Knowledge 'Translation' as social learning: negotiating the uptake of research-based knowledge in practice.

BACKGROUND: Knowledge translation and evidence-based practice have relied on research derived from clinical trials, which are considered to be methodologically rigorous. The result is practice recommendations based on a narrow view of evidence. We discuss how, within a practice environment, in fact individuals adopt and apply new evidence derived from multiple sources through ongoing, iterative learning cycles. DISCUSSION: The discussion is presented in four sections. After elaborating on the multiple forms of evidence used in practice, in section 2 we argue that the practitioner derives contextualized knowledge through reflective practice. Then, in section 3, the focus shifts from the individual to the team with consideration of social learning and theories of practice. In section 4 we discuss the implications of integrative and negotiated knowledge exchange and generation within the practice environment. Namely, how can we promote the use of research within a team-based, contextualized knowledge environment? We suggest support for: 1) collaborative learning environments for active learning and reflection, 2) engaged scholarship approaches so that practice can inform research in a collaborative manner and 3) leveraging authoritative opinion leaders for their clinical expertise during the shared negotiation of knowledge and research. Our approach also points to implications for studying evidence-informed practice: the identification of practice change (as an outcome) ought to be supplemented with understandings of how and when social negotiation processes occur to achieve integrated knowledge. This article discusses practice knowledge as dependent on the practice context and on social learning processes, and suggests how research knowledge uptake might be supported from this vantage point.

Does the treatment of spastic equinovarus deformity following stroke with botulinum toxin increase gait velocity? A systematic review and meta-analysis.

While botulinum toxin-A (BT-A) has been used to treat lower-limb focal spasticity successfully, its effect on characteristics of gait has not been well defined. The objective of this systematic review was to establish the treatment effect associated with the use of BT-A for equinovarus to improve gait velocity following stroke, using a meta-analytic technique. Relevant studies were identified through a literature search encompassing the years 1985 to November 2009. Studies were included if (i) the sample was composed of adult subjects recovering from either first or subsequent stroke, presenting with spastic equinovarus deformity of the ankle preventing full active dorsiflexion, and (ii) subjects who received BT-A were compared with subjects who had received a placebo, or (iii) in the absence of a placebo-controlled condition, subject had received BT-A and was assessed before and after treatment. A standardized mean difference (SMD) ± standard error and 95% confidence interval (CI) for gait velocity between the treatment and control group was calculated for each study, using Hedges's g, and the results pooled. Eight trials, five randomized controlled trials, and three single group intervention studies were included. Data representing 228 subjects were available for pooled analysis. Treatment with BT-A was associated with a small improvement in gait velocity (Hedge's g = 0.193 ± 0.081; 95% CI: 0.033 to 0.353, P < 0.018) representing an increase of 0.044 meters/s. The use of BT-A for lower-limb post-stroke equinovarus because of spasticity was associated with a small, but statistically significant increase in gait velocity.

Issues for selection of outcome measures in stroke rehabilitation: ICF Body Functions.

PURPOSE: To evaluate the psychometric and administrative properties of outcome measures assigned to the ICF Body Functions category, and commonly used in stroke rehabilitation research. METHOD: Critical review and synthesis of measurement properties for five commonly reported instruments in the stroke rehabilitation literature. Each instrument was rated using the eight evaluation criteria proposed by the UK Health Technology Assessment (HTA) programme. The instruments were also assessed for the rigour with which their reliability, validity and responsiveness were reported in the published literature. RESULTS: The reporting of specific measurement qualities for outcome instruments was relatively consistent across measures located within the same general ICF category. Far less information was available on the responsiveness of measures, compared with reliability and validity. The best available instruments were associated with the following body functions: cognitive impairment, depression and motor recovery. CONCLUSIONS: The reader is encouraged to examine carefully the nature and scope of outcome measurement used in reporting the strength of evidence for improved body functions in stroke rehabilitation since there is significant diversity. However there appears to be good consensus about what are the most important indicators of successful rehabilitation outcome in each domain of body function.

Issues for selection of outcome measures in stroke rehabilitation: ICF activity.

PURPOSE: To evaluate the psychometric and administrative properties of outcome measures in the WHO International Classification of Functioning, Disability and Health (ICF) Activity category used in stroke rehabilitation research and reported in the published literature. METHOD: Critical review and synthesis of measurement properties for nine commonly reported instruments in the stroke rehabilitation literature. Each instrument was rated using the eight evaluation criteria proposed by the UK Health Technology Assessment (HTA) programme. The instruments were also assessed for the rigour with which their reliability, validity and responsiveness were reported in the published literature. RESULTS: The reporting of specific measurement qualities for outcome instruments was relatively consistent across measures located within the same general ICF category. There was evidence to suggest that the measures were responsive to change as well as being valid and reliable tools. The best available instruments were associated with the assessment of activities of daily living, balance (static and dynamic), functional independence, and functional mobility. CONCLUSIONS: Given the diversity that exists among available measures, the reader is encouraged to examine carefully the nature and scope of outcome measurement used in reporting the strength of evidence for improved functional activity in stroke rehabilitation. However, there appears to be good consensus regarding the most important indicators of successful rehabilitation outcome, especially in the case of functional mobility.

Issues for selection of outcome measures in stroke rehabilitation: ICF Participation.

PURPOSE: To evaluate the psychometric and administrative properties of outcome measures in the ICF Participation category, which are used in stroke rehabilitation research and reported in the published literature. METHOD: Critical review and synthesis of measurement properties for six commonly reported instruments in the stroke rehabilitation literature. Each instrument was rated using the eight evaluation criteria proposed by the UK Health Technology Assessment (HTA) programme. The instruments were also assessed for the rigour with which their reliability, validity and responsiveness were reported in the published literature. RESULTS: Validity has been well reported for at least half of the measures reviewed. However, methods for reporting specific measurement qualities of outcome instruments were inconsistent. Responsiveness of measures has not been well documented. Of the three ICF categories, Participation seems to be most problematic with respect to: (a) lack of consensus on the range of domains required for measurement in stroke; (b) much greater emphasis on health-related quality of life, relative to subjective quality of life in general; (c) the inclusion of a mixture of measurements from all three ICF categories. CONCLUSIONS: The reader is encouraged to examine carefully the nature and scope of outcome measurement used in reporting the strength of evidence for improved participation associated with stroke rehabilitation. There is no consensus regarding the most important indicators of successful involvement in a life situation and which ones best represent the societal perspective of functioning. In particular, quality of life outcomes lack adequate conceptual frameworks to guide the process of development and validation of measures.

Data collection methods in health services research: hospital length of stay and discharge destination.

BACKGROUND: Hospital length of stay and discharge destination are important outcome measures in evaluating effectiveness and efficiency of health services. Although hospital administrative data are readily used as a data collection source in health services research, no research has assessed this data collection method against other commonly used methods. OBJECTIVE: Determine if administrative data from electronic patient management programs are an effective data collection method for key hospital outcome measures when compared with alternative hospital data collection methods. METHOD: Prospective observational study comparing the completeness of data capture and level of agreement between three data collection methods; manual data collection from ward-based sources, administrative data from an electronic patient management program (i.PM), and inpatient medical record review (gold standard) for hospital length of stay and discharge destination. RESULTS: Manual data collection from ward-based sources captured only 376 (69%) of the 542 inpatient episodes captured from the hospital administrative electronic patient management program. Administrative data from the electronic patient management program had the highest levels of agreement with inpatient medical record review for both length of stay (93.4%) and discharge destination (91%) data. CONCLUSION: This is the first paper to demonstrate differences between data collection methods for hospital length of stay and discharge destination. Administrative data from an electronic patient management program showed the highest level of completeness of capture and level of agreement with the gold standard of inpatient medical record review for both length of stay and discharge destination, and therefore may be an acceptable data collection method for these measures.

Attachment style, family and romantic relationships.

In 1987 Hazan and Shaver showed that patterns of romantic love reflected attachment styles. In an extension of that study with 39 men and 33 women in college (ages 18-36 years), this research shows that family relationships may also affect romantic relationships indirectly through their association with attachment styles.

Assessing the impact of thrombolysis on progress through inpatient rehabilitation after stroke: a multivariable approach.

BACKGROUND: Acute administration of tissue plasminogen activator has been shown to improve immediate and long-term patient recovery after ischaemic stroke. Yet, despite widespread clinical application, many patients who receive acute tissue plasminogen activator still require inpatient rehabilitation. AIMS AND HYPOTHESIS: This study aimed to examine the effect of tissue plasminogen activator administration on recovery among patients requiring inpatient rehabilitation after stroke in Ontario, Canada. It was hypothesized that after covariate adjustment, administration of tissue plasminogen activator would be associated with accelerated progress through inpatient rehabilitation. METHODS: Acute and rehabilitation data were retrieved from the Registry of the Canadian Stroke Network and the National Rehabilitation Reporting System for all ischaemic stroke patients admitted to an acute facility and a rehabilitation unit between July 1, 2003 and March 31, 2008. Patients were divided into two groups: those who received tissue plasminogen activator and those who were medically eligible but did not receive tissue plasminogen activator. Three rehabilitation progress indicators were compared between groups: Functional Independence Measure gain, active length of stay, and discharge destination. Indicators were modelled using multivariable generalized linear models or logistic regression as appropriate. RESULTS: Patients who received tissue plasminogen activator experienced shorter active lengths of stay (log estimate ± standard error: -0·04 ± 0·01 days), and were slightly more likely to be discharged home compared to controls (adjusted odds ratio 1·35, 95% confidence interval 1·004-1·82). No differences were noted on Functional Independence Measure gain during rehabilitation. CONCLUSION: Results suggest that tissue plasminogen activator may contribute to accelerated progress through inpatient rehabilitation; however, there is no evidence to suggest that it contributes to greater functional improvement as measured by the Functional Independence Measure.

Endothelin receptor coupling to potassium and chloride channels in isolated rat pulmonary arterial myocytes.

Endothelin (endothelin)-1 may in important role in the control of pulmonary arterial tone, part of its action being due to a putative ability to regulate membrane ion channel activity. Consequently, we have examined its effects on membrane currents in pulmonary arterial myocytes by using the patchclamp recording technique. Endothelin-1 (0.1-50 nM) activated an oscillatory inward current and caused a brief enhancement, followed by inhibition of the outward K+ current. Pharmacological and anion substitution experiments revealed that the oscillations of inward current were due to ET(A) receptor stimulation and subsequent activation of Ca(+2)-activated Cl- channels (EC50 > or = 16 nM). Enhancement of K+ current was inhibited by FR139317 (an ET(A) receptor antagonist) and by buffering intracellular Ca+2, which suggests that ET(A) receptor stimulation also activates Ca(+2)-activated K+ channels. Inhibition of K+ current (IC50 approximately 0.5 nM) by endothelin-1 was not dependent on phosphorylation or intracellular Ca+2 and was unaffected by FR139317 but was mimicked by ET(B) receptor agonists. It appears, therefore, that ET(A) and ET(B) receptors in pulmonary arterial myocytes are differentially coupled to Cl- and K+ channels. Modulation of these channels by endothelin-1 may prove to play an important role in regulating pulmonary arterial smooth muscle tone under both physiological and pathological conditions.

Differential electrophysiological actions of endothelin-1 on Cl- and K+ currents in myocytes isolated from aorta, basilar and pulmonary artery.

The electrophysiological effects of endothelin (ET)-1 were compared in myocytes isolated from rat small pulmonary artery, basilar artery and aorta. ET-1 evoked depolarization in all three smooth muscle cell types. Depolarizing oscillations in membrane current also were observed in pulmonary and aortic myocytes. In voltage-clamp experiments ET-1 induced a gradual inhibition of the Ca(++)-independent outward current (IK) in pulmonary and aortic myocytes, whereas in basilar myocytes ET-1 inhibited the Ca(++)-activated K+ current (IK(Ca)). ET-1 also evoked a transient enhancement of IK(Ca) and oscillations in inward current in aortic and pulmonary myocytes. The inward currents were inhibited by caffeine, which suggests Ca(++)-dependent activation. Ion-exchange experiments indicated that in pulmonary myocytes oscillatory currents were caused solely by the movement of Cl-, whereas in aortic myocytes they were the consequence of both Ca(++)-activated Cl-(ICl(Ca)) and non-selective cation currents (INS). No inward current was evoked in basilar myocytes in response to ET-1 or photorelease of Ca++, which suggests that these cells do not possess ICl(Ca). Experiments with ET receptor ligands indicated that in basilar myocytes ETA receptor stimulation is responsible for IK(Ca) inhibition, whereas in aortic and pulmonary myocytes ETB and ETA receptor stimulation mediates inhibition of IK and activation of ICl(Ca), INS and IK(Ca), respectively. In the future, it may be possible to exploit these differential effects of ET-1 pharmacologically to assist development of tissue-specific modulators for the treatment of vascular disease.

Domain-specific purinergic signaling in polarized rat cholangiocytes.

In cholangiocytes, adenine nucleotides function as autocrine/paracrine signals that modulate ductular ion transport by activation of purinergic receptors. The purpose of these studies was to identify cellular signals that modulate ATP release and nucleotide processing in polarized normal rat cholangiocytes. In Ussing chamber studies, selective exposure of the apical and basolateral membranes to ATP or adenosine 5'-O-(3-thiotriphosphate) (ATPgammaS) stimulated increases in short-circuit current. Apical purinergic receptor agonist preference was consistent with the P2Y(2) subtype. In contrast, basolateral ADP was more potent in stimulating transepithelial currents, consistent with the expression of different basolateral P2 receptor(s). Luminometric analysis revealed that both membranes exhibited constitutive ATP efflux. Hypotonic exposure enhanced ATP release in both compartments, whereas decreases in ATP efflux during hypertonicity were more prominent at the apical membrane. Increases in intracellular cAMP, cGMP, and Ca(2+) also increased ATP permeability, but selective effects on apical and basolateral ATP release differed. Finally, the kinetics of ATP degradation in apical and basolateral compartments were distinct. These findings suggest that there are domain-specific signaling pathways that contribute to purinergic responses in polarized cholangiocytes.

Integrating heterogeneous healthcare call centers.

In a relatively short period, OHS has absorbed multiple call centers supporting different LOBs from various acquisitions, functioning with diverse standards, processes, and technologies. However, customer and employee satisfaction is predicated on OHS's ability to thoroughly integrate these heterogeneous call centers. The integration was initiated and has successfully progressed through a balanced program of focused leadership and a defined strategy which includes site consolidation, sound performance management philosophies, and enabling technology. Benefits have already been achieved with even more substantive ones to occur as the integration continues to evolve.

Ca(2+)-activated Cl- and K+ channels and their modulation by endothelin-1 in rat pulmonary arterial smooth muscle cells.

Using the patch-clamp recording technique, we observed that endothelin-1 (ET-1; 0.8-16 nM) enhanced a voltage-activated outward current (Iout) and induced periodic oscillations of inward current in smooth muscle cells isolated from small pulmonary arteries (200-400 microns in diameter). Anion substitution experiments revealed that the ET-1-induced inward current was carried by Cl- ions. Application of bosentan (10 microM; and ETA and ETB receptor antagonist) and FR 139317 (1-10 microM; a selective ETA receptor antagonist) prevented initiation of inward currents or enhancement of Iout by ET-1. The ETB receptor agonist tetra-Ala-endothelin-1 (1-20 nM) failed to evoke these responses. Caffeine (10 mM) induced a single transient inward current and prevented any further activation of inward current, or enhancement of Iout, by subsequent application of 16 nM ET-1, suggesting that these currents were mediated by Ca2+ release from internal stores. Rapid intracellular release of Ca2+ by photolysis of nitr-5 activated an inward Cl- current and increased the magnitude of Iout. These results demonstrate the existence of Ca(2+)-activated Cl- and K+ channels in pulmonary arterial smooth muscle. The physiological role of these channels is at present uncertain, although their activation may be involved in the contractile responses of pulmonary arterial smooth muscle to ET-1.

Contractile agonists preferentially activate CL- over K+ currents in arterial myocytes.

Simultaneous patch-clamp and Ca2+ fluorescence measurements have revealed depolarising oscillations in the membrane potential of arterial (pulmonary) myocytes in response to adenosine 5'-triphosphate (ATP) and endothelin-1 (ET-1). These oscillations (i) are due to the preferential activation of Ca(2+)-activated Cl-, over K+ currents, (ii) occur through a mechanism involving Ca2+ release from intracellular Ca2+ stores and (iii) are likely to promote constriction. These results provide a novel perspective into the relative contribution and importance of Ca2+ activated Cl- and K+ channels in controlling membrane potential of arterial smooth muscle in response to contractile agonists.

Functional evidence for a novel suramin-insensitive pyrimidine receptor in rat small pulmonary arteries.

Uridine nucleotides are known to cause constriction of pulmonary arterial smooth muscle. However, the P2 receptor subtypes underlying the contractile effects of these nucleotides in the pulmonary circulation have not been determined. We have used myography and the patch-clamp recording technique to compare the effects of UTP and UDP in isolated small pulmonary arteries (diameter 100 to 400 microm) and their constituent smooth muscle cells. In endothelium-denuded arteries, both UTP and UDP (0.01 to 3 mmol/L) induced concentration-dependent increases in tension that were independent of P2X receptor stimulation. The UDP-mediated increase in tension was significantly less sensitive to the nonselective P2 receptor blocker suramin than the UTP-mediated increase in tension. In single isolated arterial myocytes, voltage-clamped at -50 mV (close to the resting membrane potential of these cells), application of both UTP and UDP evoked periodic oscillations of inward current primarily because of a Ca2+-activated Cl- current (ICl,Ca). Oscillations of ICl,Ca evoked by UTP were reversibly inhibited by suramin, although those evoked by UDP were insensitive to the antagonist. In addition to confirming the presence of classical P2Y2 receptors, these results also provide functional evidence for the existence of a novel UDP receptor in pulmonary arterial myocytes, which may contribute to pyrimidine-evoked vasoconstriction. This notion is supported by molecular evidence that demonstrates the presence of P2Y6 receptor transcripts in rat pulmonary arterial smooth muscle.

Endogenous ATP release regulates Cl- secretion in cultured human and rat biliary epithelial cells.

P2Y receptor stimulation increases membrane Cl- permeability in biliary epithelial cells, but the source of extracellular nucleotides and physiological relevance of purinergic signaling to biliary secretion are unknown. Our objectives were to determine whether biliary cells release ATP under physiological conditions and whether extracellular ATP contributes to cell volume regulation and transepithelial secretion. With the use of a sensitive bioluminescence assay, constitutive ATP release was detected from human Mz-ChA-1 cholangiocarcinoma cells and polarized normal rat cholangiocyte monolayers. ATP release increased rapidly during cell swelling induced by hypotonic exposure. In Mz-ChA-1 cells, removal of extracellular ATP (apyrase) and P2 receptor blockade (suramin) reversibly inhibited whole cell Cl- current activation and prevented cell volume recovery during hypotonic stress. Moreover, exposure to apyrase induced cell swelling under isotonic conditions. In intact normal rat cholangiocyte monolayers, hypotonic perfusion activated apical Cl- currents, which were inhibited by addition of apyrase and suramin to bathing media. These findings indicate that modulation of ATP release by the cellular hydration state represents a potential signal coordinating cell volume with membrane Cl- permeability and transepithelial Cl- secretion.

Reorganization of cholangiocyte membrane domains represents an early event in rat liver ischemia.

Cholangiocytes contribute significantly to bile formation through the vectorial secretion of water and electrolytes and are a focal site of injury in a number of diseases including liver ischemia and post-transplantation liver failure. Using ischemia in intact liver and adenosine triphosphate (ATP) depletion in cultured cells to model cholangiocyte injury, these studies examined the effects of metabolic inhibition on cholangiocyte viability and structure. During 120 minutes of ischemia or ATP depletion, cell viability and tight junctional integrity in cholangiocytes were maintained. However, both the in vivo and in vitro models displayed striking alterations in the secondary structure of the plasma membrane. After 120 minutes, the basolateral (BL) interdigitations were diminished and the apical (Ap) microvilli were significantly decreased in number. The BL and Ap membrane surface areas decreased by 42 +/- 8% and 63 +/- 2%, respectively. Despite these changes, F-actin remained predominantly localized to the membrane domains. In contrast, in a time course that paralleled the loss of microvilli, the actin-membrane linking protein ezrin progressively dissociated from the cytoskeleton. These studies indicate that cholangiocyte ATP depletion induces characteristic, domain-specific changes in the plasma membrane and implicate alterations in the membrane-cytoskeletal interactions in the initiation of the changes. Pending the re-establishment of the differentiated domains, the loss of specific secondary structures may contribute to impaired vectorial bile duct secretion and postischemic cholestasis.

Type II cAMP-dependent protein kinase regulates electrogenic ion transport in rabbit collecting duct.

cAMP mediates many of the effects of vasopressin, prostaglandin E2, and beta-adrenergic agents upon salt and water transport in the renal collecting duct. The present studies examined the role of cAMP-dependent protein kinase (PKA) in mediating these effects. PKA is a heterotetramer comprised of two regulatory (R) subunits and two catalytic (C) subunits. The four PKA isoforms may be distinguished by their R subunits that have been designated RIalpha, RIbeta, RIIalpha, and RIIbeta. Three regulatory subunits, RIalpha, RIIalpha, and RIIbeta, were detected by immunoblot and ribonuclease protection in both primary cultures and fresh isolates of rabbit cortical collecting ducts (CCDs). Monolayers of cultured CCDs grown on semipermeable supports were mounted in an Ussing chamber, and combinations of cAMP analogs that selectively activate PKA type I vs. PKA type II were tested for their effect on electrogenic ion transport. Short-circuit current (Isc) was significantly increased by the PKA type II-selective analog pairs N6-monobutyryl-cAMP plus 8-(4-chlorophenylthio)-cAMP or N6-monobutyryl-cAMP plus 8-chloro-cAMP. In contrast the PKA type I-selective cAMP analog pair [N6-monobutyryl-cAMP plus 8-(6-aminohexyl)-amino-cAMP] had no effect on Isc. These results suggest PKA type II is the major isozyme regulating electrogenic ion transport in the rabbit collecting duct.

Endothelin-1, delayed rectifier K channels, and pulmonary arterial smooth muscle.

Sarafotoxin S6c [STXS6c; a selective endothelin-B (ETB) receptor agonist] causes constriction of isolated pulmonary arteries. In perforated-patch experiments on pulmonary arterial myocytes, ET-1 and STXS6c induced a gradual inhibition of the delayed rectifier K current (IKV), the profile of which resembled that carried by Kv1.5. Reverse-transcriptase polymerase chain reaction (RT-PCR) experiments revealed mRNA encoding this channel, and immunolocalization experiments demonstrated expression of the channel protein in pulmonary arterial smooth muscle. It is tempting to speculate that ETB receptor coupling to Kv1.5 may be implicated in contraction after stimulation of these receptors.

ATP depletion in rat cholangiocytes leads to marked internalization of membrane proteins.

Intrahepatic bile ducts (BD) are a critical target of injury in the postischemic liver. Decreased vascular perfusion causes characteristic changes in the morphology of the ductular epithelia including a loss of secondary membrane structures and a decrease in plasma membrane surface area. Using adenosine triphosphate (ATP) depletion of cultured normal rat cholangiocytes (NRC) to model ischemic ducts, the present studies examined the fate of apical membrane proteins to determine whether membrane recycling might contribute to rapid functional recovery. Apical proteins, including gamma-glutamyl transpeptidase (GGT), Na(+)-glucose cotransporter (SGLT1), and apically biotinylated proteins, were not shed into the luminal space during ATP depletion. Instead, labeling of surface proteins after ATP depletion showed a significant decrease in GGT and SGLT1, consistent with membrane internalization. Similarly, z-axis confocal microscopy of biotinylated apical proteins also showed protein internalization. During ATP recovery, SGLT1 transport activity remained profoundly depressed even after 24 hours of recovery, indicating that the function of the internalized apical proteins is not rapidly recovered. These studies suggest that the membrane internalization in ATP-depleted cholangiocytes is a unidirectional process that contributes to prolonged functional deficits after restoration of normal cellular ATP levels. This sustained decrease in transport capacity may contribute to the development of ductular injury in postischemic livers.