A conceptual framework and protocol for defining clinical decision support objectives applicable to medical specialties.

BackgroundThe U.S. Centers for Medicare and Medicaid Services established the Electronic Health Record (EHR) Incentive Program in 2009 to stimulate the adoption of EHRs. One component of the program requires eligible providers to implement clinical decision support (CDS) interventions that can improve performance on one or more quality measures pre-selected for each specialty. Because the unique decision-making challenges and existing HIT capabilities vary widely across specialties, the development of meaningful objectives for CDS within such programs must be supported by deliberative analysis.DesignWe developed a conceptual framework and protocol that combines evidence review with expert opinion to elicit clinically meaningful objectives for CDS directly from specialists. The framework links objectives for CDS to specialty-specific performance gaps while ensuring that a workable set of CDS opportunities are available to providers to address each performance gap. Performance gaps may include those with well-established quality measures but also priorities identified by specialists based on their clinical experience. Moreover, objectives are not constrained to performance gaps with existing CDS technologies, but rather may include those for which CDS tools might reasonably be expected to be developed in the near term, for example, by the beginning of Stage 3 of the EHR Incentive program. The protocol uses a modified Delphi expert panel process to elicit and prioritize CDS meaningful use objectives. Experts first rate the importance of performance gaps, beginning with a candidate list generated through an environmental scan and supplemented through nominations by panelists. For the highest priority performance gaps, panelists then rate the extent to which existing or future CDS interventions, characterized jointly as "CDS opportunities," might impact each performance gap and the extent to which each CDS opportunity is compatible with specialists' clinical workflows. The protocol was tested by expert panels representing four clinical specialties: oncology, orthopedic surgery, interventional cardiology, and pediatrics

Distribution and Habitat of the Southern Two-Lined Salamander, Eurycea cirrigera, in Will County, Illinois: Implications For Population Management and Monitoring

The southern two-lined salamander (Eurycea cirrigera) was found to occur at numerous localities within the Kankakee River State Park in Will County, Illinois. The species is restricted to small drainages within the Kankakee River valley that have flow consisting of groundwater that discharges at seeps or springs at or within the valley bluff. Cooler water temperatures and possibly other conditions that are associated with water derived from seep or spring sources may be important factors in determining salamander abundance. This is particularly relevant to larval habitat. These observations suggest that the spring or seep-fed larval habitat may be the primary limiting factor that may explain why the distribution of E. cirrigera is restricted in northern Illinois. It is proposed, that from a conservation management perspective, individual drainages or spring runs may best be considered as subpopulations of a metapopulation that are vulnerable to both deterministic and stochastic extinction. Educational field trips conducted by faculty of Chicago State University in 1996 and 1997 have provided preliminary data of relative population size and environmental conditions at some sites. With further refinement and standardization, these census techniques may have high potential for long-term monitoring to assess population status or detect decline. The inventory and census strategies that were used may also be adapted for use with other streamside salamander species that have similar life history traits and habitat requirements

Nicotinic receptor modulation to treat alcohol and drug dependence

Alcohol and drug dependence are serious public health problems worldwide. The prevalence of alcohol and drug dependence in the United States and other parts of the world is significant. Given the limitations in the efficacy of current pharmacotherapies to treat these disorders, research in developing alternative pharmacotherapies continues. Preclinical and clinical evidence thus far has indicated that brain nicotinic acetylcholine receptors (nAChRs) are important pharmacological targets for the development of medications to treat alcohol and drug dependence. The nAChRs are a super family of ligand gated ion channels, and are expressed throughout the brain with twelve neuronal nAChR subunits (α2–α10 and β2–β4) identified. Here, we review preclinical and clinical evidence involving a number of nAChR ligands that target different nAChR subtypes in alcohol and nicotine addiction. The important ligands include cytisine, lobeline, mecamylamine, varenicline, sazetidine A and others that target α4β2* nAChR subtypes as small molecule modulators of the brain nicotinic cholinergic system are also discussed. Taken together, both preclinical and clinical data exist that support nAChR–based ligands as promising therapeutic agents for the treatment of alcohol and drug dependence

Bell nonlocality, signal locality and unpredictability (or What Bohr could have told Einstein at Solvay had he known about Bell experiments)

The 1964 theorem of John Bell shows that no model that reproduces the predictions of quantum mechanics can simultaneously satisfy the assumptions of locality and determinism. On the other hand, the assumptions of \emph{signal locality} plus \emph{predictability} are also sufficient to derive Bell inequalities. This simple theorem, previously noted but published only relatively recently by Masanes, Acin and Gisin, has fundamental implications not entirely appreciated. Firstly, nothing can be concluded about the ontological assumptions of locality or determinism independently of each other -- it is possible to reproduce quantum mechanics with deterministic models that violate locality as well as indeterministic models that satisfy locality. On the other hand, the operational assumption of signal locality is an empirically testable (and well-tested) consequence of relativity. Thus Bell inequality violations imply that we can trust that some events are fundamentally \emph{unpredictable}, even if we cannot trust that they are indeterministic. This result grounds the quantum-mechanical prohibition of arbitrarily accurate predictions on the assumption of no superluminal signalling, regardless of any postulates of quantum mechanics. It also sheds a new light on an early stage of the historical debate between Einstein and Bohr.Comment: Substantially modified version; added HMW as co-autho

Caenorhabditis elegans as a model system to identify therapeutics for alcohol use disorders

Alcohol use disorders (AUDs) cause serious problems in society and few effective treatments are available. Caenorhabditis elegans (C. elegans) is an excellent invertebrate model to study the neurobiological basis of human behavior with a conserved, fully tractable genome, and a short generation time for fast generation of data at a fraction of the cost of other organisms. C. elegans demonstrate movement toward, and concentration-dependent self-exposure to various psychoactive drugs. The discovery of opioid receptors in C. elegans provided the impetus to test the hypothesis that C. elegans may be used as a medications screen to identify new AUD treatments. We tested the effects of naltrexone, an opioid antagonist and effective treatment for AUDs, on EtOH preference in C. elegans. Six-well agar test plates were prepared with EtOH placed in a target zone on one side and water in the opposite target zone of each well. Worms were treated with naltrexone before EtOH preference testing and then placed in the center of each well. Wild-type worms exhibited a concentration-dependent preference for 50, 70 and 95% EtOH. Naltrexone blocked acute EtOH preference, but had no effect on attraction to food or benzaldehyde in wild-type worms. Npr-17 opioid receptor knockout mutants did not display a preference for EtOH. In contrast, npr-17 opioid receptor rescue mutants exhibited significant EtOH preference behavior, which was attenuated by naltrexone. Chronic EtOH exposure induced treatment resistance and compulsive-like behavior. These data indicate that C. elegans can serve as a model system to identify compounds to treat AUDs

Polysubstance addiction vulnerability in mental illness: Concurrent alcohol and nicotine self‐administration in the neurodevelopmental hippocampal lesion rat model of schizophrenia

Multiple addictions frequently occur in patients with mental illness. However, basic research on the brain‐based linkages between these comorbidities is extremely limited. Toward characterizing the first animal modeling of polysubstance use and addiction vulnerability in schizophrenia, adolescent rats with neonatal ventral hippocampal lesions (NVHLs) and controls had 19 weekdays of 1 hour/day free access to alcohol/sucrose solutions (fading from 10% sucrose to 10% alcohol/2% sucrose on day 10) during postnatal days (PD 35‐60). Starting in adulthood (PD 63), rats acquired lever pressing for concurrent oral alcohol (10% with 2% sucrose) and iv nicotine (0.015 mg/kg/injection) across 15 sessions. Subsequently, 10 operant extinction sessions and 3 reinstatement sessions examined drug seeking upon withholding of nicotine, then both nicotine and alcohol, then reintroduction. Adolescent alcohol consumption did not differ between NVHLs and controls. However, in adulthood, NVHLs showed increased lever pressing at alcohol and nicotine levers that progressed more strongly at the nicotine lever, even as most pressing by both groups was at the alcohol lever. In extinction, both groups showed expected declines in effort as drugs were withheld, but NVHLs persisted with greater pressing at both alcohol and nicotine levers. In reinstatement, alcohol reaccess increased pressing, with NVHLs showing greater nicotine lever activity overall. Developmental temporal‐limbic abnormalities that produce mental illness can thus generate adult polydrug addiction vulnerability as a mechanism independent from putative cross‐sensitization effects between addictive drugs. Further preclinical modeling of third‐order (and higher) addiction‐mental illness comorbidities may advance our understanding and treatment of these complex, yet common brain illnesses

Targeting Glutamate Uptake To Treat Alcohol Use Disorders

Alcoholism is a serious public health concern that is characterized by the development of tolerance to alcohol's effects, increased consumption, loss of control over drinking and the development of physical dependence. This cycle is often times punctuated by periods of abstinence, craving and relapse. The development of tolerance and the expression of withdrawal effects, which manifest as dependence, have been to a great extent attributed to neuroadaptations within the mesocorticolimbic and extended amygdala systems. Alcohol affects various neurotransmitter systems in the brain including the adrenergic, cholinergic, dopaminergic, GABAergic, glutamatergic, peptidergic, and serotonergic systems. Due to the myriad of neurotransmitter and neuromodulator systems affected by alcohol, the efficacies of current pharmacotherapies targeting alcohol dependence are limited. Importantly, research findings of changes in glutamatergic neurotransmission induced by alcohol self- or experimenter-administration have resulted in a focus on therapies targeting glutamatergic receptors and normalization of glutamatergic neurotransmission. Glutamatergic receptors implicated in the effects of ethanol include the ionotropic glutamate receptors (AMPA, Kainate, and NMDA) and some metabotropic glutamate receptors. Regarding glutamatergic homeostasis, ceftriaxone, MS-153, and GPI-1046, which upregulate glutamate transporter 1 (GLT1) expression in mesocorticolimbic brain regions, reduce alcohol intake in genetic animal models of alcoholism. Given the hyperglutamatergic/hyperexcitable state of the central nervous system induced by chronic alcohol abuse and withdrawal, the evidence thus far indicates that a restoration of glutamatergic concentrations and activity within the mesocorticolimbic system and extended amygdala as well as multiple memory systems holds great promise for the treatment of alcohol dependence

Secondary membranous nephropathy associated with guillain-barré syndrome.

Membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome (NS) in adults. It may be primary, usually mediated by IgG4 anti-phospholipase A2 autoantibodies or secondary to various other conditions. Guillain- Barré syndrome (GBS) has been associated with MN, but a cause and effect relation has not been proven. We present a case of concurrent development of GBS and severe NS, with renal biopsy demonstrating MN. IgG4 stain was negative, indicating that most likely, the MN was secondary and probably caused by the underlying GBS

Caffeinated Alcoholic Beverages – An Emerging Trend in Alcohol Abuse

Alcohol use disorders are pervasive in society and their impact affects quality of life, morbidity and mortality, as well as individual productivity. Alcohol has detrimental effects on an individual’s physiology and nervous system, and is associated with disorders of many organ and endocrine systems impacting an individual’s health, behavior, and ability to interact with others. Youth are particularly affected. Unfortunately, adolescent usage also increases the probability for a progression to dependence. Several areas of research indicate that the deleterious effects of alcohol abuse may be exacerbated by mixing caffeine with alcohol. Some behavioral evidence suggests that caffeine increases alcohol drinking and binge drinking episodes, which in turn can foster the development of alcohol dependence. As a relatively new public health concern, the epidemiological focus has been to establish a need for investigating the effects of caffeinated alcohol. While the trend of co-consuming these substances is growing, knowledge of the central mechanisms associated with caffeinated ethanol has been lacking. Research suggests that caffeine and ethanol can have additive or synergistic pharmacological actions and neuroadaptations, with the adenosine and dopamine systems in particular implicated. However, the limited literature on the central effects of caffeinated ethanol provides an impetus to increase our knowledge of the neuroadaptive effects of this combination and their impact on cognition and behavior. Research from our laboratories indicates that an established rodent animal model of alcoholism can be extended to investigate the acute and chronic effects of caffeinated ethanol