Patient experience in the treatment of metastatic castration-resistant prostate cancer: state of the science.

BACKGROUND: Contemporary therapies for metastatic castration-resistant prostate cancer (mCRPC) have shown survival improvements, which do not account for patient experience and health-related quality of life (HRQoL). METHODS: This literature review included a search of MEDLINE for randomized clinical trials enrolling ⩾50 patients with mCRPC and reporting on patient-reported outcomes (PROs) since 2010. RESULTS: Nineteen of 25 publications describing seven treatment regimens (10 clinical trials and nine associated secondary analyses) met the inclusion criteria and were critically appraised. The most commonly used measures were the Functional Assessment of Cancer Therapy-Prostate (n=5 trials) and Brief Pain Inventory Short Form (n=4 trials) questionnaires. The published data indicated that HRQoL and pain status augmented the clinical efficacy data by providing a better understanding of treatment impact in mCRPC. Abiraterone acetate and prednisone, enzalutamide, radium-223 dichloride and sipuleucel-T offered varying levels of HRQoL benefit and/or pain mitigation versus their respective comparators, whereas three treatments (mitoxantrone, estramustine phosphate and docetaxel, and cabazitaxel) had no meaningful impact on HRQoL or pain. The main limitation of the data were that the PROs utilized were not developed for use in mCRPC patients and hence may not have comprehensively captured symptoms important to this population. CONCLUSIONS: Recently published randomized clinical trials of new agents for mCRPC have captured elements of the patient experience while on treatment. Further research is required to standardize methods for measuring, quantifying and reporting on HRQoL and pain in patients with mCRPC in the clinical practice setting.

An evaluation of the dyslexia training program: a multisensory method for promoting reading in students with reading disabilities.

The development of reading and spelling skills in students with dyslexia, by definition, is delayed and often remains delayed despite years of instruction. Three qualities are thought to facilitate reading development in these children: the provision of a highly structured phonetic-instruction training program with heavy emphasis on the alphabetic system, drill and repetition to compensate for short-term verbal memory deficits, and multisensory methods to promote nonlanguage mental representations. The Dyslexia Training Program, a remedial reading program derived from Orton-Gillingham methods, embodies these qualities. Following their 2-year program, students displaying dyslexia demonstrated significantly higher reading recognition and comprehension compared with a control group. The two groups did not differ in spelling. In addition, the degree of improvement in reading demonstrated by students who received the Dyslexia Training Program by videotape and by those who received it live from instructors did not differ.

Surveillance in patients with stage I testicular nonseminomatous germ cell tumors.

Fourteen patients with testicular nonseminomatous germ cell tumor, clinical stage I were entered into a surveillance study. Median age was 31 (range 18-58). Three patients had pure tumor, and 11, mixed tumor. In 2 patients, vascular invasion was noted, and in 1, involvement of the spermatic cord. Serum alpha fetoprotein and beta subunit choriogonadotropin were high in 9 and in 3 patients, respectively. In median follow-up of 21 months (range 2-63), 3 patients relapsed: 1 had inguinal lymphadenopathy and 2 had lung metastases at 12, 4, and 16 months, respectively. Salvage chemotherapy PEB and PVB achieved complete response in the latter 2 patients for 6 and 49 months. Except for 1 patient lost to follow-up, all are alive.

The relationship between continuous performance tasks and neuropsychological tests in children with attention-deficit hyperactivity disorder.

We examined the relationship between measures of sustained attention and impulsivity, as obtained by computerized continuous performance tasks of the Gordon Diagnostic System and a battery of intellectual, achievement, and neuropsychological tests. Subjects were 119 boys (between the ages of 6 yr., 0 mo. and 12 yr., 11 mo.), diagnosed with Attention-deficit Hyperactivity Disorder, using DSM-III or DSM-III--R criteria. Only two measures, the number of correct responses for Vigilance and Distractibility tasks, correlated consistently with other measures (e.g., intellectual measures, the WRAT--R Arithmetic subtest, Beery Test of Visual and Motor Integration, and various sensory-motor variables from the Halstead-Reitan Neuropsychological Battery). The results suggest a unique contribution of continuous performance tasks in the measurement of attention, in a population of children with ADHD, which is not assessed by more traditional tests.

Attention deficit disorder and the mediating effect of age on academic and behavioral variables.

Seventy-nine children, independently diagnosed as having attention deficit disorder (ADD) with or without hyperactivity and ranging in age from 6 years, 0 months, to 12 years, 11 months, were administered the Wechsler Intelligence Scale for Children-Revised (WISC-R), the Wide Range Achievement Test (WRAT), and the Child Behavior Checklist (CBC). Multiple regression analyses indicated a significant multiple correlation between age and achievement variables (R = 0.42, p = 0.003) and age and behavioral (CBC) variables (R = 0.55, p = 0.01). Post hoc analyses indicated that much of this variance was accounted for by a significant negative association between age and Full Scale IQ-WRAT Arithmetic difference scores, and significant positive correlations between age and scores on the Social Withdrawal and Uncommunicative scales from the CBC. A nonparametric chi-square analysis indicated that older children with ADD are significantly more likely (p = 0.037) than younger ADD children to have a discrepancy of 15 or more points between IQ and math achievement scores. Results suggest that older ADD children are more likely than younger ADD children to experience academic and socioemotional difficulties.

The mediating effect of age on the relationship between Child Behavior Checklist hyperactivity scores and neuropsychological test performance.

The relationship between hyperactivity and neuropsychological test performance at different age levels was examined. It was found that for young children (6 to 8 years of age, n = 90), there was no significant association between hyperactivity/attentional problems (as measured by the Hyperactivity scale of the Child Behavior Checklist) and performance on neuropsychological tasks thought to contain an attentional component (WISC-R Coding, Arithmetic, and Digit Span; WRAT Arithmetic; and the Benton Visual Retention Test). However, for older children (9 to 12 years of age, n = 92), there were significant and large negative correlations between CBC Hyperactivity scores and Coding, WRAT Arithmetic, and Benton VRT scores. Multiple regression analyses supported the above results (for Coding and WRAT Arithmetic), indicating that hyperactivity/inattention has a particularly deleterious effect on test performance (relative to same-age peers) as age increases.

Personality/behavioral characteristics in children: differential effects of putative anterior versus posterior cerebral asymmetry.

The current study was carried out to examine the possible relationships among personality/behavioral characteristics and anterior/posterior (A/P) functional cerebral asymmetry in children referred for learning problems. Two hundred nineteen children between 7 and 12 years of age were administered a battery of neuropsychological measures, and their parents completed the Child Behavior Checklist (CBC) and the Personality Inventory for Children-Revised (PIC). Anterior and posterior composite scores were obtained for each subject using scores on the neuropsychological measures. Out of this subject pool, 33 children had sufficient anterior/posterior (A/P) score differences (i.e., greater than one standard deviation difference) to permit their categorization into either an A (n = 19) or P (n = 14) group. The MANOVA results showed that the A group scored significantly higher than the P group on the CBC scales of social withdrawal, aggressiveness, hyperactivity and externalizing, while the P group scored higher, though not significantly, on the (PIC) scale of anxiety. Thus, it appeared that, by using neuropsychological measures along the A/P dimension to classify children with learning problems, significant differences could also be identified on personality/ behavioral variables for some children. In addition, in the current study, children with A type functional cerebral asymmetry exhibited a relatively greater number of behavioral problems.

The clinical significance of congenital agenesis of the corpus callosum.

Three cases of congenital agenesis of the corpus callosum (ACC) are presented along with typical clinical features observed on computerized tomography and magnetic resonance imaging. Most congenital ACC cases do not display hemi-syndromes or callosal syndromes, but do exhibit some deficit in terms of hemispheric integration. The most common neuropsychological impairments are in the areas of motor and perceptual-motor functioning. Clinical guidelines in the assessment of ACC patients are given.

A system for evaluation and exercise-conditioning of paralyzed leg muscles.

The purpose of this project was to develop instrumentation and protocols in which electrical stimulation is used to induce exercise in paralyzed quadriceps muscles strength and endurance evaluation and conditioning. A computer-controlled electrical stimulation system, using surface electrodes, automatically regulates the bouts of leg extension exercise. Load weights attached just above the ankles can be progressively increased over a number of training sessions in such a manner that a measure of the fitness of the legs can be obtained. With three exercise sessions per week for 9 weeks, the strength and endurance of the quadriceps muscles of two paraplegic and four quadriplegic subjects were gradually and safely increased. During exercise at a means load weight of 5.4 kg, means heart rate did not rise above rest, whereas systolic blood pressure increased about 20 mm Hg, and skin temperature above the active muscles increased about 1.75 degrees C. Such exercise conditioning appears to be safe and may provide important health benefits, including improved fitness of the muscles and bones, better circulation in the paralyzed limbs, and enhanced self-image. Conditioned electrically stimulated paralyzed leg muscles may be used for locomotion in conjunction with special vehicles.

Effect of intra-articular corticosteroids on ligament properties: a biomechanical and histological study in rhesus knees.

The effect of intra-articular corticosteroid injections (methylprednisolone acetate) on the mechanical properties of anterior cruciate bone-ligament-bone units was determined. Fifty-one wild rhesus animals provided 88 knee ligaments units that were loaded in tension to failure under fast strain-rate conditions. Alterations in ligament strength and load-elongation properties were found to depend upon corticosteroid dosage and time after injection. Fifteen weeks after the higher drug dosage (methylprednisolone acetate, 6 mg/kg; three injections, spaced weekly) significant decreases occurred in the maximum failure load (20%), energy absorption prior to failure (11%) and linear stiffness (11%) of the ligament unit. In contrast, only minimal non-significant alterations in ligament strength properties occurred at the higher drug usage after 6 weeks in a second group of animals. this strong time-dependence may partially explain the negative findings reported in short term studies. The higher drug dosage used is approximately 10 times an equivalent human dose on a body mass basis and indicates the ability of this class of drugs to significantly alter the mechanical properties of a ligament unity. A third group of animals received a total of two intra-articular coticosteroid injections (single injections spaced two weeks apart) at a dosage (0.6 mg/kg) equivalent to that commonly used clinically in humans. Statistically significant decreases occurred in maximum failure load (9%) and energy absorption (8%); however, this change is believed of little importance to the projected functional capacity of the ligament unit. No detectable systemic effect of the intra-articular corticosteroid injections was found on the mechanical properties of the ligament unit in the extremity opposite to that which received the drug injection. Histological examination after failure showed normal cellularity and staining characteristics of the ligament, fibrocartilage junction and underlying bone. No bone resorptive changes were observed beneath the ligament insertion site. Failure by a ligamentous mode remained the most common mechanism of specimen failure. Scanning Electron Microscopy showed failure of collagen fibers at multiple levels throughout the ligament indicative of a serial pull-apart failure process. A rich supply of vessels to the anterior cruciate ligament was demonstrated and failure of the vessels occured by a necking down process. Insofar as the results apply to humans, they infer the potential for high and frequent doses of intra-articular slightly soluble corticosteroids to produce alterations in ligament strength and function. A single intra-articular injection or one repeated at intervals of several months probably carries little risk to ligament properties.