Background Many factors contribute to suboptimal diabetes control including insufficiently-intensive treatment and non-adherence to medication and lifestyle. Determining which of these is most relevant for individual patients is challenging. Patient engagement techniques may help identify contributors to suboptimal adherence and address barriers (using motivational interviewing) and help facilitate choices among treatment augmentation options (using shared decision-making). These methods have not been used in combination to improve diabetes outcomes. Objective To evaluate the impact of a telephone-based patient-centered intervention on glycosylated hemoglobin (HbA1c) control for individuals with poorly-controlled diabetes. Design Two-arm pragmatic randomized control trial within an explanatory sequential mixed-methods design. Subjects 1,400 participants 18–64 years old with poorly-controlled type 2 diabetes. Intervention The intervention was delivered over the telephone by a clinical pharmacist and consisted of a 2-step process that integrated brief negotiated interviewing and shared decision-making to identify patient goals and options for enhancing diabetes management. Main measures The primary outcome was change in HbA1c. Secondary outcomes were medication adherence measures. Outcomes were evaluated using intention-to-treat principles; multiple imputation was used for missing values in the 12-month follow-up. We used information from pharmacist notes to elicit factors to potentially explain the intervention’s effectiveness. Key results Participants had a mean age of 54.7 years (SD:8.3) and baseline HbA1c of 9.4 (SD:1.6). Change in HbA1c from baseline was -0.79 (SD:2.01) in the control arm and -0.75 (SD:1.76) in the intervention arm (difference:+0.04, 95%CI: -0.22, 0.30). There were no significant differences in adherence. In as-treated analyses, the intervention significantly improved diabetes control (-0.48, 95%CI: -0.91, -0.05). Qualitative findings provided several potential explanations for the findings, including insufficiently addressing patient barriers. Conclusions A novel telephone-based patient-centered intervention did not improve HbA1c among individuals with poorly-controlled diabetes, though as-treated analyses suggest that the intervention was effective for those who received it. Trial registration ClinicalTrials.gov NCT02910089

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Recent cannabinoid research has a primary focus on developing therapeutics against human diseases. Many studies on cannabinoids indicate important progress for protection against several neurodegenerative disorders. Agonists of cannabinoid receptors activate signalling pathways in the brain that are linked to neuronal repair and cell maintenance, and endogenous ligands can also activate neuroprotective responses. These endocannabinoids are bioactive fatty acid amides and esters that are synthesised in the brain and include arachidonoyl ethanolamide (anandamide) and 2-arachidonoyl glycerol. Endocannabinoids are released in response to pathogenic events, thus representing a potential compensatory repair mechanism. Enhancing this on-demand action of endocannabinoids is a strategy with which to promote endogenous repair signalling. For such enhancement, considerable work has gone into modulating the availability of endocannabinoids by blocking the processes of their deactivation. The targets include the anandamide-hydrolysing enzyme fatty acid amide hydrolase, the carrier-mediated anandamide transport system and 2-arachidonoyl glycerol-deactivating enzyme monoacylglycerol lipase. The activity of endocannabinoids is terminated through transport and degradation and, accordingly, selective inhibitors of these processes effectively exploit the protective nature of cannabinergic responses. This review highlights recent studies implicating the endocannabinoid system in neuroprotection against different disorders of the CNS.

CONTEXT: Recombinant human growth hormone (rhGH) improves growth in patients with growth hormone deficiency or idiopathic short stature. Its role in patients with cystic fibrosis (CF) is unclear. OBJECTIVE:To review the effectiveness of rhGH in the treatment of patients with CF. METHODS:Medline and the Cochrane Central Register of Controlled Trials were searched from the earliest date through April 2010. Randomized controlled trials, observational studies, systematic reviews/ meta-analyses, or case reports were included if rhGH therapy was administered to patients with CF and data on prespecified harms, intermediate outcomes, or final health outcomes were reported. When applicable, end points were pooled by using a random-effects model. The overall body of evidence was graded for each outcome as insufficient, low, moderate, or high. RESULTS:Ten unique controlled trials (n ϭ 312) and 8 observational studies (n ϭ 58) were included. On quantitative synthesis of controlled trials, several markers of pulmonary function, anthropometrics, and bone mineralization were significantly improved versus control. Results of single-arm observational studies for the aforementioned outcomes were generally supportive of findings in clinical trials. There is insufficient evidence to determine the effect of rhGH on intravenous antibiotic use during therapy, pulmonary exacerbations, healthrelated quality-of-life, bone consequences, or total mortality, but moderate evidence suggests that rhGH therapy reduces the rate of hospitalization versus control.CONCLUSIONS: rhGH improved almost all intermediate measures of pulmonary function, height, and weight in patients with CF. Improvements in bone mineral content are also promising. However, with the exception of hospitalizations, the benefits on final health outcomes cannot be directly determined at this time.