Linking Patient-Centered Outcomes to Neuropsychological Practice: A Conceptual Framework and Opportunities for Research.

In the current healthcare climate, reimbursement for services is increasingly linked to the ability to demonstrate beneficial patient outcomes. Neuropsychology faces some unique challenges in outcomes research, namely, that neuropsychologists often do not follow patients over time and the effect of neuropsychological services on patient outcomes may not be fully realized until under another provider's care. Yet there is an urgent need for empirical evidence linking neuropsychological practice to positive patient outcomes. To provide a framework for this research, we define a core set of patient-centered outcomes and neuropsychological processes that apply across practice settings and patient populations. Within each area, we review the available existing literature on neuropsychological outcomes, identifying substantial gaps in the literature for future research. This work will be critical for the field to demonstrate the benefit of neuropsychological services, to continue to advocate effectively for reimbursement, and to ensure high-quality patient care.

A comprehensive analysis of attempted and fatal suicide cases involving frequently used psychotropic medications.

OBJECTIVES: Self-poisoning is the most common suicide method in non-lethal suicide attempts and the third most frequent in fatal suicides. Psychoactive drugs are often used for intentional self-poisoning. While poisons centre data typically focus on survived suicide attempts and underrepresent fatal self-poisoning, medical examiner reports give insight into suicide deaths. To close this gap, we combined and compared data sets from both sources, assessing the mortality of psychotropic drugs used for self-poisoning. METHODS: Anonymized cases of self-poisoning with suicidal intention from 2000 to 2010 were extracted from the national poisons centre case database and compared with cases of suicide documented in the project "Suicides, a national survey". All cases with single substance exposure to a psychoactive drug (antidepressants, mood stabilizers, antipsychotics, sedatives) were included in the analyses. Opioids, over-the-counter- and illicit- drugs were excluded from the analysis. A mortality index was calculated by the ratio of the number of suicides and the sum of all (lethal and non-lethal) suicide attempts. RESULTS: Tricyclics had a higher mortality rate than other antidepressants. Among the sedatives, zolpidem was found to have a higher mortality index compared to benzodiazepines. Clozapine and levomepromazine were found to be the most lethal antipsychotics. Non-lethal suicide cases with single substance exposure (n = 4697) diminished as age increased, while the rate of suicide cases (n = 165) was higher in elderly subjects (>65 years of age, p < 0.001). CONCLUSION: In summary, our findings confirm previous study results on the relative toxicity of distinct classes of psychotropic drugs. In this comprehensive analysis of a national cohort lorazepam had a lower mortality rate compared to other sedatives.

Acute and chronic alcohol use correlated with methods of suicide in a Swiss national sample.

OBJECTIVES: Chronic and acute alcohol use are highly associated risk factors for suicides worldwide. Therefore, we examined suicide cases with and without alcohol use disorder (AUD) using data from the SNSF project "Suicide in Switzerland: A detailed national survey". Our investigations focus on correlations between acute and chronic alcohol use with reference to suicide and potential interactions with the methods of suicide. METHODS: We used data from the SNSF project in which all cases of registered completed suicide in Switzerland reported to any of the seven Swiss institutes of legal and forensic medicine between 2000 and 2010 were collected. We extracted cases that were tested for blood alcohol to use in our analysis. We compared clinical characteristics, blood alcohol concentrations, and methods of suicide in cases with and without AUD. RESULTS: Out of 6497 cases, 2946 subjects were tested for acute alcohol use and included in our analysis. Of the latter, 366 (12.4%) persons had a medical history of AUD. Subjects with AUD significantly had higher blood alcohol concentrations and were more often in medical treatment before suicide. Drug intoxication as method of suicide was more frequent in cases with AUD compared to NAUD. CONCLUSION: Overall, we found a high incidence of acute alcohol use at the time of death in chronic alcohol misusers (AUD). The five methods of suicide most commonly used in Switzerland differed considerably between individuals with and without AUD. Blood alcohol concentrations varied across different methods of suicide independently from the medical history in both groups.

Alcohol Consumption in Healthy OPRM1 G Allele Carriers and Its Association with Impulsive Behavior.

AIMS: A link between alcohol use disorders (AUD) and impulsivity is well established. As there is evidence for the heritability of AUD, the investigation of the underlying genetic disposition for both conditions is an important issue. An association between AUD and a coding single nucleotide polymorphism (SNP) (rs1799971 encoding an Asn40Asp amino acid substitution, A118G) within the µ-opioid receptor 1 gene (OPRM1) has been reported. Therefore we tested the association between the OPRM1 A118G polymorphism and drinking as well as impulsive behavior in social drinkers. METHODS: A total of 214 healthy male social drinkers were recruited. Each participant was genotyped for the OPRM1 A118G variant. Alcohol use was assessed with items of the Alcohol Use Disorders Identification Test (AUDIT). Impulsivity was assessed using the UPPS impulsive behavior scale. For statistical analyses, we considered correlations, t-tests and ordinal regression models using SPSS V21. RESULTS: In total, 49 out of 214 participants were carriers of the OPRM1 118G allele. On average the OPRM1 118G carriers showed a slightly higher propensity for alcohol drinking. Higher drinking frequency among the G allele carriers was linked with higher urgency and perseveration subscores of impulsivity. CONCLUSION: Our results suggest a genetically influenced higher propensity for alcohol drinking among social drinkers carrying the 118G allele of the OPRM1 gene. The positive correlation between urgency and a higher drinking frequency among the OPRM1 118G hint towards a functional meaning of the opioid system in the regulation of impulsivity.

Nanospace engineering of KOH activated carbon.

This paper demonstrates that nanospace engineering of KOH activated carbon is possible by controlling the degree of carbon consumption and metallic potassium intercalation into the carbon lattice during the activation process. High specific surface areas, porosities, sub-nanometer (<1 nm) and supra-nanometer (1-5 nm) pore volumes are quantitatively controlled by a combination of KOH concentration and activation temperature. The process typically leads to a bimodal pore size distribution, with a large, approximately constant number of sub-nanometer pores and a variable number of supra-nanometer pores. We show how to control the number of supra-nanometer pores in a manner not achieved previously by chemical activation. The chemical mechanism underlying this control is studied by following the evolution of elemental composition, specific surface area, porosity, and pore size distribution during KOH activation and preceding H(3)PO(4) activation. The oxygen, nitrogen, and hydrogen contents decrease during successive activation steps, creating a nanoporous carbon network with a porosity and surface area controllable for various applications, including gas storage. The formation of tunable sub-nanometer and supra-nanometer pores is validated by sub-critical nitrogen adsorption. Surface functional groups of KOH activated carbon are studied by microscopic infrared spectroscopy.

Enhanced hydrogen adsorption in boron substituted carbon nanospaces.

Activated carbons are one of promising groups of materials for reversible storage of hydrogen by physisorption. However, the heat of hydrogen adsorption in such materials is relatively low, in the range of about 4-8 kJ/mol, which limits the total amount of hydrogen adsorbed at P=100 bar to approximately 2 wt % at room temperature and approximately 8 wt % at 77 K. To improve the sorption characteristics the adsorbing surfaces must be modified either by substitution of some atoms in the all-carbon skeleton by other elements, or by doping/intercalation with other species. In this letter we present ab initio calculations and Monte Carlo simulations showing that substitution of 5%-10% of atoms in a nanoporous carbon by boron atoms results in significant increases in the adsorption energy (up to 10-13.5 kJ/mol) and storage capacity ( approximately 5 wt % at 298 K, 100 bar) with a 97% delivery rate.

Fluid restriction during running increases GI permeability.

The purpose of this study was to determine gastrointestinal (GI) permeability during prolonged treadmill running (60 min at 70 % V.O2max) with and without fluid intake (3 ml/kg body mass/10 min). Twenty runners (11 males, 9 females; age = 22 +/- 3 (SD) yrs; mean V.O2max = 55.7 +/- 5.0 ml/kg/min) completed four experiments: 1) rest, 2) running with no fluid (NF), 3) running with ingestion of a 4 % glucose solution (GLU), and 4) running with ingestion of a water placebo (PLA). To determine GI permeability, subjects also drank a solution containing 5 g sucrose (S), 5 g lactulose (L), and 2 g rhamnose (R) immediately prior to each trial. Gastroduodenal permeability was determined by urinary S excretion, while small intestinal permeability was determined by the L/R excretion ratio. Percent body mass loss (i.e., dehydration) was negligible during rest, GLU and PLA, while NF resulted in a 1.5 % loss of body mass (p < 0.05). Gastroduodenal and intestinal permeability were significantly (p < 0.008) increased in NF compared to rest. There were no other differences in GI permeability. These results indicate that fluid restriction during 1 h of steady-state running increases GI permeability above resting levels.

Serum from patients anesthetized with opiates less effective in the support of chondrocyte growth in vitro.

Risk of viral and/or prion disease transmission associated with the use of fetal bovine serum in clinical cell culture has led to the increasing use of autologous human serum in tissue engineering. A relatively large volume of blood is needed and so, to decrease patient discomfort, we have investigated the feasibility of taking blood when the patient is anesthetized. Two serum samples were prepared from each of 22 patients: (1). from the awake patient (PRE) and (2). from the patient 5 min after induction of general anesthesia (PER). The sera were compared for their ability to support the in vitro proliferation of primary human chondrocytes, determined by cell counting. The effects of anesthetic agents on the PER/PRE cell number ratio were established by analysis of variance and stepwise multilinear regression analysis. The PER sample supported higher growth in 2 of 22 patients, equivalent growth in another 11, and significantly lower growth in the remaining 8. Only the opiate analgesics (fentanyl [Sublimaze], alfentanyl [Rapifen], and diamorphine) had a significant and inhibitory effect on chondrocyte proliferation. It is suggested that opiate analgesics be avoided when blood is taken to support the in vitro growth of human cells.

Changes in skeletal muscle myosin heavy chain isoform content during congestive heart failure.

Recent investigations have suggested that changes in contractile protein expression contribute to reductions in skeletal muscle function during congestive heart failure (CHF). Myosin heavy chain (MHC), a major contractile protein, has been shown to undergo alterations in protein isoform expression during CHF. The purpose of this investigation was twofold: (1) to determine whether muscles of the same functional group undergo similar changes in MHC expression, and (2) determine whether the magnitude of alterations in MHC is related to the severity of CHF. Using the rat coronary ligation model, mild and severe forms of CHF were produced and muscles of the plantar flexor group were analyzed. Whole-muscle MHC isoform proportions were not altered in the soleus and white gastrocnemius muscle, however significant increases in the percentage of fast MHC isoforms (7-9% increases in MHC IIx and IIb expression) were found in the red gastrocnemius muscle. In addition, there were significant proportional increases (8%) in MHC type IIb at the expense of MHC type IIx in the plantaris muscle. Many of the changes in the proportions of MHC isoforms were significantly correlated with indices of CHF severity. This indicates that changes in skeletal muscle MHC isoform expression are related to the severity of CHF and suggests that some peripheral skeletal muscles are more susceptible to shifts in MHC expression due to CHF. These changes in MHC isoform expression may contribute to alterations in the physiological performance of skeletal muscle and exercise capacity during CHF.

Nearly space-filling fractal networks of carbon nanopores.

Small-angle x-ray scattering, nitrogen adsorption, and scanning tunneling microscopy show that a series of activated carbons host an extended fractal network of channels with dimension D(p) = 2.8-3.0 (pore fractal), channel width 15-20 A (lower end of scaling), network diameter 3000-3400 A (upper end of scaling), and porosity of 0.3-0.6. We interpret the network as a stack of quasiplanar invasion percolation clusters, formed by oxidative removal of walls between closed voids of diameter of approximately 10 A and held in registry by fibrils of the biological precursor, and point out unique applications.

Test-retest reliability of the Advanced Psychodiagnostic Interpretation (API) scoring system for the Bender Gestalt in chronic schizophrenics.

This study assesses the test-retest reliability of the revised Advanced Psychodiagnostic Interpretation (API) scoring system for the Bender Gestalt Test (BGT). The API system identifies 207 possible distortions in a BGT protocol. Test-retest reliability for 40 schizophrenic patients tested twice with a mean interval of 6.4 years (SD=3.8 years) was good, ranging from .71 to .80. Further reliability and validity studies are needed to further demonstrate the effectiveness of the system.

Value of the Bruce protocol to determine peak exercise oxygen consumption in patients evaluated for cardiac transplantation.

BACKGROUND: Peak exercise oxygen consumption (peak VO2) is an important discriminator of survival in patients with systolic heart failure and is used to select ambulatory patients for transplantation. The major trials assessing the relationship between peak VO2 and survival have used a variety of low-level exercise protocols. It is unknown how peak VO2 measured in this patient population by the more vigorous Bruce treadmill protocol compares with that obtained on less intense protocols. METHODS: We studied 15 patients (50 +/- 12 years old) with severe heart failure (left ventricular ejection fraction 23.5% +/- 8.6%). Patients randomly performed 3 exercise tests with the Bruce treadmill, modified Naughton treadmill, and modified bicycle protocols within 14 days. To determine the ability of this patient population to perform the Bruce protocol, we also retrospectively analyzed the ability of 84 patients to perform this test on their initial evaluations at our center. RESULTS: All patients reached the anaerobic threshold (AT) on all 3 protocols. The Bruce and modified Naughton treadmill protocols resulted in similar peak VO2 percent predicted peak VO2, and VO2 at AT values (17.7 +/- 3.8 mL/kg/min, 57.2% +/- 21.1% and 15.4 +/- 4.1 mL/kg/min vs 18.0 +/- 4.7 mL/kg/min, 58.1% +/- 22.5% and 15.6 +/- 4.4 mL/kg/min, respectively). Peak VO2 and VO2 at AT on both treadmill protocols were higher than those obtained with bicycle testing (15.3 +/- 3.1 and 11.8 +/- 3.0 mL/kg/min, P <.05). Exercise duration was shorter with the Bruce and bicycle protocols (6.2 +/- 2.2 and 6.7 +/- 2.4 minutes, respectively) compared with the modified Naughton protocol (9.7 +/- 4.3 minutes, both P <.005). In addition, 79 of the 84 patients (94%) evaluated were able to complete the Bruce protocol and reach AT. CONCLUSIONS: The Bruce protocol was more time efficient than the modified Naughton protocol and yielded similar peak VO2, percent predicted peak VO2, and VO2 at AT values. Bicycle exercise may underestimate peak VO2 values. The form of exercise should be considered when assessing peak VO2 criteria for transplant listing.

Accuracy of estimating exercise prescription intensity in patients with left ventricular systolic dysfunction.

PURPOSE: Exercise prescription in patients with left ventricular systolic dysfunction (LVSD) is difficult. Exercising beyond ventilatory threshold (VT) can have negative physiologic effects; therefore, exercise prescribed above VT may be detrimental. A majority of cardiac rehabilitation programs use the Karvonen/heart rate reserve (HRR) method, rating of perceived exertion (RPE), and/or a percentage of oxygen consumption to prescribe exercise intensity. The purpose of this study was to determine if these methods correlate with an exercise intensity below VT in LVSD patients. METHODS: The authors studied 52 patients (37 males, 15 females; age 52 +/- 13 years; left ventricular ejection fraction 27% +/- 8%) who underwent a symptom-limited cardiopulmonary exercise test and reached VT to determine functional capacity and exercise prescription. RESULTS: Peak heart rate (HR) as well as HRR derived minimum (60%), midpoint (70%), and maximum (80%) HR were highly correlated (P < 0.001) with HR at VT. Using these three different HR cutoff formulas from HRR, 15% to 62% of patients were prescribed exercise outside the range of VT-HR +/- 10%. The midpoint (70% HRR) best predicted exercise HR in the VT-HR +/- 10% range (73% of patients). Mean oxygen consumption at VT was 83 +/- 9% of peak oxygen consumption. There was no correlation (P < 0.16) between RPE and VT. CONCLUSIONS: The Karvonen/HRR method failed to estimate HR-VT +/- 10% in a large percentage of patients with LVSD. There was no correlation between RPE and VT. Based on these data, exercise training intensity should ideally be prescribed based on the HR identified at VT using cardiopulmonary exercise testing in patients with LVSD.

Skeletal muscle oxidative capacity and exercise tolerance in rats with heart failure.

PURPOSE: Past research has shown the development of exercise intolerance after myocardial infarction (MI). The purpose of this study was to test the hypothesis that reductions in oxidative enzyme activity, in a variety of skeletal muscles, coincide with the development of exercise intolerance in a rat model of chronic heart failure (CHF) induced by MI. METHODS: The animals were initially divided into two groups: sham-operated controls (Sham) and animals in which a MI was surgically induced. MI rats were then subdivided into two groups according to left ventricular end-diastolic pressure (LVEDP): <20 mm Hg [small MI (SMI)] and > 20 mm Hg [large MI (LMI)]. Exercise tolerance was measured by performing a progressive run to fatigue test (RTF). Citrate synthase (CS), 3-hydroxyacyl CoA dehydrogenase (HADH), and malate dehydrogenase (MDH) activities were measured in six hindlimb muscles. RESULTS: After approximately 6 wk of recovery, LVEDP differed among groups (P < 0.05): Sham (1 +/- 1 mm Hg, N = 7), SMI (7 +/- 2 mm Hg, N = 7), and LMI (30 +/- 2 mm Hg, N = 6). RTF was 20 +/- 1 min for Sham, 25 +/- 3 min for SMI, and 11 +/- 2 min for LMI (P < 0.05 for LMI vs Sham, SMI). Significant reductions in enzyme activity were found for all three enzymes in the red portion of the gastrocnemius muscles of LMI. However, no significant correlation was found between RTF and CS, HADH, or MDH in any muscle of the three groups of animals. DISCUSSION: The results of the present study demonstrate that severe left ventricular dysfunction is associated with reductions in exercise tolerance and modest decreases in oxidative enzyme activities in selected muscles. It does not appear, however, that the development of exercise intolerance in CHF and oxidative enzyme activities are mechanistically related to one another.

Correlation of the LNNB-III with the WAIS-III in a mixed psychiatric and brain-injured population.

The purpose of the study was to examine the relationship between the Luria-Nebraska Neuropsychological Battery-Third Edition (LNNB-III) and the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III). Participants were 85 adults referred for neuropsychological evaluation. The mean age of participants was 38.73 years (SD = 16.54) and average education was 13.07 years (SD = 2.60). The sample was predominantly female (52.9%), right-handed (86.3%), and Caucasian (68.6%), with the remainder of the population classified as Hispanic (13.7%), African-American (5.9%), or other (11.8%). Diagnoses included 26% psychiatric disorders, 64% neurological disorders, and 10% with no diagnosis. Pearson product correlation yielded a number of significant relationships between the WAIS-III IQ scores and the LNNB-III scales. The highest correlations were with the LNNB Intelligence, Visual-Spatial, Complex Auditory, and Arithmetic scales. Additionally, significant correlations were found between the WAIS-III subtests and a moderate proportion of the LNNB-III subtests. Correlations were also reported for the new WAIS-III scales, Letter-Number Sequencing and Matrix Reasoning. The results suggest that similar abilities are being assessed on both tests. These findings allow clinicians to not only evaluate the consistency of performance across this testing battery, but provide a useful screening instrument for intelligence.

Nonstandard roughness of terraced surfaces

We present a class of surfaces which are simultaneously flat and rough over the same range of lengths. They are self-affine, have well-defined roughness exponents, and consist of terraces of all sizes. The coexistence of flat and rough makes them respond to different external interactions with variable roughness. We demonstrate this for optical scattering (including x rays), two wetting situations, diffusion currents, and catalysis. A terraced Cu surface is a "self-assembled" experimental example, and designs for nano- and micromachined examples are presented.

Thyroid status and response to endothelin-1 in rat arterial vessels.

We have previously reported that changes in thyroid status are associated with significant alterations in skeletal muscle blood flow during exercise and that changes in endothelium-dependent vasodilation may contribute to these blood flow abnormalities. The purpose of this study was to test the hypothesis that altered endothelium-dependent vasoconstriction is also associated with changes in thyroid status. To test this hypothesis, rats were rendered hypothyroid with propylthiouracil (Hypo, n = 14) or hyperthyroid with triiodothyronine (Hyper, n = 14) over approximately 3 mo. Treatment efficacy was confirmed by altered (P < 0.05) citrate synthase activity in several hindlimb skeletal muscles from Hypo and Hyper, compared with that in muscles from euthyroid rats (Eut, n = 12). Vascular rings were prepared from abdominal aortae, and responses to several vasoactive agents were determined in vitro. As found previously, maximal acetylcholine-induced vasorelaxation was modulated by thyroid status (Eut, 47 +/- 9; Hypo, 28 +/- 6; Hyper, 68 +/- 5%; P < 0.05). Contractile responses of vascular rings with intact endothelium to the endothelium-derived constrictor endothelin-1 (ET-1), however, were similar among groups across a range of ET-1 concentrations. In addition, maximal responses [Eut, 3.75 +/- 0.47; Hypo, 2.72 +/- 0.25; Hyper, 3.22 +/- 0.42 g; not significant (NS)] and sensitivities (Eut, 8.12 +/- 0.09; Hypo, 8.10 +/- 0.06; Hyper, 8.28 +/- 0.09 -log M; NS) to ET-1 were similar among groups. If these findings from the conduit-type abdominal aorta extend into resistance vasculature, it appears that changes in endothelium-dependent vasoconstriction do not contribute to skeletal muscle blood flow abnormalities associated with thyroid disease states.

Plasma C3a and C4a levels in liver transplant recipients: a longitudinal study.

Liver transplant patients were enrolled in a study designed to investigate correlations between plasma complement C3a or C4a levels and various postoperative complications. Longitudinal EDTA-plasma levels of C3a and C4a were measured by quantitative radioimmunoassay. Acute rejection gave a characteristic and marked increase in blood C3a, C4a and gamma-glutamyl transferase (gammaGT) levels, which rapidly resolved after high dose steroid treatment. Cytomegalovirus (CMV) infections in two of three patients gave an initial small increase only in C3a levels (i.e., alternative pathway activation) followed approximately 6 weeks later by a marked increase in C4a levels (i.e., classical or lectin pathway activation). In a third patient diagnosed for CMV infection, the complement activation profile was complicated by a coincident minor rejection episode. However, a late stage elevation in C4a was also noted. Two patients experiencing biopsy proven recurrent hepatitis C infections following transplantation exhibited increases in both gammaGT and C4a levels, without a significant increase in the level of C3a. Several hepatitis C and one hepatitis B patient had multiple late activation episodes involving marked elevation in both plasma C3a and C4a levels without detectable increases in the liver enzymes conventionally used to monitor organ function. We also showed that ex vivo activation of complement in EDTA plasma from all transplant patients was abnormally high. The classical or lectin pathway is believed to be responsible for this excessive ex vivo complement activation in the plasma of these patients. Therefore, subclinical rejection episodes and/or viral infections may be effectively detected or monitored by measuring C3a and C4a levels in plasma samples from liver transplant patients. Routine measurement of plasma complement products may provide an early non-invasive mode for detecting infections and also serve to monitor chronic or acute changes in the patient's immune system.

Reliability of the Advanced Psychodiagnostic Interpretation (API) scoring system for the Bender Gestalt.

This study assesses the interrater reliability of the revised Advanced Psychodiagnostic Interpretation (API) scoring system for the Bender Gestalt Test (BGT). The API scoring system identifies 207 possible distortions in a BGT protocol. Agreement across nine raters exceeded 90% for each of three clinical protocols. Kappa statistics indicated that the API system exhibited good interrater reliability. Further research is necessary in such areas as test-retest reliability and validity to further demonstrate the effectiveness of the procedure.