Online prostate cancer screening decision aid for at-risk men: A randomized trial

Objective: This study examines the efficacy of an online decision aid (DA) for men with a family history of prostate cancer. Methods: Unaffected Australian men (40 - 79 years) with at least one affected relative completed the first online questionnaire, were randomized to read either the tailored DA (intervention) or nontailored information about prostate cancer screening (control), then completed a questionnaire postreading and 12 months later. The primary outcome was decisional conflict regarding prostate specific antigen (PSA) testing. The impact of the DA on longitudinal outcomes was analyzed by using random intercept mixed effects models. Logistic and linear regressions were used to analyze the impact of the DA on screening behavior and decision regret. Stage of decision-making was tested as a moderator for decisional conflict and decision regret. The frequency of online material access was recorded. Results: the DA had no effect on decisional conflict, knowledge, inclination toward PSA testing, accuracy of perceived risk, or screening behavior. However, among men considering PSA testing, those who read the DA had lower decision regret compared with men who read the control materials, β=.34 , p \u3c.001, 95% confidence interval (CI) = [.22, .53]. Conclusions: This is the first study to our knowledge to evaluate the uptake and efficacy of an online screening DA among men with a family history of prostate cancer. Men who were undecided about screening at baseline benefitted from the DA, experiencing less regret 12 months later. In relation to decisional conflict, the control materials may have operated as a less complex and equally informative DA

Identifying information needs of patients with IgA Nephropathy, using an innovative social media stepped analytical approach

Introduction Increasingly people with kidney disease are using social media to search for medical information and to find peer-support. IgA nephropathy (IgAN) predominantly affects young adults, demographically the biggest users of social media. This paper presents an innovative analysis of social media interactions to identify unmet education and information needs of IgAN patients. Methods Following ethical approval for the study, the IgA Nephropathy Support UK Facebook group (https://www.facebook.com/groups/915274415226674) granted us permission to anonymously collect and analyse 1959 posts and comments from 498 group users. An initial patient focus group and quantitative word frequency analysis created an initial categorisation matrix which was iteratively refined following serial analyses of the social media database to generate a final categorisation matrix of needs. We examined narrative data relating to each identified category to define patient narratives relating to each area. Results A large number of information gaps and unanswered questions were identified relating to: diet, symptoms, diagnosis, treatment and patient co-morbidities. Additionally, patient-clinician communication and the presentation of information were drawn out as cross-cutting issues. These themes differed significantly from those identified from the traditional patient focus group highlighting the value of this novel method for interrogating social media data to understand unmet patient need. Conclusions Social media data is an untapped and valuable resource which can be used to better understand patient information gaps, leading to the generation of targeted materials to address unmet educational needs. This innovative approach could be replicated across other health conditions

Metabolomics to unveil and understand phenotypic diversity between pathogen populations

Visceral leishmaniasis is caused by a parasite called Leishmania donovani, which every year infects about half a million people and claims several thousand lives. Existing treatments are now becoming less effective due to the emergence of drug resistance. Improving our understanding of the mechanisms used by the parasite to adapt to drugs and achieve resistance is crucial for developing future treatment strategies. Unfortunately, the biological mechanism whereby Leishmania acquires drug resistance is poorly understood. Recent years have brought new technologies with the potential to increase greatly our understanding of drug resistance mechanisms. The latest mass spectrometry techniques allow the metabolome of parasites to be studied rapidly and in great detail. We have applied this approach to determine the metabolome of drug-sensitive and drug-resistant parasites isolated from patients with leishmaniasis. The data show that there are wholesale differences between the isolates and that the membrane composition has been drastically modified in drug-resistant parasites compared with drug-sensitive parasites. Our findings demonstrate that untargeted metabolomics has great potential to identify major metabolic differences between closely related parasite strains and thus should find many applications in distinguishing parasite phenotypes of clinical relevance

Challenges, solutions and future directions in the evaluation of service innovations in health care and public health

HeadlineEvaluating service innovations in health care and public health requires flexibility, collaboration and pragmatism; this collection identifies robust, innovative and mixed methods to inform such evaluations.This is the final version of the article. It first appeared from the National Institute for Helath Research via http://dx.doi.org/10.3310/hsdr0416

An Examination of Chimpanzee Use in Human Cancer Research

Advocates of chimpanzee research claim the genetic similarity of humans and chimpanzees make them an indispensable research tool to combat human diseases. Given that cancer is a leading cause of human death worldwide, one might expect that if chimpanzees were needed for, or were productive in, cancer research, then they would have been widely used. This comprehensive literature analysis reveals that chimpanzees have scarcely been used in any form of cancer research, and that chimpanzee tumours are extremely rare and biologically different from human cancers. Often, chimpanzee citations described peripheral use of chimpanzee cells and genetic material in predominantly human genomic studies. Papers describing potential new cancer therapies noted significant concerns regarding the chimpanzee model. Other studies described interventions that have not been pursued clinically. Finally, available evidence indicates that chimpanzees are not essential in the development of therapeutic monoclonal antibodies. It would therefore be unscientific to claim that chimpanzees are vital to cancer research. On the contrary, it is reasonable to conclude that cancer research would not suffer, if the use of chimpanzees for this purpose were prohibited in the US. Genetic differences between humans and chimpanzees, make them an unsuitable model for cancer, as well as other human diseases

The Codevelopment of “My Kidneys & Me”: A Digital Self-management Program for People With Chronic Kidney Disease

Background: Health care self-management is important for people living with nondialysis chronic kidney disease (CKD). However, the few available resources are of variable quality. Objective: This work describes the systematic codevelopment of “My Kidneys & Me” (MK&M), a theory-driven and evidence-based digital self-management resource for people with nondialysis CKD, guided by an established process used for the successful development of the diabetes education program MyDESMOND (Diabetes Education and Self-Management for Ongoing and Newly Diagnosed, DESMOND). Methods: A multidisciplinary steering group comprising kidney health care professionals and researchers and specialists in the development of complex interventions and digital health provided expertise in the clinical and psychosocial aspects of CKD, self-management, digital health, and behavior change. A patient and public involvement group helped identify the needs and priorities of MK&M and co-design the resource. MK&M was developed in 2 sequential phases. Phase 1 involved the codevelopment process of the MK&M resource (content and materials), using Intervention Mapping (IM) as a framework. The first 4 IM steps guided the development process: needs assessment was conducted to describe the context of the intervention; intervention outcomes, performance objectives, and behavioral determinants were identified; theory- and evidence-based change methods and practical strategies to deliver change methods were selected; and program components were developed and refined. Phase 2 involved the adoption and adaptation of the existing MyDESMOND digital platform to suit the MK&M resource. Results: The needs assessment identified that individuals with CKD have multiple differing needs and that delivering a self-management program digitally would enable accessible, tailored, and interactive information and support. The intended outcomes of MK&M were to improve and maintain effective self-management behaviors, including physical activity and lifestyle, improve knowledge, promote self-care skills, increase self-efficacy, and enhance well-being. This was achieved through the provision of content and materials designed to increase CKD knowledge and patient activation, reduce health risks, manage symptoms, and improve physical function. Theories and behavior change techniques selected include Self-Management Framework, Capability, Opportunity, Motivation Behavior model components of Behaviour Change Wheel and taxonomy of behavior change techniques, Health Action Process Approach Model, Common Sense Model, and Social Cognitive Theory. The program components developed comprised educational and behavior change sessions, health trackers (eg, monitoring blood pressure, symptoms, and exercise), goal-setting features, and forums for social support. The MyDESMOND digital platform represented an ideal existing platform to host MK&M; thus, the MyDESMOND interface and features were adopted and adapted for MK&M. Conclusions: Applying the IM framework enabled the systematic application of theory, empirical evidence, and practical perspectives in the codevelopment of MK&M content and materials. Adopting and adapting a preexisting platform provided a cost- and time-efficient approach for developing our digital intervention. In the next stage of work, the efficacy of MK&M in increasing patient activation will be tested in a randomized controlled trial

Meta-analysis of genome-wide association studies of HDL cholesterol response to statins

BACKGROUND: In addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Inter-individual variation in HDL-C response to statins may be partially explained by genetic variation.METHODS AND RESULTS: We performed a meta-analysis of genome-wide association studies (GWAS) to identify variants with an effect on statin-induced high density lipoprotein cholesterol (HDL-C) changes. The 123 most promising signals with p&lt;1×10(-4) from the 16 769 statin-treated participants in the first analysis stage were followed up in an independent group of 10 951 statin-treated individuals, providing a total sample size of 27 720 individuals. The only associations of genome-wide significance (p&lt;5×10(-8)) were between minor alleles at the CETP locus and greater HDL-C response to statin treatment.CONCLUSIONS: Based on results from this study that included a relatively large sample size, we suggest that CETP may be the only detectable locus with common genetic variants that influence HDL-C response to statins substantially in individuals of European descent. Although CETP is known to be associated with HDL-C, we provide evidence that this pharmacogenetic effect is independent of its association with baseline HDL-C levels.</p

Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins

Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response

MYC functions are specific in biological subtypes of breast cancer and confers resistance to endocrine therapy in luminal tumours.

BACKGROUND: MYC is amplified in approximately 15% of breast cancers (BCs) and is associated with poor outcome. c-MYC protein is multi-faceted and participates in many aspects of cellular function and is linked with therapeutic response in BCs. We hypothesised that the functional role of c-MYC differs between molecular subtypes of BCs. METHODS: We therefore investigated the correlation between c-MYC protein expression and other proteins involved in different cellular functions together with clinicopathological parameters, patients' outcome and treatments in a large early-stage molecularly characterised series of primary invasive BCs (n=1106) using immunohistochemistry. The METABRIC BC cohort (n=1980) was evaluated for MYC mRNA expression and a systems biology approach utilised to identify genes associated with MYC in the different BC molecular subtypes. RESULTS: High MYC and c-MYC expression was significantly associated with poor prognostic factors, including grade and basal-like BCs. In luminal A tumours, c-MYC was associated with ATM (P=0.005), Cyclin B1 (P=0.002), PIK3CA (P=0.009) and Ki67 (P<0.001). In contrast, in basal-like tumours, c-MYC showed positive association with Cyclin E (P=0.003) and p16 (P=0.042) expression only. c-MYC was an independent predictor of a shorter distant metastases-free survival in luminal A LN+ tumours treated with endocrine therapy (ET; P=0.013). In luminal tumours treated with ET, MYC mRNA expression was associated with BC-specific survival (P=0.001). In ER-positive tumours, MYC was associated with expression of translational genes while in ER-negative tumours it was associated with upregulation of glucose metabolism genes. CONCLUSIONS: c-MYC function is associated with specific molecular subtypes of BCs and its overexpression confers resistance to ET. The diverse mechanisms of c-MYC function in the different molecular classes of BCs warrants further investigation particularly as potential therapeutic targets