Explore the vast range of titles available.

Sildenafil is used to treat pulmonary hypertension in neonatal intensive care unit (NICU) settings. As multiple intravenous (IV) medications are co-administered in NICU settings, we sought to investigate the physicochemical compatibility of sildenafil with a range of IV drugs. Sildenafil 600 mcg/mL or 60 mcg/mL was mixed 1:1 with the secondary drug solution to simulate Y-site co-administration procedures. Physical compatibility was evaluated by visual observation against a black and white background and under polarized light for two hours for changes in colour, precipitation, haze and evolution of gas. Chemical compatibility was determined from sildenafil concentrations, using a validated, stability-indicating high-performance liquid chromatography assay. Sildenafil 600 mcg/mL was physicochemically compatible with 29 of the 45 drugs tested at ‘high-end’ clinical concentrations and physically incompatible with 16 drugs and six ‘2-in-1’ parenteral nutrition solutions. Sildenafil 600 mcg/mL was compatible with lower, clinically relevant concentrations of calcium gluconate, heparin and hydrocortisone. Aciclovir, amoxicillin, ampicillin, ibuprofen lysine, indometacin, phenobarbitone and rifampicin were incompatible with sildenafil 600 mcg/mL, however these IV medications were compatible with sildenafil 60 mcg/mL. Sildenafil 600 mcg/mL and 60 mcg/mL were incompatible with amphotericin, flucloxacillin, furosemide, ibuprofen, meropenem and sodium bicarbonate. Sildenafil compatibility with commonly used syringe filters was also investigated. Sildenafil solution was compatible with nylon syringe filters, however, absorption/adsorption loss occurred with polyethersulfone and cellulose ester filters.

An established procedure, including a validated, stability-indicating high-performance liquid chromatography (HPLC) assay was used for evaluating the physical and chemical compatibility of the PTX-drug combinations at room temperature. 3,4,6 Briefly, clear glass vials with impermeable lids were used for each combination of drugs and the respective control solutions: PTX solution and the test drug solution were combined 1:1 in each of the four vials; PTX solution was diluted 1:1 with 0.9% w/v sodium chloride injection (n = 4 vials) as the reference solution for the purposes of visual comparison and HPLC assay, and; The test drug solution was diluted 1:1 with the applicable diluent (n = 4 vials) for the purpose of visual comparison. TABLE 1 Ratio of pentoxifylline (PTX) concentration when combined with the test drug, compared to PTX standard solution (2.5 mg/ml) Drug Test concentration Diluent PTX ratio (%) 95% CI of the ratio Acyclovir (mg/ml) 5 D5W 99.5 98.9‒100.1 Alprostadil (µg/ml) † 10 NS 99.9 99.4‒100.5 Alprostadil (µg/ml) † 20 NS 99.9 99.5‒100.3 Amoxicillin (mg/ml) 100 WfI 95.8 95.0‒96.6 Ampicillin (mg/ml) 100 WfI 96.9 95.6‒98.2 Calcium gluconate (mg/ml) †‡ 100 U 99.7 99.3‒100.0 Cloxacillin (mg/ml) 100 WfI 100.1 99.1‒101.1 Dopamine (mg/ml) 1.6 NS 97.6 95.9‒99.2 Dopamine (mg/ml) 1.6 D5W 99.3 98.7‒100.7 Dopamine (mg/ml) † 7.2 NS 99.2 98.7‒99.7 Dopamine (mg/ml) † 7 D5W 99.2 99.0‒99.4 Epinephrine (µg/ml) † 25 D5W 99.8 99.1‒100.4 Epinephrine (µg/ml) † 50 D5W 99.5 98.8‒100.1 Fentanyl (µg/ml) 5 D5W 100.0 98.7‒101.3 Fentanyl (µg/ml) 25 D5W 99.2 97.4‒101.0 Fentanyl (µg/ml) 50 U 100.1 99.6‒100.6 Fluconazole (mg/ml) ‡ 2 NS 99.4 98.8‒100.1 Furosemide (mg/ml) † 1 NS 100.0 99.7‒100.3 Furosemide (mg/ml) † 1 D5W 99.6 99.2‒100.0 Hydrocortisone (mg/ml) 2 NS 99.2 97.9‒100.5 Ibuprofen lysine (mg/ml) 4 NS 99.3 98.9‒99.8 Ibuprofen lysine (mg/ml) 4 D5W 100.4 99.1‒101.8 Midazolam (µg/ml) 120 D5W 99.4 98.6‒100.2 Midazolam (µg/ml) 120 D10 99.1 98.0‒100.2 Midazolam (µg/ml) 500 D5W 99.8 99.5‒100.1 Midazolam (µg/ml) ‡ 500 D10 99.7 99.5‒99.9 Midazolam (mg/ml) † 1 U 99.7 99.4‒100.1 Midazolam (mg/ml) †§ 1 NS 99.0 97.5‒100.5 Midazolam (mg/ml) †§ 1 D5W 99.8 99.3‒100.4 Milrinone (µg/ml) 200 NS 99.3 98.5‒100.1 Milrinone (µg/ml) 200 D5W 100.0 99.0‒101.0 Milrinone (µg/ml) † 400 NS 100.2 99.2‒101.3 Milrinone (µg/ml) †‡ 400 D5W 100.1 99.7‒100.5 Morphine hydrochloride (µg/ml) 200 NS 99.2 98.8‒99.7 Morphine hydrochloride (µg/ml) 200 D10 97.9 97.2‒98.5 Morphine hydrochloride (µg/ml) † 500 NS 99.9 99.2‒100.6 Morphine hydrochloride (µg/ml) † 500 D5W 99.4 98.8‒100.0 Morphine hydrochloride (µg/ml) † 500 D10 100.3 99.8‒100.7 Morphine sulfate (µg/ml) 200 NS 98.3 97.1‒99.6 Morphine sulfate (µg/ml) ‡ 200 D10 100.4 99.8‒101.0 Morphine sulfate (µg/ml) † 500 NS 100.3 100.0‒100.5 Morphine sulfate (µg/ml) † 500 D5W 100.2 99.8‒100.6 Morphine sulfate (µg/ml) † 500 D10 100.9 99.7‒102.1 Norepinephrine (µg/ml) ‡ 12 D5W 99.7 99.1‒100.2 Norepinephrine (µg/ml) † 64 D5W 100.1 99.5‒100.6 Norepinephrine (µg/ml) 12 NS 99.5 98.3‒100.7 Norepinephrine (µg/ml) † 64 NS 99.3 98.7‒100.0 Phenobarbitone (mg/ml) 20 NS 99.8 99.2‒100.4 Phenobarbitone (mg/ml) 20 D5W 99.9 99.1‒100.7 Piperacillin/tazobactam (mg/ml) 80 D5W 100.2 99.9‒100.5 Piperacillin/tazobactam (mg/ml) 200 WfI 100.5 99.6‒101.5 Results in bold indicate a statistically significant difference, whereby the 95% CI of the ratio did not span 100% (t-test). Abbreviations: CI, confidence interval; D5W, 5% w/v glucose injection; D10, 10% w/v glucose injection; NS, 0.9% w/v sodium chloride injection; PTX, pentoxifylline; U, undiluted; WfI, water for injection. †Duration of mixture contact time = 2 h (contact time for all other combinations = 1 h). ‡n ≥ 8 (all other combinations n = 4). §Midazolam 5 mg/ml diluted with NS/D5W; all other combinations were dilutions of midazolam 1 mg/ml injection. ¶Pentoxifylline injection was diluted in 0.9% w/v sodium chloride injection to a final concentration of 5 mg/ml to combine with the test drug solution. Dilution in 10% w/v glucose or 0.9% w/v sodium chloride showed modest reductions in concentration ratios (1%‒2% compared to control) and most likely presents no clinically significant risk when morphine is co-administered via Y-site with PTX injection for up to 1 h. 3,4 A confounding result in our current study was the unequivocal compatibility of undiluted calcium gluconate injection (100 mg/ml) with PTX injection (Table 1).

Our objective was to establish and test a machine learning‐based screening process that would be applicable to systematic reviews in pharmaceutical sciences. We used the SPIDER (Sample, Phenomenon of Interest, Design, Evaluation, Research type) model, a broad search strategy, and a machine learning tool (Research Screener) to identify relevant references related to y‐site compatibility of 95 intravenous drugs used in neonatal intensive care settings. Two independent reviewers conducted pilot studies, including manual screening and evaluation of Research Screener, and used the kappa‐coefficient for inter‐reviewer reliability. After initial deduplication of the search strategy results, 27 597 references were available for screening. Research Screener excluded 1735 references, including 451 duplicate titles and 1269 reports with no /title, which were manually screened. The remainder (25 862) were subject to the machine learning screening process. All eligible articles for the systematic review were extracted from <10% of the references available for screening. Moderate inter‐reviewer reliability was achieved, with kappa‐coefficient ≥0.75. Overall, 324 references were subject to full‐text reading and 118 were deemed relevant for the systematic review. Our study showed that a broad search strategy to optimize the literature captured for systematic reviews can be efficiently screened by the semi‐automated machine learning tool, Research Screener. Overview of systematic review search, screening and selection process.

The HPLC peak area values obtained with and without filtration were compared and data reported as per cent recovery: %Recovery=100×PTX(filtered)peakareaPTX(unfiltered)peakarea Nylon and polyether sulfone (syringe and inline) filters showed a PTX recovery >98% in all millilitre portions of the filtrate, when PTX was diluted in 0.9% w/v sodium chloride injection (figure 1). [...]our data indicate that PTX injection (5 mg/mL) is compatible with filter membranes commonly used in clinical settings, with <5% absorption/adsorption loss in each of four successive millilitre portions passed through the filters tested in the present study. Contributors All authors contributed to the study design, interpretation of data and manuscript preparation.

Purpose To investigate the physicochemical compatibility of caffeine citrate and caffeine base injections with 43 secondary intravenous (IV) drugs used in Neonatal Intensive Care Unit (NICU) settings. Methods Caffeine citrate (20 mg/mL or 10 mg/mL) or caffeine base injection (10 mg/mL) were mixed in a volume ratio of 1:1 with the secondary drug solution to simulate Y-site co-administration procedures in NICUs. Physical compatibility was evaluated based on visual observation for 2 h, against a black and white background and under polarised light, for changes in colour, precipitation, haze and evolution of gas. Chemical compatibility was determined from caffeine concentration measurements, using a validated high-performance liquid chromatography assay. Results Six of the 43 secondary drugs tested (aciclovir, amphotericin (liposomal), furosemide, hydrocortisone, ibuprofen and ibuprofen lysine) were physically incompatible with caffeine citrate undiluted injection (20 mg/mL), at their high-end, clinically relevant concentrations for NICU settings. However, when tested at lower concentrations, hydrocortisone (1 mg/mL) was physicochemically compatible, whereas furosemide (0.2 mg/mL) was physically incompatible with caffeine citrate. The six drugs which showed physical incompatibility with caffeine citrate 20 mg/mL injection were also physically incompatible with caffeine citrate 10 mg/mL solution. All 43 secondary drugs tested were physicochemically compatible with caffeine base injection. Conclusions Most secondary test drugs, except aciclovir, amphotericin (liposomal), furosemide, hydrocortisone, ibuprofen and ibuprofen lysine, were physicochemically compatible with caffeine citrate injection. Caffeine base injection was physicochemically compatible with all 43 test drugs tested.

ObjectiveTo investigate the physical and chemical compatibility of pentoxifylline (PTX) with a range of parenteral medications used in neonatal intensive care.DesignPTX and drug solutions were combined in glass vials, inspected for physical incompatibility and evaluated on the basis of PTX concentrations for chemical compatibility.ResultsNo 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%.ConclusionIn 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.

ObjectiveTo investigate the physical and chemical compatibility of pentoxifylline (PTX) with a wide range of parenteral medications used in the neonatal intensive care setting.DesignPTX and drug solutions were combined in glass phials and inspected visually for physical incompatibility. The chemical compatibility was evaluated on the basis of PTX concentrations.ResultsPrecipitation, colour change or turbidity was not visible in any of the test mixtures, indicating no observed physical incompatibility or apparent risk of blockage in narrow-bore intravenous tubing. The PTX concentration was approximately 2.5% and 4.5% lower when combined with dopamine and amoxicillin, respectively. The PTX concentration ratios for all other combinations were in the range of 99%–102%.ConclusionIn simulated Y-site conditions, physical compatibility testing of PTX and 30 parenteral medications revealed no evidence of precipitation. Based on PTX concentration tests, it could be prudent to avoid mixing PTX with dopamine or amoxicillin.

ObjectiveThe purpose of this study was to investigate the physical compatibility of intravenous lipid emulsions with parenteral medications used in neonatal intensive care.MethodsLipid emulsion and drug solutions were combined 1:1 in glass vials, inspected for physical incompatibility at 0, 1 and 2 hours, and assessed on the basis of lipid droplet size at 0 and 2 hours after mixing. Intravenous fluid controls (Water for Injection, sodium chloride 0.9% w/v, glucose 5% w/v), positive controls (gentamicin, albumin), negative controls (metronidazole, paracetamol, vancomycin) and 21 previously untested drug combinations were evaluated.ResultsNo phase separation, change in colour, gas production or other visible anomaly was observed. The between-run mean droplet diameter (MDD) for SMOFlipid20% alone (0.301±0.008 µm) was comparable to the lipid emulsion/intravenous fluid and lipid emulsion/drug solution combinations. In addition to gentamicin and albumin, caffeine citrate (20 mg/mL) was shown to be incompatible with the lipid emulsion. All other lipid:drug combinations were compatible, based on the MDD data.ConclusionIntravenous lipid emulsions were found to be compatible with 20 parenteral medications, including antimicrobial agents, inotropes, anti-inflammatory drugs and caffeine base, in simulated Y-site conditions. The lipid emulsion was incompatible with caffeine citrate injection.

SPLITTING the Newcastle Show and making the Speers Point Super Show created a rivalry between Newcastle and Lake Macquarie.

The utility of exome sequencing for most constitutional disorders in adults is unclear. In this study, exome sequencing in 3315 patients with chronic kidney disease yielded a genetic diagnosis in 307 cases (9.3%), with clinically important management implications for 89% of those reviewed.