The Effects of Previous Error and Success in Alzheimer’s Disease and Mild Cognitive Impairment

This work investigated in Alzheimer’s disease dementia (AD), whether the probability of making an error on a task (or a correct response) was influenced by the outcome of the previous trials. We used the antisaccade task (AST) as a model task given the emerging consensus that it provides a promising sensitive and early biological test of cognitive impairment in AD. It can be employed equally well in healthy young and old adults, and in clinical populations. This study examined eye-movements in a sample of 202 participants (42 with dementia due to AD; 65 with mild cognitive impairment (MCI); 95 control participants). The findings revealed an overall increase in the frequency of AST errors in AD and MCI compared to the control group, as predicted. The errors on the current trial increased in proportion to the number of consecutive errors on the previous trials. Interestingly, the probability of errors was reduced on the trials that followed a previously corrected error, compared to the trials where the error remained uncorrected, revealing a level of adaptive control in participants with MCI or AD dementia. There was an earlier peak in the AST distribution of the saccadic reaction times for the inhibitory errors in comparison to the correct saccades. These findings revealed that the inhibitory errors of the past have a negative effect on the future performance of healthy adults as well as people with a neurodegenerative cognitive impairment

Mental health problems: Are they or are they not a risk factor for dropout from drug treatment? A systematic review of the evidence

Background: A sizeable number of recent studies investigating whether clients with substance misuse and mental health problems (dual diagnosis clients) are at heightened risk of dropout from drug treatment have been published. It is timely that their findings are brought together in a comprehensive review of the current evidence. Aims: The aim of the review is to examine whether dually diagnosed clients are less likely to be retained in drug treatment than clients without mental health problems, and, if so, whether this varies for clients diagnosed with different types of mental health problems. Methods: The review considers peer-reviewed research published after 1 January 1990, which was located using the literature databases Medline and PsycInfo. Predefined search terms were used. Further papers were identified from the bibliographies of relevant publications. Findings: 58 studies (84% from the USA) met the inclusion criteria for the review. The findings suggest that for most clients, having a past history of mental health problems does not influence the likelihood of being retained in drug treatment. The body of evidence regarding concurrent mental health problems is contradictory. On the whole, the majority of studies suggest that neither presence nor severity of depressive, anxiety, or other Axis-I disorders is related to retention, but these findings are not entirely unequivocal, as a few studies report strong positive or negative associations between depression and anxiety disorders and retention. Few researchers looked separately at psychotic spectrum disorders hence no conclusions could be drawn. The presence of most personality disorders also did not appear to affect treatment tenure, with the exception of antisocial personality disorder, for which the evidence points towards a greater risk of dropout. Conclusions: The balance of evidence suggests that, overall, dual diagnosis clients with Axis-I disorders who seek treatment in drug treatment services are retained as well as clients without dual diagnosis. Subgroups of clients who appear more vulnerable to premature dropout include those with antisocial personality disorder. Methodological shortcomings of the reviewed studies and resulting implications for this review and future research are discussed

Sticking under wet conditions: the remarkable attachment abilities of the torrent frog, staurois guttatus

Tree frogs climb smooth surfaces utilising capillary forces arising from an air-fluid interface around their toe pads, whereas torrent frogs are able to climb in wet environments near waterfalls where the integrity of the meniscus is at risk. This study compares the adhesive capabilities of a torrent frog to a tree frog, investigating possible adaptations for adhesion under wet conditions. We challenged both frog species to cling to a platform which could be tilted from the horizontal to an upside-down orientation, testing the frogs on different levels of roughness and water flow. On dry, smooth surfaces, both frog species stayed attached to overhanging slopes equally well. In contrast, under both low and high flow rate conditions, the torrent frogs performed significantly better, even adhering under conditions where their toe pads were submerged in water, abolishing the meniscus that underlies capillarity. Using a transparent platform where areas of contact are illuminated, we measured the contact area of frogs during platform rotation under dry conditions. Both frog species not only used the contact area of their pads to adhere, but also large parts of their belly and thigh skin. In the tree frogs, the belly and thighs often detached on steeper slopes, whereas the torrent frogs increased the use of these areas as the slope angle increased. Probing small areas of the different skin parts with a force transducer revealed that forces declined significantly in wet conditions, with only minor differences between the frog species. The superior abilities of the torrent frogs were thus due to the large contact area they used on steep, overhanging surfaces. SEM images revealed slightly elongated cells in the periphery of the toe pads in the torrent frogs, with straightened channels in between them which could facilitate drainage of excess fluid underneath the pad

Nonsteroidal anti-inflammatory drugs for pain in women with endometriosis.

BACKGROUND: Endometriosis is a common gynaecological condition that affects women and can lead to painful symptoms and infertility. It greatly affects women's quality of life, impacting their careers, everyday activities, sexual and nonsexual relationships and fertility. Nonsteroidal anti-inflammatory drugs (NSAIDs) are most commonly used as first-line treatment for women with pain associated with endometriosis. OBJECTIVES: To assess effects of NSAIDs used for management of pain in women with endometriosis compared with placebo, other NSAIDs, other pain management drugs or no treatment. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Group Specialised Register of Controlled Trials (October 2016), published in the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, as well as MEDLINE (January 2008 to October 2016), Embase (date limited from 1 January 2016 to 19 October 2016, as all earlier references are included in CENTRAL output as a result of the Embase project), registers of ongoing trials and the reference lists of relevant publications. We identified no new randomised controlled trials. Unless we identify new evidence in the future, we will not update this review. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) describing use of NSAIDs for management of pain associated with endometriosis in women of all ages. DATA COLLECTION AND ANALYSIS: In the 2009 update of this review, two review authors (CA and SH) independently read and extracted data from each of the included studies. We analysed cross-over trials using the inverse variance method of RevMan to calculate odds ratios for binary outcomes. MAIN RESULTS: We identified no new trials for the 2016 update. This review includes two trials, but we included only one trial, with 24 women, in the analysis.The overall risk of bias was unclear owing to lack of methodological detail. Using the GRADE method, we judged the quality of the evidence to be very low. We downgraded evidence for risk of bias and for imprecision (wide confidence intervals and evidence based on a single small trial).Comparison of NSAIDs (naproxen) versus placebo revealed no evidence of a positive effect on pain relief (odds ratio (OR) 3.27, 95% confidence interval (CI) 0.61 to 17.69; one trial, 24 women; very low-quality evidence) in women with endometriosis. Evidence indicating whether women taking NSAIDs (naproxen) were less likely to require additional analgesia (OR 0.12, 95% CI 0.01 to 1.29; one trial, 24 women; very low-quality evidence) or to experience side effects (OR 0.46, 95% CI 0.09 to 2.47; one trial, 24 women; very low-quality evidence) when compared with placebo was inconclusive.Studies provided no data on quality of life, effects on daily activities, absence from work or school, need for more invasive treatment or participant satisfaction with treatment. AUTHORS' CONCLUSIONS: Owing to lack of high-quality evidence and lack of reporting of outcomes of interest for this review, we can make no judgement as to whether NSAIDs (naproxen) are effective in managing pain caused by endometriosis. No evidence shows whether any individual NSAID is more effective than another. As shown in other Cochrane reviews, women taking NSAIDs must be aware that these drugs may cause unintended effects

Growth in ataxia telangiectasia

BACKGROUND: Ataxia telangiectasia (A-T) is a DNA repair disorder that affects multiple body systems. Neurological problems and immunodeficiency are two important features of this disease. At this time, two main severity groups are defined in A-T: classic (the more severe form) and mild. Poor growth is a common problem in classic A-T. An objective of this study was to develop growth references for classic A-T. Another objective was to compare growth patterns in classic A-T and mild A-T with each other and with the general population, using the CDC growth references. A final objective was to examine the effects of chronic infection on height. RESULTS: We found that classic A-T patients were smaller overall, and suffered from height and weight faltering that continued throughout childhood and adolescence. When compared to the CDC growth references, the median heights and weights for both male and female patients eventually fell to or below the 3rd centile on the CDC charts. Height faltering was more pronounced in females. Birthweight was lower in the classic A-T group compared to mild A-T and the general population, whereas birth length was not. Finally, we investigated height and BMI faltering in relation to number of infections and found no association. CONCLUSIONS: Classic A-T appears to affect growth in utero. Although children appear to grow well in very early life, faltering begins early, and is unrelenting

Reactions to treatment debriefing among the participants of a placebo controlled trial

BACKGROUND: A significant proportion of trial participants respond to placebos for a variety of conditions. Despite the common conduct of these trials and the strong emphasis placed on informed consent, very little is known about informing participants about their individual treatment allocation at trial closure. This study aims to address this gap in the literature by exploring treatment beliefs and reactions to feedback about treatment allocation in the participants of a placebo-controlled randomized clinical trial (RCT). METHODS: Survey of trial participants using a semi-structured questionnaire including close and open-ended questions administered as telephone interviews and postal questionnaires. Trial participants were enrolled in a double-blind placebo-controlled RCT evaluating the effectiveness of corticosteroid for heel pain (ISRCTN36539116). The trial had closed and participants remained blind to treatment allocation. We assessed treatment expectations, the percentage of participants who wanted to be informed about their treatment allocation, their ability to guess and reactions to debriefing. RESULTS: Forty-six (73%) contactable participants responded to our survey. Forty-two were eligible (four participants with bilateral disease were excluded as they had received both treatments). Most (79%) participants did not have any expectations prior to receiving treatment, but many 'hoped' that something would help. Reasons for not having high expectations included the experimental nature of their care and possibility that they may get a placebo. Participants were hopeful because their pain was so severe and because they trusted the staff and services. Most (83%) wanted to be informed about their treatment allocation and study results. Over half (55%) said they could not guess which treatment they had been randomized to, and many of those who attempted a guess were incorrect. Reactions to treatment debriefing were generally positive, including in placebo responders. CONCLUSION: Our study suggests that most trial participants want to be informed about their treatment allocation and trial results. Further research is required to develop measure of hope and expectancy and to rigorously evaluate the effects of debriefing prospectively

Patients’ views on a combined action observation and motor imagery intervention for Parkinson’s disease

Background. Action observation and motor imagery activate neural structures involved in action execution, thereby facilitating movement and learning. Although some benefits of action observation and motor imagery have been reported in Parkinson’s disease (PD), methods have been based on stroke rehabilitation and may be less suitable for PD. Moreover, previous studies have focused on either observation or imagery, yet combining these enhances effects in healthy participants. The present study explores the feasibility of a PD-specific home-based intervention combining observation, imagery, and imitation of meaningful everyday actions. Methods. A focus group was conducted with six people with mild to moderate PD and two companions, exploring topics relating to the utility and feasibility of a home-based observation and imagery intervention. Results. Five themes were identified. Participants reported their experiences of exercise and use of action observation and motor imagery in everyday activities, and the need for strategies to improve movement was expressed. Motivational factors including feedback, challenge, and social support were identified as key issues. The importance of offering a broad range of actions and flexible training was also highlighted. Conclusions. A home-based intervention utilising action observation and motor imagery would be useful and feasible in mild to moderate PD

Prophylactic G-CSF in patients with early-stage breast cancer: a health economic review

Although the use of prophylactic granulocyte colony-stimulating factor (G-CSF) in conjunction with myelosuppressive chemotherapy is supported by clinical research evidence and advocated by international clinical guidelines when the consequent risk of febrile neutropenia exceeds 20%, there remains doubt as to the cost-effectiveness of the practice. There are limited economic data, and the data that are available are not necessarily applicable to the management of breast cancer in a European setting. Much of the available evidence on G-CSF in the management of febrile neutropenia is partial, focusing primarily on direct costs to the health service – that is, those related to hospitalisation and drug treatment. A full assessment of the cost effectiveness of G-CSF prophylaxis needs to take account of both costs and outcomes, including mortality, quality of life and patient functioning. As febrile neutropenia has been shown to affect productivity, consideration should also be given to quantifying the indirect costs of neutropenia

XM02 is superior to placebo and equivalent to Neupogen™ in reducing the duration of severe neutropenia and the incidence of febrile neutropenia in cycle 1 in breast cancer patients receiving docetaxel/doxorubicin chemotherapy

Abstract Background Recombinant granulocyte colony-stimulating factors (G-CSFs) such as Filgrastim are used to treat chemotherapy-induced neutropenia. We investigated a new G-CSF, XM02, and compared it to Neupogen™ after myelotoxic chemotherapy in breast cancer (BC) patients. Methods A total of 348 patients with BC receiving docetaxel/doxorubicin chemotherapy were randomised to treatment with daily injections (subcutaneous 5 μg/kg/day) for at least 5 days and a maximum of 14 days in each cycle of XM02 (n = 140), Neupogen™ (n = 136) or placebo (n = 72). The primary endpoint was the duration of severe neutropenia (DSN) in cycle 1. Results The mean DSN in cycle 1 was 1.1, 1.1, and 3.9 days in the XM02, Neupogen™, and placebo group, respectively. Superiority of XM02 over placebo and equivalence of XM02 with Neupogen™ could be demonstrated. Toxicities were similar between XM02 and Neupogen™. Conclusion XM02 was superior to placebo and equivalent to Neupogen™ in reducing DSN after myelotoxic chemotherapy. Trial Registration Current Controlled Trials ISRCTN02270769</p