Utilization of computerized clinical decision support for potentially inappropriate medications.

Background: Electronic medical record (EMR) alerts may inform point of care decisions, including the decision to prescribe potentially inappropriate medications (PIM) identified in the Beers criteria. EMR alerts may not be considered relevant or informative in the clinician context, leading to a phenomenon colloquially known as "alert fatigue." Objective: To assess the frequency of clinical interaction with EMR alerts and associated deprescribing behaviors in ambulatory settings. Methods: This is a retrospective observational study in two ambulatory clinics (the Kaye Edmonton Clinic Senior's Clinic and the Lynnwood Family Practice Clinic) in Edmonton over an observational period of 30 months. Statistical analysis was done using descriptive statistics, chi-square and regression analysis. Results: The reminder performance for interactions with the alert was 17.2% across the two clinics. The Number Needed to Remind (NNR) or mean number of alerts shown on clinician screens prior to a single interaction of any kind with the alert was 5.8. When actions were defined as a deprescribing (ie discontinuation) event that was related to the alert and that particular interaction in the EMR, the reminder performance was 1.2%, for an NNR of 82.8. Conclusion: The configuration of alerts in the EMR was not associated with a clinically detectable increase in the uptake of the Beers criteria for high hazard medications.

Chronic levodopa therapy does not improve skilled reach accuracy or reach range on a pasta matrix reaching task in 6-OHDA dopamine-depleted (hemi-Parkinson analogue) rats.

L-dopa therapy reverses some but not all of the motor deficits in human Parkinson patients. Although a number rat analogues of human Parkinson's disease have been developed for evaluating the efficacy of drug therapies, it is not known whether L-dopa has a similar selective action on the motor symptoms in the rat models. To examine the effectiveness of L-dopa in reversing the motor deficits in rats, we administered 6-OHDA unilaterally to produce hemi-Parkinson rats, which were then trained to reach for food using either their impaired (contralateral to the lesion) limb or their good (ipsilateral to the lesion) limb. To assess the skill, accuracy and range of limb movement, rats reached for pasta from a horizontal array of 260 vertically orientated pieces of pasta. The number and location of pasta pieces taken from this matrix was calculated and the qualitative aspects of the reaching movements were rated. The quantitative data on pasta sticks retrieved indicated that forelimb extension and movement radius around the shoulder joint was reduced by 6-OHDA treatment and did not improve after chronic L-dopa treatment. The qualitative analysis showed that grasping patterns, paw movements and body movements impaired by the lesion were also not improved by L-dopa treatment. These findings are the first in the rat to suggest that whereas L-dopa has a general activating effect on the rat's whole-body movements, as displayed in contralateral rotation, its effectiveness does not extend to skilled forelimb movements. The results are discussed in relationship to the idea that the restoration of some skilled movements may require normal synaptic function.

The pasta matrix reaching task: a simple test for measuring skilled reaching distance, direction, and dexterity in rats.

Skilled forelimb use has been used in many studies to examine motor system status, learning, and recovery from nervous system damage in rats. The dependent measures in many current skilled reaching models rely on endpoint measures, number of successful reaches, or qualitative measures, the movements used in performing a reach. The present study describes a new reaching task, which allows measurement of distance and direction of skilled forelimb movement while also permitting end point and qualitative measurements. Animals reached from a clear Plexiglas box through an aperture to retrieve pieces of straight, uncooked pasta from an array of 260 vertically oriented pieces of pasta arranged in rows distally and laterally away from the aperture (a matrix). By extending the range of a reach, more pasta is obtained. Limb movements, pieces of pasta removed, and the pattern of pasta removal are dependent measures. The usefulness of the test is demonstrated using control, dorsal column lesion, and unilateral dopamine depleted animals. The task uses a desired food, tests learning and skill, the range of limb movement, and the ability to reach for different distances and directions. The task can also be modified to investigate other features of limb use including skill adjustments, laterality, and force.

A grasp-related deficit in tactile discrimination following dorsal column lesion in the rat.

The dorsal columns of the spinal cord are a major source of haptic (sense of active touch) and proprioceptive input to the brainstem and sensory-motor cortex. Following injury in primates, there are impairments in two-point discrimination, direction of movement across the skin, and frequency of vibration, and qualitative control of the digits, but simple spatial discriminations recover. In the rat there are qualitative deficits in paw control in skilled reaching, but no sensory deficits have been reported. Because recent investigations of sensory control suggest that sensory functions may be related to specific actions, the present study investigated whether the dorsal columns contribute to hapsis during food grasping in the rat. Adult female Long-Evans rats were trained to reach with a single forepaw for a piece of uncooked pasta or for equivalent sized but tactually different nonfood items. One group was given lesions of the dorsal column ipsilateral to their preferred paw, while the second group served as a control. Postlesion, both groups were tested for skilled reaching success and force application as well as adhesive dot removal and forepaw placing. Performance levels on these tests were normal. Nevertheless, the rats with dorsal column lesions were unable to discriminate a food item from a tactually distinctive nonfood item as part of the reaching act, suggesting that the dorsal columns are important for on-line tactile discriminations, or "haptic actions," which contribute to the normal performance of grasping actions.

Skilled forelimb reaching for pasta guided by tactile input in the rat as measured by accuracy, spatial adjustments, and force.

Rats are capable of reaching for food with a single forelimb, but since they locate the target of their reach using olfaction, it is unclear how they adjust their limb movement to compensate for errors. Although it is thought that their reaching movement is ballistic and can only be adjusted by trial and error, whether they can use haptic cues to aid in locating and identifying a target has not been examined. The present study addressed this question by allowing rats to reach through a slot for rigidly held pieces of uncooked pasta of varying thickness, which could be oriented vertically or horizontally from different points around the slot and which were attached to a force transducer. The tasks required that animals not only adjust their reach and grasp to the target's location but also identify the target based on its texture. Acquisition curves were made of head orientation, limb transport trajectories, number of attempts per success, paw orientation, breaking direction and force of the grasp. A haptic discrimination test used pasta and similar sized metal rods with different tactile properties as discriminanda. The results indicated that whereas postural orientation and limb transport trajectory were not modified as a function of target orientation, paw orientation and grasp force did vary as a function of the sensory qualities of the target object, and the rats could make a haptic discriminative choice of a target object. The results show that the rat is capable of adjusting paw movements using haptic information, suggesting that somatosensory features of sensorimotor control of limb and paw movements in carnivores and primates are shared by rodents. This commonality points to a conservation of motor control in mammals, explains some of the idiosyncratic features of rat reaching behavior, and confirms that rodents provide a good model for investigating sensorimotor functions.

Embryonic and postnatal injections of bromodeoxyuridine produce age-dependent morphological and behavioral abnormalities.

The mitotic marker 5-bromodeoxyuridine (BrdU) was injected twice daily (60 mg/kg) into pregnant hooded rats on one of embryonic days (E) 11, 12, 13, 15, 17, or 21, or into rat pups on postnatal day (P) 10. The principal findings were the following: (1) BrdU exposure on E11 produces profound effects on body morphology, and animals must be fed a special diet because of chronic tooth abnormalities; (2) BrdU exposure at E17 or earlier produces a change in coat spotting pattern, the precise pattern varying with age; (3) BrdU exposure on E15 or earlier produces a reduction in both brain and body weight; (4) BrdU exposure on E17 or earlier reduces cortical thickness; (5) BrdU exposure on E11-E13 and at P10 reduces cerebellar size relative to cerebral size; (6) spatial learning is significantly affected after injections of BrdU at E11-E17, but the largest effect is on E17; (7) the deficit in spatial learning may be related in part to a reduction in visual acuity; and (8) skilled forelimb ability is most disrupted after BrdU exposure at E15 but is also impaired after injections on E13 or earlier. BrdU thus has teratological effects on body, brain, and behavior that vary with the developmental age of the fetus or infant.