Risk-Taking in Disorders of Natural and Drug Rewards: Neural Correlates and Effects of Probability,Valence, and Magnitude

Pathological behaviors toward drugs and food rewards have underlying commonalities. Risk-taking has a fourfold pattern varying as a function of probability and valence leading to the nonlinearity of probability weighting with overweighting of small probabilities and underweighting of large probabilities. Here we assess these influences on risk-taking in patients with pathological behaviors toward drug and food rewards and examine structural neural correlates of nonlinearity of probability weighting in healthy volunteers. In the anticipation of rewards, subjects with binge eating disorder show greater risk-taking, similar to substance-use disorders. Methamphetamine-dependent subjects had greater nonlinearity of probability weighting along with impaired subjective discrimination of probability and reward magnitude. Ex-smokers also had lower risk-taking to rewards compared with non-smokers. In the anticipation of losses, obesity without binge eating had a similar pattern to other substance-use disorders. Obese subjects with binge eating also have impaired discrimination of subjective value similar to that of the methamphetamine-dependent subjects. Nonlinearity of probability weighting was associated with lower gray matter volume in dorsolateral and ventromedial prefrontal cortex and orbitofrontal cortex in healthy volunteers. Our findings support a distinct subtype of binge eating disorder in obesity with similarities in risk-taking in the reward domain to substance use disorders. The results dovetail with the current approach of defining mechanistically based dimensional approaches rather than categorical approaches to psychiatric disorders. The relationship to risk probability and valence may underlie the propensity toward pathological behaviors toward different types of rewards.     

The individual who is severely and persistently mentally ill: directions for research and practice.

Psychiatric mental health nursing has not invested time and resources in the care of those with severe and persistent mental illness. In this article, current nursing research is reviewed and practice/research directions are delineated in the following areas: acute and chronic manifestations of symptoms, behavioral manifestations related to institutionalization, responses to psychiatric disorders over time, the long-term effects of psychotropic medication on behavior, and the impact of physical illnesses on psychiatric disorders. Knowledge is sorely needed in all of these areas to improve the nursing care of those persons with severe and persistent mental illness.     

One hertz repetitive transcranial magnetic stimulation over dorsal premotor cortex enhances offline motor memory consolidation for sequence‐specific implicit learning

Consolidation of motor memories associated with skilled practice can occur both online, concurrent with practice, and offline, after practice has ended. The current study investigated the role of dorsal premotor cortex (PMd) in early offline motor memory consolidation of implicit sequence‐specific learning. Thirty‐three participants were assigned to one of three groups of repetitive transcranial magnetic stimulation (rTMS) over left PMd (5 Hz, 1 Hz or control) immediately following practice of a novel continuous tracking task. There was no additional practice following rTMS. This procedure was repeated for 4 days. The continuous tracking task contained a repeated sequence that could be learned implicitly and random sequences that could not. On a separate fifth day, a retention test was performed to assess implicit sequence‐specific motor learning of the task. Tracking error was decreased for the group who received 1 Hz rTMS over the PMd during the early consolidation period immediately following practice compared with control or 5 Hz rTMS. Enhanced sequence‐specific learning with 1 Hz rTMS following practice was due to greater offline consolidation, not differences in online learning between the groups within practice days. A follow‐up experiment revealed that stimulation of PMd following practice did not differentially change motor cortical excitability, suggesting that changes in offline consolidation can be largely attributed to stimulation‐induced changes in PMd. These findings support a differential role for the PMd in support of online and offline sequence‐specific learning of a visuomotor task and offer converging evidence for competing memory systems.     

Comparative activity of penciclovir and acyclovir in mice infected intraperitoneally with herpes simplex virus type 1 SC16.

Penciclovir [PCV; 9-(4-hydroxy-3-hydroxymethylbut-1-yl)guanine; BRL 39123] is a potent and selective inhibitor of herpes simplex virus and varicella-zoster virus in human cell culture. We have compared the activities of PCV and acyclovir (ACV) in DBA/2 mice infected intraperitoneally with herpes simplex virus type 1 SC16 by measuring the amount of virus in peritoneal washings. In untreated mice after an eclipse phase, virus titers are maximum at 48 h after infection and decline thereafter. PCV and ACV reduced virus replication to a similar extent when given ad libitum in drinking water, even though ACV had better oral bioavailability and greater potency in murine cells. Thus, PCV was more active than had been predicted. In dose-response experiments, PCV given as a single subcutaneous dose 24 h after infection was active at a 10-fold-lower dose than ACV (P < 0.01). A single subcutaneous dose of PCV at 5 h after infection prevented virus replication for 3 days and was more effective than three doses of ACV given 1, 5, and 20 h after infection (P < 0.05). The superior activity of PCV following discrete dosing is not due to pharmacokinetic differences but is probably a reflection of the known stability of the intracellular triphosphate. In this model, the maintenance of high concentrations in blood is less important for PCV than for ACV and may lead to less-frequent doses in clinical use.     

Power and sample size for cost-effectiveness analysis: fFN neonatal screening

Randomised controlled trials (RCTs) which involve cost-effectiveness evaluations rarely use health economic input when undertaking sample size calculations for the trial design; however, in studies undertaken with cost-effectiveness as the primary outcome, sample size calculations should be directly related to the cost-effectiveness result rather than to the effectiveness outcome alone. This paper reports on a case in which a clinical trial design sample size and power calculations were determined with regard to cost-effectiveness using the net monetary benefit (NMB) approach to demonstrate the feasibility of sample size calculation for cost-effectiveness in a real life setting.The proposed RCT of fetal fibronectin screening (fFN) for women with threatened pre-term labour is discussed, followed by the design of a preliminary model to inform the trial design calculation. The predictions from this pre-trial indicate potential cost-savings, but with a marginal detrimental impact on the effectiveness endpoint, neonatal morbidity. The NMB approach for cost-effectiveness is discussed and used to calculate the required sample sizes for different powers. The sample size calculations are then recalculated using a non-inferiority margin, to ensure that the NMB sample size for the trial was also sufficient to demonstrate non-inferiority for the effectiveness endpoint. Finally, a probabilistic analysis explored uncertainty in the model parameters and the impact on sample size.Considerations of economic assessments alongside clinical trials can and should be used to guide conventional trial design. This paper demonstrates the feasibility of such calculations, whilst simultaneously highlighting limitations and demonstrating the role for economic considerations to guide non-inferiority margins.     

Five-year outcome of state-wide hip surveillance of children and adolescents with cerebral palsy

This study reports the five-year outcomes of a prospective population-based study of clinical hip surveillance for children with cerebral palsy (CP) according to evidence-based standards of care. Systematic hip surveillance commenced in Queensland, Australia as a state-wide program in 2005. Queensland represents a dispersed population across a large geographical area, creating unique challenges in terms of service delivery. Over five years, 1,115 children with CP were recruited, representing 73% of the expected population based on 1.9 to 2.1 per 1,000 live births. Standardized clinical and radiological assessments have been provided, with a median follow-up of 1.2 years (range 1 month -5(+8) yrs). Of the 1,115 children, 423 (38%) have been discharged and 692 (62%) remain on surveillance with 314 (28%) identified as having hip displacement with Migration Percentage (MP) equal to or greater than 30% (≥ 30). The incidence of marked hip displacement (MP ≥ 30) was directly related to gross motor function, classified according to the gross motor function classification system (GMFCS), with distribution of GMFCS I=10, (3%), II=40 (13%), III=53 (43%), IV=96 (59%), and V=115 (64%). This state-wide surveillance program has been successful in correctly identifying children with hip displacement (MP ≥ 30), fast tracking children for orthopedic review and discharging those at minimal risk. No child has progressed to dislocation while on surveillance without orthopedic review.     

Posttraumatic stress disorder and odds of major invasive procedures among U.S. Veterans Affairs patients

Objectives

Although individuals with posttraumatic stress disorder (PTSD) are at heightened risk for several serious health conditions, research has not examined how having PTSD impacts receipt of invasive procedures that may alleviate these problems. We examined whether PTSD, after controlling for major depression, was associated with odds of receiving common types of major invasive procedures, and whether race, ethnicity, and gender was associated with odds of procedures.

Methods

Veterans Health Administration patients with PTSD and/or depression were age-matched with patients without these disorders. The odds of invasive hip/knee, digestive system, coronary artery bypass graft/percutaneous coronary intervention (CABG/PCI), and vascular procedures during FY2006–2009 were modeled for the full sample of 501,489 patients and for at-risk subsamples with medical conditions alleviated by the procedures examined.

Results

Adjusting for demographic covariates and medical comorbidity, PTSD without depression was associated with decreased odds of all types of procedures (odds ratios [OR] range 0.74–0.82), as was depression without PTSD (OR range 0.59–0.77). In analyses of at-risk patients, those with PTSD only were less likely to undergo hip/knee (OR = 0.78) and vascular procedures (OR = 0.73) but not CABG/PCI. African-Americans and women at-risk patients were less likely to undergo hip/knee, vascular, and CABG/PCI procedures (OR range 0.31–0.82).

Conclusion

With the exception of CABG/PCI among at-risk patients, Veterans with PTSD and/or depression were less likely to undergo all types of procedures examined. Future studies should examine the reasons for this disparity and whether it is associated with subsequent adverse outcomes.