. METHODS: Shenyanyihao oral solution has been traditionally used for the treatments of chronic nephritis in clinics. Stachydrine, Danshensu, chlorogenic acid, protocatechuic acid, plantamajoside, aesculetin, isoquercitrin, ferulic acid, baicalin, and baicalein are regarded as the main compounds in Shenyanyihao oral solution. A sensitive, efficient, and precise UPLC-MS/MS method was established and validated for the quantification of the components in rat plasma after oral administration of Shenyanyihao oral solution. RESULTS: The main pharmacokinetic parameters of the components were acquired based on the analysis of the plasma sample by a noncompartmental method using the WinNonlin7.0 pharmacokinetic program. Danshensu, protocatechuic acid, isoquercitrin, and ferulic acid from Shenyanyihao oral solution were quickly absorbed, and their peak concentration occurred at less than 0.5 h. The pharmacokinetic parameter of the average t 1/2 from Danshensu was 3.91 h in rats, and it was the most rapid distribution and elimination among the components. In addition, the C max of stachydrine and baicalin were revealed as the higher plasma concentrations in rats. CONCLUSIONS: This pharmacokinetic study seems to be useful for a further clinical study of Shenyanyihao oral solution in the treatments of chronic nephritis.

A monocentric, open-label randomized standard-of-care controlled study of XONRID®, a medical device for the prevention and treatment of radiation-induced dermatitis in breast and head and neck cancer patients.

BACKGROUND: This study was an open-label, 2-arms, monocentric, randomized clinical trial comparing Xonrid®, a topical medical device, versus standard of care (SOC) in preventing and treating acute radiation dermatitis (ARD) in Head and Neck Cancer (HNC) and Breast Cancer (BC) patients undergoing radiotherapy (RT). METHODS: Eligible HNC and BC patients were randomized 1:1 to receive Xonrid® + SOC or SOC during RT. Patients were instructed to apply Xonrid® on the irradiated area three times daily, starting on the first day of RT and until 2 weeks after RT completion or until the development of grade ≥ 3 skin toxicity. The primary endpoint was to evaluate the proportion of patients who developed an ARD grade < 2 at the 5th week in both groups. Secondary endpoints were median time to grade 2 (G2) skin toxicity onset; changes in skin erythema and pigmentation and trans-epidermal water loss (TEWL); patient-reported skin symptoms. All patients were evaluated at baseline, weekly during RT and 2 weeks after treatment completion. The evaluation included: clinical toxicity assessment; reflectance spectrometry (RS) and TEWL examination; measurement of patients' quality of life (QoL) through Skindex-16 questionnaire. RESULTS: Eighty patients (40 for each cancer site) were enrolled between June 2017 and July 2018. Groups were well balanced for population characteristics. All BC patients underwent 3-Dimensional Conformal RT (3D-CRT) whereas HNC patients underwent Volumetric-Modulated Arc Therapy (VMAT). At week 5 the proportion of BC patients who did not exhibit G2 ARD was higher in Xonrid® + SOC group (p = 0.091). In the same group the onset time of G2 ARD was significantly longer than in SOC-alone group (p < 0.0491). For HNC groups there was a similar trend, but it did not reach statistical significance. For both cancer sites, patients' QoL, measured by the Skindex-16 score, was always lower in the Xonrid® + SOC group. CONCLUSION: Despite the failure to achieve the primary endpoint, this study suggests that Xonrid® may represent a valid medical device in the prevention and treatment of ARD at least in BC patients, delaying time to develop skin toxicity and reducing the proportion of patients who experienced G2 ARD during RT treatment and 2 weeks later. TRIAL REGISTRATION: The study was approved by the Ethical Committee of Fondazione IRCCS Istituto Nazionale dei Tumori di Milano (INT 52/14 - NCT02261181 ). Registered on ClinicalTrial.gov on 21st August 2017.

Ciprofloxacin/dexamethasone precipitate formation in the ear canal of a paediatric patient.

This case report describes a paediatric patient diagnosed with otitis externa and treated with topical ciprofloxacin/dexamethasone. The patient completed the course of therapy and then developed precipitate formation from the pharmacological treatment. Laboratory testing of the precipitate confirmed the presence of a large quantity of ciprofloxacin. Removal of the precipitate required the use of an elephant ear washer system and removal with surgical tweezers. This case report investigated a probable topical ciprofloxacin/dexamethasone-induced ear precipitate formation in the ear canal, which, subsequently, was successfully removed from the patient's ear canal.

Pharmacokinetics of lopinavir/ritonavir oral solution to treat COVID-19 in mechanically ventilated ICU patients.

BACKGROUND: The combination lopinavir/ritonavir is recommended to treat HIV-infected patients at the dose regimen of 400/100 mg q12h, oral route. The usual lopinavir trough plasma concentrations are 3000-8000 ng/mL. A trend towards a 28 day mortality reduction was observed in COVID-19-infected patients treated with lopinavir/ritonavir. OBJECTIVES: To assess the plasma concentrations of lopinavir and ritonavir in patients with severe COVID-19 infection and receiving lopinavir/ritonavir. PATIENTS AND METHODS: Mechanically ventilated patients with COVID-19 infection included in the French COVID-19 cohort and treated with lopinavir/ritonavir were included. Lopinavir/ritonavir combination was administered using the usual adult HIV dose regimen (400/100 mg q12h, oral solution through a nasogastric tube). A half-dose reduction to 400/100 mg q24h was proposed if lopinavir Ctrough was >8000 ng/mL, the upper limit considered as toxic and reported in HIV-infected patients. Lopinavir and ritonavir pharmacokinetic parameters were determined after an intensive pharmacokinetic analysis. Biological markers of inflammation and liver/kidney function were monitored. RESULTS: Plasma concentrations of lopinavir and ritonavir were first assessed in eight patients treated with lopinavir/ritonavir. Median (IQR) lopinavir Ctrough reached 27 908 ng/mL (15 928-32 627). After the dose reduction to 400/100 mg q24h, lopinavir/ritonavir pharmacokinetic parameters were assessed in nine patients. Lopinavir Ctrough decreased to 22 974 ng/mL (21 394-32 735). CONCLUSIONS: In mechanically ventilated patients with severe COVID-19 infections, the oral administration of lopinavir/ritonavir elicited plasma exposure of lopinavir more than 6-fold the upper usual expected range. However, it remains difficult to safely recommend its dose reduction without compromising the benefit of the antiviral strategy, and careful pharmacokinetic and toxicity monitoring are needed.

Long-term stability of an infusion containing paracetamol, alizapride, ketorolac and tramadol in glass bottles at 5±3°C.

Background and objective: Infusion containing paracetamol, alizapride, ketorolac and tramadol is used after a general anaesthesia in order to limit pain, fever and nausea. Currently, these infusions are prepared according to demand in the anaesthesia unit, but the preparation in advance could improve quality of preparation and time management. The aim of this study was to investigate the long-term stability of this infusion in glass bottles at 5°C ± 3 °C. Method: Five bottles of infusion were stored at 5°C ± 3 °C for 60 days. A visual and microscope inspection were performed periodically to observe any particle appearance or colour change. pH and absorbance at three wavelengths were measured. The concentrations were measured by ultra-high performance liquid chromatography - diode array detection. Results: Multiple verifications were performed during the first 35 days and no crystal, impurity or colour change were observed. At the next time point (42nd day), crystals were visible to the naked eye. pH and absorbance at 350 nm and 550 nm were stable. A slight increase in the absorbance at 410 nm was observed during the study, suggesting that a degradation product could be formed and absorb at this wavelength. The infusion was considered chemically stable while the lower one-sided prediction limit at 95% remains superior to 90% of the initial concentration. Concentration measurements demonstrated that ketorolac and alizapride remained stable in the infusion for 35 days. The stability of tramadol was 28 days. However, degradation of paracetamol was much faster given that concentration has fallen below 90% of the initial concentration after 7 days. Conclusion: Infusion of paracetamol, alizapride, ketorolac and tramadol remains stable for 7 days in glass bottles at 5°C ± 3 °C and could be prepared in advance with these storage conditions.

Long-term stability of ready-to-use norepinephrine solution at 0.2 and 0.5 mg/mL.

Objectives: Norepinephrine is a vasopressor frequently administered after dilution to treat hypotension and shocks in intensive care units. The stability of norepinephrine is known to be highly sensitive to storage conditions. Moreover, medication errors linked to the dilution step are frequent and may be deleterious for critically-ill patients, especially in intensive care units. This study aimed to evaluate the stability of ready-to-use diluted norepinephrine solutions prepared at two target concentrations (0.2 and 0.5 mg/mL), according to the summary of product characteristics, and stored for 365 days in two containers: AT-closed cyclic olefin copolymer vials, and polypropylene syringes. Methods: A fast reversed-phase liquid chromatography method coupled with an ultra-violet detector was developed to assess the chemical stability of norepinephrine solutions. Validation was conducted according to the linearity of the calibration ranges, selectivity, sensitivity, accuracy and precision. Dosage, sub-visible particle contamination, pH monitoring and sterility assays were performed. Chemical stability was maintained if the measured concentration respected the lower limit of 90% of the initial concentration. Containers were stored at -20±5°C, +5±3°C and +25±2°C with 60±5% relative humidity in a dark closed enclosure. Results: Stability was successfully maintained for every concentration and container tested when stored at -20±5°C and +5±3°C. In these storage conditions, particle contamination, pH monitoring and sterility assay respected the required criteria. Chemical degradation and colouring of solutions appeared before the end of the 1 year study period for most norepinephrine solutions stored at room temperature. Conclusions: Ready-to-use solutions containing 0.2 and 0.5 mg/mL norepinephrine in polypropylene syringes or cyclic olefin copolymer vials must be stored at refrigerated or frozen temperatures to obtain acceptable 1 year shelf-stability. Exposure to higher temperatures significantly decreases shelf-stability. Our study protocol for compounding polypropylene syringes and cyclic olefin copolymer vials containing norepinephrine is adapted to implementation in centralised intravenous additive services.

Formulation and Clinical Evaluation of Sodium Benzoate Oral Solution for the Treatment of Urea Cycle Disorders in Pediatric Patients.

BACKGROUND: Sodium benzoate, a common food preservative, is used in the treatment of patients with urea cycle disorders (UCDs) as it stimulates ammonia removal by a non-urea cycle-based pathway. Despite its use in the clinical routine, no commercially available oral formulations currently exist. Liquid formulation is normally well accepted in pediatric age and allows precise dosage according to the children's needs. AIMS: (1) To prepare an oral sodium benzoate solution in different tastes and determine its stability, palatability, and tolerability and (2) to describe the long-term follow-up of two pediatric patients with UCDs treated with our formulation. METHODS: We prepared five oral solutions of sodium benzoate (200 mg/ml) by adding different flavoring agents. We measured drug concentration in the samples by high-performance liquid chromatography (HPLC). We evaluated palatability and tolerability with adult volunteers. Long-term drug compliance and metabolic control were appraised in two pediatric patients. RESULTS: All the oral solutions remained stable at room temperature along the 96-day test period, and they were well tolerated. The mint-flavored solution resulted the most palatable and preferred by adult volunteers. We report good drug compliance and good metabolic outcomes for both pediatric patients during the entire follow-up. CONCLUSIONS: Our study highlighted the stability and tolerability of flavored sodium benzoate oral solutions. These solutions were well accepted during a long-term follow-up and guaranteed a good metabolic control. Since taste attributes are critical to ensure acceptable medication adherence in the pediatric age, flavored liquid formulations of sodium benzoate may be an efficient strategy to achieve therapeutic outcomes in UCD pediatric patients.

Assessment of the stability of citrate-buffered flucloxacillin for injection when stored in two commercially available ambulatory elastomeric devices: INfusor LV (Baxter) and Accufuser (Woo Young Medical): a study compliant with the NHS Yellow Cover Document (YCD) requirements.

Objectives: To investigate the effect of pH and buffers on the degradation rate of flucloxacillin and to determine if flucloxacillin can be stabilised using a buffered diluent for up to 14 days when stored at 2°C-8°C including a 24-hour infusion period at 32°C in two elastomeric devices (Accufuser and INfusor LV) filled to 240 mL. Testing as per the NHS Pharmaceutical Quality Assurance Committee Yellow Cover Document (YCD) requirements. Methods: A validated stability indicating high-performance liquid chromatography method was used for assessing the stability of flucloxacillin diluted in 0.3% w/v citrate-buffered saline pH 7.0 when stored at 2°C-8°C in two ambulatory devices (Accufuser and INfusor LV). Flucloxacillin at 10 and 50 mg/mL diluted in 0.3% w/v citrate-buffered saline pH 7.0 to a final volume of 240 mL and stored at 2°C-8°C, including 24 hours at 32°C, was tested from two batches in replicate (n=3) at five time points for up to 14 days according to the requirements of the YCD. Results: Greater than 95% of the zero-time concentration of flucloxacillin at 10 and 50 mg/mL remained when stored at 2°C-8°C after 14 days including 24 hours at 32°C in both Accufuser and INfusor LV devices. Conclusions: Flucloxacillin sodium stability was improved, and complied with UK national standards, by using a diluent of 0.3% w/v citrate-buffered saline pH 7 in both Accufuser and INfusor LV ambulatory devices when filled to 240 mL. The data support assigning a shelf-life of up to 14 days (13 days stored at 2°C-8°C and 24 hours at 32°C). Flucloxacillin may now be used appropriately as a continuous 24-hour infusion in outpatient parenteral antimicrobial therapy services, providing further opportunity to avoid or shorten patient hospital stays, as well as support ideal antimicrobial stewardship principles.

Preoperative fasting - "nihil per os" a difficult myth to break down: a randomized controlled study.

INTRODUCTION: For several years the scientific anaesthesia societies declared a preoperative fast of 6 hours for solid foods and 2 hours for clear liquids before elective surgical interventions to be sufficient. The aim of this study is to identify the extent of the gap that exists between the preoperative fasting time required and that actually encountered in operating rooms. PATIENTS AND METHODS: The safety and clinical applicability of a reduction of the preoperative fasting time was investigated through the use of oral solutions enriched with maltodextrin and their effects on the pre- and postoperative well-being that this may have on patients who are candidates for elective abdominal surgery. The study was conducted in two successive phases (I and II) and patients divided into two groups (A and B). DISCUSSION: Clinical practice is slow to change, in fact, in our study the duration of fasting was an average of 19 hours for solids and 13 hours for liquids. The duration of the fasting did not show differences in the various surgical departments, demonstrating that it is a transversal practice and is not only limited to abdominal surgery in which the utility of fasting would theoretically be greater. Among Group patients A, the fasting time for liquids was about 9 hours. This shows that the time is certainly shorter but not much different when compared to the fasting time for liquids in group B which was on average 14 hours. It is important how difficult it is to achieve good compliance from patients when trying to reduce the time of preoperative fasting based on scientific evidence that is now well established. CONCLUSION: The use of carbohydrate-enriched drinks up to 2 hours after induction of anaesthesia appears to be a safe procedure. The use of these solutions reduces the catabolic response to surgery and contributes to maintaining a pre-operative state of well-being by reducing feelings of hunger and thirst and the state of preoperative anxiety.

Intravenous supplementation type and volume are associated with 1-year outcome and major complications in patients with chronic intestinal failure.

BACKGROUND AND AIM: No marker to categorise the severity of chronic intestinal failure (CIF) has been developed. A 1-year international survey was carried out to investigate whether the European Society for Clinical Nutrition and Metabolism clinical classification of CIF, based on the type and volume of the intravenous supplementation (IVS), could be an indicator of CIF severity. METHODS: At baseline, participating home parenteral nutrition (HPN) centres enrolled all adults with ongoing CIF due to non-malignant disease; demographic data, body mass index, CIF mechanism, underlying disease, HPN duration and IVS category were recorded for each patient. The type of IVS was classified as fluid and electrolyte alone (FE) or parenteral nutrition admixture (PN). The mean daily IVS volume, calculated on a weekly basis, was categorised as <1, 1-2, 2-3 and >3 L/day. The severity of CIF was determined by patient outcome (still on HPN, weaned from HPN, deceased) and the occurrence of major HPN/CIF-related complications: intestinal failure-associated liver disease (IFALD), catheter-related venous thrombosis and catheter-related bloodstream infection (CRBSI). RESULTS: Fifty-one HPN centres included 2194 patients. The analysis showed that both IVS type and volume were independently associated with the odds of weaning from HPN (significantly higher for PN <1 L/day than for FE and all PN >1 L/day), patients' death (lower for FE, p=0.079), presence of IFALD cholestasis/liver failure and occurrence of CRBSI (significantly higher for PN 2-3 and PN >3 L/day). CONCLUSIONS: The type and volume of IVS required by patients with CIF could be indicators to categorise the severity of CIF in both clinical practice and research protocols.

Compatibility of pentoxifylline and parenteral medications.

OBJECTIVE: To investigate the physical and chemical compatibility of pentoxifylline (PTX) with a range of parenteral medications used in neonatal intensive care. DESIGN: PTX and drug solutions were combined in glass vials, inspected for physical incompatibility and evaluated on the basis of PTX concentrations for chemical compatibility. RESULTS: No precipitation, colour change or turbidity was observed in any of the test mixtures. The PTX concentration was approximately 5.5% lower when combined with undiluted calcium gluconate injection (100 mg/mL). The PTX concentration ratios for all other combinations, including diluted calcium gluconate injection (50 mg/mL), were in the range of 99.5%-102%. CONCLUSION: In simulated Y-site conditions, PTX was found to be compatible with 15 parenteral medications and six total parenteral nutrition solutions. Based on PTX concentration tests, it would be prudent to avoid mixing PTX with undiluted calcium gluconate injection.

SIC-8000 versus hetastarch as a submucosal injection fluid for EMR: a randomized controlled trial.

BACKGROUND AND AIMS: Viscous solutions provide a superior submucosal cushion for EMR. SIC-8000 (Eleview; Aries Pharmaceuticals, La Jolla, Calif) is a commercially available U.S. Food and Drug Administration-approved solution, but hetastarch is also advocated. We performed a randomized trial comparing SIC-8000 with hetastarch as submucosal injection agents for colorectal EMR. METHODS: This was a single-center, double-blinded, randomized controlled trial performed at a tertiary referral center. Patients were referred to our center with flat or sessile lesions measuring ≥15 mm in size. The primary outcome measures were the Sydney resection quotient (SRQ) and the rate of en bloc resections. Secondary outcomes were total volume needed for a sufficient lift, number of resected pieces, and adverse events. RESULTS: There were 158 patients with 159 adenomas (SIC-8000, 84; hetastarch, 75) and 57 serrated lesions (SIC-8000, 30; hetastarch, 27). SRQ was significantly better in the SIC-8000 group compared with hetastarch group (9.3 vs 8.1, P = .001). There was no difference in the proportion of lesions with en bloc resections. The total volume of injectate was significantly lower with SIC-8000 (14.8 mL vs 20.6 mL, P = .038). CONCLUSIONS: SIC-8000 is superior to hetastarch for use during EMR in terms of SRQ and total volume needed, although the absolute differences were small. (Clinical trial registration number: NCT03350217.).