Long-term benefits and risks of frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic phase: 5-year update of the randomized ENESTnd trial.

In the phase 3 Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Newly Diagnosed Patients (ENESTnd) study, nilotinib resulted in earlier and higher response rates and a lower risk of progression to accelerated phase/blast crisis (AP/BC) than imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP). Here, patients' long-term outcomes in ENESTnd are evaluated after a minimum follow-up of 5 years. By 5 years, more than half of all patients in each nilotinib arm (300 mg twice daily, 54%; 400 mg twice daily, 52%) achieved a molecular response 4.5 (MR(4.5); BCR-ABL⩽0.0032% on the International Scale) compared with 31% of patients in the imatinib arm. A benefit of nilotinib was observed across all Sokal risk groups. Overall, safety results remained consistent with those from previous reports. Numerically more cardiovascular events (CVEs) occurred in patients receiving nilotinib vs imatinib, and elevations in blood cholesterol and glucose levels were also more frequent with nilotinib. In contrast to the high mortality rate associated with CML progression, few deaths in any arm were associated with CVEs, infections or pulmonary diseases. These long-term results support the positive benefit-risk profile of frontline nilotinib 300 mg twice daily in patients with CML-CP.

CT scan findings in oesophagogastric perforation after out of hospital cardiopulmonary resuscitation.

Rupture of the oesophagus or stomach at the time of cardiopulmonary resuscitation can occur with accidental oesophageal intubation. The common site of rupture is the lesser curvature of the stomach, but can also occur at the oesophagogastric junction. The patient presented with a massive pneumoperitoneum after an out of hospital ventricular fibrillation arrest. CT scanning was helpful in making the diagnosis. In out of hospital resuscitation, current JRCALC (Joint Royal Colleges Ambulance Liaison Committee) recommendations may not avoid this complication.

Effects of brief yoga exercises and motivational preparatory interventions in distance runners: results of a controlled trial.

OBJECTIVE: To examine the efficacy of two preparatory interventions on one mile run performance in 90 high school long distance runners. METHOD: After participants had completed a one mile baseline run, they were randomly assigned to participate in either one of two interventions (brief yoga exercises, motivational shouting exercises) or a no intervention control condition. Experimental conditions were implemented one week after the baseline run about 20 minutes before a second one mile trial. RESULTS: Participants assigned to the motivational intervention improved their running performance significantly more than those assigned to the other two conditions. Although the magnitude of the effect was small, participants assigned to yoga exercises showed significant improvements in running performance relative to control condition participants. Consumer satisfaction ratings indicated that participants who were assigned to the motivational and yoga exercise groups liked their interventions more than those assigned to the control group. CONCLUSION: Motivational and yoga interventions designed to improve long distance running performance were equally acceptable to the participants, but the former had a greater effect.

Improving athletes' perspectives of sport psychology consultation: a controlled evaluation of two interview methods.

Although investigations have consistently demonstrated the effectiveness of sport psychology interventions, these methods have been underutilized by athletes. In this study, 124 athletes completed the athletes' Attitudes Toward Seeking Sport Psychology Consultation Questionnaire (ATSSPCQ) and were subsequently randomly assigned to receive one of the two semistructured interview formats. One interview focused on discussing the athlete's experiences in sports, and the other focused on delineating sport psychology and its potential benefits to the athlete. Upon being interviewed, athletes were readministered the ATSSPCQ. Discussing sport psychology and its personal benefits was more effective in enhancing athletes' perception of need for sport psychology than discussing sport experiences. However, neither interview format enhanced athletes' perceptions of openness to discuss personal issues with a sport psychology consultant and tolerance of stigma associated with sport psychology consultation. Indeed, participants who received the discussion of sports intervention reported a significant decrease in personal openness to discuss personal issues relevant to sports psychology from pre- to postintervention. Intervention effects were similar for male and female athletes. Study implications and future directions are discussed in light of these results.

Satisfaction of parents with their conduct-disordered and substance-abusing youth.

This study examined parental satisfaction (using the Parent Satisfaction With Youth Scale) in 132 parents of adolescents who were dually diagnosed with conduct disorder/oppositional defiant disorder and drug abuse/dependence. Results indicated parental satisfaction did not vary as a function of age, ethnic minority status, or gender. Parents of younger youth were generally more dissatisfied than parents of older adolescents although younger youth were no more delinquent than older youth. These results suggest that parents of delinquent youth become tolerant of their children's behavior problems with time. As expected, parents were most dissatisfied with their youth's use of drugs, illicit behavior, school performance, and response to discipline. Parents who endorsed lower levels of satisfaction reported their youth engaged in more pronounced levels of problem behavior and more drug use than did parents who were relatively more satisfied with their youth. Study implications and future directions are discussed.

Satisfaction of conduct-disordered and substance-abusing youth with their parents.

Conduct-disordered and substance-abusing adolescents (N = 132) completed the Youth Happiness With Parent Scale (YHPS). The YHPS measures youth happiness with parental behaviors across 11 domains (e.g., communication, chores, and discipline) as well as a single item reflecting overall happiness. Results indicated that youth satisfaction did not vary as a function of parents' or youths' age, ethnic minority status, or gender. Although youth were relatively dissatisfied with their parents across behavioral domains (particularly illegal behaviors, drug use, school conduct, and alcohol use), they were fairly satisfied with their parents overall. Youth happiness with parental behaviors was negatively related to externalizing but not internalizing behavioral problems of the youth. Study implications and future directions are discussed in light of the results.

Prevalence and treatment of substance abuse in the mentally retarded population: an empirical review.

This article presents the first comprehensive review of studies of alcohol and illicit substance use in mentally retarded individuals, including prevalence, and recommendations for assessment and treatment. Mentally retarded persons appear to use/abuse alcohol at about the same rate as their noncognitively-impaired counterparts, and illicit drugs at moderately lower rates. However, little is known regarding which assessments and interventions are most effective in this population, given the absence of published treatment outcome studies and case examples. This is particularly disconcerting as detrimental consequences resulting from substance use have been identified in mentally retarded samples. Anecdotal data suggests that treatment for these individuals require modifications of existing empirically-derived substance abuse interventions to accommodate their unique needs.

The relationship of neuropsychological functioning to measures of substance use in an adolescent drug abusing sample.

The purpose of this research was to investigate the relationship between recent and long term substance use on adolescents' neuropsychological functioning. Subjects were 77 adolescents who were referred for outpatient treatment for drug and conduct problems. Subjects were administered the Luria-Nebraska Neuropsychological Battery-III, structured interviews to assess substance use, and urine tests. Subjects were divided into neuropsychologically impaired and nonimpaired groups. Results indicated no significant group differences for: self-reports of lifetime use of alcohol, cannabis, and hard drugs; self or collateral reports of recent (past 30 days) use of alcohol, cannabis, and hard drugs; or urinalysis detection of alcohol, cannabis, and hard drugs. Correlations between these dependent measures of substance use and neuropsychological functioning were also nonsignificant (all ps > .05). Although neuropsychological impairment was observed for some subjects in this sample, it was unrelated to their cannabis, hard drug, or alcohol use. These results are consistent with those found in the adult literature, given the relatively short period of time that these youth have used such substances. However, given the severity of their absolute levels of substance usage, they may be at greater risk for developing future neuropsychological problems, related directly to the ingestion of alcohol and illicit drugs, and to their secondary effects (e.g., head traumas, malnutrition).

Identification of neuropsychological subtypes in a sample of delinquent adolescents.

Although research has long recognized a relationship between neurological dysfunction and delinquency, the nature of this relationship is unclear. Based on the theory that there may be clusters of delinquents with different types of neurological dysfunction which contribute to the delinquency in different ways, the present research attempted to identify these subtypes using neuropsychological testing. Seventy-seven such adolescents were administered the full Luria-Nebraska Neuropsychological Battery-III (LNNB-III) and a battery of assessments measuring behavioral functioning and substance use. A Hierarchical Cluster Analysis yielded four identifiable neuropsychological clusters: Verbal/Left-Hemispheric Deficits, Subcortical-Frontal Deficits, Mild-Verbal Deficits, and Normals. The distinctiveness of these subtypes was confirmed by univariate analyses. Results further indicated that the number of LNNB scales that were in the abnormal range differed per subtype, with each subtype differing significantly from one another. These neuropsychological subtypes were found to be associated with specific psychological and behavioral problems.

A functional lesion in developmental dyslexia: left angular gyral blood flow predicts severity.

Functional imaging studies have shown reduced regional cerebral blood flow (rCBF) in temporal and inferior parietal regions in dyslexia. To relate such abnormalities to the severity of dyslexia, correlations between reading skill and rCBF during a series of reading tasks and visual fixation were mapped for 17 right-handed dyslexic men, ages 18-40, and 14 matched controls. These correlations uniquely identified the left angular gyrus as the most probable site of a functional lesion in dyslexia: Here, higher rCBF was associated with better reading skill in controls (p <.01), but with worse reading skill in dyslexia (p <.01). This suggests that greater reliance on this region normally facilitates reading, but impairs reading in dyslexia. Thus, developmental dyslexia may share a common localization with alexia.

Substance refusal skills in a population of adolescents diagnosed with conduct disorder and substance abuse.

The present study examined substance refusal skills of 44 conduct-disordered male adolescents. Fifty percent of these adolescents were dually diagnosed with substance abuse/dependence. Substance refusal skills were assessed utilizing a role-play test that consisted of four interpersonal scenarios in which a confederate prompted youths to engage in illicit drug and alcohol activity. The test demonstrated adequate interrater agreement and validity. Overall skill in refusing alcohol was positively related to adolescents' perceptions of belonging and attention, and overall skill in refusing illicit drugs was positively related to school performance and social competence. Contrary to expectations, substance refusal skills of dually diagnosed adolescents were comparable to their non-substance-abusing counterparts. Clinical implications of this study are discussed.

Long-term outcome after primary angioplasty: report from the primary angioplasty in myocardial infarction (PAMI-I) trial.

OBJECTIVES: This study sought to compare the two-year outcome after primary percutaneous coronary angioplasty or thrombolytic therapy for acute myocardial infarction. BACKGROUND: Primary angioplasty, that is, angioplasty without antecedent thrombolytic therapy, has been shown to be an effective reperfusion modality for patients suffering an acute myocardial infarction. This report reviews the two-year clinical outcome of patients randomized in the Primary Angioplasty in Myocardial Infarction trial. METHODS: At 12 clinical centers, 395 patients who presented within 12 h of the onset of myocardial infarction were randomized to undergo primary angioplasty (195 patients) or to receive tissue-type plasminogen activator (t-PA) (200 patients) followed by conservative care. Patients were followed by physician visits, phone call, letter and review of hospital records for any hospital admission at one month, six months, one year and two years. RESULTS: At two years, patients undergoing primary angioplasty had less recurrent ischemia (36.4% vs. 48% for t-PA, p = 0.026), lower reintervention rates (27.2% vs. 46.5% for t-PA, p < 0.0001) and reduced hospital readmission rates (58.5% vs. 69.0% for t-PA, p = 0.035). The combined end point of death or reinfarction was 14.9% for angioplasty versus 23% for t-PA, p = 0.034. Multivariate analysis found angioplasty to be independently predictive of a reduction in death, reinfarction or target vessel revascularization (p = 0.0001). CONCLUSIONS: The initial benefit of primary angioplasty performed by experienced operators is maintained over a two-year follow-up period with improved infarct-free survival and reduced rate of reintervention.

Functional connectivity of the angular gyrus in normal reading and dyslexia.

The classic neurologic model for reading, based on studies of patients with acquired alexia, hypothesizes functional linkages between the angular gyrus in the left hemisphere and visual association areas in the occipital and temporal lobes. The angular gyrus also is thought to have functional links with posterior language areas (e.g., Wernicke's area), because it is presumed to be involved in mapping visually presented inputs onto linguistic representations. Using positron emission tomography , we demonstrate in normal men that regional cerebral blood flow in the left angular gyrus shows strong within-task, across-subjects correlations (i.e., functional connectivity) with regional cerebral blood flow in extrastriate occipital and temporal lobe regions during single word reading. In contrast, the left angular gyrus is functionally disconnected from these regions in men with persistent developmental dyslexia, suggesting that the anatomical disconnection of the left angular gyrus from other brain regions that are part of the "normal" brain reading network in many cases of acquired alexia is mirrored by its functional disconnection in developmental dyslexia.

Safety and cost-effectiveness of early discharge after primary angioplasty in low risk patients with acute myocardial infarction. PAMI-II Investigators. Primary Angioplasty in Myocardial Infarction.

OBJECTIVES: The second Primary Angioplasty in Myocardial Infarction (PAMI-II) study evaluated the hypothesis that primary percutaneous transluminal coronary angioplasty (PTCA), with subsequent discharge from the hospital 3 days later, is safe and cost-effective in low risk patients. BACKGROUND: In low risk patients with myocardial infarction (MI), few data exist regarding the need for intensive care and noninvasive testing or the appropriate length of hospital stay. METHODS: Patients with acute MI underwent emergency catheterization with primary PTCA when appropriate. Low risk patients (age <70 years, left ventricular ejection fraction >45%, one- or two-vessel disease, successful PTCA, no persistent arrhythmias) were randomized to receive accelerated care (admission to a nonintensive care unit and day 3 hospital discharge without noninvasive testing [n = 237] or traditional care [n = 234]). RESULTS: Patients who received accelerated care had similar in-hospital outcomes but were discharged 3 days earlier (4.2+/-2.3 vs. 7.1+/-4.7 days, p = 0.0001) and had lower hospital costs ($9,658+/-5,287 vs. $11,604+/-6,125 p = 0.002) than the patients who received traditional care. At 6 months, accelerated and traditional care groups had a similar rate of mortality (0.8% vs. 0.4%, p = 1.00), unstable ischemia (10.1% vs. 12.0%, p = 0.52), reinfarction (0.8% vs. 0.4%, p = 1.00), stroke (0.4% vs. 2.6%, p = 0.07), congestive heart failure (4.6% vs. 4.3%, p = 0.85) or their combined occurrence (15.2% vs. 17.5%, p = 0.49). The study was designed to detect a 10% difference in event rates; at 6 months, only a 2.3% difference was measured between groups, indicating an actual power of 0.19. CONCLUSIONS: Early identification of low risk patients with MI allowed safe omission of the intensive care phase and noninvasive testing, and a day 3 hospital discharge strategy, resulting in substantial cost savings.

A magnetic resonance imaging study of planum temporale asymmetry in men with developmental dyslexia.

BACKGROUND: Imaging studies have suggested anomalous anatomical asymmetries in language-related regions of the temporal and parietal lobes in individuals with developmental dyslexia. Autopsy studies have reported unusual symmetry of the planum temporale (PT) in patients with dyslexia. Methodological limitations characterize much of this literature, however. OBJECTIVE: To examine the size and asymmetry of the PT and its extension into the parietal lobe (planum parietale [PP]) in men with well-characterized, persistent dyslexia by using magnetic resonance imaging and 3-dimensional surface rendering techniques. METHODS: The brains of 16 right-handed dyslexic men aged 18 to 40 years and 14 matched control subjects were studied with magnetic resonance imaging. Most of these subjects were previously studied with positron emission tomography, which demonstrated functional abnormalities in temporal and parietal brain regions in the dyslexic group. The area of the PT was determined with the aid of 3-dimensional surface-rendering techniques. The size of the PP was estimated by measuring the length of the posterior ascending ramus on 3 parasagittal slices. RESULTS: Approximately 70% to 80% of both groups showed equivalent leftward (left > right) asymmetries of the PT; approximately 50% to 60% showed equivalent rightward (right > left) asymmetries of the PP. These asymmetries showed equivalent moderate inverse correlations with each other in both groups. CONCLUSIONS: These results challenge the notion that anomalous asymmetry of the PT is strongly associated with developmental dyslexia. Given the heterogeneity of the dyslexic population, some subgroup of dyslexic individuals (i.e., those with developmental language disorders) may show unusual symmetry or reversed asymmetry in this region. However, anomalous asymmetry of the planum did not contribute to functional abnormalities demonstrated in these patients by positron emission tomography.

A prospective, randomized evaluation of prophylactic intraaortic balloon counterpulsation in high risk patients with acute myocardial infarction treated with primary angioplasty. Second Primary Angioplasty in Myocardial Infarction (PAMI-II) Trial Investigators.

OBJECTIVES: A large, international, multicenter, prospective, randomized trial was performed to determine the role of prophylactic intraaortic balloon pump (IABP) counterpulsation after primary percutaneous transluminal coronary angioplasty (PTCA) in acute myocardial infarction (AMI). BACKGROUND: Previous studies have suggested that routine IABP use after primary PTCA reduces infarct-related artery reocclusion, augments myocardial recovery and improves clinical outcomes. METHODS: Cardiac catheterization was performed in 1,100 patients within 12 h of onset of AMI at 34 clinical centers. Clinical and angiographic variables were used to stratify patients undergoing primary PTCA into high and low risk groups. High risk patients were then randomized to 36 to 48 h of IABP (n = 211) or traditional care (n = 226). The study had 80% power to detect a reduction in the primary end point from 30% to 20%. RESULTS: There was no significant difference in the predefined primary combined end point of death, reinfarction, infarct-related artery reocclusion, stroke or new-onset heart failure or sustained hypotension in patients treated with an IABP versus those treated conservatively (28.9% vs. 29.2%, p = 0.95). The IABP strategy conferred modest benefits in reduction of recurrent ischemia (13.3% vs. 19.6%, p = 0.08) and subsequent unscheduled repeat catheterization (7.6% vs. 13.3%, p = 0.05) but did not reduce the rate of infarct-related artery reocclusion (6.7% vs. 5.5%, p = 0.64), reinfarction (6.2% vs. 8.0%, p = 0.46) or mortality (4.3% vs. 3.1%) and was associated with a higher incidence of stroke (2.4% vs. 0%, p = 0.03). IABP use did not result in enhanced myocardial recovery as assessed by paired admission to predischarge and 6-week rest and exercise left ventricular ejection fraction. CONCLUSIONS: In contrast to previous studies, a prophylactic IABP strategy after primary PTCA in hemodynamically stable high risk patients with AMI does not decrease the rates of infarct-related artery reocclusion or reinfarction, promote myocardial recovery or improve overall clinical outcome.

Phonological and orthographic components of word recognition. A PET-rCBF study.

Pronunciation (of irregular/inconsistent words and of pseudowords) and lexical decision-making tasks were used with 15O PET to examine the neural correlates of phonological and orthographic processing in 14 healthy right-handed men (aged 18-40 years). Relative to a visual-fixation control task, all four experimental tasks elicited a left-lateralized stream of activation involving the lingual and fusiform gyri, perirolandic cortex, thalamus and anterior cingulate. Both pronunciation tasks activated the left superior temporal gyrus, with significantly greater activation seen there during phonological (pseudoword) than during orthographic (real word) pronunciation. The left inferior frontal cortex was activated by both decision-making tasks; more intense and widespread activation was seen there during phonological, than during orthographic, decision making, with the activation during phonological decision-making extending into the left insula. Correlations of reference voxels in the left superior temporal gyrus and left inferior frontal region with the rest of the brain were highly similar for the phonological and orthographic versions of each task type. These results are consistent with connectionist models of reading, which hypothesize that both real words and pseudowords are processed within a common neural network.

Three-dimensional cortical morphometry of the planum temporale in childhood-onset schizophrenia.

OBJECTIVE: Anomalous planum temporale asymmetry has been linked to both schizophrenia and dyslexia. The authors examined the planum temporale of adolescents with childhood-onset schizophrenia who had a high rate of prepsychotic language disorders. METHOD: Planum temporale area and asymmetry were measured in 16 right-handed adolescent patients with schizophrenia who had experienced onset of psychosis by age 12. The same measures were made in 16 healthy adolescents matched for age, sex, and handedness. RESULTS: No differences between the healthy adolescents and those with schizophrenia in planum temporale area or asymmetry were observed. Prepsychotic language disorder predicted abnormal planum temporale asymmetry in the adolescents with schizophrenia. CONCLUSIONS: These findings do not support anomalous planum temporale asymmetry as a basis for psychopathology in childhood-onset schizophrenia.

A positron emission tomographic study of impaired word recognition and phonological processing in dyslexic men.

BACKGROUND: Developmental dyslexia is characterized by impaired word recognition, which is thought to result from deficits in phonological processing. Improvements during the course of development are thought to disproportionately involve orthographic components of reading; phonological deficits persist into adulthood. OBJECTIVE: To localize the neural correlates of impaired word recognition and phonological processing in men with developmental dyslexia. METHODS: Regional cerebral blood flow was measured with oxygen 15 positron emission tomography in 17 men with dyslexia and in 14 matched controls during the performance of phonological and orthographic tasks--pronunciation (reading aloud) and lexical decision making--designed to activate posterior and anterior perisylvian cortices, respectively. RESULTS: Altered patterns of activation (reduced activation, unusual deactivation) were seen in dyslexic men in mid- to posterior temporal cortex bilaterally and in inferior parietal cortex, predominantly on the left, during both pronunciation and decision making. In contrast, dyslexic men demonstrated essentially normal activation of left inferior frontal cortex during both phonological and orthographic decision making. CONCLUSION: These, along with prior findings, are compatible with a hypothesis of bilateral involvement of posterior temporal and parietal cortices in dyslexia.

Behavioral treatment of conversion disorder in adolescence. A case example of Globus Hystericus.

The present single case study evaluated the efficacy of a cognitive-behavioral intervention for the treatment of a patient diagnosed with globus hystericus, a conversion disorder characterized by a perceived lump in the throat. The patient was a non-mentally retarded 12-year-old female who refused to swallow solids because she thought that her throat muscles would involuntarily constrict and result in choking. She lost approximately .5 lbs. per week during the 6 months prior to treatment. Improvements in weight gain were demonstrated consequent to the implementation of behavior therapy, with weight gain being particularly pronounced after contingency contracting was added to therapy. Weight gain was maintained at 1, 6, and 10 months posttreatment.