Simvastatin improves the sexual health-related quality of life in men aged 40 years and over with erectile dysfunction : Additional data from the Erectile Dysfunction and Statin trial

© 2014 Trivedi et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Background: Erectile dysfunction is prevalent in men over 40 years, affecting their quality of life and that of their partners. The aims of this study were:a)To evaluate the internal reliability of the male erectile dysfunction specific quality of life (MED-QoL) scale and explore its factor structure.b)To evaluate the effect of simvastatin on subscales of the MED-QoL in men over forty years with erectile dysfunction. Methods: This is a double blind randomised controlled trial of 40 mg simvastatin or placebo given once daily for six months to men over forty years with untreated erectile dysfunction, who were not at high cardiovascular risk and were not on anti-hypertensive or lipid-lowering medication. 173 eligible men were recruited from 10 general practices in East of England. Data were collected at two points over 30 weeks. We report on the factor structure of MED-QoL, the internal reliability of the scale and the derived subscales, and the effect of simvastatin on MED-QoL subscales. Results: An initial analysis of the MED-QoL items suggested that a number of items should be removed (MED-QoL-R). Exploratory factor analysis identified three subscales within the MED-QoL-R which accounted for 96% of the variance, related to feelings of Control, initiating Intimacy, and Emotional response to erectile dysfunction. The alpha value for the revised scale (MED-Qol-R) was >0.95 and exceeded .82 for each subscale. Regression analysis showed that patients in the placebo group experienced a significantly reduced feeling of Control over erectile dysfunction than those in the statin group. Those in the placebo group had significantly lower Emotional response than those in the statin group at the close of trial, but there was no significant treatment effect on Intimacy. Conclusions: Our revised MED-QoL-R identified three subscales. Secondary analysis showed a significant improvement in sexual health related quality of life, specifically in relation to perception of control and emotional health in men with untreated erectile dysfunction given 40 mg simvastatin for six months. Trial registration: Current Controlled Trials ISRCTN66772971.Peer reviewe

Curing HIV: Pharmacologic Approaches to Target HIV-1 Latency

HIV-1 infection persists even after years of antiretroviral therapy (ART). Although ART can halt viral replication and thereby reduce viremia to clinically undetectable levels, proviral latency established within the host genome remains largely unaffected by ART and can replenish systemic infection following interruption of therapy. Pharmacologic strategies, which not only target viral replication but also deplete proviral infection, are required for successful clearance of HIV-1 infection. This review highlights the current understanding of molecular mechanisms that establish and maintain HIV-1 latency in its major reservoir, the resting memory CD4+ T cell. We also identify the molecular targets that might be exploited to induce HIV-1 expression, remove epigenetic restrictions, or enhance effective transcription. Finally, we discuss the potential pharmacologic approaches toward targeting viral persistence in different cellular and anatomical reservoirs to achieve a cure of HIV-1 infection

A 4-year follow-up of patients with medication-overuse headache previously included in a randomized multicentre study

The aim of this study was to evaluate the long-term outcome in 61 patients with medication-overuse headache (MOH) who 4 years previously had been included in a randomized open-label prospective multicentre study. Sixty patients still alive after 4 years were invited to a follow-up investigation. Fifty patients (83%) participated. Sixteen visited a neurologist, 22 were interviewed through telephone, 2 gave response by a letter, and 10 were evaluated through hospital records. The influence of baseline characteristics on outcome 4 years later was evaluated by non-parametric tests. p values below 0.01 were considered significant. At follow-up, the 50 persons had a mean reduction of 6.5 headache days/month (p < 0.001) and 9.5 acute headache medication days/month (p < 0.001) compared to baseline. Headache index/month was reduced from 449 to 321 (p < 0.001). Sixteen persons (32%) were considered as responders due to a ≥50% reduction in headache frequency from baseline, whereas 17 (34%) persons met the criteria for MOH. None of the baseline characteristics consistently influenced all five outcome measures. Total Hospital Anxiety and Depression Scale (HADS) score at baseline was predictors (p < 0.005) for being a responder after 4 years. At 4 years’ follow-up, one-third of the 50 MOH patients had ≥50% reduction in headache frequency from baseline. A low total HADS score at baseline was associated with the most favorable outcome

Sensitivity to change of the Neck Pain and Disability Scale

The Neck Pain and Disability Scale (NPAD) is a 20-item instrument to measure neck pain and related disability. The aim of this study was to assess sensitivity to change of the NPAD. A total of 411 participants from 15 general practices in the middle of Germany completed a multidimensional questionnaire including the German version of the NPAD and self-reported demographic and clinical information. Sensitivity to change was analysed by linear regression analysis of the NPAD at follow-up and educational level, age class, depression, anxiety, and deficits in social support, respectively, and by Pearson’s correlation analyses between mean change in NPAD at follow-up and mean change in prognostic markers. Those having more than basic education (regression coefficient −7.2, p < 0.001) and/or being in a younger age class (−2.9, p = 0.020) consistently reported significantly lower average NPAD scores at follow-up compared to those with basic education and/or a older age class. In contrast, those who were classified to be depressed (regression coefficient 2.1, p < 0.001), anxious (1.9, p < 0.001), or having deficits in social support (5.5, p = 0.004) reported significantly higher NPAD scores. Change in depression, anxiety, and social support scale between baseline and follow-up was significantly correlated with change in the NPAD score. Hence, these data are in the direction anticipated across all baseline factors investigated. In conclusion, the NPAD seems to be a sensitive measure for use in clinical practice and future studies of neck pain and related disability

Age-related changes in global motion coherence: conflicting haemodynamic and perceptual responses

Our aim was to use both behavioural and neuroimaging data to identify indicators of perceptual decline in motion processing. We employed a global motion coherence task and functional Near Infrared Spectroscopy (fNIRS). Healthy adults (n = 72, 18-85) were recruited into the following groups: young (n = 28, mean age = 28), middle-aged (n = 22, mean age = 50), and older adults (n = 23, mean age = 70). Participants were assessed on their motion coherence thresholds at 3 different speeds using a psychophysical design. As expected, we report age group differences in motion processing as demonstrated by higher motion coherence thresholds in older adults. Crucially, we add correlational data showing that global motion perception declines linearly as a function of age. The associated fNIRS recordings provide a clear physiological correlate of global motion perception. The crux of this study lies in the robust linear correlation between age and haemodynamic response for both measures of oxygenation. We hypothesise that there is an increase in neural recruitment, necessitating an increase in metabolic need and blood flow, which presents as a higher oxygenated haemoglobin response. We report age-related changes in motion perception with poorer behavioural performance (high motion coherence thresholds) associated with an increased haemodynamic response

The genesis and development of landfall and its influence in relation to the culture of New Zealand and the Commonwealth

All the research and development of the following dissertation has been made possible by the award of a New Zealand Commonwealth Scholarship (1970-1972) tenable at the University of Canterbury in Christchurch. The spirit in which the Scholarship is awarded is one of mutual understanding between Commonwealth countries, as a first step to better international understanding among all countries, and it is sincerely hoped that this thesis will, in some small way, contribute to the spirit of friendship and cooperation that exists between Canada and New Zealand. It is my opinion that no two Western countries have greater common interests; in peacekeeping and peacemaking; in trade and non-alignment with military blocs; in standard of living and quality of life; in relations between ethnic minorities and powerful majorities in sovereign states: and I believe that our histories have led us in comparable cultural, social, and political directions. The original goal that led me to pursue doctoral studies was to present a major comparative study of "the social and literary mythology" (ideas discussed by Northrop Frye in Fables of Identity) of Canada, New Zealand and Australia. The comparative aspect of this goal is now planned for a future book. The extensive and rich documentation of the story of New Zealand, available in the many city, provincial, university and private libraries throughout the country, has made the confines of a Ph.D. thesis hard to determine. As a result, and in order to choose a suitable and original topic, the thesis has been confined to a discussion of post-war New Zealand literature and culture as presented in the quarterly Landfall under its first editor, Charles Brasch (1947-1966). The Introduction to the thesis explains the approach towards the topic: "The Genesis and Development of Landfall and its influence in Relation to the Culture of New Zealand and the Commonwealth." The term "Commonwealth" has been alluded to so that the thesis can be regarded in terms of the future comparative study. I believe that the term "Commonwealth literature", as accepted at the Conference on Commonwealth Literature held in Leeds (9-12 September 1964); can be used for the time being as a premise for comparative study. The chapter on historic influences on Landfall is a survey of intellectual periodicals that developed out of the radical years of the Depression. A discussion of Charles Brasch and editorial policy arose from the comment by E.H. McCormick that "the periodical is best approached through a consideration of its editor"

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Correlation versus Causation? Pharmacovigilance of the Analgesic Flupirtine Exemplifies the Need for Refined Spontaneous ADR Reporting

Annually, adverse drug reactions result in more than 2,000,000 hospitalizations and rank among the top 10 causes of death in the United States. Consequently, there is a need to continuously monitor and to improve the safety assessment of marketed drugs. Nonetheless, pharmacovigilance practice frequently lacks causality assessment. Here, we report the case of flupirtine, a centrally acting non-opioid analgesic. We re-evaluated the plausibility and causality of 226 unselected, spontaneously reported hepatobiliary adverse drug reactions according to the adapted Bradford-Hill criteria, CIOMS score and WHO-UMC scales. Thorough re-evaluation showed that only about 20% of the reported cases were probable or likely for flupirtine treatment, suggesting an incidence of flupirtine-related liver injury of 1∶ 100,000 when estimated prescription data are considered, or 0.8 in 10,000 on the basis of all 226 reported adverse drug reactions. Neither daily or cumulative dose nor duration of treatment correlated with markers of liver injury. In the majority of cases (151/226), an average of 3 co-medications with drugs known for their liver liability was observed that may well be causative for adverse drug reactions, but were reported under a suspected flupirtine ADR. Our study highlights the need to improve the quality and standards of ADR reporting. This should be done with utmost care taking into account contributing factors such as concomitant medications including over-the-counter drugs, the medical history and current health conditions, in order to avoid unjustified flagging and drug warnings that may erroneously cause uncertainty among healthcare professionals and patients, and may eventually lead to unjustified safety signals of useful drugs with a reasonable risk to benefit ratio

Inhibitory control, but not prolonged object-related experience appears to affect physical problem-solving performance of pet dogs

Human infants develop an understanding of their physical environment through playful interactions with objects. Similar processes may influence also the performance of non-human animals in physical problem-solving tasks, but to date there is little empirical data to evaluate this hypothesis. In addition or alternatively to prior experiences, inhibitory control has been suggested as a factor underlying the considerable individual differences in performance reported for many species. Here we report a study in which we manipulated the extent of object-related experience for a cohort of dogs (Canis familiaris) of the breed Border Collie over a period of 18 months, and assessed their level of inhibitory control, prior to testing them in a series of four physical problem-solving tasks. We found no evidence that differences in object-related experience explain variability in performance in these tasks. It thus appears that dogs do not transfer knowledge about physical rules from one physical problem-solving task to another, but rather approach each task as a novel problem. Our results, however, suggest that individual performance in these tasks is influenced in a complex way by the subject’s level of inhibitory control. Depending on the task, inhibitory control had a positive or a negative effect on performance and different aspects of inhibitory control turned out to be the best predictors of individual performance in the different tasks. Therefore, studying the interplay between inhibitory control and problem-solving performance will make an important contribution to our understanding of individual and species differences in physical problem-solving performance