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111.
BACKGROUND & AIMS: Substance P, a member of the tachykinin family, is a prosecretory neuropeptide distributed widely throughout the enteric nervous system. Implicated in inflammatory states, its role in enterotoxigenic water and electrolyte secretion is unclear. We assessed the effect of substance P antagonists and neurokinin receptor antagonists on cholera toxin-, Escherichia coli heat-labile enterotoxin (LT)-, and heat-stable enterotoxin (STa)-induced water secretion in an in vivo rat jejunal perfusion model. METHODS: Anesthetized adult male Wistar rats were pretreated with substance P antagonists (D-Pro(2), D-Trp(79), substance P, 0.1-3.0 mg/kg; or CP 96,345/4, 0.3-3 mg/kg) or neurokinin (NK)-1 (sendide, 1.0 mg/kg), NK-2 (GR83074, 1.0 mg/kg), or NK-3 ([Trp(7),betaAla(8)]NKA(4-10), 1.0 mg/kg) receptor antagonists. In a subgroup, extrinsic sensory afferents were ablated by pretreatment with capsaicin. Jejunal perfusion, with a plasma electrolyte solution containing a nonabsorbable marker, was undertaken after exposure to cholera toxin (25 microg), LT (25 microg), STa (200 microg/L), or saline. Results: Cholera toxin-induced water and electrolyte secretion was inhibited by the substance P antagonists and the NK-1 and NK-2 receptor antagonists, but not by the NK-3 receptor antagonist or by pretreatment with capsaicin. Neither LT- nor STa-induced secretions were affected by the pretreatments. CONCLUSIONS: Prosecretory pathways involving NK-1 and NK-2 receptors specifically mediate the actions of cholera toxin in the small intestine. 相似文献
112.
Case finding and referral model for emergency department elders: a randomized clinical trial 总被引:8,自引:0,他引:8
Mion LC Palmer RM Meldon SW Bass DM Singer ME Payne SM Lewicki LJ Drew BL Connor JT Campbell JW Emerman C 《Annals of emergency medicine》2003,41(1):57-68
STUDY OBJECTIVE: Elderly emergency department patients have complex medical needs and limited social support. A transitional model of care adapted from hospitals was tested for its effectiveness in the ED in reducing subsequent service use. METHODS: A randomized clinical trial was conducted at 2 urban, academically affiliated hospitals. Participants were 650 community-residing individuals 65 years or older who were discharged home after an ED visit. Main outcomes were service use rates, defined as repeat ED visits, hospitalizations, or nursing home admissions, and health care costs at 30 and 120 days. Intervention consisted of comprehensive geriatric assessment in the ED by an advanced practice nurse and subsequent referral to a community or social agency, primary care provider, and/or geriatric clinic for unmet health, social, and medical needs. Control group participants received usual and customary ED care. RESULTS: The intervention had no effect on overall service use rates at 30 or 120 days. However, the intervention was effective in lowering nursing home admissions at 30 days (0.7% versus 3%; odds ratio 0.21; 95% confidence interval [CI] 0.05 to 0.99) and in increasing patient satisfaction with ED discharge care (3.41 versus 3.03; mean difference 0.37; 95% CI 0.13 to 0.62). The intervention was more effective for high-risk than low-risk elders. CONCLUSION: An ED-based transitional model of care reduced subsequent nursing home admissions but did not decrease overall service use for older ED patients. Further studies are needed to determine the best models of care for this setting and for at-risk patients. 相似文献
113.
Cameron J.B. Cunningham Heather C. Finlayson William R. Henderson Russell J. O’Connor Andrew Travlos 《PM & R》2018,10(5):494-500
Background
Critical illness polyneuromyopathy (CIPNM) increasingly is recognized as a source of disability in patients requiring intensive care unit (ICU) admission. The prevalence and impact of CIPNM on patients in the rehabilitation setting has not been established.Objectives
To determine the proportion of at-risk rehabilitation inpatients with evidence of CIPNM and the functional sequelae of this disorder.Design
Prospective observational study.Setting
Tertiary academic rehabilitation hospital.Patients
Rehabilitation inpatients with a history of ICU admission for at least 72 hours.Methods
Electrodiagnostic studies were performed to evaluate for axonal neuropathy and/or myopathy in at least one upper and one lower limb.Main Outcome Measurements
The primary outcome was prevalence of CIPNM. Secondary outcomes included Functional Independence Measure (FIM) scores, rehabilitation length of stay (RLOS), and discharge disposition.Results
A total of 33 participants were enrolled; 70% had evidence of CIPNM. Admission FIM score, discharge FIM, FIM gain, and FIM efficiency were 64.1, 89.9, 25.5, and 0.31 in those with CIPNM versus 78.4, 94.6, 16.1, and 0.33 in those without CIPNM, respectively. Average RLOS was 123 days versus 76 days and discharge to home was 57% versus 90% in the CIPNM and non-CIPNM groups, respectively.Conclusions
CIPNM is very common in rehabilitation inpatients with a history of ICU admission. It was associated with a lower functional status at rehabilitation admission, but functional improvement was at a similar rate to those without CIPNM. Longer RLOS stay may be required to achieve the same functional level.Level of Evidence
III 相似文献114.
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Ofir Moreno Todd Butler Vanessa Zann Ashley Willson Pui Leung Alyson Connor 《Clinical therapeutics》2018,40(11):1855-1867
Purpose
ME-401 is a novel selective inhibitor of phosphatidylinositol 3 kinase p110δ, an enzyme often found overexpressed and overactive in B-cell malignancies. The current study was performed to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of single ascending oral doses of ME-401 in healthy volunteers.Methods
This analysis was an open-label, nonrandomized study in healthy male volunteers. Three sequential groups were dosed. Each group received single doses of ME-401 on two occasions; the doses tested ranged from 10 to 150 mg. Blood was drawn at various time points to analyze plasma concentrations of ME-401 and inhibition of basophil activation, a marker of phosphatidylinositol 3 kinase p110δ inhibition.Findings
Fifteen subjects received a single dose of ME-401 on two occasions. Three adverse events that were considered possibly related to the study drug were reported: one event of pain, one event of headache, and one event of upper abdominal pain. ME-401 exhibited dose proportionality up to 60 mg, and supra-proportional increases in exposure were observed above doses of 60 mg. In addition, there was a dose-proportional increase in the inhibition of basophil activation up to 60 mg. Mean t1/2 ranged from 9.36 to 29.23 hours across the dose range. A 60 mg dose of ME-401 approached 90% inhibition of basophil activation, and thereafter no further increase to the percent inhibition of basophil activation was observed for higher doses. Once-daily dosing of 60 mg ME-401 was forecasted to result in trough plasma levels exceeding the concentration needed for 90% inhibition of basophil activation.Implications
This first-in-human study showed that ME-401 was well tolerated after single doses up to 150 mg. Pharmacologic activity was confirmed after administration of single ascending oral doses of 10 to 150 mg. ME-401 60 mg, administered once daily, was selected as the starting dose for patient studies. ClinicalTrials.gov identifier: NCT02521389. 相似文献118.
Kirstine Shrubsole Linda Worrall Emma Power Denise A. OConnor 《Archives of physical medicine and rehabilitation》2018,99(7):1413-1423.e24
Objective
To identify implementation priorities for poststroke aphasia management relevant to the Australian health care context.Data Sources
Using systematized searches of databases (CINAHL and MEDLINE), guideline and stroke websites, and other sources, evidence was identified and extracted for 7 implementation criteria for 13 topic areas relevant to aphasia management. These 7 priority-setting criteria were identified in the implementation literature: strength of the evidence, current evidence-practice gap, clinician preference, patient preference, modifiability, measurability, and health effect.Study Selection
Articles were included if they were in English, related to a specific recommendation requiring implementation, and contained information pertaining to any of the 7 prioritization criteria.Data Extraction
The scoping review methodology was chosen to address the broad nature of the topic. Evidence was extracted and placed in an evidence matrix. After this, evidence was summarized and then aphasia rehabilitation topics were prioritized using an approach developed by the research team.Data Synthesis
Evidence from 100 documents was extracted and summarized. Four topic areas were identified as implementation priorities for aphasia: timing, amount, and intensity of therapy; goal setting; information, education, and aphasia-friendly information; and constraint-induced language therapy.Conclusions
Closing the evidence-practice gaps in the 4 priority areas identified may deliver the greatest gains in outcomes for Australian stroke survivors with aphasia. Our approach to developing implementation priorities may be useful for identifying priorities for implementation in other health care areas. 相似文献119.
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