Opening the black box of cancer surgery quality: WebSMR and the Alberta experience.

A web-based synoptic operative report, the WebSMR (Surgical Medical Record), was developed to define and improve the quality of cancer surgery. Surgeons accurately record the essential steps of an operation including important decision-making in an analyzable format. Outcomes can be reviewed with provincial aggregates for quality improvement and maintenance of certification. Future synoptic pathology and follow-up templates will open the "black box" of surgical processes to define quality indicators for the improvement of cancer outcomes.

Successes and challenges in a field-based, multi-method study of home telehealth.

We are conducting a three-year study of telehealth in 11 home care offices that serve rural clients in Alberta. Three hundred and twenty palliative home care clients are being recruited to participate in a randomized controlled trial (RCT) to answer three questions about the use of video-phones and their effect on symptom management, quality of life and cost, as well as readiness to use the technology. Both successes and challenges have been identified in three main areas: technology, people/organizational issues and study design. Maintaining study integrity has been the key factor in decision making, as adjustments from the original proposal are made. It is already clear that field-based RCTs are feasible, but require commitment and flexibility on the part of researchers and community partners to work through the study implementation.

Predicting success: stakeholder readiness for home telecare diabetic support.

Readiness to adopt a new technology is one factor that contributes to the success of a telehealth programme. Since one goal of telehealth is to improve care, it is appropriate to determine its success through a quality-of-care framework that addresses structure, process and outcome. A qualitative case study of home care in the Calgary Health Region in Alberta set out to understand how clients, nurses, physicians and managers perceived their readiness to use video-visits for home care. Focus groups, home visits, and telephone and face-to-face interviews were used to collect data. Readiness to adopt home telecare was compared between groups, as well as with behaviour predicted in the literature. Differences in perceptions were identified among the four participant groups. Clients and managers identified a higher degree of readiness-clients because of the potential to support independence in their homes and managers because of the potential efficiencies in the system.

Predicting success: stakeholder readiness for home telecare diabetic support.

Readiness to adopt a new technology is one factor that contributes to the success of a telehealth programme. Since one goal of telehealth is to improve care, it is appropriate to determine its success through a quality-of-care framework that addresses structure, process and outcome. A qualitative case study of home care in the Calgary Health Region in Alberta set out to understand how clients, nurses, physicians and managers perceived their readiness to use video-visits for home care. Focus groups, home visits, and telephone and face-to-face interviews were used to collect data. Readiness to adopt home telecare was compared between groups, as well as with behaviour predicted in the literature. Differences in perceptions were identified among the four participant groups. Clients and managers identified a higher degree of readiness - clients because of the potential to support independence in their homes and managers because of the potential efficiencies in the system.

What constitutes success in telehealth?

Before telehealth applications can be judged, there must be some general understanding about what constitutes success. At first sight it seems that defining success in a telehealth application should be relatively easy: a successful application is one that produces high-quality care at low cost. However, the calculation of cost requires some care, since it depends on assuming a particular financial perspective (the patient's, the health-care provider's, or society's) and is meaningless without a statement of the workload being handled. Other factors include the context in which the service is being delivered. Ultimately, the political imperative may override any rational judgement of success.

Protein phosphorylation cascades associated with methamphetamine-induced glial activation.

Reactive gliosis is the most prominent response to diverse forms of central nervous system (CNS) injury. The signaling events that mediate this characteristic response to neural injury are under intense investigation. Several studies have demonstrated the activation of phosphoproteins within the mitogen-activated protein kinase (MAPK) and Janus kinase (JAK) pathways following neural insult. These signaling pathways may be involved or responsible for the glial response following injury, by virtue of their ability to phosphorylate and dynamically regulate the activity of various transcription factors. This study sought to delineate, in vivo, the relative contribution of MAPK- and JAK-signaling components to reactive gliosis as measured by induction of glial-fibrillary acidic protein (GFAP), following chemical-induced neural damage. At time points (6, 24, and 48 h) following methamphetamine (METH, 10 mg/kg x 4, s.c.) administration, female C57BL/6J mice were sacrificed by focused microwave irradiation, a technique that preserves steady-state phosphorylation. Striatal (target) and nontarget (hippocampus) homogenates were assayed for METH-induced changes in markers of dopamine (DA) neuron integrity as well as differences in the levels of activated phosphoproteins. GFAP upregulation occurred as early as 6 h, reaching a threefold induction 48 h following METH exposure. Neurotoxicant-induced reductions in striatal levels of DA and tyrosine hydroxylase (TH) paralleled the temporal profile of GFAP induction. Blots of striatal homogenates, probed with phosphorylation-state specific antibodies, demonstrated significant changes in activated forms of extracellular-regulated kinase 1/2 (ERK 1/2), c-jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK), MAPK/ERK kinase (MEK1/2), 70-kDa ribosomal S6 kinase (p70 S6), cAMP responsive element binding protein (CREB), and signal transducer and activator of transcription 3 (STAT3). MAPK-related phosphoproteins exhibited an activation profile that peaked at 6 h, remained significantly increased at 24, and fell to baseline levels 48 h following neurotoxicant treatment. The ribosomal S6 kinase was enhanced over 60% for all time points examined. Immunoreactivity profiles for the transcription factors CREB and STAT3 indicated maximal increases in phosphorylation occurring at 24 h, and measuring greater than 2- or 17-fold, respectively. Specific signaling events were found to occur with a time course suggestive of their involvement in the gliotic response. The toxicant-induced activation of these growth-associated signaling cascades suggests that these pathways could be obligatory for the triggering and/or persistence of reactive gliosis and may therefore serve as potential targets for modulation of glial response to neural damage.

Effects of social defeat and of diazepam on behavior in a resident-intruder test in male DBA/2 mice.

Social stress induces robust behavioral and physiological changes, some of which may alter the responsiveness to pharmacological agents, including diazepam (DZP). We used a resident-intruder paradigm to (1) develop a comprehensive ethogram of behavioral changes following social defeat (SD) in the socially reactive strain, DBA/2 male mice, (2) determine whether acute exposure of DBA/2 mice to low-dose DZP would induce flight or aggressive behavior, both of which have been observed in other rodent models and (3) to test whether prior social stress affects responses to DZP. Behavioral responses to a nonaggressive intruder (NAI) mouse 24 h post-SD were measured in resident subject mice exposed to DZP (0, 0.5, 2.0 mg/kg, ip) either prior to the resident-intruder test (Experiment 1) or immediately post-SD (Experiment 2); control mice were not defeated (NOSD). In general, SD mice displayed increased passive and active avoidance, defense, immobility, and risk assessment relative to NOSD mice. In Experiment 1, mice treated acutely with 0.5 mg/kg DZP had more approach and flight behavior, while those treated with 2.0 mg/kg DZP had more avoidance than vehicle-treated mice, independent of SD. In Experiment 2, acute DZP (2 mg/kg) induced effects 24 h later, possibly secondary to withdrawal. In a nonsocial context (Experiment 3), DZP increased exploratory activity.

Cocaine produces panic-like flight responses in mice in the mouse defense test battery.

There is an emerging body of clinical evidence that cocaine use in humans can result in serious fear or panic-related emotional disturbances. The present study evaluated the effects of cocaine administration upon defensive responses of mice to a predator (rat) in a Mouse Defense Test Battery (MDTB) that permits the display of the full range of the mouse defensive behaviors: avoidance/escape, flight, freezing, defensive upright, and defensive threat and attack. Mice were tested 30 min following intraperitoneal (IP) injections of either 0, 10, 20, or 30 mg/kg cocaine hydrochloride suspended in physiological saline. Cocaine produced an increase in flight and escape responses throughout the subtests comprising the MDTB. The percentage of subjects exhibiting escape increased in cocaine-treated mice in the Predator Avoidance Test. Cocaine increased mean flight speed and maximum flight speed in the Flight/Chase Test; frequency of flight responses in the Straight Alley Test; and the number of flight attempts in the Forced Contact test. The predominance of flight responding throughout the tests masked any possible cocaine effects on other defenses. The present findings indicate that cocaine may exert its panic-producing effects by acting upon particular neurobehavioral systems subserving defensive behavior.

Amygdala lesions produce analgesia in a novel, ethologically relevant acute pain test.

Acute pain tests using mechanical stimuli typically do not involve objects important in the evolutionary history of the subjects, and may fail to evaluate the contribution of biobehavioral defensive reactions to the total pain response. Spines are common structural defenses that protect plants and animals against predation. The present studies examined the reaction to contact with such natural, mechanical pain stimuli in the laboratory rat, utilizing a floor board with protruding pins located in the middle of a novel alley (the "fakir" test). Behavioral responses were characterized in 10-min tests (Experiment 1). Subjects showed voluntary contact with the pins followed by patterns of avoidance and risk assessment (stretch attend and stretch approach). Few subjects crossed the array of pins. The amygdala has been implicated in the perception of pain, particularly in stressful or fearful contexts. In Experiment 2, the fakir test was used to examine, concurrently, the effects of amygdala lesions on analgesiometric (frequency and duration of pin crossings) and anxiometric (risk assessment) measures. Large, bilateral, lesions of the amygdala significantly increased both the number of pin crossings and time spent on the pins without affecting the risk assessment measures. These findings suggest a possible dissociation between anxiety and pain perception with an important (nonaffective) role for the amygdala in the latter.

Intravenous cocaine precipitates panic-like flight responses and lasting hyperdefensiveness in laboratory rats.

There is an emerging body of clinical evidence that cocaine use in humans can result in serious fear or panic-related emotional disturbances. The present study evaluated the effects of intravenous cocaine administration upon defensive responses of rats to a threatening conspecific in a test situation, an oval runaway, permitting the display of the full range of the rat defensive repertoire. A battery of tests was employed to evaluate avoidance/escape, flight, freezing, defensive upright and defensive attack behaviors. In the first experiment male Long-Evans rats implanted with a chronic indwelling jugular catheter were placed in the runway and tested immediately after administration of either 0, 1, or 4 mg/kg of cocaine hydrochloride. The 4-mg/kg dose produced a dramatic flight response, the direction of which depended upon the direction of the approaching threat source. The same dose produced increased defensive upright postures during forced contact with the stimulus animal. Experiment 2 examined the time course for cocaine-induced hyperdefensiveness. Rats were administered either saline or 4 mg/kg cocaine intravenously and were tested following a delay of either 0, 5, 15, or 30 min following infusion. Cocaine-treated rats again displayed high levels of flight, which declined with increased time between infusion and testing. However, increased defensiveness persisted even at the 30 min delay for several defensive measures including avoidance, freezing, and defensive upright posture. Thus, following an initial period of rapid flight with intravenous cocaine administration, there was a lasting hyperdefensiveness in cocaine-treated rats. The present results suggest that cocaine may exert its panic-producing effects by acting upon neurobehavioral systems subserving defensive behavior, and that understanding of these systems is critical for understanding the neurobiology of panic disorder.

Age-related reductions in [3H]WIN 35,428 binding to the dopamine transporter in nigrostriatal and mesolimbic brain regions of the fischer 344 rat.

In the present study, we used the potent cocaine analog [3H]WIN 35, 428 to map and quantify binding to the dopamine transporter (DAT) within the dorsal striatum, nucleus accumbens, substantia nigra, and ventral tegmental area in young (6-month-old), middle-aged (12-month-old), and aged (18- and 24-month-old) Fischer 344 rats. Quantitative autoradiographic analysis of indirect [3H]WIN 35,428 saturation curves revealed two-site binding for all four brain regions in every age group. The percentage of binding to the high- or low-affinity sites did not differ with age or region and was approximately 50%. However, significant age-related decreases in the overall density (Bmax) of [3H]WIN 35,428-binding sites were observed in the striatum, nucleus accumbens, substantia nigra, and ventral tegmental area. The Bmax within all brain regions declined by more than 15% every 6 months, with the Bmax in the aged (24-month-old) group being approximately half that measured in the young adult (6-month-old) group. Competition experiments indicated that nomifensine also exhibited two-site binding to the DAT in Fischer 344 rats. No consistent age-related differences in binding affinities were noted with either [3H]WIN 35,428 or nomifensine. Taken together, these results support the hypothesis that functional DATs within the nigrostriatal and mesolimbic systems are down-regulated with age, without changing their affinity for ligands.

Age-related changes in the capacity, rate, and modulation of dopamine uptake within the striatum and nucleus accumbens of Fischer 344 rats: an in vivo electrochemical study.

Age-related changes in the capacity, rate, and modulation of dopamine (DA) uptake within the striatum and the nucleus accumbens core of Fischer 344 rats were investigated using in vivo electrochemical recordings coupled with local drug application techniques. Equimolar amounts of DA were pressure ejected into the striatum and the nucleus accumbens of 6-, 12-, 18-, and 24-month old rats. The DA ejections produced larger DA signal amplitudes in the older rats, suggesting age-related differences in the capacity to clear extracellular DA. Within the striatum, the capacity and rate of DA uptake were reduced by 50% in the aged groups (18 and 24 months) compared with the younger rats (6 and 12 months). In the nucleus accumbens, significant reductions in DA uptake capacity and rate were observed in the 24-month group. In both brain regions and in all age groups studied, the rate of DA uptake was found to be concentration-dependent until a maximal rate was reached. The maximum rate of DA transport was significantly reduced in both the striatum and the nucleus accumbens of aged rats (18 and 24 months versus 6 and 12 months). The ability of nomifensine, an inhibitor of the DA transporter, to modulate DA signal amplitudes in the striatum and the nucleus accumbens was also decreased with age (24 months versus 6 months). Taken together, these findings demonstrate substantial age-related deficits in DA uptake processes within the striatum and the nucleus accumbens, consistent with the hypothesis that DA uptake may be slowed in aged animals to compensate for reductions in DA release.

Defensive behaviors in wild and laboratory (Swiss) mice: the mouse defense test battery.

The development of laboratory rodent models for elicitation and measurement of a range of defensive behaviors raises the question of the relationship between defense in these animals and those of their wild congeners. To evaluate this relationship for mice, defensive responses to an anesthetized rat were compared for fourth-generation laboratory-bred wild mice and Swiss CD-1 (Swiss-Webster derived) laboratory mice in a Mouse Defense Test Battery. Wild mice showed enhanced levels of both freezing and flight, fleeing from distant approach of the predator in several situations and fleeing more quickly than the Swiss mice. However, Swiss mice did flee upon contact with the rat and also showed levels of several other defensive behaviors (risk assessment, defensive threat, and attack) that were often reliably higher than those of the wild mice. However, when wild mice were prevented from fleeing, their levels of defensive threat and attack were as high as, or at very short prey-predator distances higher than, those of the Swiss mice. These findings suggest that flight and freezing are the major defensive behaviors reduced in Swiss mice and that these reductions allow the appearance of higher levels of additional defensive behaviors in the laboratory animals. However, although Swiss mice do show lower levels of flight and freezing, their patterns of defensive behavior are sufficiently similar to those of wild mice that they provide adequate subjects for research on the biologic bases of defensive behavior. A final experiment indicated that when wild mice are familiarized with a chamber providing a place of concealment, they flee directly to this chamber on presentation of a rat, indicating that flight is a targeted response and not simply an abrupt increase in forward locomotion. Over 10 rat presentation trials with a blocked chamber entrance, however, this response declines.

Normal and drug-induced locomotor behavior in aging: comparison to evoked DA release and tissue content in fischer 344 rats.

The consequences of aging on dopamine (DA) regulation within the nigrostriatal and mesolimbic systems were investigated with a combination of behavioral, in vivo electrochemical, and high-performance liquid chromatography measurements using 6-, 12-, 18- and 24-month old male Fischer 344 (F344) rats. Spontaneous locomotor testing demonstrated that aged (18- and 24-month) rats moved significantly less and at a slower speed than younger (6- and 12-month) animals. Additionally, systemic injection (intraperitoneal) of the DA uptake inhibitor, nomifensine, was significantly less efficacious in augmenting the locomotor activity of aged rats compared to the younger animals. Age-dependent alterations in the release capacity of DA neurons within the regions involved in movement were investigated using in vivo electrochemistry. These recordings indicated that both the magnitude and temporal dynamics of potassium (70 mM)-evoked DA overflow were affected by the aging process. Signal amplitudes recorded in the 24-month rats were 30-60% reduced in both the striatum and nucleus accumbens as compared to the young adult groups. In addition, the duration of the electrochemical DA signals recorded within the striatum of 24-month old rats was twice that in the younger animals (6- and 12-month). Whole tissue measurements of DA and DA metabolites suggest age-related deficits in locomotion and DA release were not related to decreases in the storage or synthesis of DA within the striatum, nucleus accumbens, substantia nigra, ventral tegmental area or medial prefrontal cortex. Taken together, these results indicate age-dependent deficits in movement are related to the dynamic properties of DA release and not static measures of DA content.

Age-related decline in striatal dopamine release and motoric function in brown Norway/Fischer 344 hybrid rats.

The Brown Norway/Fischer 344 F1 hybrid rats (F344BNF1) is a newer rat model and is emerging as an important rodent model of aging. In the present study we used motoric performance tests, intracerebral microdialysis, and neurochemical measures of postmortem brain tissue to investigate the effects of aging in young (4-5 months), middle-aged (18-19), and old (24-25 months) F344BNF1 hybrid rats. We observed that old F344BNF1 rats exhibited decreased motoric performance, and lower levels of spontaneous and d-amphetamine-induced locomotor activity than those observed in young F344BNF1 rats. Microdialysis measures of extracellular basal levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and 4-hydroxy-3-methoxyphenylacetic acid (HVA) were significantly diminished in the striata of the middle-aged and old rats as compared to levels in young animals. In addition, d-amphetamine-evoked overflow of DA was significantly decreased in the middle-aged and aged rat striatum as compared to DA overflow in young F344BNF1 rats. Studies of postmortem brain tissue showed that the changes in overflow of DA correlated with significantly lower DA tissue content in ventral striatum and midbrain. Moreover, both dopamine turnover ratios (DOPAC/DA, HVA/DA) and the serotonin turnover ratio (5-HIAA/5-HT) were significantly elevated in the ventral striatum and nucleus accumbens. The results of this study demonstrate a correlation between reductions in striatal DA neurochemistry and diminished motor function in aged F344BNF1 rats.

Impact of IT on health care professionals: changes in work and the productivity paradox.

Health care organizations are under increasing pressure to become more efficient while at the same time maintaining or improving the quality of care. Information technology (IT), with its potential to increase efficiency, accuracy and accessibility of information, has been expected to play an important role in supporting these changes. We report the impact of patient care information systems on health care professionals in five community hospitals. The study framework incorporated both quality of care in Donabedian's elements of structure-process-outcome and Grusec's three levels of IT impact: direct substitution, proceduralization and new capabilities. The study results suggest that, for specific tasks, IT increased efficiency and productivity--a single employee was able to complete more tasks. However, this produced other consequences not predicted. Participants noted this change did not 'free up time' to spend with patients, but meant there were potentially more opportunities to provide services and more tasks to complete. Other effects included: reduced job satisfaction as more time was spent on the computer; less frequent interactions with patients and for shorter duration; and an increasingly 'visible' accountability as performance was easily monitored. There were also changes in roles and responsibilities as the computer enabled tasks to be carried out from a number of locations and by a variety of personnel. When innovations are introduced into organizations there are both expected and unexpected consequences. Increased awareness of the interactive relationship between computer users and the technology helps organizations better understand why results do, or do not, occur. One must look beyond just simply increasing productivity by replacing manual tasks with automated ones, to examining how the changes influence the nature of work and relationships within the organization.

Acute cocaine effects on stereotype and defense: an ethoexperimental approach.

Cocaine administration to laboratory animals may produce locomotor hyperactivity and stereotypies that include sniffing and rearing, in addition to anxiety-like effects. A time-sampling study of the effects of 3, 10 or 30 mg/kg cocaine (i.p.) over time following injection indicated early enhancement of locomotion and crouching, with the latter most increased in low- and intermediate-dose cocaine groups, with increased rearing and standing during the second hour of the test period. Additional analyses at 30-60 min post-injection suggested qualitative changes in rearing, with high dose animals showing more, but shorter, rears, and a higher frequency of sniffing. The high dose cocaine enhancement of sniffing was strongly associated with rear and stand behaviors, but also occurred while the animal was crouching. This pattern of changes, with initial crouching/freezing and locomotion (flight?), followed by rearing, standing, and sniffing behaviors similar to those seen in risk assessment suggests that cocaine, particularly at high doses, may elicit defense. An additional study using only saline or the high (30 mg/kg) dose indicated that cocaine produced more sniffing regardless of the direction from which the air stream entered the test cage (i.e. top or bottom). However, cocaine animals oriented their sniffing behaviors toward the incoming air, with reliably more sniffs up in cages with the air stream entering from the top, and more sniffs down, when the air stream entered through a wire mesh cage bottom. Controls showed the same pattern, but their sniff orientation differences were not reliable. These results indicate that the sniffing that follows acute high dose cocaine administration is appropriately oriented toward relevant environmental stimuli, a factor disconsonant with the interpretation of sniffing as a stereotypical behavior, but one that is in agreement with the view that it may reflect a risk assessment component of the defense pattern.

Behavioral and neurochemical effects of intranigral administration of glial cell line-derived neurotrophic factor on aged Fischer 344 rats.

To investigate the efficacy of glial cell line-derived neurotrophic factor (GDNF) in the augmentation of functional dopaminergic (DAergic) indices in aged rats, 24-month-old Fischer 344 (F344) rats received single intranigral injections of 10 microg GDNF (in 10 microl phosphate-buffered saline) or 10 microl phosphate-buffered saline. In locomotor activity tests, the GDNF-treated animals exhibited significant increases in both total distance traveled and movement speed compared with the vehicle group, 3 weeks after injections. In vivo microdialysis studies showed that basal extracellular levels of dopamine (DA) and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, were significantly increased in the striatum of the GDNF-treated rats. In addition, both potassium- (100 mM, K+) and d-amphetamine (250 microM)-induced DA overflow were augmented in the striatum and nucleus accumbens of the aged rats injected with GDNF. Whole-tissue levels of DA and DA metabolites, as measured by high-performance liquid chromatography coupled with electrochemical detection, in the nucleus accumbens and substantia nigra were also elevated after GDNF administration. These results indicate that a single intranigral injection of GDNF is capable of augmenting locomotor behavior and DAergic function in the aged rat striatum and nucleus accumbens. This is the first report to demonstrate that a single intranigral injection of GDNF can improve the functional capacity of DAergic neurons of aged F344 rats.

Functional effects of GDNF in normal rat striatum: presynaptic studies using in vivo electrochemistry and microdialysis.

The functional effects of a single dual-site intranigral administration (10 micrograms) of glial cell line-derived neurotrophic factor (GDNF) on dopamine (DA) neurons in the basal ganglia of young Fischer 344 rats were investigated. A combination of behavioral, in vivo electrochemical, microdialysis and high-performance liquid chromatography methods were used to study the effects of this novel peptide. Behaviorally, significant changes in spontaneous locomotor activity were found 1 week, but not 3 weeks, after GDNF treatment. However, the velocity of movements was increased in the GDNF-treated animals 3 weeks after GDNF administration, a result that corresponded to significant enhancement of stimulus-evoked release of DA. Two-fold increases in potassium-evoked DA overflow were seen throughout the striatum by means of high-speed chronoamperometry 3 weeks after GDNF injection. No significant change in basal levels of DA was measured by microdialysis, although both potassium-evoked and d-amphetamine-induced DA overflow were significantly increased 3 weeks after treatment. Finally, significant changes in whole-tissue levels of DA were seen in the substantia nigra 1 week, but not 3 weeks, after GDNF administration. These data represent the first studies demonstrating that GDNF has long-lasting functional presynaptic effects on DA-containing neurons in the rat striatum.