Randomized, double-blind, placebo-controlled study to assess the efficacy and toxicity of subcutaneous ketamine in the management of cancer pain

Purpose: The anesthetic ketamine is widely used for pain related to cancer, but the evidence to support its use in this setting is weak. This study aimed to determine whether ketamine is more effective than placebo when used in conjunction with opioids and standard adjuvant therapy in the management of chronic uncontrolled cancer pain. Ketamine would be considered of net benefit if it provided clinically relevant improvement in pain with limited breakthrough analgesia and acceptable toxicity. Patients and Methods: In this multisite, dose-escalation, double-blind, randomized, placebo-controlled phase III trial, ketamine or placebo was delivered subcutaneously over 3 to 5 days. Results: In all, 185 participants were included in the primary analysis. There was no significant difference between the proportion of positive outcomes (0.04; 95% CI, -0.10 to 0.18; P = .55) in the placebo and intervention arms (response rates, 27% [25 of 92] and 31% [29 of 93]). Pain type (nociceptive v neuropathic) was not a predictor of response. There was almost twice the incidence of adverse events worse than baseline in the ketamine group after day 1 (incidence rate ratio, 1.95; 95% CI, 1.46 to 2.61; P < .001) and throughout the study. Those receiving ketamine were more likely to experience a more severe grade of adverse event per day (odds ratio, 1.09; 95% CI, 1.00 to 1.18; P = .039). The number of patients needed to treat for one additional patient to have a positive outcome from ketamine was 25 (95% CI, six to ∞). The number needed to harm, because of toxicity-related withdrawal, was six (95% CI, four to 13). Conclusion: Ketamine does not have net clinical benefit when used as an adjunct to opioids and standard coanalgesics in cancer pain. © 2012 by American Society of Clinical Oncology

Bereavement help-seeking following an 'expected' death: a cross-sectional randomised face-to-face population survey

© 2008 Currow et al; licensee BioMed Central Ltd. 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 cited.Background : This study examines the prevalence and nature of bereavement help-seeking among the population who experienced an "expected" death in the five years before their survey response. Such whole population data are not limited by identification through previous access to specific services nor practitioners. Methods : In a randomised, cross-sectional, state-wide population-based survey, 6034 people over two years completed face-to-face interviews in South Australia by trained interviewers using piloted questions (74.2% participation rate). Respondent demographics, type of grief help sought, and circumstantial characteristics were collected. Uni- and multi-variate logistic regression models were created. Results : One in three people (1965/6034) had experienced an 'expected' death of someone close to them in the last five years. Thirteen per cent sought help for their grief from one or more: friend/family members (10.7%); grief counselors (2.2%); spiritual advisers (1.9%); nurses/doctors (1.5%). Twenty five respondents (1.3%) had not sought, but would have valued help with their grief. In multi-variate regression modeling, those who sought professional help (3.4% of the bereaved) had provided more intense care (OR 5.39; CI 1.94 to14.98; p < 0.001), identified that they were less able to 'move on' with their lives (OR 7.08; CI 2.49 to 20.13; p = 0.001) and were more likely not to be in full- or part-time work (OR 3.75; CI 2.31 – 11.82; p = 0.024; Nagelkerke's R2 = 0.33). Conclusion : These data provide a whole-of-population baseline of bereavement help-seeking. The uniquely identified group who wished they had sought help is one where potentially significant health gains could be made as we seek to understand better any improved health outcomes as a result of involving bereavement services

Tracking the Impact of Excisional Cervical Treatment on the Cervix using Biospectroscopy

Local excisional treatment for cervical intra-epithelial neoplasia (CIN) is linked to significant adverse sequelae including preterm birth, with cone depth and radicality of treatment correlating to the frequency and severity of adverse events. Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy can detect underlying cervical disease more accurately than conventional cytology. The chemical profile of cells pre- and post-treatment may differ as a result of altered biochemical processes due to excision, or treatment of the disease. Since pre-treatment cervical length varies amongst women, the percentage of cervix excised may correlate more accurately to risk than absolute dimensions. We show that treatment for CIN significantly alters the biochemistry of the cervix, compared with women who have not had treatment; this is due to the removal of cervical tissue rather than the removal of the disease. However, the spectra do not seem to correlate to the cone depth or proportion of cervical length excised. Future research should aim to explore the impact of treatment in a larger cohort

Twelve Not So Angry Men:Inclusive Masculinities in Australian Contact Sports

Sport’s utility in the development of a conservative orthodox ideal of masculinity based upon homophobia, aggression and emotional restrictiveness, is well evidenced in critical masculinities scholarship. However, contemporary research is reflecting a more nuanced understanding of male behaviour in many Western contexts, with men performing softer and more inclusive versions of masculinities. Through exploring the experiences of twelve Australian contact sport athletes, this research establishes findings to support the growing body of inclusive masculinities research. Results show that these men value a softer representation of masculinity based upon pro-gay sentiments and being emotionally open; while often being critical of aspects of orthodox masculinities which male team sport previously promoted

Use of anthropogenic material affects bird nest arthropod community structure: influence of urbanisation, and consequences for ectoparasites and fledging success

Nests are a critically important factor in determining the breeding success of many species of birds. Nevertheless, we have surprisingly little understanding of how local environment helps shape materials used in construction, how this differs among related species using similar nest sites, or if materials used directly or indirectly influence the numbers of offspring successfully reared. We also have little understanding of any potential links between nest construction and the assemblage of invertebrates which inhabit the nest and in particular, with ectoparasites. We addressed these questions by monitoring the success rates of nest-box using Blue Tits Cyanistes caeruleus and Great Tits Parus major, from rural, urban greenspace and urban garden settings. We collected used nests, identified arthropods present, and measured the proportions of highly processed anthropogenic materials used in their construction. Some 25% of Great Tit nest materials were of an anthropogenic source and this was consistent across habitats, while Blue Tits used little (1-2%) except in gardens (~16%), suggesting that Great Tits preferentially sought out these materials. In fledged nests, increasing use of anthropogenic material was associated with lower general arthropod diversity and ectoparasite predator abundance (Blue Tits only) but higher levels of Siphonapterans (fleas). Higher arthropod diversity was associated with lower flea numbers, suggesting that increased diversity played a role in limiting flea numbers. No direct link was found between breeding success and either anthropogenic material usage, or arthropod diversity and abundance. However, breeding success declined with increasing urbanisation in both species and increased with nest weight in Blue Tits. The interplay between urbanisation and bird ecology is complex; our work shows that subtle anthropogenic influences may have indirect and unexpected consequences for urban birds

Change Point Estimation in Monitoring Survival Time

Precise identification of the time when a change in a hospital outcome has occurred enables clinical experts to search for a potential special cause more effectively. In this paper, we develop change point estimation methods for survival time of a clinical procedure in the presence of patient mix in a Bayesian framework. We apply Bayesian hierarchical models to formulate the change point where there exists a step change in the mean survival time of patients who underwent cardiac surgery. The data are right censored since the monitoring is conducted over a limited follow-up period. We capture the effect of risk factors prior to the surgery using a Weibull accelerated failure time regression model. Markov Chain Monte Carlo is used to obtain posterior distributions of the change point parameters including location and magnitude of changes and also corresponding probabilistic intervals and inferences. The performance of the Bayesian estimator is investigated through simulations and the result shows that precise estimates can be obtained when they are used in conjunction with the risk-adjusted survival time CUSUM control charts for different magnitude scenarios. The proposed estimator shows a better performance where a longer follow-up period, censoring time, is applied. In comparison with the alternative built-in CUSUM estimator, more accurate and precise estimates are obtained by the Bayesian estimator. These superiorities are enhanced when probability quantification, flexibility and generalizability of the Bayesian change point detection model are also considered

WoMMBAT: A user interface for hierarchical Bayesian estimation of working memory capacity

The change detection paradigm has become an important tool for researchers studying working memory. Change detection is especially useful for studying visual working memory, because recall paradigms are difficult to employ in the visual modality. Pashler (Perception & Psychophysics, 44, 369–378, 1988) and Cowan (Behavioral and Brain Sciences, 24, 87–114, 2001) suggested formulas for estimating working memory capacity from change detection data. Although these formulas have become widely used, Morey (Journal of Mathematical Psychology, 55, 8–24, 2011) showed that the formulas suffer from a number of issues, including inefficient use of information, bias, volatility, uninterpretable parameter estimates, and violation of ANOVA assumptions. Morey presented a hierarchical Bayesian extension of Pashler’s and Cowan’s basic models that mitigates these issues. Here, we present WoMMBAT (Working Memory Modeling using Bayesian Analysis Techniques) software for fitting Morey’s model to data. WoMMBAT has a graphical user interface, is freely available, and is cross-platform, running on Windows, Linux, and Mac operating systems

A review of elliptical and disc galaxy structure, and modern scaling laws

A century ago, in 1911 and 1913, Plummer and then Reynolds introduced their models to describe the radial distribution of stars in `nebulae'. This article reviews the progress since then, providing both an historical perspective and a contemporary review of the stellar structure of bulges, discs and elliptical galaxies. The quantification of galaxy nuclei, such as central mass deficits and excess nuclear light, plus the structure of dark matter halos and cD galaxy envelopes, are discussed. Issues pertaining to spiral galaxies including dust, bulge-to-disc ratios, bulgeless galaxies, bars and the identification of pseudobulges are also reviewed. An array of modern scaling relations involving sizes, luminosities, surface brightnesses and stellar concentrations are presented, many of which are shown to be curved. These 'redshift zero' relations not only quantify the behavior and nature of galaxies in the Universe today, but are the modern benchmark for evolutionary studies of galaxies, whether based on observations, N-body-simulations or semi-analytical modelling. For example, it is shown that some of the recently discovered compact elliptical galaxies at 1.5 < z < 2.5 may be the bulges of modern disc galaxies.Comment: Condensed version (due to Contract) of an invited review article to appear in "Planets, Stars and Stellar Systems"(www.springer.com/astronomy/book/978-90-481-8818-5). 500+ references incl. many somewhat forgotten, pioneer papers. Original submission to Springer: 07-June-201

Prevalence and determinants of human papillomavirus genital infection in men

Four-hundred-forty-five husbands of women with invasive cervical carcinoma, 165 of women with in situ cervical cancer, and 717 of control women (age range 19–82 years) were interviewed and a sample of exfoliated cells from the penis obtained in seven case–control studies conducted by the International Agency for Research on Cancer. The characteristics of human papillomavirus-positive and human papillomavirus-negative husbands were compared using odds ratios and 95% confidence intervals. Thirteen per cent of the husbands of control women, 18% of the husbands of women with invasive cervical carcinoma, and 21% of the husbands of in situ cervical carcinoma women were positive for penile human papillomavirus DNA. Human papillomavirus 16 was detected in 45 husbands, human papillomavirus 18, 31 or 33 in 19, and human papillomavirus 6/11 in 6, but the majority of human papillomavirus infection (158) was with other or unspecified human papillomavirus types. The same human papillomavirus type was seldom identified in both husband and wife. The strongest variation in penile human papillomavirus infection was by country, with percentages among the husbands of control women ranging between 3% in Spain and 39% in Brazil. Having had over 50 lifetime sexual partners, compared with only one, was associated with an odds ratio of 2.3

'Relief of oppression': An organizing principle for researchers' obligations to participants in observational studies in the developing world

<p>Abstract</p> <p>Background</p> <p>A central question in the debate about exploitation in international research is whether investigators and sponsors from high-income countries (HIC) have obligations to address background conditions of injustice in the communities in which they conduct their research, beyond the healthcare and other research-related needs of participants, to aspects of their basic life circumstances.</p> <p>Discussion</p> <p>In this paper, we describe <b>t</b>he Majengo sexually transmitted disease (STD) Cohort study, a long-term prospective, observational cohort of sex workers in Nairobi, Kenya. Despite important scientific contributions and a wide range of benefits to the women of the cohort, most of the women have remained in the sex trade during their long-standing participation in the cohort, prompting allegations of exploitation. The Majengo STD cohort case extends the debate about justice in international research ethics beyond clinical trials into long-term observational research. We sketch the basic features of a new approach to understanding and operationalizing obligations of observational researchers, which we call 'relief of oppression'. 'Relief of oppression' is an organizing principle, analogous to the principle of harm reduction that is now widely applied in public health practice. Relief of oppression aims to help observational researchers working in conditions of injustice and deprivation to clarify their ethical obligations to participants. It aims to bridge the gap between a narrow, transaction-oriented account of avoiding exploitation and a broad account emphasizing obligations of reparation for historic injustices. We propose that relief of oppression might focus researchers' consideration of benefits on those that have some relevance to background conditions of injustice, and so elevate the priority of these benefits, in relation to others that might be considered and negotiated with participants, according to the degree to which the participating communities are constrained in their realization of fundamental freedoms.</p> <p>Summary</p> <p>The over-arching aim of relief of oppression is that, within the range of benefits negotiated over time with the local communities and organizations, an increasing proportion reflects a shared interest in improving participants' fundamental freedoms. We describe how harm reduction serves as a useful analogy for how we envision relief of oppression functioning in international research.</p