Specific Cognitive Deficits in ADHD: A Diagnostic Concern in Differential Diagnosis

We present a critical account of existing tools used to diagnose children with Attention Deficit Hyperactivity Disorder and to make a case for the assessment of cognitive impairments as a part of diagnostic system. Surveys have shown that clinicians rely almost entirely upon subjective reports or their own clinical judgment when arriving at diagnostic decisions relating to this prevalent disorder. While information from parents and teachers should always be carefully considered, they are often influenced by a host of emotional and perceptual factors. It increases the possibility for misdiagnosis of a condition like ADHD. Recent experimental literature on ADHD has identified unique underlying cognitive dysfunction, specific to ADHD. Therefore, we propose that there is a need to incorporate information on cognitive mechanisms underlying ADHD and inculcate such information in the diagnostic system, which will provide a more sensitive as well as specific tool in differential diagnosis of ADHD

Changing behaviour 'more or less'-do theories of behaviour inform strategies for implementation and de-implementation? A critical interpretive synthesis

BACKGROUND: Implementing evidence-based care requires healthcare practitioners to do less of some things (de-implementation) and more of others (implementation). Variations in effectiveness of behaviour change interventions may result from failure to consider a distinction between approaches by which behaviour increases and decreases in frequency. The distinction is not well represented in methods for designing interventions. This review aimed to identify whether there is a theoretical rationale to support this distinction. METHODS: Using Critical Interpretative Synthesis, this conceptual review included papers from a broad range of fields (biology, psychology, education, business) likely to report approaches for increasing or decreasing behaviour. Articles were identified from databases using search terms related to theory and behaviour change. Articles reporting changes in frequency of behaviour and explicit use of theory were included. Data extracted were direction of behaviour change, how theory was operationalised, and theory-based recommendations for behaviour change. Analyses of extracted data were conducted iteratively and involved inductive coding and critical exploration of ideas and purposive sampling of additional papers to explore theoretical concepts in greater detail. RESULTS: Critical analysis of 66 papers and their theoretical sources identified three key findings: (1) 9 of the 15 behavioural theories identified do not distinguish between implementation and de-implementation (5 theories were applied to only implementation or de-implementation, not both); (2) a common strategy for decreasing frequency was substituting one behaviour with another. No theoretical basis for this strategy was articulated, nor were methods proposed for selecting appropriate substitute behaviours; (3) Operant Learning Theory makes an explicit distinction between techniques for increasing and decreasing frequency. DISCUSSION: Behavioural theories provide little insight into the distinction between implementation and de-implementation. Operant Learning Theory identified different strategies for implementation and de-implementation, but these strategies may not be acceptable in health systems. Additionally, if behaviour substitution is an approach for de-implementation, further investigation may inform methods or rationale for selecting the substitute behaviour

Erratum to: ’Effectiveness and cost-effectiveness of a patient-initiated botulinum toxin treatment model for blepharospasm and hemifacial spasm compared to standard care: study protocol for a randomised controlled trial’.

Blepharospasm and hemifacial spasm are debilitating conditions that significantly impact on patient quality of life. Cyclical treatment with botulinum toxin injections offers temporary relief, but the duration of treatment efficacy is variable. The standard model of patient care defines routine fixed-time based scheduled treatment cycles which may lead to unnecessarily frequent treatment for some patients and experience of distressing symptoms in others, if symptoms return before the scheduled follow-up period

Evolving uses of oral reverse transcriptase inhibitors in the HIV-1 epidemic: From treatment to prevention

The HIV epidemic continues unabated, with no highly effective vaccine and no cure. Each new infection has significant economic, social and human costs and prevention efforts are now as great a priority as global antiretroviral therapy (ART) scale up. Reverse transcriptase inhibitors, the first licensed class of ART, have been at the forefront of treatment and prevention of mother to child transmission over the past two decades. Now, their use in adult prevention is being

The Oldest Case of Decapitation in the New World (Lapa do Santo, East-Central Brazil)

We present here evidence for an early Holocene case of decapitation in the New World (Burial 26), found in the rock shelter of Lapa do Santo in 2007. Lapa do Santo is an archaeological site located in the Lagoa Santa karst in east-central Brazil with evidence of human occupation dating as far back as 11.7-12.7 cal kyBP (95.4% interval). An ultra-filtered AMS age determination on a fragment of the sphenoid provided an age range of 9.1-9.4 cal kyBP (95.4% interval) for Burial 26. The interment was composed of an articulated cranium, mandible and first six cervical vertebrae. Cut marks with a v-shaped profile were observed in the mandible and sixth cervical vertebra. The right hand was amputated and laid over the left side of the face with distal phalanges pointing to the chin and the left hand was amputated and laid over the right side of the face with distal phalanges pointing to the forehead. Strontium analysis comparing Burial 26's isotopic signature to other specimens from Lapa do Santo suggests this was a local member of the group. Therefore, we suggest a ritualized decapitation instead of trophy-taking, testifying for the sophistication of mortuary rituals among hunter-gatherers in the Americas during the early Archaic period. In the apparent absence of wealth goods or elaborated architecture, Lapa do Santo's inhabitants seemed to use the human body to express their cosmological principles regarding death

Cognitive Dysfunction in Adult Chd With Different Structural Complexity

OBJECTIVE: We carried out a cross-sectional study to assess cognitive function in a sample of adult CHD patients, within the Functioning in Adult Congenital Heart Disease study London. The association between cognitive functioning and disease complexity was examined. METHODS: A total of 310 patients participated in this study. Patients were classified into four structural complexity groups – tetralogy of Fallot, transposition of the great arteries, single ventricle, and simple conditions. Each patient underwent neuropsychological assessment to evaluate cognitive function, including memory and executive function, and completed questionnaires to assess depression and anxiety. RESULTS: Among all, 41% of the sample showed impaired performance (>1.5 SD below the normative mean) on at least three tests of cognitive function compared with established normative data. This was higher than the 8% that was expected in a normal population. The sample exhibited significant deficits in divided attention, motor function, and executive functioning. There was a significant group difference in divided attention (F=5.01, p=0.002) and the mean total composite score (F=5.19, p=0.002) between different structural complexity groups, with the simple group displaying better cognitive function. CONCLUSION: The results indicate that many adult CHD patients display impaired cognitive function relative to a healthy population, which differs in relation to disease complexity. These findings may have implications for clinical decision making in this group of patients during childhood. Possible mechanisms underlying these deficits and how they may be reduced or prevented are discussed; however, further work is needed to draw conclusive judgements

Smoking Comorbidity in Alcoholism: Neurobiological and Neurocognitive Consequences

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65249/1/j.1530-0277.2006.00034.x.pd

Comparison of Influenza and SIV Specific CD8 T Cell Responses in Macaques

Macaques are a potentially useful non-human primate model to compare memory T-cell immunity to acute virus pathogens such as influenza virus and effector T-cell responses to chronic viral pathogens such as SIV. However, immunological reagents to study influenza CD8+ T-cell responses in the macaque model are limited. We recently developed an influenza-SIV vaccination model of pigtail macaques (Macaca nemestrina) and used this to study both influenza-specific and SIV-specific CD8+ T-cells in 39 pigtail macaques expressing the common Mane-A*10+ (Mane-A01*084) MHC-I allele. To perform comparative studies between influenza and SIV responses a common influenza nucleoprotein-specific CD8+ T-cell response was mapped to a minimal epitope (termed RA9), MHC-restricted to Mane-A*10 and an MHC tetramer developed to study this response. Influenza-specific memory CD8+ T-cell response maintained a highly functional profile in terms of multitude of effector molecule expression (CD107a, IFN-γ, TNF-α, MIP-1β and IL-2) and showed high avidity even in the setting of SIV infection. In contrast, within weeks following active SIV infection, SIV-specific CD8+ effector T-cells expressed fewer cytokines/degranulation markers and had a lower avidity compared to influenza specific CD8+ T-cells. Further, the influenza specific memory CD8 T-cell response retained stable expression of the exhaustion marker programmed death-marker-1 (PD-1) and co-stimulatory molecule CD28 following infection with SIV. This contrasted with the effector SIV-specific CD8+ T-cells following SIV infection which expressed significantly higher amounts of PD-1 and lower amounts of CD28. Our results suggest that strategies to maintain a more functional CD8+ T-cell response, profile may assist in controlling HIV disease

Cancer cell sensitivity to bortezomib is associated with survivin expression and p53 status but not cancer cell types

<p>Abstract</p> <p>Background</p> <p>Survivin is known playing a role in drug resistance. However, its role in bortezomib-mediated inhibition of growth and induction of apoptosis is unclear. There are conflicting reports for the effect of bortezomib on survivin expression, which lacks of a plausible explanation. Methods: In this study, we tested cancer cells with both p53 wild type and mutant/null background for the relationship of bortezomib resistance with survivin expression and p53 status using MTT assay, flow cytometry, DNA fragmentation, caspase activation, western blots and RNAi technology.</p> <p>Results</p> <p>We found that cancer cells with wild type p53 show a low level expression of survivin and are sensitive to treatment with bortezomib, while cancer cells with a mutant or null p53 show a high level expression of survivin and are resistant to bortezomib-mediated apoptosis induction. However, silencing of survivin expression utilizing survivin mRNA-specific siRNA/shRNA in p53 mutant or null cells sensitized cancer cells to bortezomib mediated apoptosis induction, suggesting a role for survivin in bortezomib resistance. We further noted that modulation of survivin expression by bortezomib is dependent on p53 status but independent of cancer cell types. In cancer cells with mutated p53 or p53 null, bortezomib appears to induce survivin expression, while in cancer cells with wild type p53, bortezomib downregulates or shows no significant effect on survivin expression, which is dependent on the drug concentration, cell line and exposure time.</p> <p>Conclusions</p> <p>Our findings, for the first time, unify the current inconsistent findings for bortezomib treatment and survivin expression, and linked the effect of bortezomib on survivin expression, apoptosis induction and bortezomib resistance in the relationship with p53 status, which is independent of cancer cell types. Further mechanistic studies along with this line may impact the optimal clinical application of bortezomib in solid cancer therapeutics.</p

The Maastricht Ultrasound Shoulder pain trial (MUST): Ultrasound imaging as a diagnostic triage tool to improve management of patients with non-chronic shoulder pain in primary care

<p>Abstract</p> <p>Background</p> <p>Subacromial disorders are considered to be one of the most common pathologies affecting the shoulder. Optimal therapy for shoulder pain (SP) in primary care is yet unknown, since clinical history and physical examination do not provide decisive evidence as to the patho-anatomical origin of the symptoms. Optimal decision strategies can be furthered by applying ultrasound imaging (US), an accurate method in diagnosing SP, demonstrating a clear relationship between diagnosis and available therapies. Yet, the clinical cost-effectiveness of applying US in the management of SP in primary care has not been studied. The aim of this paper is to describe the design and methods of a trial assessing the cost-effectiveness of ultrasound imaging as a diagnostic triage tool to improve management of primary care patients with non-chronic shoulder pain.</p> <p>Methods/Design</p> <p>This randomised controlled trial (RCT) will involve 226 adult patients with suspected subacromial disorders recruited by general practitioners. During a Qualification period of two weeks, patients receive care as usual as advised by the Dutch College of General Practitioners, and patients are referred for US. Patients with insufficient improvement qualify for the RCT. These patients are then randomly assigned to the intervention or the control group. The therapies used in both groups are the same (corticosteroid injections, referral to a physiotherapist or orthopedic surgeon) except that therapies used in the intervention group will be tailored based on the US results. Ultrasound diagnosed disorders include tendinopathy, calcific tendinitis, partial and full thickness tears, and subacromial bursitis. The primary outcome is patient-perceived recovery at 52 weeks, using the Global Perceived Effect questionnaire. Secondary outcomes are disease specific and generic quality of life, cost-effectiveness, and the adherence to the initial applied treatment. Outcome measures will be assessed at baseline, 13, 26, 39 and 52 weeks after inclusion. An economic evaluation will be performed from both a health care and societal perspective with a time horizon of 52 weeks.</p> <p>Discussion</p> <p>The results of this trial will give unique evidence regarding the cost-effectiveness of US as a diagnostic triage tool in the management of SP in primary care.</p