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In early 2020, the World Health Organization (WHO) declared the coronavirus disease 2019 (COVID-19) outbreak a global pandemic. In response, two novel messenger RNA (mRNA)-based vaccines: mRNA-1273 (Moderna) and BNT162b2 (Pfizer-BioNTech) were rapidly developed. A thorough understanding of the differences in workflow requirements between the two vaccines may lead to improved efficiencies and reduced economic burden, both of which are crucial for streamlining vaccine deployment and minimizing wastage. Vaccine administration workflow costs are borne by providers and reimbursed separately from dose acquisition in the United States. Currently, mRNA-1273 and BNT162b2 are the most administered COVID-19 vaccines in the United States. In this study, US-licensed and practicing pharmacists were interviewed to collect data on differences in terms of labor costs associated with the workflows for mRNA-1273 and BNT162b2. Results suggest the cost differential for mRNA-1273 compared to BNT162b2 is −$0.82 (or −$1.01 when assuming volume equivalency). If extrapolated to even just a proportion of the remaining unvaccinated US population, this can amount to significant workflow efficiencies and lower vaccine administration costs. Further, as key differences in the vaccine workflow steps between the two vaccines would be similar in other settings/regions, these findings are likely transferable to health-care systems worldwide.

Background: Retrospective auditing identified the need to implement a client centered tool to measure occupational performance and re engagement in activities after burn injury. The Canadian Occupational Performance Measure (COPM) was chosen as it has a broad focus on occupational performance across the lifespan. However, given the time constraints that acute care clinicians work within in a tertiary teaching hospital, a feasibility study was warranted to identify the time to complete the COPM and any potential barriers which may arise in order to evaluate the appropriateness of using this tool.Methods: This project was a prospective cohort study. All patients presenting to the ward and the Specialist Burns Outpatient Clinic were consecutively enrolled in this study. Information was collected regarding administration of the COPM including administration time, number of interruptions and reasons for non-completion of the outcome measure e.g. wound dressing procedures, surgery, scheduling conflicts. A survey method was used to explore the perceptions of Occupational Therapy clinicians regarding use of the COPM in clinical practice.Results: Over the course of the study period 70 COPM's were administered. The average time for administration across both settings was 9 min. Individually the average time taken for administration of the COPM with inpatients was 11.21 min, in the outpatient setting 7.85 min. The Survey Monkey questionnaire was emailed to 58 occupational therapy clinicians working at the facility associated with the study. The response rate was 41.4% (24).Discussion: Patient reported outcome measures are central to patient centred care which is a core element of health care provision. Results from this study found that the COPM took approximately 9 min to administer, which is suitable within the time constraints of an acute tertiary environment and would be feasible in our setting. Fifty one percent of the participants identified return to work as the activity of daily living most impacted by their burn injury. As burn injuries impact all domains of daily life the use of patient reported outcome measures to direct goal orientated care is imperative.Conclusion: This study found that the time to administer the COPM is feasible within the acute tertiary setting. Perceived barriers identified can be overcome with increased knowledge of client centred practice and the importance of goal directed care. The use of patient reported outcome measures in clinical practice empowers consumers to identify what goals they would like to achieve. [ABSTRACT FROM AUTHOR]

Introduction: The initial post-surgical radioactive iodine (RAI) therapy for patients with papillary thyroid cancer (PTC) is postponed due to increased demand as well as the limited number of centers to provide RAI therapy. Hence, our aim was to investigate the role of first RAI administration time following thyroidectomy on the number of incomplete response (IR) during the initial follow up, while considering other prognostic factors. Methods: Two hundred and thirty-five PTC patients who were admitted to our department for RAI therapy were included in this study. They were allocated into two groups with <3 months (early group) and = 3 months (delayed group) time interval after the first RAI therapy, and the total thyroidectomy. Then, based on the response to RAI therapy, patients were categorized as excellent, biochemical incomplete, structural incomplete, or indeterminate responses (ER, BIR, SIR or IDR, respectively). Results: With respect to age, gender, pathologic variables, RAI dose rate and IR (BIR+SIR) rate, significant differences were found between the two groups. The findings identified that early RAI failed to affect the rate of IR (univariate analysis: HR=1.09, 95%CI: 0.69-1.74, P=0.71; Cox model: HR=0.81, 95%CI: 0.46-1.44, P=0.47). However, Cox multivariate analysis found lymph node status and thyroglobulin level (Lymph node status: HR=2.88, 95%CI: 1.07-7.78, P=0 .04) as independent risk factors for IR during the initial follow up. Conclusion: Therefore, timing of the first post-surgery RAI therapy is not a significant prognosticator of the initial response of patients to therapy. [ABSTRACT FROM AUTHOR]

Airway hyperresponsiveness (AHR) is one of the most important features of asthma. Our previous study showed that inhaled transgelin-2 agonist, TSG12, effectively reduced pulmonary resistance in a mouse model of asthma in a dose-dependent manner. However, the optimal administration time of TSG12 to reduce AHR and the pharmacological effects are still unclear. In this study, the effects of TSG12 inhalation before and during AHR occurrence were examined. The results showed that the pulmonary resistance was reduced by 57% and the dynamic compliance was increased by 46% in the TSG12 Mch group (atomize TSG12 10 min before methacholine, p < 0.05 vs. model). The pulmonary resistance was reduced by 61% and the dynamic compliance was increased by 47% in the TSG12 + Mch group (atomize TSG12 and methacholine together, p < 0.05 vs. model). Quantitative real-time PCR showed that the gene expression levels of transgelin-2, myosin phosphatase target subunit-1, and myosin light chain were up-regulated by 6.4-, 1.9-, and 2.8-fold, respectively, in the TSG12 Mch group. The gene expression levels of transgelin-2, myosin phosphatase target subunit-1, and myosin light chain were up-regulated by 3.2-, 1.4-, and 1.9-fold, respectively, in the TSG12 + Mch group. The results suggested that TSG12 effectively reduces pulmonary resistance when TSG12 inhalation occurred both before and during AHR occurrence. Gene expression levels of transgelin-2 and myosin light chain were significantly up-regulated when TSG12 inhalation occurred before AHR occurrence. This study may provide a basis for the administration time of TSG12 for asthma treatment in the future. [ABSTRACT FROM AUTHOR]

Abstract Background The morning blood pressure surge (MBPS) is related to an exaggerated risk of cardiovascular diseases and mortality. With increasing attention on circadian change in blood pressure and extensive use of ambulatory blood pressure monitoring (ABPM), chronotherapy that administration of medication according to biological rhythm, is reported to improve cardiovascular outcomes. The aim of this study is to evaluate the influence of chronotherapy of antihypertensive drugs upon MBPS in hypertensive patients. Methods A search strategy was applied in Ovid MEDLINE, EMBASE, Cochrane (Wiley) CENTRAL Register of Controlled Trials, Cochrane Database of Systematic Reviews, and the Chinese Biomedical literature database. No language and date restrictions. Randomized controlled trials (RCT) assessing the efficacy of evening and morning administration of the same medications in adult patients with primary hypertension were included. Results A total of ten trials, comprising 1724 participants with a mean age of 61 and 51% female, were included in this study. Combined analysis observed significant reduction of MBPS (− 5.30 mmHg, 95% CI − 8.80 to − 1.80), night-time SBP (− 2.29 mmHg, 95% CI − 4.43 to − 0.15), night-time DBP (− 1.63 mmHg, 95 %CI − 3.23 to − 0.04) and increase in night blood pressure dipping (3.23%, 95% CI 5.37 to 1.10) in evening dosage compared with traditional morning dosage of blood pressure-lowering drugs. No significant difference was found in the incidence of overall adverse effects (RR 0.65, 95% CI 0.30 to 1.41) and withdrawal due to adverse effects (RR 0.95, 95% CI 0.53 to 1.71). Conclusions Our study suggested that evening administration of antihypertensive medications exerted better blood pressure-lowering effect on MBPS compared with conventional morning dosage. Safety assessment also indicated that the evening regimen did not increase the risk of adverse events. However, endpoint studies need to be carried out to confirm the significance and feasibility of this treatment regimen in clinical practice.

Airway hyperresponsiveness (AHR) is one of the most important features of asthma. Our previous study showed that inhaled transgelin-2 agonist, TSG12, effectively reduced pulmonary resistance in a mouse model of asthma in a dose-dependent manner. However, the optimal administration time of TSG12 to reduce AHR and the pharmacological effects are still unclear. In this study, the effects of TSG12 inhalation before and during AHR occurrence were examined. The results showed that the pulmonary resistance was reduced by 57% and the dynamic compliance was increased by 46% in the TSG12 Mch group (atomize TSG12 10 min before methacholine, p < 0.05 vs. model). The pulmonary resistance was reduced by 61% and the dynamic compliance was increased by 47% in the TSG12 + Mch group (atomize TSG12 and methacholine together, p < 0.05 vs. model). Quantitative real-time PCR showed that the gene expression levels of transgelin-2, myosin phosphatase target subunit-1, and myosin light chain were up-regulated by 6.4-, 1.9-, and 2.8-fold, respectively, in the TSG12 Mch group. The gene expression levels of transgelin-2, myosin phosphatase target subunit-1, and myosin light chain were up-regulated by 3.2-, 1.4-, and 1.9-fold, respectively, in the TSG12 + Mch group. The results suggested that TSG12 effectively reduces pulmonary resistance when TSG12 inhalation occurred both before and during AHR occurrence. Gene expression levels of transgelin-2 and myosin light chain were significantly up-regulated when TSG12 inhalation occurred before AHR occurrence. This study may provide a basis for the administration time of TSG12 for asthma treatment in the future.

Background: The morning blood pressure surge (MBPS) is related to an exaggerated risk of cardiovascular diseases and mortality. With increasing attention on circadian change in blood pressure and extensive use of ambulatory blood pressure monitoring (ABPM), chronotherapy that administration of medication according to biological rhythm, is reported to improve cardiovascular outcomes. The aim of this study is to evaluate the influence of chronotherapy of antihypertensive drugs upon MBPS in hypertensive patients.Methods: A search strategy was applied in Ovid MEDLINE, EMBASE, Cochrane (Wiley) CENTRAL Register of Controlled Trials, Cochrane Database of Systematic Reviews, and the Chinese Biomedical literature database. No language and date restrictions. Randomized controlled trials (RCT) assessing the efficacy of evening and morning administration of the same medications in adult patients with primary hypertension were included.Results: A total of ten trials, comprising 1724 participants with a mean age of 61 and 51% female, were included in this study. Combined analysis observed significant reduction of MBPS (- 5.30 mmHg, 95% CI - 8.80 to - 1.80), night-time SBP (- 2.29 mmHg, 95% CI - 4.43 to - 0.15), night-time DBP (- 1.63 mmHg, 95 %CI - 3.23 to - 0.04) and increase in night blood pressure dipping (3.23%, 95% CI 5.37 to 1.10) in evening dosage compared with traditional morning dosage of blood pressure-lowering drugs. No significant difference was found in the incidence of overall adverse effects (RR 0.65, 95% CI 0.30 to 1.41) and withdrawal due to adverse effects (RR 0.95, 95% CI 0.53 to 1.71).Conclusions: Our study suggested that evening administration of antihypertensive medications exerted better blood pressure-lowering effect on MBPS compared with conventional morning dosage. Safety assessment also indicated that the evening regimen did not increase the risk of adverse events. However, endpoint studies need to be carried out to confirm the significance and feasibility of this treatment regimen in clinical practice. [ABSTRACT FROM AUTHOR]

Circadian rhythms play crucial roles in the action and pharmacokinetics of a drug. The processes from drug absorption to excretion, which participate in pharmacokinetic steps, are circadian time-dependent. Our previous study has demonstrated that the analgesic effect of bucinnazine, an anesthetic analgesic drug, revealed significant circadian variation. In the current study, we aimed to investigate the effect of different administration time on the pharmacokinetic process of bucinnazine in rats. Male Sprague Dawley rats were randomly divided into 9:00 am and 9:00 pm groups. Blood samples (0.4 ml) were, respectively, collected at 0, 0.033, 0.083, 0.17, 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, and 8 h after intraperitoneal injection of 20 mg/kg bucinnazine and determined using the established liquid chromatography-tandem mass spectrometry method. DAS 2.0 was used to calculate the pharmacokinetic parameters. The pharmacokinetics of bucinnazine exhibited significant circadian-time dependence. AUC and Cmax of bucinnazine increased significantly at 9:00 am compared with that at 9:00 pm (P < 0.05), while Tmax was significantly decreased at 9:00 am than at 9:00 pm (P < 0.05). Pharmacokinetic processes of bucinnazine significantly varied along with administration time, indicating that attention should be paid to the time in clinical practice to improve analgesic effects and to decrease adverse reactions. [ABSTRACT FROM AUTHOR]

• An FCA method of the MMPI-2-RF provides similar information as a full administration. • Time savings are 40% to 80% depending on the number of MMPI-2-RF domains administered. The Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) has empirically validated utility in presurgical psychological evaluations of bariatric surgery patients. However, clinicians may prefer shorter, symptom-focused measures. The purpose of the present study is to evaluate the feasibility and potential administration time savings of a proposed flexible and conditional (FCA) administration of the MMPI-2-RF in presurgical evaluations of bariatric surgery candidates. Bariatric surgery candidates evaluated at a large hospital as well as a private practice in the Midwest. MMPI-2-RF scores were available for a total of 4099 adult bariatric surgery candidates from 2 separate samples. The hospital sample included 911 males and 2430 females. The average BMI was 49.3 kg/m2 (SD = 11.0). The private practice sample included 105 males, 640 females, and 13 individuals who did not report gender. The average BMI was 48.8 kg/m2 (SD = 8.4). The authors used a simulation design in which existing MMPI-2-RF responses were used to simulate an FCA administration. The findings indicated that an FCA of the MMPI-2-RF closely approximates the amount of information typically gained from a full administration of the test in the 2 samples of bariatric surgery candidates. Items savings and estimated time savings ranged from 44% to 88% in both samples, depending on the number of conditionally administered scales. The present study supports the feasibility of an FCA of the MMPI-2-RF, potentially shortening administration time and reducing patient burden. However, the findings are limited because the accuracy and time savings are based on a simulation, not actual FCA administrations. [ABSTRACT FROM AUTHOR]

Over the past several decades, use of broadband personality assessments has decreased, with some clinicians favoring shorter, symptom-focused measures with a shorter administration time. The purpose of this study is to describe, derive rules for, and evaluate a flexible and conditional administration of the Minnesota Multiphasic Personality Inventory (MMPI)-2-Restructured Form (MMPI-2-RF). In this approach, elevated scores on higher level scales are used to trigger administration of lower-level scales within the same assessment domain to minimize administration time. We conducted a real-data simulation to derive rules for and evaluate this administration strategy using the MMPI-2-RF normative sample and a community mental health center comparison group. These samples allow for comparing the utility of the method in populations with relatively low and high base rates of psychopathology, respectively. The flexible and conditional administration strategy resulted in minimal loss of information in separate subsamples used to evaluate the method. However, item savings were more pronounced in the normative sample, in which administration time was decreased by 40% to 80% depending on the number of substantive domains assessed. Overall, flexible and conditional administration of the MMPI-2-RF appears to hold substantial promise in settings with time constraints and relatively low base rates of psychopathology, such as medical patient and neuropsychological evaluations as well as assessments of candidates for public safety positions. Other implications of these findings and limitations of this study are discussed. (PsycINFO Database Record [ABSTRACT FROM AUTHOR]

An appreciable number of medicines have a recommended unique single time-of-day or asymmetrical or unequal-interval multiple-daily administration schedule. Many prescription and over-the-counter (OTC) products, according to administration time, can exert positive or negative impact on nighttime sleep and daytime wakefulness. Intuitively, medicines used to manage nighttime sleep and daytime wake disorders should be taken, respectively, at night before bedtime and morning after arising. However, some utilized for other medical conditions, if improperly timed, may compromise nocturnal sleep and diurnal attentiveness. We conducted a comprehensive review of the American Prescribers' Digital Reference, internet version of the Physician's Desk Reference, for the recommended scheduling of medications and OTC remedies that can impact sleep and wakefulness. The search revealed several hundred therapies of various classes -- α 2 -receptor agonists, antidepressants, barbiturates, central nervous system stimulants, benzodiazepines, dopamine agonists, dopamine norepinephrine reuptake inhibitors, selective norepinephrine reuptake inhibitors, eugeroics, γ-aminobutyric acid modulators, H 1 and H 3 -receptor antagonists, melatonin analogues, OTC melatonin-containing products, non-benzodiazepine benzodiazepine-receptor agonists, dual orexin-receptor antagonists, and serotonin modulators -- that have a recommended unique dosing schedule. The tables and text of this article are intended to guide the proper scheduling of these medicines to optimize desired and/or minimize undesired effects. [ABSTRACT FROM AUTHOR]

Background: Esomeprazole has been reported to show a strong acid suppression following preprandial as compared to postprandial administration, though no known study has compared the acid suppressing effects of other proton pump inhibitors between those administrations. The aim of this study was to compare intragastric pH levels following pre- and postprandial administrations of rabeprazole and esomeprazole. Methods: In 15 Helicobacter pylori -negative healthy volunteers, we measured intragastric pH after 7 days of pre- and postprandial administrations of rabeprazole (10 mg) or esomeprazole (20 mg) using a 5-way crossover design. Results: Preprandial administration of esomeprazole showed stronger acid suppression than postprandial administration. The values for percent time at pH >4.0 over a 24- hour period increased from 45.3% with postprandial administration of esomeprazole to 54.4% with preprandial administration, while the percent time at pH >4.0 during daytime was increased to a greater extent from 51.4 to 66.5% with preprandial administration (p = 0.05). On the other hand, the acid suppressing effect of rabeprazole was not influenced by the timing of administration. Conclusions: The acid suppressing effect of esomeprazole is influenced by administration timing. In contrast, the acid suppressing effect of rabeprazole is not augmented by preprandial administration. [ABSTRACT FROM AUTHOR]

Introduction The anticonvulsant effects of melatonin (MT) have been demonstrated in several different experimental seizure models. Thus, the present study aimed to determine the anticonvulsant efficacy of MT, the optimum time for its administration prior to the induction of a seizure, and its effective dose in a rat model of hyperthermic febrile seizures (FSs). Methods The present study included 72 male Sprague–Dawley rat pups divided into eight groups. The seizures were induced by keeping the rats in 45 °C water and the experiments were performed in two steps. In the first step, the control group was given a vehicle injection and the study groups were given a MT injection (150 mg/kg, intraperitoneal [i.p.]) at either 5, 10, or 15 min prior to the induction of the seizure to determine the anticonvulsant effects of MT and its optimum time of administration. In the second step, a vehicle injection and three different doses of MT (80, 100, and 150 mg/kg, i.p.) were administered 15 min prior to the induction of the seizure to determine the dose at which anticonvulsant effects could be achieved. The anticonvulsant effects were assessed based on the latency of the FSs. Results In the first-step experiments, the FS latency of the control group was 143.4 ± 15.3 s and the latencies of the groups given melatonin at either 5, 10, or 15 min prior to the seizure were 174.2 ± 28.9, 177.4 ± 21.0, and 193.7 ± 17.6 s, respectively. Compared with the control group, the latencies for each of the study groups were significantly longer ( p < 0.001), with the longest latency observed in the group given melatonin 15 min before the seizure. In the second-step experiments, the FS latencies of the groups that were given 80, 100, and 150 mg/kg of MT 15 min before the seizure were 238.7 ± 4.0, 240.0 ± 0.0, and 193.7 ± 17.6 s, respectively. These latencies were significantly longer than those of the control group (172.3 ± 30.3 s, p < 0.001). Conclusion The present study demonstrated that MT exerts anticonvulsant effects in a rat model of hyperthermic FSs and achieved its optimum efficacy at a dose of 80 mg/kg when administered 15 min prior to the induction of a seizure. [ABSTRACT FROM AUTHOR]

Objectives To examine the difference in improvement of lower urinary tract symptoms between morning and evening dosing of α1-blocker naftopidil. Methods A total of 177 male patients with nocturia were included in the present study and randomized to morning or evening dosing of naftopidil. The International Prostate Symptom Score, quality of life index and nocturia quality of life index were compared between the two study groups at 12 weeks. Results A total of 143 patients (morning group: n = 70, evening group: n = 73) were analyzed as a result of the dropout of 34 patients because of failure to give consent, adverse events and failure to attend. Nocturia, quality of life index and nocturia quality of life index at 12 weeks were significantly better in the evening group compared with the morning group. In a multivariate model, both the dosing time of naftopidil and the initial nocturia quality of life index were significantly associated with change in nocturia quality of life index. Conclusions Evening dosing of naftopidil seems to be more effective in treating nocturia in male patients with lower urinary tract symptoms. [ABSTRACT FROM AUTHOR]

Background: A significant proportion of patients with connective tissue disease (CTD) have gastric esophageal reflux disease (GERD) symptoms despite receiving proton pump inhibitors (PPIs). Although pre-meal administration of PPIs is recommended in Western countries, the benefit of this administration timing in Japanese CTD patients with refractory GERD symptoms has not been proven. Objective: To determine whether pre-dinner administration of PPIs is more efficacious for refractory GERD symptoms in Japanese CTD patients. Methods: CTD patients receiving oral PPIs were instructed to take PPIs 1 h before dinner. Gastrointestinal symptoms were evaluated with frequency scale for the symptoms of GERD (FSSG) and gastrointestinal symptom rating scale (GSRS) before and after the intervention. Results: Pre-dinner administration of PPIs significantly improved FSSG total score, from a median of 8 to 6.5 ( P = 0.005). Pre-dinner administration was more effective in patients with overt GERD symptoms (from median 18 to 10, P < 0.001) than in those with mild GERD symptoms (from median 2 to 2, P = 0.201). In addition to reflux syndrome, pre-dinner administration of PPIs significantly decreased abdominal pain syndrome and constipation syndrome of GSRS. Conclusion: Pre-dinner administration of PPIs may increase their efficacy in Japanese CTD patients with GERD, especially those with overt symptoms. [ABSTRACT FROM AUTHOR]

The best time of G-CSF administration for PBPC collection remains to be defined. We aimed to identify optimal G-CSF administration timing for efficient autologous stem cell collection. A total of 262 lymphoma or multiple myeloma patients, who underwent PBPC collection from January 2000 to March 2008, were included. PBPCs were mobilized with chemotherapy followed by lenograstim at 10 μg/kg/day. Patients received lenograstim at 2000 hours, about half a day before leukapheresis (PM group) before November 2004, and at 0600 hours, 3 h before apheresis (AM group) subsequently. In the AM group, the median number of total collected CD34+ cells/kg was greater over a shorter duration of apheresis, and the median number of collected CD34+ cells/kg at first leukapheresis was larger. Stem cell collection efficacy (ratio of total collected CD34+ cells/kg per number of leukapheresis procedures) was higher, and proportion of patients who yielded an optimum harvest was larger. The statistically significant between-group difference was observed only in patients with high-dose CY chemotherapy for stem cell mobilization in subgroup analysis. The present study showed that G-CSF injection 3 h before apheresis improved the efficacy of autologous stem cell collection. [ABSTRACT FROM AUTHOR]

Administration time of 1 min for semantic verbal fluency measures can be overly long and therefore bothersome for aphasic patients because they can often retrieve only a few items after a certain period of time. The purpose of this study was to determine whether an administration time of 30 s would be more efficient in differentiating among aphasics, nonaphasic stroke patients, and normal controls. The subjects were 53 stroke patients and 28 normal controls. They had to generate as many animal names as they could within a given time. The number of animal names is gradually diminished in three groups (p < 0.001) in each time frame, that is, during the entire 60 s, the initial 30 s, and the following 30 s. The reaction time (RT) measure indicated that the RT of the aphasic patients was significantly increased compared to those of the other two groups (p < 0.001). The most optimal cutoff scores that differentiated each group are presented. These results suggest that an administration time of 30 s has discriminative validity to differentiate between the two patient groups. This shorter administration time could make the test more efficient by reducing the burden on both examiners and aphasic patients. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: In the present study, we used the infectious spleen and kidney necrosis virus (ISKNV) and zebrafish model system to investigate the inhibitory effect of recombinant zebrafish interferon 1 (zfrIFN1) on acute viral infection and the impact of time of zfrIFN1 administration on its protective efficacy. In vivo experiments showed that administration of recombinant zfrINF1 up-regulated expression of several IFN-stimulated genes within 24 h of injection, and expression levels of these genes dropped to normal levels similar to those in control fish within three days. However, the transcriptions of two viral genes, the major capsid protein and virus protein 48 genes, were significantly inhibited for at least three days, indicating a longer duration of the zfrIFN1-mediated innate immune effect. To evaluate the protective efficacy of zfrIFN1 against ISKNV infection, we compared the relative percentage survival (RPS) of ISKNV-infected zebrafish by intraperitoneally (IP) injecting the fish with zfrIFN1 at different time points before or after infection. IP injection with 1 μg zfrIFN1/g fish body weight at 24, 6 or 0 h before virus infection or 6 h after virus infection significantly improved fish survival. However, IP injection with an equal dose of zfrIFN1 24 h post-infection did not provide significant protection to the fish. Our results suggest that zfrIFN1 is potent in inhibiting ISKNV acute infection and initiating the innate immune response in zebrafish, but its efficiency depends on the time of administration. This study shows the protective effects of interferon against a DNA-virus in fish for the first time and provides information about the efficacy of fish interferon that will prove useful in possible therapeutic applications. [Copyright &y& Elsevier]

In order to assess whether dinnertime administration of a once daily dose of famotidine is more advantageous than a bedtime dose in suppressing evening and nocturnal gastric acidity, we gave nine patients with a past history of duodenal ulcer in double-blind, randomized fashion either (1) placebo at 6 p.m. and 10 p.m., (2) famotidine 40 mg at 6 p.m. (Fam 6) + placebo at 10 p.m. or (3) placebo at 6 p.m. + famotidine at 10 p.m. (Fam 10) on three separate occasions. Comparison of the 24-h median pH values showed that the two administrations of famotidine were superior to placebo, while Fam 6 was significantly more effective than Fam 10. The gain in acid suppression of Fam 6 with respect to Fam 10 was particularly evident from 6 p.m. to midnight. Although the antisecretory effectiveness of Fam 6 was lower than that of Fam 10 from 4 a.m. to 8 a.m., it remained clearly higher than that of placebo and ensured virtual anacidity (median pH=6.7) even in this time segment. We conclude that a once daily dose of famotidine at 6 p.m. is better than bedtime administration at covering the long period of continuous unbuffered intragastric acidity which extends from after the evening meal to breakfast. [ABSTRACT FROM AUTHOR]

In early 2020, the World Health Organization (WHO) declared the coronavirus disease 2019 (COVID-19) outbreak a global pandemic. In response, two novel messenger RNA (mRNA)-based vaccines: mRNA-1273 (Moderna) and BNT162b2 (Pfizer-BioNTech) were rapidly developed. A thorough understanding of the differences in workflow requirements between the two vaccines may lead to improved efficiencies and reduced economic burden, both of which are crucial for streamlining vaccine deployment and minimizing wastage. Vaccine administration workflow costs are borne by providers and reimbursed separately from dose acquisition in the United States. Currently, mRNA-1273 and BNT162b2 are the most administered COVID-19 vaccines in the United States. In this study, US-licensed and practicing pharmacists were interviewed to collect data on differences in terms of labor costs associated with the workflows for mRNA-1273 and BNT162b2. Results suggest the cost differential for mRNA-1273 compared to BNT162b2 is -$0.82 (or -$1.01 when assuming volume equivalency). If extrapolated to even just a proportion of the remaining unvaccinated US population, this can amount to significant workflow efficiencies and lower vaccine administration costs. Further, as key differences in the vaccine workflow steps between the two vaccines would be similar in other settings/regions, these findings are likely transferable to health-care systems worldwide.

Hypersensitivity reactions, including anaphylaxis, are common side effects associated with docetaxel treatment in breast cancer patients. However, preventive measures have not yet been established. In this study, we retrospectively analyzed the risk factors for developing anaphylaxis in 182 female breast cancer patients treated with docetaxel. We found that 6.6% of all patients (n = 12) experienced anaphylaxis. Multivariate analyses indicated that concentration of docetaxel higher than 0.275 mg/m 2 /mL, docetaxel dose rate higher than 1.15 mg/m 2 /min, and white blood cell count less than 4290 cells/mL are risk factors for developing docetaxel-related anaphylaxis. In particular, concentrations of docetaxel or doses per administration time were associated with a high odds ratio (11.88 or 11.60) for docetaxel-related anaphylaxis. Moreover, patients receiving doses in 250 mL volume experienced anaphylaxis more frequently than those receiving doses in 500 mL (7.0 vs. 0.9%, p = 0.0236). Additionally, patients receiving treatments over 60 min tended to experience anaphylaxis more frequently than those who were treated over 90 min (6.7 vs. 1.1%, p = 0.0637). The present results indicate that high docetaxel concentrations, high dose rates, and low white blood cell counts are risk factors for developing docetaxel-related anaphylaxis, and administering docetaxel diluted in 500 mL over 90 min may limit docetaxel-induced hypersensitivity reactions.

The effect of altering the timing of gliclazide administration in relation to a meal was studied in ten type 2 (non-insulin dependent) chronically treated diabetics. Gliclazide was given 30 min before, at the start of and 30 min after breakfast or omitted altogether. Plasma gliclazide was present at greater than 2 mg/l throughout the study periods. Administration at 30 min after the meal significantly delayed the time to peak for plasma gliclazide. No significant difference was noted in plasma glucose, insulin or c-peptide patterns with any protocol. It is concluded that, in clinical practice, with chronically treated diabetics the timing of gliclazide ingestion in relation to meals is not critical. [ABSTRACT FROM AUTHOR]

Objective: Strategies that reduce the time to antimicrobial administration, such as the availability of premix antimicrobials (PMAs) in the emergency department (ED), may better align with the goals of the Surviving Sepsis Campaign and improve outcomes in septic patients. The objective of this study was to evaluate the impact of antimicrobial preparation on time to administration in septic patients located in the emergency department (ED)., Methods: This was a retrospective, single-center, cohort study and adult patients with a diagnosis of sepsis who received at least one initial intravenous (IV) antimicrobial in the ED were included. Time to complete an empiric antimicrobial therapy was defined as the time between prescriber order entry and the infusion initiation time of the final antimicrobial agent of a patient's antimicrobial regimen. Appropriate, empiric antimicrobial therapy was based on treatment recommendations by nationally accepted guidelines for the specific indication., Results: The first antimicrobial was initiated earlier when available as a PMA preparation (median (IQR): premix 25 minutes (16.5-42.3) vs. non-premix 46 minutes (20-102), p=0.027). When comparing complete, empiric antimicrobial regimen administration, there was no difference in time to administration between regimens containing one or more non-premix antimicrobials and regimens containing all PMAs (median (IQR): premix 69 minutes (21-115) vs. non-premix 65 minutes (38.5-133.8); p=0.455)., Conclusions: PMA preparations significantly reduced time to administration of the first antimicrobial agent for septic patients treated in the ED, but time to administration of subsequent antimicrobials were not improved.