Efficacy of Canakinumab vs. triamcinolone acetonide according to multiple gouty arthritis-related health outcomes measures.

AIM: Canakinumab (CAN), a selective, fully human, anti-IL-1ß monoclonal antibody, has demonstrated long-term benefits in gouty arthritis (GA) patients, who have contraindications for, or are unresponsive or intolerant of, non-steroidal anti-inflammatory drugs (NSAIDs) or colchicine (two trials:ß-RELIEVED [n = 228]; ß-RELIEVED II [n = 226]). The trials collected different responses, including patient-reported outcomes (PRO). A composite response end-point (CRE) was used to interpret each patient's overall response to treatment. METHODS: Data from ß-RELIEVED trials were pooled for this retrospective analysis. The CRE representing overall change in GA-related health outcomes, from baseline to 12 weeks, included clinical markers; PROs from the Gout Impact Scale (GIS); and the SF-36 bodily pain scale. Response to each variable (i.e. markedly important difference) was determined a priori. Variable values [1 (responder) or 0 (non-responder)] were summed to create a CRE score for each patient. RESULTS: For eight of 12 variables measured, the percentage of CAN responders was significantly greater than for TA (p < 0.05). On average, patients receiving CAN met a higher percentage of response criteria (65%) than patients receiving triamcinolone acetonide (TA) (49%), p < 0.001. Mean CRE scores were significantly higher for CAN vs. TA (mean [SD]; 4.7 [2.7] vs. 3.7 [2.4], p < 0.001). Treatment differences remained even after serially removing individual responder variables and domains from the composite end-point, indicating that the differences between CAN and TA were robust. CONCLUSION: CAN was superior to TA across multiple health-outcome variables comprising clinical markers and PRO over 12 weeks in patients contraindicated, intolerant or unresponsive to NSAIDs and/or colchicine.

Effects of schizophrenia and aging on pupillographic measures of working memory.

The amount of cognitive resources used to perform a task can be indexed as changes in pupil size. In a previous study, we examined pupillary response measures of slave store and central executive cognitive resources during a working memory task and found abnormally reduced utilization of these resources in schizophrenia. In the present study, multiple regression analyses were performed to examine the independent and combined effects of aging and schizophrenia on pupillary response and recall measures in a larger sample of community-dwelling schizophrenia patients. Schizophrenia was associated with a significant decline in working memory capacity, and an additional moderate decline was associated with aging, but these two factors did not interact. Baseline pupil size was significantly correlated with symptom severity, independent of medication. However, pupillary responses evoked by the working memory task and recall scores were not related to symptom severity. Results were consistent with an additive, rather than a synergistic, relationship between aging and schizophrenia, and suggested that working memory impairment in noninstitutionalized outpatients with schizophrenia may remain stable across symptom status and across the life span.

Pupillary responses index overload of working memory resources in schizophrenia.

The authors examined the hypothesis that schizophrenia patients have reduced availability of working memory resources by using pupillary responses as an index of resource overload. Pupillary responses were recorded during a verbal working memory task (digit recall) in 24 schizophrenia patients and 32 normal controls. Pupil size increased with increased processing load (digit-span length) but changed little or declined when processing demands exceeded available resources (overload). The schizophrenia patients showed impaired digit recall and abnormally small pupillary responses during digit presentation only in the higher processing load conditions, but they showed abnormally small pupillary responses during digit retrieval in all processing load conditions. The results suggest reduced availability of slave store and central executive working memory resources in schizophrenia. This study serves as an example of how pupillography methods can be used to test current hypotheses regarding overload of cognitive capacities in schizophrenia patients.

Positive and negative schizotypal symptoms relate to different aspects of crossover reaction time task performance.

Although the expressions of both positive and negative symptoms in schizophrenia spectrum illnesses can each occur with varying degrees of severity, researchers have often dichotomized patients as generally positive or negative subtypes. Studies of schizophrenia and schizotypal personality disorder (SPD) have not typically controlled for the severity of the other symptom types when examining the relationship between positive and negative symptom subtypes and cognitive impairment. The present study investigated the relationship between the severity of both symptom types and reaction time crossover task performance in SPD in groups made equivalent on the severity of the other type of symptom. Fifty-eight out of 458 undergraduates were screened into one of four groups (high negative-high positive, low negative-low positive, high negative-low positive or low negative-high positive) by the Schizotypal Personality Questionnaire and assessed with the reaction time crossover task. The results indicated that negative schizotypal symptoms were associated with the early crossover pattern, while positive schizotypal symptoms related to longer overall reaction time. Therefore, different cognitive mechanisms involved in crossover task performance appeared to be associated with different symptom subtypes.

Reaction time crossover with an interfering task.

The present study investigated reaction time with and without tapping as an interfering task. 66 undergraduate students were instructed to press and hold a button when a stimulus disappeared from a computer screen, then release it as quickly as possible when it reappeared at the end of each preparatory interval, using the preferred hand. Lengths of preparatory intervals were either 1, 2, 4, 8, 16, or 25 sec. and occurred sometimes in a regular sequence of preparatory intervals of the same length and sometimes in an irregular randomly ordered sequence. Half of the participants were assigned to tap the tabletop with the forefinger of the nonpreferred hand throughout the task. A 2 x 6 x 2 analysis of variance showed significant effects for regularity, length of preparatory interval, and the interaction between regularity and length of preparatory interval. A significant main effect for tapping indicated that reaction times were slower in the tapping group. There were no significant interactions between tapping and other variables, indicating that the pattern of reaction times did not differ significantly between the two groups. Tapping produces a dual-task interference that increases reaction time similarly across different conditions.

Interpersonal deficits and time spent in exercise or active recreation.

This study was designed to investigate the hypothesis that people with interpersonal deficits would spend less time in exercise or active recreation. Participants completed a questionnaire about the time spent per week in exercise or active recreation as well as in other activities such as reading and watching television. They also completed a questionnaire designed to measure both interpersonal and cognitive-perceptual deficits. Interpersonal deficits measured were social anxiety, constricted affect, and lack of close friends. Cognitive-perceptual deficits measured were perceptual aberration, magical ideation, and ideas of reference. Analysis showed that interpersonal deficits were related to reduced time spent in exercise or active recreation. Cognitive-perceptual deficits were not associated with time spent in exercise or active recreation.

The effects of a community-based literacy program on young children's language and conceptual development.

Effects of a community-based literacy program on 1-, 2-, and 3-year-old children's language and conceptual development were assessed. University students were trained to teach Head Start parents effective methods for reading to their children. Families were randomly assigned to receive 18, 3, or 0 instructional visits. Results indicated that parents in the 18-instructional-visit program increased their participation in appropriate literacy behaviors such as reading to their children, teaching concepts to their children, and using the library, more than parents in the 0-instructional-visit groups. Children in the 18-instructional-visit program showed greater gains in language and conceptual development than children in the 0-instructional-visit group. Few differences were found between children in the 3-visit and 0-instructional-visit groups. Thus, only a high-intensity community-based intervention designed to train parents was effective in increasing emergent literacy in low-income ethnic children.

Pupillary responses index cognitive resource limitations.

Cognitive task-evoked pupillary responses reliably index information-processing loads. However, previous studies have reported inconsistent findings regarding the nature of the pupillary response when processing demands approach or exceed available processing resources. This condition was examined in 22 normal undergraduates by using pupillometric recordings during a digit span recall task, with 5 (low load), 9 (moderate load), and 13 (excessive load) digits per string. Pupillary responses increased systematically with increased processing load (to-be-recalled digits) until the limit of available resources (memory capacity of 7 +/- 2 digits), when they reached asymptote and then declined with resource overload (> 9 digits). These findings suggest that pupillary responses increase systematically with increased processing demands that are below resource limits, change little during active processing at or near resource limits, and begin to decline when processing demands exceed available resources.