The objective of this study was to examine the antinociceptive effects of peripherally restricted kappa-opioid receptor agonists (ORAs) in a rat model of inflammatory bowel disease produced by intracolonic instillation of trinitrobenzine sulfonic acid (TNBS). Antinociceptive effects of mu-(morphine) and kappa-ORAs (EMD 61,753 and ICI 204,488) were evaluated in a behavioral model of visceral nociception. The effects of these agonists and a delta-ORA (SNC 80) on responses of pelvic nerve afferent fibers innervating the colon were also tested. In the behavioral study, systemic injections of morphine and both kappa-ORAs dose-dependently inhibited the visceromotor response to colorectal distension in rats with uninflamed or inflamed colons. The inhibitory effects of kappa-ORAs, but not morphine, were significantly greater in rats with colons inflamed 4 days previously by TNBS. A mu-receptor-selective dose (30 microg/kg) of naloxone methiodide (NLXM) blocked the inhibitory effect of morphine, but not of EMD 61,753. In the single-fiber study, neither morphine nor the delta-ORA SNC 80 attenuated the responses of pelvic nerve afferent fibers, whereas kappa-ORAs dose-dependently inhibited responses of pelvic nerve afferent fibers with significantly greater potency in the inflamed colon. Pretreatment with a non-opioid receptor-selective dose (2 mg/kg) of NLXM produced a rightward shift in the dose-response function of EMD 61,753. The greater potency of kappa-ORAs in the TNBS-inflamed condition suggests a peripheral upregulation of kappa-opioid receptors in colonic inflammation.

Background: Little research has focused on implementation of electronic Patient Reported Outcomes (e-PROs) for meaningful use in patient management in 'real-world' oncology practices. Our quality improvement collaborative used multi-faceted implementation strategies including audit and feedback, disease-site champions and practice coaching, core training of clinicians in a person-centered clinical method for use of e-PROs in shared treatment planning and patient activation, ongoing educational outreach and shared collaborative learnings to facilitate integration of e-PROs data in multi-sites in Ontario and Quebec, Canada for personalized management of generic and targeted symptoms of pain, fatigue, and emotional distress (depression, anxiety). Patients and methods: We used a mixed-methods (qualitative and quantitative data) program evaluation design to assess process/implementation outcomes including e-PROs completion rates, acceptability/use from the perspective of patients/clinicians, and patient experience (surveys, qualitative focus groups). We secondarily explored impact on symptom severity, patient activation and healthcare utilization (Ontario sites only) comparing a pre/post population cohort not exposed/exposed to our implementation intervention using Mann Whitney U tests. We hypothesized that the iPEHOC intervention would result in a reduction in symptom severity, healthcare utilization, and higher patient activation. We also identified key implementation strategies that sites perceived as most valuable to uptake and any barriers.

, Char les Cun ning ham, PhD 7Key Words: attention-deficit hy per ac tiv ity dis or der, ADHD, sys tem atic re view, treat ment, stimu lants, be hav ioural ther apy A ttention-deficit hy per ac tiv ity dis or der (ADHD) (1) is a com mon psy chi at ric dis or der oc cur ring in ap proximately 5% of school-aged chil dren, ado les cents, and adults (1,2). It is a fre quent rea son for re fer ral to men tal health services (3). ADHD is first evi dent in the pre school years (4) and per sists in as many as 70% of in di vidu als through out childhood and ado les cence and into adult hood (5,6). Af fected in dividu als are at risk for op po si tional de fi ant dis or der (ODD), con duct dis or der (CD), de pres sion, anxi ety, and learn ing disabil ity (LD) (7). They are also at risk for the de vel op ment of de lin quency or crimi nal ity, and for school sus pen sion, academic un dera chieve ment, low self-esteem, and sub stance abuse (8). Treat ments must be of suf fi cient in ten sity to have an im me di ate im pact on the core ADHD symp toms, and they We un der took a sys tem atic re view of the lit era ture on the long-term treat ment of attentiondeficit hy per ac tiv ity dis or der (ADHD). We used sys tem atic strate gies to iden tify ran domized treat ment stud ies in which treat ment was ad min is tered for 12 weeks or more. We included 14 stud ies in volv ing 1379 sub jects. Be cause of the lim ited number of high-quality stud ies and the het ero ge ne ity of out come meas ures, we did not per form metaana ly sis. We rated 5 stud ies as ade quate for meth odo logi cal qual ity. Five stud ies fol lowed chil dren for more than 26 weeks. Phar ma cologic in ter ven tions were stud ied more fre quently than nonphar ma cologic ones. Six stud ies per mit ted evalua tion of the ef fects of com bined drug and be hav ioural in ter ven tion. Twenty-five dif fer ent out comes were meas ured us ing 26 dif fer ent tests. Stimu lant medi ca tion ap pears to re duce ADHD (7 stud ies), dys func tional so cial behav iour (6 stud ies), and in ter nal iz ing symp toms (2 stud ies). Avail able stud ies pro vide lit tle evi dence for im proved aca demic per form ance with stimu lants (3 stud ies). Medi ca tions other than stimu lants have not been stud ied ex ten sively (3 stud ies). Only 1 study showed that com bi na tion ther apy adds to the ef fects of medi ca tion. Rig or ous treat ment re search among rep re sen ta tive sam ples of ADHD in di vidu als is needed.(Can J Psy chia try 2002;47:337-348) Clini cal Im pli ca tions• Sys tem atic re views are im por tant tools for de ci sion mak ers but the meth odo logi cal rig our of ran dom ized con trolled tri als (RCTs) of long-term attention-deficit hy per ac tiv ity dis or d er (ADHD) treat ment is low.• These stud ies do not clar ify the ef fect of treat ment on im por tant out comes.• Com bined phar ma cologic and non phar ma cologic in ter ven tions yield the best out comes. Limi ta tions• The ef fects of non phar ma cologic treat ment and drugs other than stimu lants are lit ...