Postsynaptic dorsal column pathway activation during spinal cord stimulation in patients with chronic pain.

Spinal cord stimulation (SCS) treatment for chronic pain relies on the activation of primary sensory fibres ascending to the brain in the dorsal columns. While the efficacy of SCS has been demonstrated, the precise mechanism of action and nature of the fibres activated by stimulation remain largely unexplored. Our investigation in humans with chronic neuropathic pain undergoing SCS therapy, found that post-synaptic dorsal column (PSDC) fibres can be activated synaptically by the primary afferents recruited by stimulation, and axonically by the stimulation pulses directly.

ECAP-controlled closed-loop versus open-loop SCS for the treatment of chronic pain: 36-month results of the EVOKE blinded randomized clinical trial.

Introduction: The evidence for spinal cord stimulation (SCS) has been criticized for the absence of blinded, parallel randomized controlled trials (RCTs) and limited evaluations of the long-term effects of SCS in RCTs. The aim of this study was to determine whether evoked compound action potential (ECAP)-controlled, closed-loop SCS (CL-SCS) is associated with better outcomes when compared with fixed-output, open-loop SCS (OL-SCS) 36 months following implant.

Methods: The EVOKE study was a multicenter, participant-blinded, investigator-blinded, and outcome assessor-blinded, randomized, controlled, parallel-arm clinical trial that compared ECAP-controlled CL-SCS with fixed-output OL-SCS.

Durability of Clinical and Quality-of-Life Outcomes of Closed-Loop Spinal Cord Stimulation for Chronic Back and Leg Pain: A Secondary Analysis of the Evoke Randomized Clinical Trial.

Importance: Chronic pain is debilitating and profoundly affects health-related quality of life. Spinal cord stimulation (SCS) is a well-established therapy for chronic pain; however, SCS has been limited by the inability to directly measure the elicited neural response, precluding confirmation of neural activation and continuous therapy. A novel SCS system measures the evoked compound action potentials (ECAPs) to produce a real-time physiological closed-loop control system.

Electrophysiological Responses in the Human S3 Nerve During Sacral Neuromodulation for Fecal Incontinence.

Intra-operative electrode placement for sacral neuromodulation (SNM) relies on visual observation of motor contractions alone, lacking complete information on neural activation from stimulation. This study aimed to determine whether electrophysiological responses can be recorded directly from the S3 sacral nerve during therapeutic SNM in patients with fecal incontinence, and to characterize such responses in order to better understand the mechanism of action (MOA) and whether stimulation is subject to changes in posture. Eleven patients undergoing SNM were prospectively recruited.

ECAP-Controlled Closed-Loop Spinal Cord Stimulation Efficacy and Opioid Reduction Over 24-Months: Final Results of the Prospective, Multicenter, Open-Label Avalon Study.

Introduction: Chronic pain is a major public health concern, as is the associated use of opioid medications, highlighting the importance of alternative treatments, such as spinal cord stimulation (SCS). Here, we present the final 24-month results of the Avalon study, which investigated the use of the first closed-loop SCS system in patients with chronic pain. The system measures the evoked compound action potentials (ECAPs) elicited by each stimulus pulse and drives a feedback loop to maintain the ECAP amplitude near constant.

The Effect of Spinal Cord Stimulation Frequency on the Neural Response and Perceived Sensation in Patients With Chronic Pain.

Background: The effect of spinal cord stimulation (SCS) amplitude on the activation of dorsal column fibres has been widely studied through the recording of Evoked Compound Action Potentials (ECAPs), the sum of all action potentials elicited by an electrical stimulus applied to the fibres. ECAP amplitude grows linearly with stimulus current after a threshold, and a larger ECAP results in a stronger stimulus sensation for patients. This study investigates the effect of stimulus frequency on both the ECAP amplitude as well as the perceived stimulus sensation in patients undergoing SCS therapy for chronic back and/or leg pain.

Sustained Long-Term Outcomes With Closed-Loop Spinal Cord Stimulation: 12-Month Results of the Prospective, Multicenter, Open-Label Avalon Study.

Background: Spinal cord stimulation (SCS) activates the dorsal column fibers using electrical stimuli. Current SCS systems function in fixed-output mode, delivering the same stimulus regardless of spinal cord (SC) activation.

Objective: To present long-term outcomes of a novel closed-loop SCS system that aims to maintain the SC activation near a set target level and within a therapeutic window for each patient.

Quantifying harms to others due to alcohol consumption in Germany: a register-based study.

Background: The consumption of alcohol increases the risk of drinkers harming others. The extent of alcohol's morbidity and mortality harms to others in Germany in 2014 was estimated for (1) fetal alcohol syndrome (FAS) or fetal alcohol spectrum disorders (FASD) among newborns, (2) road traffic fatalities, and (3) interpersonal violence-related deaths.

Methods: The incidences of FAS and FASD were estimated by means of a meta-analytical approach, combining data on alcohol use during pregnancy and the risk relationship between alcohol consumption during pregnancy and FAS/FASD.

Are the "Best Buys" for Alcohol Control Still Valid? An Update on the Comparative Cost-Effectiveness of Alcohol Control Strategies at the Global Level.

Objective: Evidence on the comparative cost-effectiveness of alcohol control strategies is a relevant input into public policy and resource allocation. At the global level, this evidence has been used to identify so-called best buys for noncommunicable disease prevention and control. This article uses global evidence on alcohol use exposures and risk relations, as well as on intervention costs and impacts, to re-examine the comparative cost-effectiveness of a range of alcohol control strategies.

The effect of a reduction in alcohol consumption on blood pressure: a systematic review and meta-analysis.

Background: Although it is well established that heavy alcohol consumption increases the risk of hypertension, little is known about the effect of a reduction of alcohol intake on blood pressure. We aimed to assess the effect of a reduction in alcohol consumption on change in blood pressure stratified by initial amount of alcohol consumption and sex in adults.

Methods: In this systematic review and meta-analysis, we searched MedLine, Embase, CENTRAL, and ClinicalTrials.

Towards new recommendations to reduce the burden of alcohol-induced hypertension in the European Union.

Background: Hazardous and harmful alcohol use and high blood pressure are central risk factors related to premature non-communicable disease (NCD) mortality worldwide. A reduction in the prevalence of both risk factors has been suggested as a route to reach the global NCD targets. This study aims to highlight that screening and interventions for hypertension and hazardous and harmful alcohol use in primary healthcare can contribute substantially to achieving the NCD targets.

Global prevalence of alcohol use and binge drinking during pregnancy, and fetal alcohol spectrum disorder.

Alcohol use during pregnancy is an established cause of fetal alcohol spectrum disorder (FASD), with heavy drinking during pregnancy being explicitly linked to fetal alcohol syndrome (FAS). This paper presents recent estimates of the prevalence of: (i) any amount of alcohol use during pregnancy; (ii) one or more binge drinking episode(s) (4 or more standard drinks on a single occasion) during pregnancy; (iii) FAS; and (iv) FASD among the general population globally and by World Health Organization region. It is apparent, based on the presented estimates, that alcohol use and binge drinking occur frequently among pregnant women in many countries and as a result, FASD is a prevalent alcohol-related developmental disability.

Global Prevalence of Fetal Alcohol Spectrum Disorder Among Children and Youth: A Systematic Review and Meta-analysis.

Importance: Prevalence estimates are essential to effectively prioritize, plan, and deliver health care to high-needs populations such as children and youth with fetal alcohol spectrum disorder (FASD). However, most countries do not have population-level prevalence data for FASD.

Objective: To obtain prevalence estimates of FASD among children and youth in the general population by country, by World Health Organization (WHO) region, and globally.

Life-time risk of mortality due to different levels of alcohol consumption in seven European countries: implications for low-risk drinking guidelines.

Background And Aims: Low-risk alcohol drinking guidelines require a scientific basis that extends beyond individual or group judgements of risk. Life-time mortality risks, judged against established thresholds for acceptable risk, may provide such a basis for guidelines. Therefore, the aim of this study was to estimate alcohol mortality risks for seven European countries based on different average daily alcohol consumption amounts.

Estimating the harms and costs of cannabis-attributable collisions in the Canadian provinces.

Introduction: In 2012, 10% of Canadians used cannabis and just under half of those who use cannabis were estimated to have driven under the influence of cannabis. Substantial evidence has accumulated to indicate that driving after cannabis use increases collision risk significantly; however, little is known about the extent and costs associated with cannabis-related traffic collisions. This study quantifies the costs of cannabis-related traffic collisions in the Canadian provinces.

The relationship between different dimensions of alcohol use and the burden of disease-an update.

Background And Aims: Alcohol use is a major contributor to injuries, mortality and the burden of disease. This review updates knowledge on risk relations between dimensions of alcohol use and health outcomes to be used in global and national Comparative Risk Assessments (CRAs).

Methods: Systematic review of reviews and meta-analyses on alcohol consumption and health outcomes attributable to alcohol use.

Estimation of national, regional, and global prevalence of alcohol use during pregnancy and fetal alcohol syndrome: a systematic review and meta-analysis.

Background: Alcohol use during pregnancy is the direct cause of fetal alcohol syndrome (FAS). We aimed to estimate the prevalence of alcohol use during pregnancy and FAS in the general population and, by linking these two indicators, estimate the number of pregnant women that consumed alcohol during pregnancy per one case of FAS.

Methods: We began by doing two independent comprehensive systematic literature searches using multiple electronic databases for original quantitative studies that reported the prevalence in the general population of the respective country of alcohol use during pregnancy published from Jan 1, 1984, to June 30, 2014, or the prevalence of FAS published from Nov 1, 1973, to June 30, 2015, in a peer-reviewed journal or scholarly report.

Reduction of mortality following better detection of hypertension and alcohol problems in primary health care in Spain.

Through a simulation study, we estimated the potential effects of better detection of hypertension and improved screening for alcohol problems with subsequent interventions. Results showed that if 50% of Spanish males between 40 and 64 years of age who are currently unaware of their hypertension become aware of their condition and receive the usual treatment, and 50% of these males with hypertension are screened for alcohol and are treated for hazardous drinking or alcohol use disorders, then the percentage of uncontrolled hypertension among men with hypertension decreases from 61.2% to 55.

Modelling the impact of alcohol consumption on cardiovascular disease mortality for comparative risk assessments: an overview.

Background: Although alcohol consumption has long been considered as a risk factor for chronic disease, the relationship to cardiovascular disease (CVD) is complex and involves at least two dimensions: average volume of alcohol consumption and patterns of drinking. The objective of this contribution was to estimate the burden of CVD mortality caused by alcohol consumption.

Methods: Risk assessment modelling with alcohol-attributable CVD mortality as primary outcome.

Temporal changes in alcohol-related mortality and morbidity in Australia.

Background And Aims: Alcohol consumption is an avoidable risk factor for morbidity and mortality. Studies have examined relative risks and outcomes of alcohol-related harms in Australia at discrete times, limiting the ability to examine changes across time. This paper examined alcohol consumption and its contribution to deaths, illness and injury at two time-points, 2001 and 2010.

A new biomarker for subthalamic deep brain stimulation for patients with advanced Parkinson's disease--a pilot study.

Objective: Deep brain stimulation (DBS) has become the standard treatment for advanced stages of Parkinson's disease (PD) and other motor disorders. Although the surgical procedure has improved in accuracy over the years thanks to imaging and microelectrode recordings, the underlying principles that render DBS effective are still debated today. The aim of this paper is to present initial findings around a new biomarker that is capable of assessing the efficacy of DBS treatment for PD which could be used both as a research tool, as well as in the context of a closed-loop stimulator.

Temporal Changes in Alcohol-Related Morbidity and Mortality in Germany.

Aims: Trends in morbidity and mortality, fully or partially attributable to alcohol, for adults aged 18-64 were assessed for Germany.

Methods: The underestimation of population exposure was corrected by triangulating survey data with per capita consumption. Alcohol-attributable fractions by sex and two age groups were estimated for major disease categories causally linked to alcohol.

Prevalence of and potential influencing factors for alcohol dependence in Europe.

Alcohol use disorders (AUDs), and alcohol dependence (AD) in particular, are prevalent and associated with a large burden of disability and mortality. The aim of this study was to estimate prevalence of AD in the European Union (EU), Iceland, Norway, and Switzerland for the year 2010, and to investigate potential influencing factors. The 1-year prevalence of AD in the EU was estimated at 3.