The alpha-1A-adrenergic receptor (AR) subtype is associated with cardioprotective signaling in the mouse and human heart. The rabbit is useful for cardiac disease modeling, but data on the alpha-1A ...in the rabbit heart are limited. Our objective was to test for expression and function of the alpha-1A in rabbit heart. By quantitative real-time reverse transcription PCR (qPCR) on mRNA from ventricular myocardium of adult male New Zealand White rabbits, the alpha-1B was 99% of total alpha-1-AR mRNA, with <1% alpha-1A and alpha-1D, whereas alpha-1A mRNA was over 50% of total in brain and liver. Saturation radioligand binding identified ~4 fmol total alpha-1-ARs per mg myocardial protein, with 17% alpha-1A by competition with the selective antagonist 5-methylurapidil. The alpha-1D was not detected by competition with BMY-7378, indicating that 83% of alpha-1-ARs were alpha-1B. In isolated left ventricle and right ventricle, the selective alpha-1A agonist A61603 stimulated a negative inotropic effect, versus a positive inotropic effect with the nonselective alpha-1-agonist phenylephrine and the beta-agonist isoproterenol. Blood pressure assay in conscious rabbits using an indwelling aortic telemeter showed that A61603 by bolus intravenous dosing increased mean arterial pressure by 20 mm Hg at 0.14 μg/kg, 10-fold lower than norepinephrine, and chronic A61603 infusion by iPRECIO programmable micro Infusion pump did not increase BP at 22 μg/kg/d. A myocardial slice model useful in human myocardium and an anthracycline cardiotoxicity model useful in mouse were both problematic in rabbit. We conclude that alpha-1A mRNA is very low in rabbit heart, but the receptor is present by binding and mediates a negative inotropic response. Expression and function of the alpha-1A in rabbit heart differ from mouse and human, but the vasopressor response is similar to mouse.
Echolocating bats are able to discriminate between different surface textures based on the spectral properties of returning echoes. This capability is likely to be important for recognizing prey and ...for finding suitably perching sites along smooth cave walls. Previous studies showed that bats may exploit echo spectral interference patterns in returning echoes to classify surface textures, but a systematic assessment of the limits of their discrimination performance is lacking and may provide important clues about the neural mechanisms by which bats reconstruct target features based on echo acoustic cues. We trained three Mexican free-tailed bats (
Tadarida brasiliensis
) on a Y-maze to discriminate between the surfaces of 10 different sheets of aluminum-oxide abrasive sandpapers differing in standardized grit sizes ranging from 40 grit (coarse, 425 μm mean particle diameter) to 240 grit (fine, 54 μm mean particle diameter). Bats were rewarded for choosing the coarsest of two choices. All three bats easily discriminated all abrasive surfaces from a smooth plexiglass control and between all sandpaper comparisons except the two with the smallest absolute difference in mean particle sizes, the 150 vs. 180 grit (92 vs. 82 μm) and the 220 vs. 240 grit (68 vs. 54 μm) surfaces. These results indicate that echolocating free-tailed bats can use slight variations in the echo spectral envelope to remotely classify very fine surface textures with an acuity of at least 23 μm, which rivals direct tactile discrimination performance of the human hand.
Abstract
Background
Governments internationally have invested hugely in the implementation and scale-up of school-based physical activity interventions, but have little evidence of how to best ...sustain these interventions once active implementation support ceases. This study will assess the effectiveness of a multi-strategy sustainability intervention on classroom teachers’ sustainment of energisers (short 3–5 min physical activity breaks during class-time) scheduled across the school day from baseline to 12 and 24-month follow-up.
Methods
A cluster randomised controlled trial will be conducted in 50 primary schools within the Hunter New England, Illawarra Shoalhaven, Murrumbidgee and Northern New South Wales (NSW) Local Health Districts of NSW Australia. Schools will be randomly allocated to receive either usual support or the multi-strategy sustainability intervention that includes: centralised technical assistance from a trained project officer; formal commitment and mandated change obtained from school principals; training in-school champions; reminders for teachers; educational materials provided to teachers; capturing and sharing local knowledge; and engagement of parents, carers and the wider school community. The primary trial outcome will be measured via a teacher logbook to determine the between-group difference in the change in mean minutes of energisers scheduled across the school day at 12 and 24-month follow-up compared to baseline. Analyses will be performed using an intention to treat framework. Linear mixed models will be used to assess intervention effects on the primary outcome at both follow-up periods.
Discussion
This study will be one of the first randomised controlled trials to examine the impact of a multi-strategy sustainability intervention to support schools’ sustainment of a physical activity intervention. The proposed research will generate new evidence needed for the partnering organisations to protect their considerable investments to date in physical activity promotion in this setting and will provide seminal evidence for the field globally.
Trial registration
ACTRN12620000372987 version 1 registered 17
th
March 2020. Version 3 (current version) updated 4
th
August 2023.
Summary The authors used 52 nonfailing and failing human hearts to develop a simple, high throughput left ventricular myocardial slice model that is stable by ATP and viability assays for at least 3 ...days. The model supports studies of signaling, contraction, and viral transduction. They use the model to show for the first time that the alpha-1A-adrenergic receptor, which is present at very low abundance in the human myocardium, activates cardioprotective ERK with nanomolar EC50 in failing heart slices and stimulates a positive inotropic effect. This model should be useful for translational studies, to test whether molecules discovered in basic experiments are functional in the human heart.
Objective: Incomplete medication histories obtained on hospital admission are responsible for more than 25% of prescribing errors. This study aimed to evaluate whether pharmacy technicians can assist ...hospital physicians′ in obtaining medication histories by performing medication reconciliation and prescribing reviews. A secondary aim was to evaluate whether the interventions made by pharmacy technicians could reduce the time spent by the nurses on administration of medications to the patients. Methods: This observational study was conducted over a 7 week period in the geriatric ward at Odense University Hospital, Denmark. Two pharmacy technicians conducted medication reconciliation and prescribing reviews at the time of patients′ admission to the ward. The reviews were conducted according to standard operating procedures developed by a clinical pharmacist and approved by the Head of the Geriatric Department. Findings: In total, 629 discrepancies were detected during the conducted medication reconciliations, in average 3 for each patient. About 45% of the prescribing discrepancies were accepted and corrected by the physicians. "Medication omission" was the most frequently detected discrepancy (46% of total). During the prescribing reviews, a total of 860 prescription errors were detected, approximately one per medication review. Almost all of the detected prescription errors were later accepted and/or corrected by the physicians. "Dosage and time interval errors" were the most frequently detected error (48% of total). The time used by nurses for administration of medicines was reduced in the study period. Conclusion: This study suggests that pharmacy technicians can contribute to a substantial reduction in medication discrepancies in acutely admitted patients by performing medication reconciliation and focused medication reviews. Further randomized, controlled studies including a larger number of patients are required to elucidate whether these observations are of significance and of importance for securing patient safety.
Background
Medication histories (MHs) obtained at the time of patients’ admission to hospital are often incomplete, and lack of information about patients’ actual medicine use can potentially lead to ...prescribing failures and serious adverse events. Uses of clinical pharmacists in obtaining MHs are beneficial, but due to limited economic resources clinical pharmacists cannot be present in every hospital ward, and therefore pharmacy technicians (PTs) could probably be trained in obtaining MHs.
Objective
To compare discrepancies in MHs obtained by physicians and PTs in an emergency department. Second to evaluate, whether PTs could assist and/or replace physicians in obtaining MHs.
Methods
The study was conducted in the emergency department at Svendborg Hospital, Denmark and patients treated with a minimum of three prescribed medicines were included. On patients’ admission to hospital, physicians recorded the primary MHs, and within 48 h the secondary MHs were made by PTs. All MHs were conducted using standard guidelines. A clinical pharmacist reviewed the MHs, and based on these reviews, a final medication list was defined, and the MHs were compared to this. The discrepancies were registered with respect to type and therapeutic group (medicines).
Results
A total of 113 patients were included in this study, and data for 106 patients were analysed. On average, three discrepancies were detected for each patient in the primary MHs, and less than one discrepancy per patient in the secondary MHs. A total of 1075 prescriptions were registered, and for the physicians, 287 discrepancies (27 % of total prescriptions) were found, and for PTs the number was 28 (2 % of total prescriptions). The commonly detected discrepancy was “drug missing in the electronic patient record”. The largest number of discrepancies was found for nervous system medications (ATC group N), medicines from ATC group A (alimentary tract and metabolism) and respiratory medicine (ATC group R).
Conclusion
Fewer discrepancies in the MHs obtained by PTs than physicians were detected compared to standard medicine lists made by an experienced clinical pharmacist.
Aims
Drug‐related problems are a common complication in the transition from hospital to primary care and are associated with morbidity and increased health care costs. In this study, we evaluated the ...cost and consequences of a comprehensive pharmaceutical intervention compared with usual care, comprised of a medication review and patient interview before discharge and follow‐up for polypharmacy patients.
Methods
This economic evaluation was embedded within a randomized clinical trial. Patients were randomized to either the basic intervention group (n = 493) which received a medication review, the extended intervention group (n = 476) which received a medication review, discharge interview, and follow‐up, or the control group (n = 498) which received standard care. Total health care costs were estimated over a period of 180 days at individual patient level from a health sector perspective.
Results
The mean cost per patient was lower in the intervention groups (basic, €16 748; extended, €15 631) compared with the control group (€17 288), although these differences did not reach statistical significance. The costs of additional time used on medication reviews, patient interviews, and follow‐ups (€88) were outweighed by a decrease in costs of readmissions. The results of the clinical study favored the extended intervention group on clinical outcomes, with statistical significance on a composite of readmissions or emergency department visits within 180 days after inclusion (hazard ratio 0.77, 95% confidence interval 0.64‐0.93).
Conclusions
This comprehensive pharmaceutical intervention was not costly and positive effects were seen in the clinical outcomes, thereby reaching a decrease in total cost per patient on average. The results thus indicate that the intervention is cost‐effective and that the positive net effects can justify costs of the intervention.
Objective To assess the effects and cost effects of introducing clinical pharmacists on hospital wards. Methods Comparative prospective study on four orthopaedic surgical wards in two hospitals. The ...primary effect variables were 10 target areas widely considered to be indicators of good prescription practice. Prescriptions not following good practice in these intervention areas were defined as “sub-optimal prescriptions,” and then discussed between a physician and a clinical pharmacist. The primary parameter was the difference in the number of days with a sub-optimal prescription (Mann-Whitney test). Results On an average 20% of all the patients had a sub-optimal prescription. Of these, 70% were changed by the physician after intervention by the clinical pharmacist. There was a statistically significant difference in the duration of days in treatment with a sub-optimal prescription. Where sub-optimal prescriptions were changed, 43% resulted in cost reductions. The reductions achieved could cover 47% of the costs of clinical pharmacy service. Conclusions Clinical pharmacy services offered to four orthopaedic surgical wards resulted in reduction of sub-optimal prescriptions. Every time the pharmacist screened seven patients one sub-optimal prescription was found and adjusted. The reduction in medicine costs due to adjusted sub-optimal prescriptions could not cover the whole cost of clinical pharmacy service.
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