Controlled Trial’s scientific contributions

Introduction: The aim of this study was to assess the effects of pioglitazone on blood glucose control and inflammatory biomarkers in diabetic patients receiving insulin after kidney transplantation. Materials and methods: In a randomized placebo-controlled trial, 62 diabetic kidney transplant patients were followed for 4 months after randomly assigned to placebo and pioglitazone (30 mg/d) groups. All of the patients continued their insulin therapy irrespective of the group that they were assigned to, in order to evaluate the effects of addition of pioglitazone on blood glucose and inflammation biomarkers including serum C-reactive protein, high-sensitivity C-reactive protein, and interleukin-18 levels, as well as erythrocyte sedimentation rate. Results: At baseline, there were no significant differences in laboratory studies between the two groups. After 4 months of intervention, along with significant improvement in hemoglobin A1c in the pioglitazone group, daily insulin requirements also decreased and lipid profile improved significantly. In addition, erythrocyte sedimentation rate, C-reactive protein, and high-sensitivity C-reactive protein values were significantly lower in the pioglitazone group (P = .03, P < .001, and P = .01). Interleukin-18 levels were not significantly different at the end of the study between the two groups, but it had a decreasing trend in the pioglitazone group (P = .002). Conclusions: Pioglitazone complementing insulin in diabetic kidney transplant patients not only improved glycemic control, evidenced by hemoglobin A1c, and reduced daily insulin requirement, but also decreased inflammatory markers which may have an impact on overall cardiovascular events and mortalities beyond glycemic control.

Context Protocolized sedation and daily sedation interruption are 2 strategies to minimize sedation and reduce the duration of mechanical ventilation and intensive care unit (ICU) stay. We hypothesized that combining these strategies would augment the benefits. Objective To compare protocolized sedation with protocolized sedation plus daily sedation interruption in critically ill patients. Design, Setting, and Patients Randomized controlled trial of 430 critically ill, mechanically ventilated adults conducted in 16 tertiary care medical and surgical ICUs in Canada and the United States between January 2008 and July 2011. Intervention Continuous opioid and/or benzodiazepine infusions and random allocation to protocolized sedation (n = 209) (control) or to protocolized sedation plus daily sedation interruption (n = 214). Using validated scales, nurses titrated infusions to achieve light sedation. For patients receiving daily interruption, nurses resumed infusions, if indicated, at half of previous doses. Patients were assessed for delirium and for readiness for unassisted breathing. Main Outcome Measure Time to successful extubation. Secondary outcomes included duration of stay, doses of sedatives and opioids, unintentional device removal, delirium, and nurse and respiratory therapist clinical workload (on a 10-point visual analog scale [VAS]). Results Median time to successful extubation was 7 days in both the interruption and control groups (median [IQR], 7 [4-13] vs 7 [3-12]; interruption group hazard ratio, 1.08; 95% CI, 0.86-1.35; P = .52). Duration of ICU stay (median [IQR], 10 [5-17] days vs 10 [6-20] days; P = .36) and hospital stay (median [IQR], 20 [10-36] days vs 20 [10-48] days; P = .42) did not differ between the daily interruption and control groups, respectively. Daily interruption was associated with higher mean daily doses of midazolam (102 mg/d vs 82 mg/d; P = .04) and fentanyl (median [IQR], 550 [50-1850] vs 260 [0-1400]; P < .001) and more daily boluses of benzodiazepines (mean, 0.253 vs 0.177; P = .007) and opiates (mean, 2.18 vs 1.79; P < .001). Unintentional endotracheal tube removal occurred in 10 of 214 (4.7%) vs 12 of 207 patients (5.8%) in the interruption and control groups, respectively (relative risk, 0.82; 95% CI, 0.36-1.84; P = .64). Rates of delirium were not significantly different between groups (53.3% vs 54.1%; relative risk, 0.98; 95% CI, 0.82-1.17; P = .83). Nurse workload was greater in the interruption group (VAS score, 4.22 vs 3.80; mean difference, 0.41; 95% CI, 0.17-0.66; P = .001). Conclusion For mechanically ventilated adults managed with protocolized sedation, the addition of daily sedation interruption did not reduce the duration of mechanical ventilation or ICU stay. Trial Registration clinicaltrials.gov Identifier: NCT00675363

A LZHEIMER DISEASE (AD) IS A neurodegenerative disorder characterized by cognitive decline , impaired performance of activities of daily living, and behav-ioral and psychiatric signs and symptoms. Pathological features of AD include intraneuronal neurofibrillary tangles containing abnormally phos-phorylated tau protein, extracellular amyloid plaques containing the pep-tide amyloid, neuronal cell death, and anatomic as well as functional impairment of neurotransmitter systems. 1,2 Alzheimer disease affects approximately 4.5 million people in the United States. 3 Treatments approved by the Food and Drug Administration were previously limited to monotherapy with cholinesterase inhibitors in patients with mild to moderate AD. 2 In Octo-ber 2003, the Food and Drug Administration approved memantine for the treatment of moderate to severe AD; memantine is now available in more than 40 countries worldwide. Memantine, a low-to moderate-affinity, uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist , represents the first member of a new class of medications showing clinical benefit and good tolerability in AD. Although other NMDA receptor modula-tors (eg, milacemide and D-cycloser-ine) have failed in development as Context Memantine is a low-to moderate-affinity, uncompetitive N-methyl-D-aspartate receptor antagonist. Controlled trials have demonstrated the safety and efficacy of memantine monotherapy for patients with moderate to severe Alzheimer disease (AD) but no controlled trials of memantine in patients receiving a cholinesterase inhibitor have been performed. Objective To compare the efficacy and safety of memantine vs placebo in patients with moderate to severe AD already receiving stable treatment with donepezil.

Background: Neck pain is a common problem, but the