Executive functions and adaptive functioning in young adult attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is associated with impairments in occupational, social, and educational functioning in adults. This study examined relations of adaptive impairment to ADHD symptom domains (inattentive-disorganized and hyperactive-impulsive) and to deficits in executive functioning (EF) in 195 well-characterized adults (105 ADHD, 90 non-ADHD, between ages 18 and 37). Participants completed a battery of EF measures as well as assessments of adaptive functioning. Confirmatory factor analyses were used to validate latent factors for adaptive functioning and EF. In a measurement model, weaker EF was associated with poorer adaptive functioning (r = -.30). When multi-informant composite variables for current inattentive-disorganized and hyperactive-impulsive ADHD symptoms were included in the structural model, EF no longer predicted adaptive functioning. While both symptom composites were similarly related to EF (inattentive-disorganized r = .36; hyperactive-impulsive r = .29), inattentive-disorganized symptoms accounted for more variance in adaptive functioning (67.2% vs. 3.6%). Furthermore, for retrospectively reported childhood symptoms of ADHD, only the inattentive-disorganized symptom domain was related to EF or adaptive impairment. These results suggest that, in adults with ADHD, inattentive-disorganized symptoms may be the primary contributor to key aspects of poorer adaptive function and may be the behavioral path through which EF deficits lead to adaptive impairment.     

Precision of Image-Guided Radiotherapy (IGRT) in Six Degrees of Freedom and Limitations in Clinical Practice

PURPOSE: To evaluate the precision of image-guided radiotherapy (IGRT) using cone-beam computed tomography (CB-CT) for volume imaging and a robotic couch for correcting setup errors in six degrees of freedom. PATIENTS AND METHODS: 47 consecutive patients with 372 fractions were classified according to whether a patient fixation device was used (pat(fix): n = 28) or not (pat(non-fix): n = 19). Prior to treatment a CB-CT was acquired and translational and rotational setup errors were corrected online without an action level using a robotic couch (HexaPOD). A second CB-CT was acquired after the correction process and after treatment in 134 and 238 fractions, respectively. RESULTS: In 17 fractions (4.6%) rotational errors > 3 degrees exceeded the motion range of the HexaPOD. Errors (3D vector) after the correction process were significantly smaller for pat(fix) compared to pat(non-fix) (p < 0.001): 0.9 mm +/- 0.5 mm and 1.6 mm +/- 0.8 mm, respectively. For pat(non-fix) the correction of rotational errors resulted in displacements of the patients on the angled couch of 0.6 mm/1 degree. Intrafractional motion further decreased precision in pat(non-fix) but not in pat(fix). CONCLUSION: Very high precision in cranial and extracranial treatment of immobilized patients was demonstrated. Without application of adequate immobilization the correction of rotational errors and intrafractional patient motion significantly decreased the accuracy of the online correction protocol.     

Secretory immunoglobulin‐A reactivity following increases in workload intensity using the Defined Intensity Stressor Simulation (DISS)

Previous work suggests that secretory immunoglobulin‐A (S‐IgA) reactivity is inversely related to the perceived demands of the stressor. The Defined Intensity Stressor Simulation (DISS) comprises eight stressor modules, and allows for the manipulation of stress either through increasing the number of modules, or increasing the workload of the modules. The current study assessed the effect of increasing the workload of four modules upon S‐IgA reactivity and perceived demands. Participants (N = 14) attended three sessions on consecutive days where they provided a timed saliva sample immediately before and after 5 min on the DISS at low, medium and high workload. Following each session participants recorded their perceptions of the task with regard to workload and levels of stress and arousal. Perceived workload and stress, but not arousal, increased in accordance with increases in workload, however, differential S‐IgA reactivity was observed. Low workload resulted in a slight increase in S‐IgA secretion; medium workload elicited significant up‐regulation, while down‐regulation of S‐IgA occurred following high workload. As DISS is analogous to a variety of working environments it is suggested that the observed S‐IgA reactivity is indicative of how individuals react to multi‐tasking environments when faced with increases in objective or perceived workload demands. As S‐IgA levels are related to protection from illness, down‐regulation of S‐IgA in those who perceive greater demands may lead to greater vulnerability to ill‐health. Copyright © 2005 John Wiley & Sons, Ltd.     

Immediate versus delayed chemotherapy in patients with asymptomatic incurable metastatic cancer

Aim: To examine the evidence of benefit in initiating immediate chemotherapy in patients with newly diagnosed asymptomatic metastatic incurable cancer, compared with delaying chemotherapy until symptomatic progression. Methods: Through an extensive review of published reports, we examined the biological, clinical, psychological and ethical background of the issue and reported on the available clinical trial evidence in a variety of tumor types. Results: Only a limited number of clinical trials have directly examined the role of immediate versus delayed chemotherapy in patients with incurable asymptomatic metastatic cancer. Small studies in mesothelioma, colorectal cancer, breast cancer, myeloma, and low‐grade lymphoma suggest no survival benefit for the immediate initiation of chemotherapy. However, there was no evidence in other tumor types. Conclusion: The appropriate timing of chemotherapy initiation in an asymptomatic patient with metastatic cancer remains a substantial question in oncology. Many factors are likely to impact on the decision. However, little if any evidence demonstrates a clear advantage in the immediate initiation of chemotherapy in this setting.     

Oral health of the methamphetamine abuser.

PURPOSE: The pharmacology of methamphetamine is reviewed, and the effects of methamphetamine use on oral health are described. SUMMARY: Methamphetamine is a highly addictive amphetamine analogue, initially synthesized in 1919. Illicit methamphetamine use leads to devastating effects on health, particularly the dentition. Illegal production of methamphetamine has skyrocketed in recent years, as have the number of users. The chief complaint of methamphetamine users is xerostomia. Without the protective effects of saliva, caries development in these patients is rampant. The typical pattern of decay involves the facial and cervical areas of both the maxillary and mandibular teeth, with eventual progression to frank coronal involvement. The acidic substances used to manufacture this drug have also been implicated as a cause of tooth decay and wear in users, as has bruxism as a result of drug-induced hyperactivity. When possible, these patients should be referred to a dentist to improve their oral health status and minimize the potential for adverse cardiovascular sequelae. Other preventive measures for methamphetamine users include stimulating saliva flow and increasing fluoride supplementation. Pharmacists should also counsel users to avoid carbohydrate-rich soft drinks in favor of water. Oral moisturizers may also be effective. CONCLUSION: Methamphetamine use causes xerostomia secondary to sympathetic central nervous system activation, rampant caries caused by high-sugar intake in the absence of protective saliva, and bruxism as a result of hyperactivity. Practitioners should know how to recognize the signs of and manage the oral health of patients with a history of methamphetamine use.     

Establishing the Cost-Effectiveness of New Pharmaceuticals under Conditions of Uncertainty—When Is There Sufficient Evidence?

Decisions about which health-care interventions represent adequate value to collectively funded health-care systems are as widespread as they are unavoidable. In the case of new pharmaceuticals, many countries now require formal cost-effectiveness analysis to inform this decision-making process. This requires evidence on parameters associated with health-related utilities, treatment effects, resource use, and costs, for which data from available regulatory trials are invariably absent or highly uncertain. This uncertainty results from a number of factors including the predominance of intermediate end points in the clinical evidence-base and the limited period of follow-up of patients in clinical studies. Despite these imperfections in the evidence base, decisions about whether new pharmaceuticals are sufficiently cost-effective for reimbursement cannot be side-stepped. Data limitations do, however, require the use of rigorous analytical methods to support decision making. Probabilistic decision models and value of information analysis offer a means of structuring decision problems, synthesizing all available data, characterizing the uncertainty in the decision, quantifying the cost of uncertainty, and establishing the expected value of perfect information. This analytical framework is important because it addresses two fundamental questions about new pharmaceuticals. First, is the product expected to be cost-effective on the basis of existing evidence? Second, is additional research concerning the product itself cost-effective? In addressing these questions, the analytical framework can establish when sufficient evidence exists to sustain a claim for a new pharmaceutical to be cost-effective.