Exploring Heterogeneity in Histology-Independent Technologies and the Implications for Cost-Effectiveness

Background: The National Institute for Health and Care Excellence and a number of international health technology assessment agencies have recently undertaken appraisals of histology-independent technologies (HITs). A strong and untested assumption inherent in the submissions included identical clinical response across all tumour histologies, including ‘new’ histologies unrepresented in the trial. Challenging this assumption and exploring the potential for heterogeneity has the potential to impact upon cost-effectiveness. Method: Using published response data for a HIT, a Bayesian hierarchical model (BHM) was used to identify heterogeneity in response and to estimate the probability of response for each histology included in single-arm studies which informed the submission for the HIT, larotrectinib. The probability of response for a ‘new’ histology was estimated. Results were inputted into a simplified response-based economic model using hypothetical parameters. Histology-independent and histology-specific incremental cost-effectiveness ratios (ICERs) accounting for heterogeneity were generated. Results: The results of the BHM show considerable heterogeneity in response rates across histologies. The predicted probability of response estimated by the BHM is 60.9% (95% CrI 16.0; 91.8%), lower than the naively pooled probability of 74.5%. A mean response probability of 56.9% (0.2; 99.9%) is predicted for an unrepresented histology. Based on the economic analysis, the probability of the hypothetical HIT being cost effective under the assumption of identical response is 78%. Allowing for heterogeneity, the probability of various approval decisions being cost effective ranges from 93% to 11%. Conclusions: Central to the challenge of reimbursement of HITs is the potential for heterogeneity. This study illustrates how heterogeneity in clinical-effectiveness can result in highly variable and uncertain estimates of cost-effectiveness. This analysis can help understand the consequences of histology-independent vs histology-specific decisions

Global Profiling of DNA Replication Timing and Efficiency Reveals that Efficient Replication/Firing Occurs Late during S-Phase in S. pombe

10.1371/journal.pone.0000722PLoS ONE2

Porn video shows, local brew, and transactional sex: HIV risk among youth in Kisumu, Kenya

Background: Kisumu has shown a rising HIV prevalence over the past sentinel surveillance surveys, and most new infections are occurring among youth. We conducted a qualitative study to explore risk situations that can explain the high HIV prevalence among youth in Kisumu town, Kenya Methods: We conducted in-depth interviews with 150 adolescents aged 15 to 20, held 4 focus group discussions, and made 48 observations at places where youth spend their free time. Results: Porn video shows and local brew dens were identified as popular events where unprotected multipartner, concurrent, coerced and transactional sex occurs between adolescents. Video halls - rooms with a TV and VCR - often show pornography at night for a very small fee, and minors are allowed. Forced sex, gang rape and multiple concurrent relationships characterised the sexual encounters of youth, frequently facilitated by the abuse of alcohol, which is available for minors at low cost in local brew dens. For many sexually active girls, their vulnerability to STI/HIV infection is enhanced due to financial inequality, gender-related power difference and cultural norms. The desire for love and sexual pleasure also contributed to their multiple concurrent partnerships. A substantial number of girls and young women engaged in transactional sex, often with much older working partners. These partners had a stronger socio-economic position than young women, enabling them to use money/gifts as leverage for sex. Condom use was irregular during all types of sexual encounters. Conclusions: In Kisumu, local brew dens and porn video halls facilitate risky sexual encounters between youth. These places should be regulated and monitored by the government. Our study strongly points to female vulnerabilities and the role of men in perpetuating the local epidemic. Young men should be targeted in prevention activities, to change their attitudes related to power and control in relationships. Girls should be empowered how to negotiate safe sex, and their poverty should be addressed through income-generating activities.</p

A rapid synthesis of the evidence on interventions supporting self-management for people with long-term conditions. (PRISMS Practical systematic RevIew of Self-Management Support for long-term conditions)

Background: Despite robust evidence concerning self-management for some long-term conditions (LTCs), others lack research explicitly on self-management and, consequently, some patient groups may be overlooked. Aim: To undertake a rapid, systematic overview of the evidence on self-management support for LTCs to inform health-care commissioners and providers about what works, for whom, and in what contexts. Methods: Self-management is ‘the tasks . . . individuals must undertake to live with one or more chronic conditions . . . [including] . . . having the confidence to deal with medical management, role management and emotional management of their conditions’. We convened an expert workshop and identified characteristics of LTCs potentially of relevance to self-management and 14 diverse exemplar LTCs (stroke, asthma, type 2 diabetes mellitus, depression, chronic obstructive pulmonary disease, chronic kidney disease, dementia, epilepsy, hypertension, inflammatory arthropathies, irritable bowel syndrome, low back pain, progressive neurological disorders and type 1 diabetes mellitus). For each LTC we conducted systematic overviews of systematic reviews of randomised controlled trials (RCTs) of self-management support interventions (‘quantitative meta-reviews’); and systematic overviews of systematic reviews of qualitative studies of patients’ experiences relating to self-management (‘qualitative meta-reviews’). We also conducted an original systematic review of implementation studies of self-management support in the LTCs. We synthesised all our data considering the different characteristics of LTCs. In parallel, we developed a taxonomy of the potential components of self-management support. Results: We included 30 qualitative systematic reviews (including 515 unique studies), 102 quantitative systematic reviews (including 969 RCTs), and 61 studies in the implementation systematic review. Effective self-management support interventions are multifaceted, should be tailored to the individual, their culture and beliefs, a specific LTC and position on the disease trajectory, and underpinned by a collaborative/communicative relationship between the patient and health-care professional (HCP) within the context of a health-care organisation that actively promotes self-management. Self-management support is a complex intervention and although many components were described and trialled in the studies no single component stood out as more important than any other. Core components include (1) provision of education about the LTC, recognising the importance of understanding patients’ pre-existing knowledge and beliefs about their LTC; (2) psychological strategies to support adjustment to life with a LTC; (3) strategies specifically to support adherence to treatments; (4) practical support tailored to the specific LTC, including support around activities of daily living for disabling conditions, action plans in conditions subject to marked exacerbations, intensive disease-specific training to enable self-management of specific clinical tasks; and (5) social support as appropriate. Implementation requires a whole-systems approach which intervenes at the level of the patient, the HCP and the organisation. The health-care organisation is responsible for providing the means (both training and time/material resources) to enable HCPs to implement, and patients to benefit from, self-management support, regularly evaluating self-management processes and clinical outcomes. More widely there is a societal need to address public understanding of LTCs. The lack of public story for many conditions impacted on patient help-seeking behaviour and public perceptions of need. Conclusions: Supporting self-management is inseparable from the high-quality care for LTCs. Commissioners and health-care providers should promote a culture of actively supporting self-management as a normal, expected, monitored and rewarded aspect of care. Further research is needed to understand how health service managers and staff can achieve this culture change in their health-care organisations. Study registration: This study is registered as PROSPERO CRD42012002898. Funding: The National Institute for Health Research Health Services and Delivery Research programme

Advanced therapeutic dressings for effective wound healing

Advanced therapeutic dressings that take active part in wound healing to achieve rapid and complete healing of chronic wounds is of current research interest. There is a desire for novel strategies to achieve expeditious wound healing due to the enormous financial burden worldwide. This paper reviews the current state of wound healing and wound management products, with emphasis on the demand for more advanced forms of wound therapy and some of the current challenges and driving forces behind this demand. The paper reviews information mainly from peer reviewed literature and other publicly available sources such as the FDA. A major focus is the treatment of chronic wounds including amputations, diabetic and leg ulcers, pressure sores, surgical and traumatic wounds (e.g. accidents and burns) where patient immunity is low and the risk of infections and complications are high. The main dressings include medicated moist dressings, tissue engineered substitutes, biomaterials based biological dressings, biological and naturally derived dressings, medicated sutures and various combinations of the above classes. Finally, the review briefly discusses possible prospects of advanced wound healing including some of the emerging approaches such as hyperbaric oxygen, negative pressure wound therapy and laser wound healing, in routine clinical care

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Librarianship and the Open Access Journal : State of the Union

A panel presentation on the state of open access publishing regarding librarianship

The Making of a Journal: Disseminating Research to Inform Practice

Objective: The journal Evidence Based Library and Information Practice (EBLIP) published its first issue in March 2006. The purpose of the journal is to provide a forum for librarians and other information professionals to discover research that may contribute to decision making in professional practice. EBLIP publishes original research and commentary on the topic of evidence based library and information practice, as well as reviews of previously published research (evidence summaries) on a wide number of topics. Setting: EBLIP is an international, peer reviewed, open access journal published quarterly by the University of Alberta Learning Services, using the Open Journal Systems (OJS) Software. Participants: The journal is comprised of an editorial team of four editors, five copyeditors, more than 40 editorial advisory board members, and more than 20 evidence summary team writers. Program: This paper will detail the process of creating a new journal to support evidence based librarianship. The process of establishing the journal and the evolution that occurred over the first year will be discussed. The authors will discuss reasons why the journal was necessary and the various roles of sections and the content within. The importance of open access to the dissemination of this literature will also be discussed. Main Results: By May 2007, EBLIP will have published 5 issues. We will examine the number of submissions to the journal for the first year, topics included, and average turnaround time from submission to publication. Conclusion: With a full year’s publication complete and moving forward into the second year, the editors will reflect on their experience and discuss future directions for EBLIP

Evidence Based Practice Outside the Box (Editorial)

I love food. I love cooking, baking, testing, and eating. I read about food preparation, food facts, and food service. Over the years I’ve developed my fair share of knowledge about cooking and I’m a decent cook, but I’m no chef. I guess I’m what you’d call a “foodie”. However, I have the good fortune to have a friend who is a chef and owns one of the best, and certainly the most innovative, restaurants in town. During this summer I hosted a cooking class in my home for my family with my chef friend as instructor. The Tex-Mex barbecue theme was a big hit (you can contact me for recipes, if you like), but much more fascinating was the explanation of the science behind the cooking. It turns out that there is a term for this: molecular gastronomy. Another term, and hence the genesis of my “Eureka!” moment of the summer, is evidence based cooking. Good cooking is not just following a recipe (not all of which are evidence based) but at its best is the culmination of heaps of tested information regarding why and how chemical and environmental factors work together to result in a gastronomical delight. For example, will brining or marinating a pork chop make it moister? And, if brining, what temperature should the water be, how long should it soak, and how much salt is needed? Why does pounding meat increase its tenderness? What will keep guacamole from browning better – the pit or lime juice? What does baking soda do in a chocolate cake? Eggs or no eggs in fresh pasta? Like most librarians, I tend not to take information at face value. I want to know where information comes from and whether or not it is valid, based on specific factors. I’ve come to notice that evidence based, or evidence informed, practice is everywhere and has a tremendous impact on our lives. Why do you rotate the tires on your car? Evidence shows that the front tires wear more quickly (think about all those 3-pointturns, the braking, etc) and therefore, switching the front tires with the back tires will increase the life span of the tires. Ergonomics is based heavily on human factors research and usability testing; theme park design is largely affected by studies onthe psychology of waiting; the study of local weather patterns and temperatures directly affects landscape architecture; advertising is strategically designed and presented based upon sociological studies such as demographics and viewing/reading behaviour. Could one argue that natural evolution is a result of nature’s long-term evidence-based practice? I know that I’m not alone in finding this fascinating, especially since the basis of these studies is information. While my own work may focus more on medical and health information, I feel that as an information specialist I can take pride in the fact that the soul of my field, information, is essential to the world around me. Think about this when you feel yourself getting cynical about research and the validity of your profession (don’t tell me you’ve never been there). I will be the first to admit that evidence is not always the be-all and end-all. There is a lot to be said for spontaneity (i.e. Hmmmm… I wonder if a sprig of fresh thyme would taste good in the mushroom sauce?”) and happenstance (i.e. “Well, whaddaya know... penicillin!”). I certainly don’t think that every decision needs to be researched. But thank goodness for many research based decisions, without which the world would be a very different place and, heaven forbid, the perfect crème brulée may not exist