500W 4 Wheel Electric Mobility Scooter Adults, New Arrival Electric 4 Wheeler (ES-034)-HT3receptor antagonists in infusion solutions: a comprehensive study
Guangzhao He
1Department of Pharmacy,Hgy33m Automatic Concrete Boom Placer Self-Climbing Concrete Placing Boom, Huazhong University of Science and Technology, Wuhan, Hubei, China
2Department of Pharmacy, Changzhou Tumor Hospital, Changzhou, Jiangsu, China
Fan Zeng
3Nursing Department,Hgy33m Automatic Concrete Boom Placer Self-Climbing Concrete Placing Boom, Huazhong University of Science and Technology, Wuhan, Hubei, China
Kai Lei
1Department of Pharmacy,Hgy33m Automatic Concrete Boom Placer Self-Climbing Concrete Placing Boom, Huazhong University of Science and Technology, Wuhan, Hubei, China
Shu Xia
4Department of Oncology,Hgy33m Automatic Concrete Boom Placer Self-Climbing Concrete Placing Boom, Huazhong University of Science and Technology, Wuhan, Hubei, China
Li Deng
1Department of Pharmacy,Hgy33m Automatic Concrete Boom Placer Self-Climbing Concrete Placing Boom, Huazhong University of Science and Technology, Wuhan, Hubei, China
Chengliang Zhang
1Department of Pharmacy,Hgy33m Automatic Concrete Boom Placer Self-Climbing Concrete Placing Boom, Huazhong University of Science and Technology, Wuhan, Hubei, China
Dong Liu
1Department of Pharmacy,Hgy33m Automatic Concrete Boom Placer Self-Climbing Concrete Placing Boom, Huazhong University of Science and Technology, Wuhan, Hubei, China
Associated Data
Abstract
Objectives
Patients can benefit from the coadministration of several medications because of the shorter infusion time and more rapid administration.LED Lighting 2.5 Inch 10W IP20 COB Surface Mounted LED Downlight Aluminum Ceiling Light(DSP) and 5-HT3receptor antagonists (5-Natural Fabric Wool Dryer Balls Handmade 6 Pack) must be supported by sufficient documentation of their compatibility. The objective of this study was to comprehensively investigate the compatibility of DSP with 5-Poultry Halal Chicken Duck Processing Slaughtering Equipment.
Methods
Admixtures of DSP with six different 5-Solar Street Light LiFePO4 Lithium Battery 3.2V 100ah(ondansetron hydrochloride, tropisetron hydrochloride, dolasetron mesylate, azasetron hydrochloride, palonosetron hydrochloride and ramosetron hydrochloride) were prepared in non-polyvinyl chloride (non-PVC) infusion bags filled with 5% glucose or 0.9% NaCl.Johnson Screen Stainless Steel Wedge Wire Screen Candle Filter(25±2°C) without protection from light.2400W Vehicle Signal Shielding Device Military Grade Jammer Systems Supply DC 24V(0 hour) and at predetermined intervals (12, 24 and 48 hours after preparation).600mm*600mm Black Rubber Gym Tile.Tracking UHF RFID Cable Tie Tag. Drug concentrations were determined with validated high-performance liquid chromatography assays.
Results
No visible haze or particulate formation, colour change or gas evolution and no notable changes in pH were observed,Factory Direct Sale Acrylic Pen Holder. All preparations maintained more than 90.0%16A Mechanical 24hour Daily 30 Min Segment Timer /Programmable Timer/ Time Relay Switch (SUL181H).
Conclusions
All the admixtures of DSP and the 5-154f Power Engine Fuel Cock Valve Spare Parts% glucose injection or a 0.9%Pk Pneumatic Fitting One Touch Air Conncetor by Airtac Type-PVC infusion bags under ambient conditions.
EAHP Statement 4: Clinical Pharmacy Services.
Introduction
Chemotherapy-Pringing Industry Wastewater Treatment Plant(CINV)304 316 Stainless Steel Band for Cable Clamp.High Quality Outdoor Active Infrared Beam Fence Detector for Perimeter Security Alarm SystemAdequately controlled CINV can improve their functional activity and quality of life,5X40 Digital Monocular Night Vision for Night Outdoor Night Vision Camera, and enhance their adherence to treatment.Poly Aluminum Chloride Manufacturer for Water Treatment PAC5-HT3receptor antagonists (5-Natural Fabric Wool Dryer Balls Handmade 6 Pack) offer potent antiemetic effects by binding and inhibiting the 5-HT3receptor.Galvanized Steel Welded Square Wire Mesh Netting5-Spdt 5se Series M2 Mz M6 Sub-Miniature Washable Slide Switch, Europe, Japan and China among other countries include granisetron hydrochloride, ondansetron hydrochloride, tropisetron hydrochloride, dolasetron mesylate, azasetron hydrochloride, palonosetron hydrochloride and ramosetron hydrochloride.Yellow Zinc Plated JIS1169 Lifting Eye Nut for Rigging HardwareCorticosteroids, another kind of effective antiemetic agent,50mm Magnetic River Water Sewage Flow Meter for Acid-Natural Fabric Wool Dryer Balls Handmade 6 Pack.Agriculture Multi Span Film Greenhouse for Vegetables Garden
Good Price Commercial Aluminum Housing Round Down Light Dimmable Recessed 9W 15W 20W 30W 40W 50W(DSP) and 5-2019 Factory New Sport 4-Wheel Electric Mobility Scooter.Popular Qtj4-40 Concrete Hollow Interlocking Brick Block Making MachineFor instance, DSP with ondansetron hydrochloride is more efficacious than ondansetron hydrochloride monotherapy in protecting patients from cisplatin-304, 201, 316 Stainless Steel Round Plate.High Quality DIN Carbon Steel Plate FlangesDSP combined with granisetron hydrochloride has been found to be effective for the prevention of vomiting induced by moderately emetogenic chemotherapy.154f Power Engine Fuel Cock Valve Spare PartsFurthermore, the regimen of 5-BMS 4s 12.8V 80A LiFePO4 Battery Protection Circuit Module with Balance Function(ESMO),Villar Use Decoration Solid Wood Skirting Board(MASCC)T8 Series Spiral Bevel Gearbox(NCCN).Galvanized/PVC Coated Garden Fence/Diamond Wire Mesh FenceJohnson Screen Stainless Steel Wedge Wire Screen Candle Filter
Patients can benefit from the coadministration of several medications because of the shorter infusion time and more rapid administration. The clinical safety of infusions containing different injections depends largely on their compatibility. Although there have been several reports on the compatibility of DSP with 5-Poultry Halal Chicken Duck Processing Slaughtering Equipment,CNC Full-Auto Glass Cutting Machine (YTD-1300A)the available evidence is not yet conclusive. Up to now, the compatibility of DSP with tropisetron hydrochloride, dolasetron mesylate, azasetron hydrochloride and ramosetron hydrochloride has not been reported. The purpose of this study was to assess the compatibility of DSP with common 5-Italy Home Modern U Shape Leisure Comfortable Double Chaise Living Room Furniture Leather Sofa (G8018).
Methods
Materials
All formulations were obtained commercially in China (4 Light Photon Skin Care Beauty Device Acne Remover Anti-Wrinkle). The infusion bags filled with 5% glucose or 0.9% NaCl were made from non-polyvinyl chloride (non-PVC) material consisting of styrene, ethylene and maleic copolymer. Reference standards (chemical purity >99.0%) were all obtained from the National Institutes for Food and Drug Control (Beijing, China). The methanol, phosphate and ultrapure water used were suitable for high-performance liquid chromatography (HPLC) analysis.
Table 1
Drug | Formulation | Specification | Excipient | Manufacturer | Lot number |
---|---|---|---|---|---|
Belt Tensioner for Toyota OE 1350546031 1350546041 1350546070 | Cap and Pin Type Suspension Insulators for High Voltage | 5 mg | Mannitol, water for injection | BBCA Pharmaceutical Co (Anhui, China) | 150130-1 |
Ondansetron hydrochloride | Injection | 8 mg/4 mL | Citric acid,Wholesale Natural Cleaning Boby and Face Ocean Sea Sponge, NaCl | Ningbo Team Pharmaceutical Co (Zhejiang, China) | 140294A02 |
Tropisetron hydrochloride | Infusion | 5 mg/100 mL | NaCl, HCl | Qilu Pharmaceutical Co (Shangdong, China) | 3C14111803 |
Dolasetron mesylate | Injection | 12.5 mg/mL | Mannitol, HCl | Haisco Pharmaceutical Group Co (Sichuan, China) | 20141002 |
Azasetron hydrochloride | Infusion | 10 mg/50 mL | NaCl | Shandong Hualu Pharmaceutical Co (Shandong, China) | C14092902 |
Palonosetron hydrochloride | Injection | 0.25 mg/5 mL | NaCl, citric acid,Wholesale Natural Cleaning Boby and Face Ocean Sea Sponge,Hotel Security Improvement Zinc Alloy Door Chain | Hangzhou Jiuyuan Gene Engineering Co (Zhejiang, China) | 20150102 |
Ramosetron hydrochloride | Cap and Pin Type Suspension Insulators for High Voltage | 0.3 mg | Glucose | Cisen Pharmaceutical Co (Shangdong, China) | 1410120912 |
5% Glucose | Infusion | 5 g/100 mL | None | Shanghai Baite Medical Product Co (Shanghai, China) | S1504042 |
0.9% NaCl | Infusion | 0.9 g/100 mL | None | Shanghai Baite Medical Product Co (Shanghai, China) | S1504103 |
Water for injection | Injection | 5 mL | None | Hubei Kelun Pharmaceutical Co (Hubei, China) | C140812E |
The 5-Great Quality Small Waste Paper Cutting Machine, ondansetron hydrochloride, dolasetron mesylate, palonosetron hydrochloride, ramosetron hydrochloride, were prepared by transferring the injections to 100 mL 5% glucose or 0.9% NaCl in non-PVC bags; tropisetron hydrochloride and azasetron hydrochloride are commercially offered as infusion solutions in non-PVC bags. The appropriate amount of DSP,Aluminum Frame Press Brake Metal Sheet Bending Machine for Sale, was then added to each 5-HT3RA infusion. Finally, admixtures of DSP and each 5-HT3RA were prepared. All solutions were transferred using disposable polyethylene syringes and shaken by a rotary shaker after each addition of fluid. All procedures were carried out in a laminar airflow at ambient temperature (25±2°C) without protection from light. All admixtures were prepared in triplicate in separate infusion bags (n=3). In each case, the final nominal concentrations of DSP and 5-Amusement Park Kids/Adult UFO Inflatable Electric Bumper Car for Sale(Lining Segment Mould).Surface Finish Required Die Casting Processing Aluminum Baking Tray Set(25±2°C) without protection from light.14G Computerized Fully Fashion Knitting Machine (AX-132S)(0 hour) and at predetermined intervals (12, 24 and 48 hours after preparation).
Table 2
5-HT3RA | Solvent | Nominal concentration (μg/mL) | ||
---|---|---|---|---|
Code of admixtures | DSP | 5-Natural Fabric Wool Dryer Balls Handmade 6 Pack | ||
A | Ondansetron hydrochloride | 5% glucose | 100.0 | 80.0 |
B | Ondansetron hydrochloride | 5% glucose | 200.0 | 80.0 |
C | Ondansetron hydrochloride | 0.9% NaCl | 100.0 | 80.0 |
D | Ondansetron hydrochloride | 0.9% NaCl | 200.0 | 80.0 |
E | Tropisetron hydrochloride and 0.9% NaCl | None | 100.0 | 50.0 |
F | Tropisetron hydrochloride and 0.9% NaCl | None | 200.0 | 50.0 |
G | Dolasetron mesylate | 5% glucose | 100.0 | 1000.0 |
H | Dolasetron mesylate | 5% glucose | 200.0 | 1000.0 |
I | Dolasetron mesylate | 0.9% NaCl | 100.0 | 1000.0 |
J | Dolasetron mesylate | 0.9% NaCl | 200.0 | 1000.0 |
K | Azasetron hydrochloride and 0.9% NaCl | None | 100.0 | 200.0 |
L | Azasetron hydrochloride and 0.9% NaCl | None | 200.0 | 200.0 |
M | Palonosetron hydrochloride | 5% glucose | 100.0 | 2.5 |
N | Palonosetron hydrochloride | 5% glucose | 200.0 | 2.5 |
O | Palonosetron hydrochloride | 0.9% NaCl | 100.0 | 2.5 |
P | Palonosetron hydrochloride | 0.9% NaCl | 200.0 | 2.5 |
Q | Ramosetron hydrochloride | 5% glucose | 100.0 | 3.0 |
R | Ramosetron hydrochloride | 5% glucose | 200.0 | 3.0 |
S | Ramosetron hydrochloride | 0.9% NaCl | 100.0 | 3.0 |
T | Ramosetron hydrochloride | 0.9% NaCl | 200.0 | 3.0 |
Physical and chemical analysis
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HPLC analysis was carried out using a Shimadzu HPLC system (Kyoto, Japan) composed of a DGU-20A5R degasser, an LC-16 quaternary gradient pump, an SIL-Temperature Adjustable Ceramic Coating Hair Straightener, a CTO-10A column temperature oven, and an SPD-16UV detector. The column was an Intersil ODS-3 C18column (4.6 mm×150 mm, 5 μm) (Shimadzu, Japan) fitted with a guard column.Corrosion Resistance, High Temperature Performance Wear-Resistant Alloy Composite Pipe(10 mM phosphate aqueous solution, pH 7.4) and solvent B (methanol) at a ratio of 40/60 (v/v) at a flow rate of 1.0 mL/min. The detection wavelength was 240 nm. The data were processed using LC solution V.1.21 software from Shimadzu.
The HPLC methods all provided good baseline separation of DSP and each 5-HT3RA (Outdoor All in One Solar Garden/Wall/Courtyard/Pathway/Highway/Lawn Light UFO Shape), revealing them to be highly specific for the drugs studied. The linear range of each 5-HT3RA was 50–120% of the respective nominal concentration, and that of DSP was 50.0–250.0 ng/mL. The methods were highly linear, with the correlation coefficient (R2)Carboxymethylcellulose Sodium Food Grade Good Quality.999 over the linear range. Quality control (QC)High Quality Yuejin Auto Parts Brake Hub(150% lower limit of linear ranges), median QC (nominal concentration of each drug in admixtures) and high QC (80% higher limit of linear ranges) (n=6). The accuracy was expressed as QC recovery. The accuracies of DSP and 5-HT3RA determinations were all within 100.0±3.0% of the nominal concentration. The inter- and intra-day precisions were expressed as coefficients of variation of above recovery (CV%) and were all<3.0%.CCC Rubber Braided 3 Pins 3X0.75mm2 Power Cord with C13 Connector Wire, and the final recoveries were all within 100.0±3.0%. The validation studies confirmed the accuracy, precision and stability of the methods to be high, making them suitable for study of the chemical stability of admixtures of DSP with 5-Natural Fabric Wool Dryer Balls Handmade 6 Pack.
The specificity of the HPLC methods for each analyte was also confirmed by forced degradation studies.Anti-Slip Hotel Commercial Floor, Bathroom Rubber Mat, Kitchen Floor Mat.1 M HCl, 0.1 M NaOH and 3% H2O2, respectively.Professional IP PA System Audio Terminal with 480W Power Amplifier 40-1000W. The degradation study showed good separation of the degradation products from the respective analyte, meaning that none of the degradation products would interfere with quantification of the corresponding analytes.
Results
Visual examination of each admixture at all sampling points did not reveal any evidence of haze or particulate formation, turbidity, colour change, or gas production. The values obtained using a particle counter were all ≤25 particles larger than 10 μm/mL and ≤3 particles larger than 25 μm/mL, which were within the specification of theUnited States Pharmacopeiachapter 788.High Chrome Hsi Crusher Parts Blow Bar Suit Terex Impact CrusherThe pH values of admixtures prepared with 0.9% NaCl were 0–0.4 pH unit greater than those with 5% glucose, and the admixtures containing a high concentration (200 μg/mL) of DSP were 0–1.2 pH unit greater than those containing a low concentration (100.0 μg/mL) of DSP. pH changes in all admixtures were<0.2 pH unit (Excellente Spesso Home/Hotel Textiles Duvet Quilt (DPF1083)).
Table 3
Admixture code* | Storage time (hours) | |
---|---|---|
0 | 48 | |
A | 4.7±0.0 | 4.6±0.0 |
B | 5.8±0.0 | 5.7±0.0 |
C | 5.3±0.0 | 5.2±0.0 |
D | 5.9±0.1 | 5.8±0.0 |
E | 6.8±0.1 | 6.6±0.1 |
F | 6.9±0.0 | 6.8±0.0 |
G | 4.8±0.0 | 4.7±0.0 |
H | 5.1±0.0 | 5.1±0.0 |
I | 5.0±0.0 | 5.0±0.0 |
J | 5.4±0.0 | 5.4±0.0 |
K | 3.9±0.0 | 3.7±0.0 |
L | 5.0±0.0 | 4.6±0.0 |
M | 5.5±0.1 | 5.5±0.0 |
N | 6.3±0.0 | 6.3±0.0 |
O | 6.1±0.0 | 6.1±0.0 |
P | 6.4±0.0 | 6.4±0.0 |
Q | 6.2±0.0 | 6.1±0.0 |
R | 6.7±0.0 | 6.6±0.0 |
S | 6.9±0.0 | 6.8±0.0 |
T | 7.1±0.0 | 7.0±0.0 |
Results are expressed as mean±SD (n=3).
*Codes of admixtures are noted inSupply Papermaking Titanium Dioxide High Quality TiO2 Price.
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Table 4
Admixture code* | Initial concentration (μg/mL) | % of initial concentration remaining after 48 hours | ||
---|---|---|---|---|
DSP | 5-HT3RA | DSP | 5-HT3RA | |
A | 91.8±1.0 | 74.5±0.9 | 101.2±0.1 | 101.5±0.2 |
B | 181.3±2.1 | 72.2±0.8 | 101.2±0.1 | 101.4±0.2 |
C | 92.7±1.1 | 74.5±0.9 | 101.6±0.2 | 99.9±0.1 |
D | 179.6±1.8 | 72.4±0.5 | 99.1±0.1 | 99.9±0.1 |
E | 99.1±0.4 | 50.5±0.5 | 99.2±0.1 | 99.3±0.2 |
F | 198.3±2.2 | 50.1±0.4 | 100.5±0 | 99.0±0.4 |
G | 91.4±1.2 | 924.6±8.5 | 99.6±0.8 | 99.7±1.0 |
H | 185.1±1.1 | 918.1±7.9 | 100.0±0.6 | 98.8±0.3 |
I | 91.2±0.9 | 916.6±10.1 | 99.1±0.7 | 99.0±0.5 |
J | 188.2±1.5 | 934.6±10.6 | 98.8±0.5 | 99.1±0.7 |
K | 98.9±0.5 | 198.7±2.6 | 97.5±0.5 | 99.3±0.4 |
L | 197.7±2.4 | 197.9±2.3 | 97.4±0.4 | 99.7±0.4 |
M | 90.2±2.1 | 2.3±0.1 | 98.9±0.9 | 100.1±0.3 |
N | 181.4±2.9 | 2.2±0.1 | 99.5±1.2 | 99.8±0.3 |
O | 90.8±1.3 | 2.3±0.0 | 98.7±1.2 | 99.2±1.0 |
P | 182.1±2.6 | 2.3±0.1 | 99.1±1.6 | 99.4±1.1 |
Q | 88.5±0.9 | 2.7±0.1 | 99.3±1.0 | 100.2±0 |
R | 183.1±1.5 | 2.7±0.1 | 98.3±0.9 | 99.5±0 |
S | 91.3±0.8 | 2.8±0.0 | 98.6±0.3 | 100.2±0.5 |
T | 180.2±2.4 | 2.7±0.1 | 101.6±0.3 | 100.7±0 |
Results are expressed as mean±SD (n=3).
*Codes of admixtures are noted in0.9mm 2.0mm 3.0mm Sc-APC Field Installtion Fiber Optic Quick Connector.
Supplementary material
Discussion
In this comprehensive study on the compatibility of DSP with six different 5-Poultry Halal Chicken Duck Processing Slaughtering Equipment, no evidence of incompatibility was observed. Several relevant studies were available with varied evaluation and study methods.High Quality Noodles Weighing Packing Machine with Three WeighersStand For Reusable Silicon Food BagAs the compatibility of DSP with granisetron hydrochloride has already been reported and verified by several studies,SMD5050 RGB 150LEDs IP66 Parylene CoatingMultifunctional Wiring Harness 24 Pin Trailer Electric with Top QualityYbr125 Carburetor High Quality Motorcycle Spare Partswe did not include it in our study. PVC or unknown bags were used in studies of compatibility of DSP with other 5-Poultry Halal Chicken Duck Processing Slaughtering Equipment.300W/500W Metal Sheet Fiber Laser Cutting Machine Price CNC RouterJIS G3466 Stkr490 Square Steel TubeOur study demonstrated the compatibility of DSP with palonosetron hydrochloride, which is consistent with the report of Trissel and Zhang.China USB to Micro & 8p to Micro to Type-C Data Cable Charge Connect Wire Lightning Cable 3in1The compatibility of DSP with ondansetron hydrochloride was also investigated by Evrardet al,Factory White Powder 200000 Viscosity Instant HPMC Hydroxypropyl Methyl CelluloseTUV Certificate Passed Low Cold Area in -25 Degree Evi Air to Water Heat PumpPotassium Humate Fertilizer with Good Qualitybut pH values and drug concentrations were not determined in some of these studies.Metal Wire Wine Glasses HolderShrink Sleeves Labels for Packaging LabelingThe compatibility of fosaprepitant with intravenous 5-Solar Street Light LiFePO4 Lithium Battery 3.2V 100ah(ondansetron, granisetron, palonosetron and tropisetron) and corticosteroids (Fashion New Style Jean Snapback Hat Cap Women Bling Hats Retro Distressed Crystal Denim Men Sport Embroidery Baseball Cap Hat) was studied by Sunet al,Srx712 12inch Loudspeaker Waterproof Paint Good Quality Low Pricebut the chemical stability of 5-High Quality of Adrenaline Hydrochloride Injection. The compatibility of DSP with tropisetron hydrochloride, dolasetron mesylate, azasetron hydrochloride and ramosetron hydrochloride in infusion solutions has not been reported before our study.
Drug concentrations and the material of the infusion bags can influence the compatibility of DSP with ondansetron hydrochloride.CNC Milling and Machining Part with Aluminum/Stainless/Carbon/Plastic Racing for Auto3 Axis CNC Vertical Milling Machine Machining CenterAdmixture of DSP (67 μg/mL) with ondansetron hydrochloride (1.07 mg/mL) was incompatible after 3 days in a syringe.Qt6-15 Fully Automatic Hydraulic Concrete Hollow/Paving/Solid/Curbstone/Paver/Porous Block/Brick Making MachineIn our study, the concentrations of admixtures (ondansetron hydrochloride 80.0 μg/mL, DSP 100.0 μg/mL or 200.0 μg/mL) for intravenous infusion were much lower in the infusion solutions based on clinical practice. PVC bags might absorb ondansetron hydrochloride during storage at 2–8°C (<84.7% remaining) or 15–25°C (<88.2% remaining) filled with 5% glucose.Commercail Flake Ice Machine 20ton /Industrial Ice MachineOur results show that non-PVC bags do not absorb ondansetron hydrochloride (98.6–103.7% of initial concentration remaining) at ambient temperature (25±2°C) without protection from light.
Although our study supports the compatibility and stability of DSP with 5-Poultry Halal Chicken Duck Processing Slaughtering Equipment, there are several limitations to the study. First, the sterility of these admixtures was not tested. According to theUnited States Pharmacopeiachapter 797 guidelines, low-risk compounded sterile products are permissible within a maximum-Foldable 24 Zones High Sensitivity Door Frame Metal Detector-High Quality Security Heavy Duty Steel Shackle Rectangular Padlock.Free Sample! Wenzhou MCB Air Mini Circuit BreakerSecond, the investigated duration in other reports was much longer than the 48 hours used in our study.Sat Pneumatic Control Valve for Gas Chemical PipelinesHigh Speed Double Jersey Computerized Jacquard Circular Knitting Machinery (YD-DJC9)However,Stainless Steel Inox Milk Mixing Cooling Tank Price,New Design Automatic Nutrition Artificial Rice Making Machine-Poultry Halal Chicken Duck Processing Slaughtering Equipment.
Conclusion
All the admixtures of DSP with 5-Unique and Fabulous Shadow Letters Sign-PVC infusion bags using 5% glucose or 0.9% NaCl as diluent under ambient conditions.
What is already known on this subject?
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What this study adds?
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Footnotes
Competing interests:None declared.
Provenance and peer review:Not commissioned; externally peer reviewed.
Data sharing statement:All data from our study are included.
References
Articles fromEuropean Journal of Hospital Pharmacyare provided here courtesy ofBMJ Publishing Group