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101.
Despite considerable research activity and application in treatment, the construct of craving remains poorly understood. We propose that cravings and urges are cognitive–emotional events in time, characterised by frequency, duration, intensity and salience. Commonly used measures of alcohol craving are reviewed, and their strengths and weaknesses identified. Most measures confound craving with behaviours, or with separable cognitive phenomena such as expectancies, intentions, or perceived behavioural control. These confounds have limited our advances in understanding the determinants and consequences of craving. Based on the criteria applied in this review, among the better performing multi-item measures are the Penn Alcohol Craving Scale and Obsessive subscale of the Obsessive–Compulsive Drinking Scale. Optimal assessment strategies are likely to involve daily assessments of peak intensity of cravings, desires or urges and of the frequency and duration of craving episodes. Of particular interest are measures of intensity at times when individuals are at risk of drinking or of other functional impacts from craving.  相似文献   
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IntroductionOverexpression of antiapoptotic B-cell lymphoma (Bcl-2) proteins confers the dysregulation of apoptosis and results in drug resistance in a variety of cancers, including those of the genitourinary tract. Inhibitors that target prosurvival Bcl-2 proteins are in preclinical and clinical development. The objective of this review is to assess the involvement of Bcl-2 proteins as well as the preclinical and clinical activity of Bcl-2 inhibitors under evaluation for genitourinary neoplasms.Materials and MethodsPubMed was used with both medical subject heading terms and free search to identify the relevant literature. Information on clinical trials was obtained using http://Clincaltrials.gov, EU Clinical Trials Register, and meeting abstracts of the American Society of Clinical Oncology.ResultsTo date, 2 Bcl-2 inhibitors have been evaluated in clinical trials for genitourinary tumors (oblimersen and AT-101 (R-(–)-gossypol)). Both agents demonstrated some success in early stages of development, but their clinical activity did not meet expectations. Preclinical studies are under way for other Bcl-2 inhibitors including ABT-737, HA14-1, and Bcl-2 homology 3 inhibitors.ConclusionAntiapoptotic Bcl-2 proteins are potential molecular targets in genitourinary cancers. Bcl-2 inhibitors might be effective as single agents or in combination with conventional therapies. However, the biology of the Bcl-2 family in genitourinary cancers remains poorly understood and robust preclinical studies are needed to inform clinical development. Such studies should aim to identify: (1) pharmacodynamic markers that could help guide patient selection for treatment with Bcl-2 inhibitors, and (2) optimal combinations of Bcl-2 inhibitors with other anticancer agents for future clinical investigation.  相似文献   
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Digestive Diseases and Sciences - Women with inflammatory bowel disease (IBD) with poor IBD-specific reproductive knowledge experience more childlessness and fear of IBD medications in pregnancy....  相似文献   
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Neurokinin 1 and 2 receptors mediate cholera toxin secretion in rat jejunum   总被引:1,自引:0,他引:1  
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   
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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   
110.

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   
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