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Objective We utilized a computerized order entry system–integrated function referred to as “void” to identify erroneous orders (ie, a “void” order). Using voided orders, we aimed to (1) identify the nature and characteristics of medication ordering errors, (2) investigate the risk factors associated with medication ordering errors, and (3) explore potential strategies to mitigate these risk factors. Materials and Methods We collected data on voided orders using clinician interviews and surveys within 24 hours of the voided order and using chart reviews. Interviews were informed by the human factors–based SEIPS (Systems Engineering Initiative for Patient Safety) model to characterize the work systems–based risk factors contributing to ordering errors; chart reviews were used to establish whether a voided order was a true medication ordering error and ascertain its impact on patient safety. Results During the 16-month study period (August 25, 2017, to December 31, 2018), 1074 medication orders were voided; 842 voided orders were true medication errors (positive predictive value = 78.3 ± 1.2%). A total of 22% (n = 190) of the medication ordering errors reached the patient, with at least a single administration, without causing patient harm. Interviews were conducted on 355 voided orders (33% response). Errors were not uniquely associated with a single risk factor, but the causal contributors of medication ordering errors were multifactorial, arising from a combination of technological-, cognitive-, environmental-, social-, and organizational-level factors. Conclusions The void function offers a practical, standardized method to create a rich database of medication ordering errors. We highlight implications for utilizing the void function for future research, practice and learning opportunities.

Clinical studies have shown that the rapid antidepressant effect of the glutamate N-methyl-D-aspartate receptor antagonist ketamine generally disappears within 1 week but can be maintained by repeated administration. Preclinical studies showed that a single ketamine injection immediately increases the firing and burst activity of norepinephrine (NE) neurons, but not that of serotonin (5-HT) neurons. It also enhances the population activity of dopamine (DA) neurons. In the present study, we investigated whether such alterations of monoamine neuronal firing are still present 1 day after a single injection, and whether they can be maintained by repeated injections.Rats received a single ketamine injection or 6 over 2 weeks and the firing activity of dorsal raphe nucleus 5-HT, locus coeruleus NE, and ventral tegmental area DA neurons was assessed.One day following a single injection of ketamine, there was no change in the firing activity of 5-HT, NE, or DA neurons. One day after repeated ketamine administration, however, there was a robust increase of the firing activity of NE neurons and an enhancement of burst and population activities of DA neurons, but still no change in firing parameters of 5-HT neurons. The increased activity of NE neurons was no longer present 3 days after the last injection, whereas that of DA neurons was still present. DA neurons were firing normally 7 days after repeated injections.These results imply that the enhanced activity of NE and DA neurons may play a significant role in the maintenance of the antidepressant action of ketamine.

Objective: Highly accepted animal models are of the greatest importance in studying drug-induced liver injury (DILI), especially for those induced by the traditional Chinese medicine-Polygonum multiflorum Thunb (Chinese name: He-Shou-Wu, PMT) because of the difficulties in successfully simulating an animal model that can match the characteristics shown in humans. This research aims to establish an early-warning animal model to investigate the potential mechanisms of DILI related to the toll-like receptor 4 (TLR4), and to verify the effectiveness of serum microRNA-122 as a candidate biomarker for DILI. Methods: 2 hours after LPS injection, rats were administrated with PMT for 7 consecutive days Qd. On the 2nd h, 14th h, 5th day and 8th day, serum samples were collected for an ALT/ALP test and TaqMan detection of the microRNA-122 expression. After weighing the organ to body ratio for each rat, liver samples were treated for histopathology observation and mTLR-4 detection by RT-PCR. Results: Comparing against a single administration with PMT, livers collected from animals pretreated with an LPS injection were injured to various extents and underwent hepatocyte degeneration. Meanwhile, the expression of liver mTLR4 and serum microRNA-122 increased significantly (p < 0.05). Conclusions: Activated by LPS, this rat model of DILI for PMT was established successfully and its potential association with TLR4 was established. Serum microRNA-122 might be used as a candidate biomarker for PMT-DILI.

Synovex Plus (SP) is a product that delivers 28 mg of estradiol benzoate (EB) and 200 mg of trenbolone acetate (TBA). We studied the impact of a polymeric, porous coating on SP implants (CSP) to prolong release of EB and TBA, and stimulate feedlot performance of feedlot cattle for an extended period. In an explant study, 30 steers were implanted with SP in one ear and CSP in the contralateral ear. Cattle (n = 6/d) were necropsied 40, 81, 120, 160, and 200 d after treatment, and remaining EB and TBA were quantifi ed. Linear regression of EB and TBA remaining as a function of time for each treatment were computed. Rates of EB and TBA depletion from SP were -0.1980 (r 2 = 0.9994) and -1.7073 mg/d (r 2 = 0.9644), respectively, and for CSP rates of EB and TBA depletion were -0.1049 (r 2 = 0.9123) and -0.9466 mg/d (r 2 = 0.9297), respectively. The effect of treatment on depletion rates of each analyte were signifi cant (P < 0.05). Data also showed EB and TBA were delivered from CSP at least 200 d but were delivered from SP about 120 d. Multisite trials with beef-type steers (4 sites) and heifers (4 sites) evaluated feedlot performance and carcass characteristics in response to a CSP implant or when sham implanted (SC). A randomized complete block design with 9 blocks and 2 treatments was used per site within animal gender. Across sites, steers (n = 342, BW = 297 kg) were fed fi nishing rations for 190 to 202 d (mean 198 d) and heifers (n = 342, BW = 289 kg) were fed fi nishing rations for 191 to 201 d (mean 198 d). Cattle were harvested and carcasses evaluated. Data were pooled across sites within gender for statistical analysis. Steers and heifers treated with CSP yielded greater (P ≤ 0.003) ADG, DMI, and G:F than SC steers and heifers. Mean BW differences between CSP and SC continued to increase throughout the study, indicating CSP stimulated growth of steers and heifers for 198 d. Mean carcass weights of CSP steers (P = 0.005) and heifers (P = 0.004) were greater than those of SP steers and heifers by 26.2 and 20.6 kg, respectively. The LM area was larger (P < 0.001) in CSP steers and heifers than SC cattle. Marbling decreased with CSP treatment (P ≤ 0.031), which caused reductions (P ≤ 0.006) in proportions of carcasses grading Prime or Choice. Evidence from these studies showed that a single administration of CSP increased feedlot cattle performance for at least 198 d, compared with SC, and may reduce the need to reimplant cattle.

Aims: The purpose of this study was to evaluate the effect of naltrexone treatment for 21 consecutive days on short-term memory in ethanol-preferring and non-preferring outbred rats. Methods: Ethanol preferring, non-preferring and control Wistar rats were treated with naltrexone (0.1 mg/kg intraperitoneally (i.p.)) for 21 consecutive days. Short-term memory was assessed by using an olfactory social recognition test. Results: A single administration of naltrexone (0.1 mg/kg i.p.) to non-ethanol-treated animals facilitated social memory, whereas the drug did not affect short-term memory in either group of chronically ethanol-treated rats. Multiple naltrexone treatment also lowered alcohol intake in ethanol-preferring rats. Conclusion: Naltrexone-ethanol interaction does not seem to produce any negative effect on the short-term memory in outbred rats.

We investigated the transfer of dietary bovine lactoferrin (LF) and its functional lactoferricin (LFcin) B-containing fragments to the portal blood of healthy adult rats by using several techniques. After a single administration of (125)I-labeled LF, radioactive bands were detected in autoradioluminograms of the portal blood, but similar bands were also observed after the administration of [(125)I]NaI. Although ovalbumin was detected by ELISA at 3-18 ng/ml in the portal blood plasma after an overnight administration, no LF was detected (or =1.5 ng/ml). The antibody-captured ovalbumin fragments, but not the LF fragments, were detected in the plasma by surface-enhanced laser desorption/ionization affinity mass spectrometry (SELDI affinity MS). We finally attempted to detect the LFcin B-containing fragments by SELDI affinity MS with on-chip LFcin B-conversion, but could not detect them (or =1 ng/ml) in the portal blood after the LF ingestion. The level of LF or its functional fragments transferred to the portal blood was therefore extremely low, if any.

Background and Purpose. Shoulder scales are often used to evaluate treatment efficacy, yet little is known about the psychometric properties of these scales. Only one scale has undergone psychometric scrutiny: the Shoulder Pain and Disability Index (SPADI). This study compared 2 shoulder measures—the University of California-Los Angeles (UCLA) Shoulder Scale and the Simple Shoulder Test (SST)—with the SPADI. Subjects. One hundred ninety-two patients with shoulder disorders were recruited from one physician's office to complete the self-report sections of the 3 scales. Methods. Cronbach alpha values and standard errors of measurement (SEM) were calculated for each of the multi-item subscales. Validity was examined through calculation of correlation coefficients among the 3 scales. Factor analysis was completed to assess the underlying constructs of the SPADI and the SST. Results. Cronbach alpha values ranged from .85 to .95. The SEM values for the multi-item scales ranged from 4.75 to 11.65. Evidence for validity to reflect function was indicated by the correlation between the SST and the SPADI disability subscale. The factor analysis of the SPADI revealed loading on 1 factor, whereas the SST loaded on 2 factors. Conclusion and Discussion. All scales demonstrated good internal consistency, suggesting that all items for each scale measure the same construct. However, the SEMs for all scales were high. Factor loading was inconsistent, suggesting that patients may not distinguish between pain and function.

Background: The subject matter of this study was to investigate, for the first time, the immediate-preventive effect of probiotics, composed of bacillus species, in a murine model of Campylobacter infection. Methods: An established model of Campylobacter infection in mice with a defined LD50 was utilized to assess the protective effect of probiotics. Results: The results obtained demonstrate that the level of animal protection, after a single administration of the new probiotics biosporin and subalin, reached 90-100% at LD50 and 80% at LD100. Conclusions: Such efficacy of probiotics is considered to be due to their high antagonistic activity against those pathogens registered in vitro. Antagonistic activity of other tested probiotics (bactisubtil and cereobiogen) to different cultures of Campylobacter was not manifested.

In earlier IVF programmes, subcutaneous buserelin (Suprefact, Hoechst) was initially administered three times per day (200 micrograms x 3); then twice daily (300 micrograms x 2). We now suggest that a single administration of 600 micrograms daily may be equally effective. In a preliminary study, 20 patients were selected on the basis of tubal or idiopathic infertility and received 0.6 ml buserelin subcutaneously once a day, beginning on day 1 or 2 of the cycle. A sufficient pituitary desensitization was obtained on day 10 in 75% of patients and on day 16 for 100% and the ongoing pregnancy rate was 35% per treatment cycle. A randomized study comparing the effect of 600 micrograms of buserelin administered in one (n = 50) or two injections (n = 46), has been carried out and indicates that the results in terms of the ovarian suppression and pregnancy rates, were similar. Therefore, this protocol represents a simplification of the treatment with buserelin.

In 1977, the Commission of the European Communities initiated an intercomparison study to determine the single administration oral LD50 value in rats of each of 5 chemicals with the aims of comparing experimentation technologies, determining the degree of variation in the results and the various parameters used to establish the LD50 value, and establishing a common protocol for the determination of the LD50 value. Sixty-five laboratories in 8 countries took part in the first study. The significant variation in protocol may have led to the large interlaboratory variation observed in the results. Therefore, participating laboratories carried out a second study using a common protocol, preceded by a pilot study. A total of 100 laboratories in 13 countries participated. A majority of results of the second study are currently being analyzed, and the indications are that the interlaboratory variation has been significantly reduced.

In therapeutic studies of the effectiveness of promin in either experimental or clinical tuberculosis, the drug has been administered for long periods. In the initial study of the influence of promin in combating experimental tuberculosis the drug was provided in the diet of guinea-pigs for 164 days. Clinically, the drug has been administered for periods ranging up to six months. In my study of the toxicity of the drug on the erythrocytes I gave varying amounts to experimental animais daily for three weeks. Nothing is known, however, of the immediate effects of the drug: how rapidly erythrocytes are damaged or how long toxic effects of a single administration may persist. This report covers the results of a single oral administration of 400 mg. of promin to adult maie guinea-pigs.

A high-performance liquid chromatographic method is described for the simultaneous determination of ajmaline and quinidine in human plasma. With 0·5 ml plasma samples of ajmaline and quinidine, concentrations as low as 0·001 and 0·01 μg ml−1, respectively, could be detected and the technique could be used to investigate the effect of quinidine on the pharmacokinetics of ajmaline. Four healthy subjects were given oral ajmaline (50 mg) alone or in combination with quinidine sulphate (200 mg) on separate occasions. When ajmaline was administered alone, its plasma concentrations were less than 0·03 μg ml−1. Quinidine induced a marked increase to give a mean peak concentration of ajmaline which increased from 0·018 μg ml−1 after a single administration to 0·141 μg ml−1 in combination with quinidine. The area under the ajmaline concentration-time curves was increased 10 to 30-fold by the concurrent administration of quinidine. According to the one compartment open model, the absorption rate constant of ajmaline did not change appreciably, but the elimination rate constant was reduced to approximately 50% of the value in the absence of quinidine. The results indicate the existence of a significant interaction between oral ajmaline and quinidine.