Effect of 1 night of total sleep deprivation on cerebrospinal fluid β-amyloid 42 in healthy middle-aged men:a randomized clinical trial

\u3cp\u3eIMPORTANCE: Increasing evidence suggests a relationship between poor sleep and the risk of developing Alzheimer disease. A previous study found an effect of sleep on β-amyloid (Aβ), which is a key protein in Alzheimer disease pathology.\u3c/p\u3e\u3cp\u3eOBJECTIVE: To determine the effect of 1 night of total sleep deprivation on cerebrospinal fluid Aβ42 protein levels in healthy middle-aged men.\u3c/p\u3e\u3cp\u3eDESIGN, SETTING, AND PARTICIPANTS: The Alzheimer, Wakefulness, and Amyloid Kinetics (AWAKE) study at the Radboud Alzheimer Center, a randomized clinical trial that took place between June 1, 2012, and October 1, 2012. Participants were cognitively normal middle-aged men (40-60 years of age) with normal sleep (n = 26) recruited from the local population.\u3c/p\u3e\u3cp\u3eINTERVENTIONS: Participants were randomized to 1 night with unrestricted sleep (n = 13) or 1 night of total sleep deprivation (24 hours of wakefulness) (n = 13).\u3c/p\u3e\u3cp\u3eMAIN OUTCOMES AND MEASURES: Sleep was monitored using continuous polysomnographic recording from 3 pm until 10 am. Cerebrospinal fluid samples were collected using an intrathecal catheter at defined times to compare cerebral Aβ42 concentrations between evening and morning.\u3c/p\u3e\u3cp\u3eRESULTS: A night of unrestricted sleep led to a 6% decrease in Aβ42 levels of 25.3 pg/mL (95% CI [0.94, 49.6], P = .04), whereas sleep deprivation counteracted this decrease. When accounting for the individual trajectories of Aβ42 over time, a difference of 75.8 pg/mL of Aβ42 was shown between the unrestricted sleep and sleep deprivation group (95% CI [3.4, 148.4], P = .04). The individual trajectories of evening and morning Aβ42 concentrations differed between the unrestricted sleep and sleep deprivation groups (P = .04) in contrast to stable Aβ40, tau, and total protein levels.\u3c/p\u3e\u3cp\u3eCONCLUSIONS AND RELEVANCE: Sleep deprivation, or prolonged wakefulness, interferes with a physiological morning decrease in Aβ42. We hypothesize that chronic sleep deprivation increases cerebral Aβ42 levels, which elevates the risk of Alzheimer disease.\u3c/p\u3e\u3cp\u3eTRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01194713.\u3c/p\u3

Outcomes and resource use of non-small cell lung cancer (NSCLC) patients treated with first-line platinum-based chemotherapy across Europe: FRAME prospective observational study

Introduction: FRAME was a prospective observational study that captured real-world data on patients with advanced or metastatic non-small cell lung cancer (NSCLC) receiving platinum-based chemotherapies as first-line treatment (FLT) across Europe. As previously reported, most patients observed in the study had initiated FLT with either pemetrexed, gemcitabine, vinorelbine or taxanes in combination with a platinum. Baseline patient and disease characteristics including age, performance status, and histology varied (all p < 0.01) across cohorts. Methods: Consenting adult patients initiating FLT for advanced or metastatic NSCLC with platinum-based chemotherapy, with or without a targeted agent, entered the study between April 2009 and February 2011. The choice of FLT was left to physicians' discretion per routine clinical practice. The primary objective was to evaluate overall survival (OS) across platinum-based doublet chemotherapy cohorts and key secondary objectives included the evaluation of OS in patients with different histological subtypes of NSCLC. Survival outcomes were assessed using Kaplan-Meier analysis, and unadjusted estimates are presented. Results: Median OS in months was 10.3 across cohorts (n = 1524), 10.7 for pemetrexed (n = 569), 10.0 for gemcitabine (n = 360), 9.1 for taxanes (n = 295), and 10.7 for vinorelbine (n = 300). For patients with non-squamous NSCLC who received cisplatin (n = 616, 40% of total), median OS in months was 10.6 across the cohorts, 11.6 for pemetrexed, 8.4 for gemcitabine, 9.6 for taxanes, and 9.9 for vinorelbine. Conclusions: FRAME describes real-world treatment patterns and survival for patients initiating FLT for advanced or metastatic NSCLC between 2009 and 2011 across Europe. (C) 2015 Elsevier Ireland Ltd. All rights reserved

Rationale, design, and implementation protocol of the Dutch clinical practice guideline Pain in patients with cancer: a cluster randomised controlled trial with short message service (SMS) and interactive voice response (IVR)

<p>Abstract</p> <p>Background</p> <p>One-half of patients with cancer have pain. In nearly one out of two cancer patients with pain, this was undertreated. Inadequate pain control still remains an important problem in this group of patients. Therefore, in 2008 a national, evidence-based multidisciplinary clinical practice guideline 'pain in patients with cancer' has been developed. Yet, publishing a guideline is not enough. Implementation is needed to improve pain management. An innovative implementation strategy, Short Message Service with Interactive Voice Response (SVS-IVR), has been developed and pilot tested. This study aims to evaluate on effectiveness of this strategy to improve pain reporting, pain measurement and adequate pain therapy. In addition, whether the active role of the patient and involvement of caregivers in pain management may change.</p> <p>Methods/design</p> <p>A cluster randomised controlled trial with two arms will be performed in six oncology outpatient clinics of hospitals in the Southeastern region of the Netherlands, with three hospitals in the intervention and three in the control condition. Follow-up measurements will be conducted in all hospitals to study the long-term effect of the intervention. The intervention includes training of professionals (medical oncologists, nurses, and general practitioners) and SMS-IVR to report pain in patients with cancer to improve pain reporting by patients, pain management by medical oncologists, nurses, and general practitioners, and decrease pain intensity.</p> <p>Discussion</p> <p>This innovative implementation strategy with technical tools and the involvement of patients, may enhance the use of the guideline 'pain in patients with cancer' for pain management. Short Message Service alerts may serve as a tool to support self-management of patients. Therefore, the SMS-IVR intervention may increase the feeling of having control over one's life.</p> <p>Trail registration</p> <p>Netherlands Trial Register (NTR): <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2739">NTR2739</a></p