Application of real-time global media monitoring and ‘derived questions’ for enhancing communication by regulatory bodies:the case of human papillomavirus vaccines

Abstract Background The benefit-risk balance of vaccines is regularly debated by the public, but the utility of media monitoring for regulatory bodies is unclear. A media monitoring study was conducted at the European Medicines Agency (EMA) concerning human papillomavirus (HPV) vaccines during a European Union (EU) referral procedure assessing the potential causality of complex regional pain syndrome (CRPS) and postural orthostatic tachycardia syndrome (POTS) reported to the authorities as suspected adverse reactions. Methods To evaluate the utility of media monitoring in real life, prospective real-time monitoring of worldwide online news was conducted from September to December 2015 with inductive content analysis, generating ‘derived questions’. The evaluation was performed through the validation of the predictive capacity of these questions against journalists’ queries, review of the EMA’s public statement and feedback from EU regulators. Results A total of 4230 news items were identified, containing personal stories, scientific and policy/process-related topics. Explicit and implicit concerns were identified, including those raised due to lack of knowledge or anticipated once more information would be published. Fifty derived questions were generated and categorised into 12 themes. The evaluation demonstrated that providing the media monitoring findings to assessors and communicators resulted in (1) confirming that public concerns regarding CRPS and POTS would be covered by the assessment; (2) meeting specific information needs proactively in the public statement; (3) predicting all queries from journalists; and (4) altering the tone of the public statement with respectful acknowledgement of the health status of patients with CRSP or POTS. Conclusions The study demonstrated the potential utility of media monitoring for regulatory bodies to support communication proactivity and preparedness, intended to support trusted safe and effective vaccine use. Derived questions seem to be a familiar and effective format for presenting media monitoring results in the scientific-regulatory environment. It is suggested that media monitoring could form part of regular surveillance for medicines of high public interest. Future work is recommended to develop efficient monitoring strategies for that purpose

Application of real-time global media monitoring and ‘derived questions’ for enhancing communication by regulatory bodies:the case of human papillomavirus vaccines

Abstract Background The benefit-risk balance of vaccines is regularly debated by the public, but the utility of media monitoring for regulatory bodies is unclear. A media monitoring study was conducted at the European Medicines Agency (EMA) concerning human papillomavirus (HPV) vaccines during a European Union (EU) referral procedure assessing the potential causality of complex regional pain syndrome (CRPS) and postural orthostatic tachycardia syndrome (POTS) reported to the authorities as suspected adverse reactions. Methods To evaluate the utility of media monitoring in real life, prospective real-time monitoring of worldwide online news was conducted from September to December 2015 with inductive content analysis, generating ‘derived questions’. The evaluation was performed through the validation of the predictive capacity of these questions against journalists’ queries, review of the EMA’s public statement and feedback from EU regulators. Results A total of 4230 news items were identified, containing personal stories, scientific and policy/process-related topics. Explicit and implicit concerns were identified, including those raised due to lack of knowledge or anticipated once more information would be published. Fifty derived questions were generated and categorised into 12 themes. The evaluation demonstrated that providing the media monitoring findings to assessors and communicators resulted in (1) confirming that public concerns regarding CRPS and POTS would be covered by the assessment; (2) meeting specific information needs proactively in the public statement; (3) predicting all queries from journalists; and (4) altering the tone of the public statement with respectful acknowledgement of the health status of patients with CRSP or POTS. Conclusions The study demonstrated the potential utility of media monitoring for regulatory bodies to support communication proactivity and preparedness, intended to support trusted safe and effective vaccine use. Derived questions seem to be a familiar and effective format for presenting media monitoring results in the scientific-regulatory environment. It is suggested that media monitoring could form part of regular surveillance for medicines of high public interest. Future work is recommended to develop efficient monitoring strategies for that purpose

Pathway-based expression profiling of benign prostatic hyperplasia and prostate cancer delineates an immunophilin molecule associated with cancer progression

Aberrant restoration of AR activity is linked with prostate tumor growth, therapeutic failures and development of castrate-resistant prostate cancer. Understanding the processes leading to ARreactivation should provide the foundation for novel avenues of drug discovery. A differential gene expression study was conducted using biopsies from CaP and BPH patients to identify the components putatively responsible for reinstating AR activity in CaP. From the set of genes upregulated in CaP, FKBP52, an AR co-chaperone, was selected for further analysis. Expression of FKBP52 was positively correlated with that of c-Myc. The functional cross-talk between c-Myc and FKBP52 was established using c-Myc specific-siRNA to LNCaP cells that resulted in reduction of FKBP52. A non-canonical E-box sequence housing a putative c-Myc binding site was detected on the FKBP4 promoter using in silico search. LNCaP cells transfected with the FKBP52 promoter cloned in pGL3 basic showed increased luciferase activity which declined considerably when the promoter-construct was co-transfected with c-Myc specific-siRNA. ChIP-PCR confirmed the binding of c-Myc with the conserved E-box located in the FKBP52 promoter. c-Myc downregulation concomitantly affected expression of FGF8. Since expression of FGF8 is controlled by AR, our study unveiled a novel functional axis between c-Myc, AR and FGF8 operating through FKBP52

Identifying Hallmark Symptoms of Developmental Prosopagnosia for Non-Experts

Developmental prosopagnosia (DP) is characterised by a severe and relatively selective deficit in face recognition, in the absence of neurological injury. Because public and professional awareness of DP is low, many adults and children are not identified for formal testing. This may partly result from the lack of appropriate screening tools that can be used by non-experts in either professional or personal settings. To address this issue, the current study sought to (a) explore when DP can first be detected in oneself and another, and (b) identify a list of the condition’s everyday behavioural manifestations. Questionnaires and interviews were administered to large samples of adult DPs, their unaffected significant others, and parents of children with the condition; and data were analysed using inductive content analysis. It was found that DPs have limited insight into their difficulties, with most only achieving realisation in adulthood. Nevertheless, the DPs’ reflections on their childhood experiences, together with the parental responses, revealed specific indicators that can potentially be used to spot the condition in early childhood. These everyday hallmark symptoms may aid the detection of individuals who would benefit from objective testing, in oneself (in adults) or another person (for both adults and children)

Do-not-attempt-cardiopulmonary-resuscitation decisions : an evidence synthesis

Background: Cardiac arrest is the final common step in the dying process. In the right context, resuscitation can reverse the dying process, yet success rates are low. However, cardiopulmonary resuscitation (CPR) is a highly invasive medical treatment, which, if applied in the wrong setting, can deprive the patient of dignified death. Do-not-attempt-cardiopulmonary-resuscitation (DNACPR) decisions provide a mechanism to withhold CPR. Recent scientific and lay press reports suggest that the implementation of DNACPR decisions in NHS practice is problematic. Aims and objectives: This project sought to identify reasons why conflict and complaints arise, identify inconsistencies in NHS trusts’ implementation of national guidelines, understand health professionals’ experience in relation to DNACPR, its process and ethical challenges, and explore the literature for evidence to improve DNACPR policy and practice. Methods: A systematic review synthesised evidence of processes, barriers and facilitators related to DNACPR decision-making and implementation. Reports from NHS trusts, the National Reporting and Learning System, the Parliamentary and Health Service Ombudsman, the Office of the Chief Coroner, trust resuscitation policies and telephone calls to a patient information line were reviewed. Multiple focus groups explored service-provider perspectives on DNACPR decisions. A stakeholder group discussed the research findings and identified priorities for future research. Results: The literature review found evidence that structured discussions at admission to hospital or following deterioration improved patient involvement and decision-making. Linking DNACPR to overall treatment plans improved clarity about goals of care, aided communication and reduced harms. Standardised documentation improved the frequency and quality of recording decisions. Approximately 1500 DNACPR incidents are reported annually. One-third of these report harms, including some instances of death. Problems with communication and variation in trusts’ implementation of national guidelines were common. Members of the public were concerned that their wishes with regard to resuscitation would not be respected. Clinicians felt that DNACPR decisions should be considered within the overall care of individual patients. Some clinicians avoid raising discussions about CPR for fear of conflict or complaint. A key theme across all focus groups, and reinforced by the literature review, was the negative impact on overall patient care of having a DNACPR decision and the conflation of ‘do not resuscitate’ with ‘do not provide active treatment’. Limitations: The variable quality of some data sources allows potential overstatement or understatement of findings. However, data source triangulation identified common issues. Conclusion: There is evidence of variation and suboptimal practice in relation to DNACPR decisions across health-care settings. There were deficiencies in considering, discussing and implementing the decision, as well as unintended consequences of DNACPR decisions being made on other aspects of patient care. Future work: Recommendations supported by the stakeholder group are standardising NHS policies and forms, ensuring cross-boundary recognition of DNACPR decisions, integrating decisions with overall treatment plans and developing tools and training strategies to support clinician and patient decision-making, including improving communication. Study registration: This study is registered as PROSPERO CRD42012002669. Funding: The National Institute for Health Research Health Services and Delivery Research programme

Oro-facial pain experience among symphony orchestra musicians in Finland is associated with reported stress, sleep bruxism and disrupted sleep-Independent of the instrument group

Background To evaluate whether oro-facial pain experience was related to the type of musical instrument and to learn more about the roles of sleep and sleep-related issues in the pain among professional musicians. Objectives A standard questionnaire was sent to all Finnish symphony orchestras (n = 19), with altogether 1005 professional musicians and other personnel. Methods The questionnaire covered descriptive data, instrument group, items on perceived quality of sleep, possible sleep bruxism, stress experience and oro-facial pain experience during the past 30 days. Results In the present study, which included the musicians only, the response rate was 58.7% (n = 488). All orchestras participated in the study, and there was no significant difference in the response rate between the orchestras. The mean age of men (52.3%) was 47.7 (SD 10.3) and of women (47.7%) was 43.4 (SD 9.8) years (P <0.001). Overall, current pain in the oro-facial area was reported by 28.9%, frequent bruxism by 12.1% and frequent stress by 20.8%. According to Somers' d, there were statistically significant but moderate correlations between overall pain reports in the oro-facial area and disrupted sleep (d = 0.127, P = 0.001), sleep bruxism (d = 0.241, P <0.001) and stress experiences (d = 0.193, P <0.001). Logistic regression revealed, independent of the instrument group (string, woodwind, brass wind, percussion), that current oro-facial pain experience was significantly associated with disrupted sleep (P = 0.001), frequent sleep bruxism (P <0.001) and frequent stress (P = 0.002) experiences. Conclusions Among symphony orchestra musicians, oro-facial pain experience seems to be related to perceptions of stress, sleep bruxism and disrupted sleep rather than the instrument group.Peer reviewe

Pedometer use and self-determined motivation for walking in a cardiac telerehabilitation program: a qualitative study

BACKGROUND: Exercise-based cardiac rehabilitation reduces morbidity and mortality. Walking is a convenient activity suitable for people with cardiac disease. Pedometers count steps, measure walking activity and motivate people to increase physical activity. In this study, patients participating in cardiac telerehabilitation were provided with a pedometer to support motivation for physical activity with the purpose of exploring pedometer use and self-determined motivation for walking experienced by patients and health professionals during a cardiac telerehabilitation program. METHODS: A qualitative research design consisting of observations, individual interviews and patient documents made the basis for a content analysis. Data was analysed deductively using Self Determination Theory as a frame for analysis and discussion, focusing on the psychological needs of autonomy, competence and relatedness. Twelve cardiac patients, 11 health professionals, 6 physiotherapists and 5 registered nurses were included. RESULTS: The pedometer offered independence from standardised rehabilitation since the pedometer supported tailoring, individualised walking activity based on the patient’s choice. This led to an increased autonomy. The patients felt consciously aware of health benefits of walking, and the pedometer provided feedback on walking activity leading to an increased competence to achieve goals for steps. Finally, the pedometer supported relatedness with others. The health professionals’ surveillance of patients’ steps, made the patients feel observed, yet supported, furthermore, their next of kin appeared to be supportive as walking partners. CONCLUSION: Cardiac patients’ motivation for walking was evident due to pedometer use. Even though not all aspects of motivation were autonomous and self determined, the patients felt motivated for walking. The visible steps and continuous monitoring of own walking activity made it possible for each individual patient to choose their desired kind of activity and perform ongoing adjustments of walking activity. The immediate feedback on step activity and the expectations of health benefits resulted in motivation for walking. Finally, pedometer supported walking made surveillance possible, giving the patients a feeling of being looked after and supported. TRIAL REGISTRATION: Current study is a part of The Teledi@log project

Preclinical students’ experiences in early clerkships after skills training partly offered in primary health care centers: a qualitative study from Indonesia

BACKGROUND: Students may encounter difficulties when they have to apply clinical skills trained in their pre-clinical studies in clerkships. Early clinical exposure in the pre-clinical phase has been recommended to reduce these transition problems. The aim of this study is to explore differences in students' experiences during the first clerkships between students exclusively trained in a skills laboratory and peers for whom part of their skills training was substituted by early clinical experiences (ECE). METHODS: Thirty pre-clinical students trained clinical skills exclusively in a skills laboratory; 30 peers received part of their skills training in PHC centers. Within half a year after commencing their clerkships all 60 students shared their experiences in focus group discussions (FGDs). Verbatim transcripts of FGDs were analyzed using Atlas-Ti software. RESULTS: Clerkship students who had participated in ECE in PHC centers felt better prepared to perform their clinical skills during the first clerkships than peers who had only practiced in a skills laboratory. ECE in PHC centers impacted positively in particular on students’ confidence, clinical reasoning, and interpersonal communication. CONCLUSION: In the Indonesian setting ECE in PHC centers reduce difficulties commonly encountered by medical students in the first clerkships

A Comparison Analysis Between Pre-departure and Transitioned Expat-Preneurs

This paper contributes to the understanding on the reasons that lead to entrepreneurship in other countries. We focus on expat-preneurs, those who decided to undertake business opportunities in other countries (before or after settling there). Using comparison analysis and logistic regression, we examine pre-departure and transitioned expat-preneurs’ demographic characteristics and push-pull factors that lead them to expatriate. From a survey conducted in 2015-2016 of 5,532 Lithuanians expatriated in 24 countries, a sample of 308 respondents with their own businesses abroad was selected. This research contributes to the literature on expat-preneurs, with empirical evidence on pre-departure and transitioned self-initiated (SI) expat-preneurs. The results revealed that demographic features matter when studying such global entrepreneurs. It is a process experienced differently by males and females and, as such, it can be considered as gender selective. Thus, more pre-departure expat-preneurs are male than female, but there is a growing number of female transitioned expat-preneurs. Pre-departure expat-preneurs are older and less educated than transitioned ones and have been pushed to move abroad by issues such as political corruption or a nonsupportive tax system, and are attracted by a higher possibility of self-realisation as well as the prestige of the host country. Meanwhile, transitioned expat-preneurs have been pushed to emigrate due to family reasons or too few employment opportunities in their home country.Lithuanian Council of Science S-MIP-17-11

Missing value imputation improves clustering and interpretation of gene expression microarray data

<p>Abstract</p> <p>Background</p> <p>Missing values frequently pose problems in gene expression microarray experiments as they can hinder downstream analysis of the datasets. While several missing value imputation approaches are available to the microarray users and new ones are constantly being developed, there is no general consensus on how to choose between the different methods since their performance seems to vary drastically depending on the dataset being used.</p> <p>Results</p> <p>We show that this discrepancy can mostly be attributed to the way in which imputation methods have traditionally been developed and evaluated. By comparing a number of advanced imputation methods on recent microarray datasets, we show that even when there are marked differences in the measurement-level imputation accuracies across the datasets, these differences become negligible when the methods are evaluated in terms of how well they can reproduce the original gene clusters or their biological interpretations. Regardless of the evaluation approach, however, imputation always gave better results than ignoring missing data points or replacing them with zeros or average values, emphasizing the continued importance of using more advanced imputation methods.</p> <p>Conclusion</p> <p>The results demonstrate that, while missing values are still severely complicating microarray data analysis, their impact on the discovery of biologically meaningful gene groups can – up to a certain degree – be reduced by using readily available and relatively fast imputation methods, such as the Bayesian Principal Components Algorithm (BPCA).</p