Conflict of interest policies at Australian medical schools.

BACKGROUND: Pharmaceutical industry exposure is widespread during medical training and may affect education and clinical decision-making. Medical faculties' conflict of interest (COI) policies help to limit this exposure and protect students against commercial influence. AIMS: Our aim was to investigate the prevalence, content and strength of COI policies at Australian medical schools and changes since a previous assessment conducted in 2009. METHODS: We identified policies by searching medical school and host university websites in January 2021, and contacted deans to identify any missed policies. We applied a modified version of a scorecard developed in previous studies to examine the content of COI policies. All data were coded in duplicate. COI policies were rated on a scale from 0 (no policy) to 2 (strong policy) across 11 items per medical school. Oversight mechanisms and sanctions were also assessed, and current policies were compared with the 2009 study. RESULTS: Of 155 potentially relevant policies, 153 were university-wide and two were specific to medical schools. No policies covered sales representatives, on-site sponsored education or free samples. Oversight of consultancies had improved substantially, with 76% of schools requiring preapproval. Disclosure policies, while usually present, were weak, with no public disclosure required. CONCLUSION: We found little indication that Australian medical students are protected from commercial influence on medical education, and there has been limited COI policy development within the past decade. More attention is needed to ensure the independence of medical education in Australia.

Low-risk prostate lesions: An evidence review to inform discussion on losing the "cancer" label.

BACKGROUND: Active surveillance (AS) mitigates harms from overtreatment of low-risk prostate lesions. Recalibration of diagnostic thresholds to redefine which prostate lesions are considered "cancer" and/or adopting alternative diagnostic labels could increase AS uptake and continuation. METHODS: We searched PubMed and EMBASE to October 2021 for evidence on: (1) clinical outcomes of AS, (2) subclinical prostate cancer at autopsy, (3) reproducibility of histopathological diagnosis, and (4) diagnostic drift. Evidence is presented via narrative synthesis. RESULTS: AS: one systematic review (13 studies) of men undergoing AS found that prostate cancer-specific mortality was 0%-6% at 15 years. There was eventual termination of AS and conversion to treatment in 45%-66% of men. Four additional cohort studies reported very low rates of metastasis (0%-2.1%) and prostate cancer-specific mortality (0%-0.1%) over follow-up to 15 years. Overall, AS was terminated without medical indication in 1%-9% of men. Subclinical reservoir: 1 systematic review (29 studies) estimated that the subclinical cancer prevalence was 5% at <30 years, and increased nonlinearly to 59% by >79 years. Four additional autopsy studies (mean age: 54-72 years) reported prevalences of 12%-43%. Reproducibility: 1 recent well-conducted study found high reproducibility for low-risk prostate cancer diagnosis, but this was more variable in 7 other studies. Diagnostic drift: 4 studies provided consistent evidence of diagnostic drift, with the most recent (published 2020) reporting that 66% of cases were upgraded and 3% were downgraded when using contemporary diagnostic criteria compared to original diagnoses (1985-1995). CONCLUSIONS: Evidence collated may inform discussion of diagnostic changes for low-risk prostate lesions.

Should low-risk DCIS lose the cancer label? An evidence review.

BACKGROUND: Population mammographic screening for breast cancer has led to large increases in the diagnosis and treatment of ductal carcinoma in situ (DCIS). Active surveillance has been proposed as a management strategy for low-risk DCIS to mitigate against potential overdiagnosis and overtreatment. However, clinicians and patients remain reluctant to choose active surveillance, even within a trial setting. Re-calibration of the diagnostic threshold for low-risk DCIS and/or use of a label that does not include the word 'cancer' might encourage the uptake of active surveillance and other conservative treatment options. We aimed to identify and collate relevant epidemiological evidence to inform further discussion on these ideas. METHODS: We searched PubMed and EMBASE databases for low-risk DCIS studies in four categories: (1) natural history; (2) subclinical cancer found at autopsy; (3) diagnostic reproducibility (two or more pathologist interpretations at a single time point); and (4) diagnostic drift (two or more pathologist interpretations at different time points). Where we identified a pre-existing systematic review, the search was restricted to studies published after the inclusion period of the review. Two authors screened records, extracted data, and performed risk of bias assessment. We undertook a narrative synthesis of the included evidence within each category. RESULTS: Natural History (n = 11): one systematic review and nine primary studies were included, but only five provided evidence on the prognosis of women with low-risk DCIS. These studies reported that women with low-risk DCIS had comparable outcomes whether or not they had surgery. The risk of invasive breast cancer in patients with low-risk DCIS ranged from 6.5% (7.5 years) to 10.8% (10 years). The risk of dying from breast cancer in patients with low-risk DCIS ranged from 1.2 to 2.2% (10 years). Subclinical cancer at autopsy (n = 1): one systematic review of 13 studies estimated the mean prevalence of subclinical in situ breast cancer to be 8.9%. Diagnostic reproducibility (n = 13): two systematic reviews and 11 primary studies found at most moderate agreement in differentiating low-grade DCIS from other diagnoses. Diagnostic drift: no studies found. CONCLUSION: Epidemiological evidence supports consideration of relabelling and/or recalibrating diagnostic thresholds for low-risk DCIS. Such diagnostic changes would need agreement on the definition of low-risk DCIS and improved diagnostic reproducibility.

Objective metrics for hand-sewn bowel anastomoses can differentiate novice from expert surgeons.

BACKGROUND: Assessing performance automatically in a virtual reality trainer or from recorded videos is advantageous but needs validated objective metrics. The purpose of this study is to obtain expert consensus and validate task-specific metrics developed for assessing performance in double-layered end-to-end anastomosis. MATERIALS AND METHODS: Subjects were recruited into expert (PGY 4-5, colorectal surgery residents, and attendings) and novice (PGY 1-3) groups. Weighted average scores of experts for each metric item, completion time, and the total scores computed using global and task-specific metrics were computed for assessment. RESULTS: A total of 43 expert surgeons rated our task-specific metric items with weighted averages ranging from 3.33 to 4.5 on a 5-point Likert scale. A total of 20 subjects (10 novices and 10 experts) participated in validation study. The novice group completed the task significantly more slowly than the experienced group (37.67 ± 7.09 vs 25.47 ± 7.82 min, p = 0.001). In addition, both the global rating scale (23.47 ± 4.28 vs 28.3 ± 3.85, p = 0.016) and the task-specific metrics showed a significant difference in performance between the two groups (38.77 ± 2.83 vs 42.58 ± 4.56 p = 0.027) following partial least-squares (PLS) regression. Furthermore, PLS regression showed that only two metric items (Stay suture tension and Tool handling) could reliably differentiate the performance between the groups (20.41 ± 2.42 vs 24.28 ± 4.09 vs, p = 0.037). CONCLUSIONS: Our study shows that our task-specific metrics have significant discriminant validity and can be used to evaluate the technical skills for this procedure.

A new paradigm for investigating real-world social behavior and its neural underpinnings.

Eye tracking and other behavioral measurements collected from patient-participants in their hospital rooms afford a unique opportunity to study natural behavior for basic and clinical translational research. We describe an immersive social and behavioral paradigm implemented in patients undergoing evaluation for surgical treatment of epilepsy, with electrodes implanted in the brain to determine the source of their seizures. Our studies entail collecting eye tracking with other behavioral and psychophysiological measurements from patient-participants during unscripted behavior, including social interactions with clinical staff, friends, and family in the hospital room. This approach affords a unique opportunity to study the neurobiology of natural social behavior, though it requires carefully addressing distinct logistical, technical, and ethical challenges. Collecting neurophysiological data synchronized to behavioral and psychophysiological measures helps us to study the relationship between behavior and physiology. Combining across these rich data sources while participants eat, read, converse with friends and family, etc., enables clinical-translational research aimed at understanding the participants' disorders and clinician-patient interactions, as well as basic research into natural, real-world behavior. We discuss data acquisition, quality control, annotation, and analysis pipelines that are required for our studies. We also discuss the clinical, logistical, and ethical and privacy considerations critical to working in the hospital setting.

Branded Care: The Policy Implications of Pharmaceutical Industry-Funded Nursing Care Related to Specialty Medicines.

An increasing proportion of new drugs approved for market worldwide are now high cost, specialty medicines. Pharmaceutical marketers face the challenge of convincing payers, prescribers, and patients that the cost and complexity of care associated with specialty medicines is worth the trouble, and now offer patient support programs, free of charge, to patients prescribed their drug. We conducted a secondary, qualitative, interpretive analysis of 24 interviews with leaders of patient groups and members of hospital formulary committees in Australia to describe the work of pharmaceutical company-employed or contracted nurses who provide support to patients prescribed specialty medicines, and to prompt discussion around the policy implications of relying on industry-funded nursing care within publicly funded health systems. Participants affirmed the value of specialist, holistic, person-centered nursing care, but perceived gaps within the public health system related to the availability and provision of nursing care for people living with chronic disease. Consequently, participants described the pharmaceutical industry as addressing health system gaps through sponsorship or direct provision of medication-related nursing care, but recognized that care was contingent on commercial interest. Participants highlighted a number of ethical and policy concerns stemming from industry-funded nursing care of people prescribed specialty medicines related to patient safety, continuity of care, inducement to prescribe, and health equity. This analysis suggests that outsourcing necessary medication-related care to pharmaceutical companies has implications for the health system and equitable, sustainable pharmaceutical policy that extend far beyond the care encounter.

Microsampling to support pharmacokinetic clinical studies in pediatrics.

BACKGROUND: Conventional sampling for pharmacokinetic clinical studies requires removal of large blood volumes from patients. This can result in a physiological/emotional burden for children. Microsampling to support pharmacokinetic clinical studies in pediatrics may reduce this burden. METHODS: Parents/guardians and bedside nurses completed a questionnaire describing their perception of the use of microsampling compared to conventional sampling to collect blood samples, based on their child's participation or their own role within a paired-sample pharmacokinetic clinical study. Responses were based on a seven-point Likert scale and were analyzed using frequency distributions. RESULTS: Fifty-one parents/guardians and seven bedside nurses completed a questionnaire. Parents/guardians (96%) and bedside nurses (100%) indicated that microsampling was highly acceptable and recommended as a method for collecting blood samples for pediatric patients. Responding to a question about the child indicating pain during the blood sampling procedure, 61% of parent/guardians reported no pain in their children, 14% remained neutral, and 26% reported that their child indicated pain; 71% of the bedside nurses slightly agreed that the children indicated pain. CONCLUSIONS: This study strongly suggests that parents/guardians and bedside nurses prefer microsampling to conventional sampling to conduct pediatric pharmacokinetic clinical studies. Employing microsampling may support increased participation by children in these studies. IMPACT: Pharmacokinetic clinical studies require the withdrawal of blood samples at multiple times during a dosing interval. This can result in a physiological or emotional burden, particularly for neonates or pediatric patients. Microsampling offers an important opportunity for pharmacokinetic clinical studies in vulnerable patient populations, where smaller sample volumes can be collected. However, microsampling is not commonly used in clinical studies. Understanding the perceptions of parents/guardians and bedside nurses about microsampling may ascertain if this technique offers an improvement to conventional blood sample collection to perform pharmacokinetic clinical studies for pediatric patients.

Disclosure, transparency, and accountability: a qualitative survey of public sector pharmaceutical committee conflict of interest policies in the World Health Organization South-East Asia Region.

BACKGROUND: Weak governance over public sector pharmaceutical policy and practice limits access to essential medicines, inflates pharmaceutical prices, and wastes scarce health system resources. Pharmaceutical systems are technically complex and involve extensive interactions between the private and public sectors. For members of public sector pharmaceutical committees, relationships with the private sector can result in conflicts of interest, which may introduce commercial biases into decision-making, potentially compromising public health objectives and health system sustainability. We conducted a descriptive, qualitative study of conflict of interest policies and practices in the public pharmaceutical sector in ten countries in the World Health Organization (WHO) South-East Asia Region (SEAR) (Bangladesh, Bhutan, India, Indonesia, Maldives, Myanmar, Nepal, Sri Lanka, Thailand, and Timor-Leste) between September 2020 and March 2021. RESULTS: We identified 45 policy and regulatory documents and triangulated documentary data with 21 expert interviews. Key informants articulated very different governance priorities and conflict of interest concerns depending on the features of their country's pharmaceutical industry, market size, and national economic objectives related to the domestic pharmaceutical industry. Public sector pharmaceutical policies and regulations consistently contained provisions for pharmaceutical committee members to disclose relevant interests, but contained little detail about what should be declared, when, and how often, nor whether disclosures are evaluated and by whom. Processes for preventing or managing conflicts of interest were less well developed than those for disclosure except for a few key procurement processes. Where processes for managing conflicts of interest were specified, the dominant strategy was to recuse committee members with a conflict of interest from relevant work. Policies rarely specified that committee members should divest or otherwise be free from conflicts of interest. CONCLUSIONS: Robust processes for conflict of interest prevention and management could ensure the integrity of decision-making and build public trust in pharmaceutical processes to achieve public health objectives. Upstream approaches including supportive legislative frameworks, the creation of oversight bodies, and strengthening regulatory institutions can also contribute to building cultures of transparency, accountability, and trust.

Bioethics in the Current Climate.

Drawing on insights from feminist epistemology and experience in genomics-related bioethics research, this essay offers three suggestions that may enable bioethics to contribute more persuasively to urgent issues affecting the health and well-being of individuals, communities, and the world they inhabit. First, it suggests that bioethics pay more attention to people's feelings, particularly those that help constitute their self-identities, and to the role of those feelings in their health-relevant behaviors. Further, it proposes conceiving of health-relevant behaviors expansively. Second, it suggests that bioethics advocate for a longer time horizon for the conduct of empirical bioethics research and other types of research addressing complex, systemic factors influencing health. Third, it suggests that bioethics play a larger role in illuminating and applauding the evolving nature of scientific knowledge.

Role of unfolded proteins in lung disease.

The lungs are exposed to a range of environmental toxins (including cigarette smoke, air pollution, asbestos) and pathogens (bacterial, viral and fungal), and most respiratory diseases are associated with local or systemic hypoxia. All of these adverse factors can trigger endoplasmic reticulum (ER) stress. The ER is a key intracellular site for synthesis of secretory and membrane proteins, regulating their folding, assembly into complexes, transport and degradation. Accumulation of misfolded proteins within the lumen results in ER stress, which activates the unfolded protein response (UPR). Effectors of the UPR temporarily reduce protein synthesis, while enhancing degradation of misfolded proteins and increasing the folding capacity of the ER. If successful, homeostasis is restored and protein synthesis resumes, but if ER stress persists, cell death pathways are activated. ER stress and the resulting UPR occur in a range of pulmonary insults and the outcome plays an important role in many respiratory diseases. The UPR is triggered in the airway of patients with several respiratory diseases and in corresponding experimental models. ER stress has been implicated in the initiation and progression of pulmonary fibrosis, and evidence is accumulating suggesting that ER stress occurs in obstructive lung diseases (particularly in asthma), in pulmonary infections (some viral infections and in the setting of the cystic fibrosis airway) and in lung cancer. While a number of small molecule inhibitors have been used to interrogate the role of the UPR in disease models, many of these tools have complex and off-target effects, hence additional evidence (eg, from genetic manipulation) may be required to support conclusions based on the impact of such pharmacological agents. Aberrant activation of the UPR may be linked to disease pathogenesis and progression, but at present, our understanding of the context-specific and disease-specific mechanisms linking these processes is incomplete. Despite this, the ability of the UPR to defend against ER stress and influence a range of respiratory diseases is becoming increasingly evident, and the UPR is therefore attracting attention as a prospective target for therapeutic intervention strategies.

"There are ways drug companies will get into DTC decisions": How Australian drug and therapeutics committees address pharmaceutical industry influence.

AIMS: One tool for protecting quality use of medicines in hospitals is a drug and therapeutics committee (DTC) that oversees medicines availability. Pharmaceutical industry marketing to prescribers is associated with less appropriate prescribing and increased costs. There is little data on decision-making practices of DTCs so it is unknown whether or how they might be vulnerable to pharmaceutical industry influence. This project explores DTC decision-making with a focus on how pharmaceutical industry influence on access and use of medicines is identified and managed. METHODS: We used a qualitative methodology with individual interviews of 29 participants who were current or recent members of public hospital DTCs across New South Wales, Australia. Participants included medical, pharmacy and nursing staff and 1 citizen. Committees were linked to specific hospitals or regions, and some were affiliated with paediatric, neonatal, rural or mental health services. RESULTS: Drug committee processes for oversight of medicines in public hospitals are vulnerable to pharmaceutical industry influence at several points. Applications for formulary additions are sometimes initiated and completed by company representatives. Conflict of interest disclosures among applicants and committee members may be incomplete. In some institutions, medicines are available from pharmaceutical companies without committee review, including through free samples and industry-supported medicines access programmes. Participants noticed the presence and impact of pharmaceutical company marketing activities to local clinicians, resulting in increased prescriber demand for products. CONCLUSION: Improved DTC practices and review of hospital policies concerning pharmaceutical marketing activities might preserve the independence of evidence-based decision-making for safe, cost-effective prescribing.

The Ethics of Tobacco Harm Reduction: An Analysis of E-Cigarette Availability From the Perspectives of Utilitarianism, Bioethics, and Public Health Ethics.

Much evidence suggests e-cigarettes are substantially less harmful than combustible cigarettes. Assuming this is true, we analyze the ethical case for a policy of e-cigarette availability (ECA) as a tobacco harm reduction strategy. ECA involves making e-cigarettes available to allow smokers to switch to them, and informing smokers of the lower risks of e-cigarettes vis-à-vis smoking. After suggesting that utilitarian/consequentialist considerations do not provide an adequate ethical analysis, we analyze ECA using two other ethical frameworks. First, ECA is supported by a public health ethics framework. ECA is a population-level intervention consistent with respecting individual autonomy by using the least restrictive means to accomplish public health goals, and it supports equity and justice. Second, ECA is supported by four principles that form a biomedical ethics framework. By reducing smokers' health risks and not harming them, ECA fulfills principles of beneficence and non-maleficence. Because ECA allows smokers to make informed health decisions for themselves, it fulfills the principle requiring respect for persons and their autonomy. Here, we consider whether nicotine addiction and thus ECA undermine autonomy, and also discuss the ethical warrant for special protections for youth. Finally, ECA can also advance justice by providing a harm reduction alternative for disadvantaged groups that disproportionately bear the devastating consequences of smoking. Policies of differential taxation of cigarettes and e-cigarettes can facilitate adoption of less harmful alternatives by those economically disadvantaged. We conclude that public health and biomedical ethics frameworks are mutually reinforcing and supportive of ECA as a tobacco harm reduction strategy. Implications: Making e-cigarettes and information about them available is supported as ethical from multiple ethical perspectives.

DUSP10 Negatively Regulates the Inflammatory Response to Rhinovirus through Interleukin-1ß Signaling.

Rhinoviral infection is a common trigger of the excessive inflammation observed during exacerbations of asthma and chronic obstructive pulmonary disease. Rhinovirus (RV) recognition by pattern recognition receptors activates the mitogen-activated protein kinase (MAPK) pathways, which are common inducers of inflammatory gene production. A family of dual-specificity phosphatases (DUSPs) can regulate MAPK function, but their roles in rhinoviral infection are not known. We hypothesized that DUSPs would negatively regulate the inflammatory response to RV infection. Our results revealed that the p38 and c-Jun N-terminal kinase (JNK) MAPKs play key roles in the inflammatory response of epithelial cells to RV infection. Three DUSPs previously shown to have roles in innate immunity (DUSPs 1, 4, and 10) were expressed in primary bronchial epithelial cells, and one of them, DUSP10, was downregulated by RV infection. Small interfering RNA-mediated knockdown of DUSP10 identified a role for the protein in negatively regulating inflammatory cytokine production in response to interleukin-1ß (IL-1ß), alone and in combination with RV, without any effect on RV replication. This study identifies DUSP10 as an important regulator of airway inflammation in respiratory viral infection.IMPORTANCE Rhinoviruses are one of the causes of the common cold. In patients with asthma or chronic obstructive pulmonary disease, viral infections, including those with rhinovirus, are the commonest cause of exacerbations. Novel therapeutics to limit viral inflammation are clearly required. The work presented here identifies DUSP10 as an important protein involved in limiting the inflammatory response in the airway without affecting immune control of the virus.

Digital contact tracing technologies in epidemics: a rapid review.

BACKGROUND: Reducing the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global priority. Contact tracing identifies people who were recently in contact with an infected individual, in order to isolate them and reduce further transmission. Digital technology could be implemented to augment and accelerate manual contact tracing. Digital tools for contact tracing may be grouped into three areas: 1) outbreak response; 2) proximity tracing; and 3) symptom tracking. We conducted a rapid review on the effectiveness of digital solutions to contact tracing during infectious disease outbreaks. OBJECTIVES: To assess the benefits, harms, and acceptability of personal digital contact tracing solutions for identifying contacts of an identified positive case of an infectious disease. SEARCH METHODS: An information specialist searched the literature from 1 January 2000 to 5 May 2020 in CENTRAL, MEDLINE, and Embase. Additionally, we screened the Cochrane COVID-19 Study Register. SELECTION CRITERIA: We included randomised controlled trials (RCTs), cluster-RCTs, quasi-RCTs, cohort studies, cross-sectional studies and modelling studies, in general populations. We preferentially included studies of contact tracing during infectious disease outbreaks (including COVID-19, Ebola, tuberculosis, severe acute respiratory syndrome virus, and Middle East respiratory syndrome) as direct evidence, but considered comparative studies of contact tracing outside an outbreak as indirect evidence. The digital solutions varied but typically included software (or firmware) for users to install on their devices or to be uploaded to devices provided by governments or third parties. Control measures included traditional or manual contact tracing, self-reported diaries and surveys, interviews, other standard methods for determining close contacts, and other technologies compared to digital solutions (e.g. electronic medical records). DATA COLLECTION AND ANALYSIS: Two review authors independently screened records and all potentially relevant full-text publications. One review author extracted data for 50% of the included studies, another extracted data for the remaining 50%; the second review author checked all the extracted data. One review author assessed quality of included studies and a second checked the assessments. Our outcomes were identification of secondary cases and close contacts, time to complete contact tracing, acceptability and accessibility issues, privacy and safety concerns, and any other ethical issue identified. Though modelling studies will predict estimates of the effects of different contact tracing solutions on outcomes of interest, cohort studies provide empirically measured estimates of the effects of different contact tracing solutions on outcomes of interest. We used GRADE-CERQual to describe certainty of evidence from qualitative data and GRADE for modelling and cohort studies. MAIN RESULTS: We identified six cohort studies reporting quantitative data and six modelling studies reporting simulations of digital solutions for contact tracing. Two cohort studies also provided qualitative data. Three cohort studies looked at contact tracing during an outbreak, whilst three emulated an outbreak in non-outbreak settings (schools). Of the six modelling studies, four evaluated digital solutions for contact tracing in simulated COVID-19 scenarios, while two simulated close contacts in non-specific outbreak settings. Modelling studies Two modelling studies provided low-certainty evidence of a reduction in secondary cases using digital contact tracing (measured as average number of secondary cases per index case - effective reproductive number (R eff)). One study estimated an 18% reduction in R eff with digital contact tracing compared to self-isolation alone, and a 35% reduction with manual contact-tracing. Another found a reduction in R eff for digital contact tracing compared to self-isolation alone (26% reduction) and a reduction in R eff for manual contact tracing compared to self-isolation alone (53% reduction). However, the certainty of evidence was reduced by unclear specifications of their models, and assumptions about the effectiveness of manual contact tracing (assumed 95% to 100% of contacts traced), and the proportion of the population who would have the app (53%). Cohort studies Two cohort studies provided very low-certainty evidence of a benefit of digital over manual contact tracing. During an Ebola outbreak, contact tracers using an app found twice as many close contacts per case on average than those using paper forms. Similarly, after a pertussis outbreak in a US hospital, researchers found that radio-frequency identification identified 45 close contacts but searches of electronic medical records found 13. The certainty of evidence was reduced by concerns about imprecision, and serious risk of bias due to the inability of contact tracing study designs to identify the true number of close contacts. One cohort study provided very low-certainty evidence that an app could reduce the time to complete a set of close contacts. The certainty of evidence for this outcome was affected by imprecision and serious risk of bias. Contact tracing teams reported that digital data entry and management systems were faster to use than paper systems and possibly less prone to data loss. Two studies from lower- or middle-income countries, reported that contact tracing teams found digital systems simpler to use and generally preferred them over paper systems; they saved personnel time, reportedly improved accuracy with large data sets, and were easier to transport compared with paper forms. However, personnel faced increased costs and internet access problems with digital compared to paper systems. Devices in the cohort studies appeared to have privacy from contacts regarding the exposed or diagnosed users. However, there were risks of privacy breaches from snoopers if linkage attacks occurred, particularly for wearable devices. AUTHORS' CONCLUSIONS: The effectiveness of digital solutions is largely unproven as there are very few published data in real-world outbreak settings. Modelling studies provide low-certainty evidence of a reduction in secondary cases if digital contact tracing is used together with other public health measures such as self-isolation. Cohort studies provide very low-certainty evidence that digital contact tracing may produce more reliable counts of contacts and reduce time to complete contact tracing. Digital solutions may have equity implications for at-risk populations with poor internet access and poor access to digital technology. Stronger primary research on the effectiveness of contact tracing technologies is needed, including research into use of digital solutions in conjunction with manual systems, as digital solutions are unlikely to be used alone in real-world settings. Future studies should consider access to and acceptability of digital solutions, and the resultant impact on equity. Studies should also make acceptability and uptake a primary research question, as privacy concerns can prevent uptake and effectiveness of these technologies.

Variations in processes for guideline adaptation: a qualitative study of World Health Organization staff experiences in implementing guidelines.

BACKGROUND: The World Health Organisation (WHO) publishes a large number of clinical practice and public health guidelines to promote evidence-based practice across the world. Due to the variety of health system capacities and contextual issues in different regions and countries, adapting the recommendations in the guidelines to the local situation is vital for the success of their implementation. We aim to understand the range of experiences with guideline adaptation from the perspectives of those working in WHO regional and country offices. Our findings will inform development of guidance on how to improve adaptability of WHO guidelines. METHODS: A grounded theory-informed, qualitative study was carried out between March 2018 and December 2018. Seventeen semi-structured interviews were conducted with participants who included WHO guideline developers and staff in the headquarters, regional and country offices recruited from a sample of published WHO guidelines. Participants were eligible for recruitment if they had recent experience in clinical practice or public health guideline implementation. Deidentified transcripts of these interview were analysed through three cycles of coding. RESULTS: We categorised the adaptation processes described by the participants into two dominant models along a spectrum of guideline adaptation processes. First, the Copy or Customise Model is a pragmatic approach of either copying or customising WHO guidelines to suit local needs. This is done by local health authorities and/or clinicians directly through consultations with WHO staff. Selections and adjustments of guideline recommendations are made according to what the implementers deemed important, feasible and applicable through the consensus discussions. Second, the Capacity Building Model focuses on WHO building local capacity in evidence synthesis methods and adaptation frameworks to support local development of a national guideline informed by international guidelines. CONCLUSIONS: In comparing and contrasting these two models of guideline adaptation, we outline the different kinds of support from WHO that may be necessary to improve the effectiveness and efficiency of the respective models. We also suggest clarifications in the descriptions of the process of guideline adaptation in WHO and academic literature, to help guideline adaptors and implementers decide on the appropriate course of action according to their specific circumstances. ETHICS: This project was conducted with ethics approval from The University of Sydney (Project number: 2017/723) and WHO (Protocol ID: 00001).

Normative and conceptual ELSI research: what it is, and why it's important.

The Ethical, Legal, and Social Implications (ELSI) Research Program of the National Human Genome Research Institute sponsors research examining ethical, legal, and social issues arising in the context of genetics/genomics. The ELSI Program endorses an understanding of research not as the sole province of empirical study, but instead as systematic study or inquiry, of which there are many types and methods. ELSI research employs both empirical and nonempirical methods. Because the latter remain relatively unfamiliar to biomedical and translational scientists, this paper seeks to elucidate the relationship between empirical and nonempirical methods in ELSI research. It pays particular attention to the research questions and methods of normative and conceptual research, which examine questions of value and meaning, respectively. To illustrate the distinct but interrelated roles of empirical and nonempirical methods in ELSI research, including normative and conceptual research, the paper demonstrates how a range of methods may be employed both to examine the evolution of the concept of incidental findings (including the recent step toward terming them 'secondary findings'), and to address the normative question of how genomic researchers and clinicians should manage incidental such findings.

Health promoter, advocate, legitimiser - the many roles of WHO guidelines: a qualitative study.

BACKGROUND: Properly implemented evidence-based clinical and public health guidelines can improve patient outcomes. WHO has been a major contributor to guideline development, publishing more than 250 guidelines on various topics since 2008. However, well-developed guidelines can only be effective if they are adequately and appropriately implemented. Herein, we aimed to explore whether and how WHO guidelines are implemented in local contexts to inform the success of future guideline implementation. METHODS: Seventeen interviews were carried out between March 2018 and December 2018 with WHO guideline developers, headquarter staff, and regional and country office staff. Participants were purposely sampled from a variety of WHO guidelines and snowball sampling was used to identify regional and country office staff. The deidentified transcripts were analysed through three phases of coding, using grounded theory as the analytic approach. RESULTS: WHO guidelines played a variety of roles in the work of WHO at all levels. WHO officers and local government officials used WHO guidelines to influence health policy. We categorised the uses of guidelines as (1) directly changing policy, (2) justifying policy change, (3) engaging stakeholders, (4) being guarantors of legitimacy, (5) being advocacy tools, and (6) intertwining with WHO's various roles. Participants refuted the perception of the guidelines as mere lists of technical recommendations that needed to be implemented in different contexts. We found that the existence, quality and credibility, rather than the content of the guidelines, are the keys to health policy change initiatives in different local contexts. CONCLUSIONS: Used as a guarantor of legitimacy by policy-makers, WHO guidelines can be better positioned to influence health policy and practice change. Understanding the various roles of guidelines can help WHO developers package guidelines to optimise their effective implementation. ETHICS: This project was conducted with ethics approval from The University of Sydney (Project number: 2017/723) and WHO (Protocol ID: 00001).

Emerging Regulatory Roles of Dual-Specificity Phosphatases in Inflammatory Airway Disease.

Inflammatory airway disease, such as asthma and chronic obstructive pulmonary disease (COPD), is a major health burden worldwide. These diseases cause large numbers of deaths each year due to airway obstruction, which is exacerbated by respiratory viral infection. The inflammatory response in the airway is mediated in part through the MAPK pathways: p38, JNK and ERK. These pathways also have roles in interferon production, viral replication, mucus production, and T cell responses, all of which are important processes in inflammatory airway disease. Dual-specificity phosphatases (DUSPs) are known to regulate the MAPKs, and roles for this family of proteins in the pathogenesis of airway disease are emerging. This review summarizes the function of DUSPs in regulation of cytokine expression, mucin production, and viral replication in the airway. The central role of DUSPs in T cell responses, including T cell activation, differentiation, and proliferation, will also be highlighted. In addition, the importance of this protein family in the lung, and the necessity of further investigation into their roles in airway disease, will be discussed.

Narrative methods for assessing "quality of life" in hand transplantation: five case studies with bioethical commentary.

Despite having paved the way for face, womb and penis transplants, hand transplantation today remains a small hybrid of reconstructive microsurgery and transplant immunology. An exceptionally limited patient population internationally (N < 200) complicates medical researchers' efforts to parse outcomes "objectively." Presumed functional and psychosocial benefits of gaining a transplant hand must be weighed in both patient decisions and bioethical discussions against the difficulty of adhering to post-transplant medications, the physical demands of hand transplant recovery on the patient, and the serious long-term health risks of immunosuppressant drugs. This paper relates five narratives of hand transplantation drawn from an oral history project to show how narrative methods can and should inform ethical evaluations and the clinical process of hand transplantation. The interviews with patients and their partners analyzed here lead us to suggest that qualitative accounts of patient experiences should be used to complement clinical case studies reported in medical journals and to help develop instruments to assess outcomes more systematically.

Mental Health Messages in Prominent Mental Health Apps.

PURPOSE: Many who seek primary health care advice about mental health may be using mobile applications (apps) claiming to improve well-being or relieve symptoms. We aimed to identify how prominent mental health apps frame mental health, including who has problems and how they should be managed. METHODS: We conducted a qualitative content analysis of advertising material for mental health apps found online in the United States, the United Kingdom, Canada, and Australia during late 2016. Apps were included if they explicitly referenced mental health diagnoses or symptoms and offered diagnosis and guidance, or made health claims. Two independent coders analyzed app store descriptions and linked websites using a structured, open-ended instrument. We conducted interpretive analysis to identify key themes and the range of messages. RESULTS: We identified 61 mental health apps: 34 addressed predominantly anxiety, panic, and stress (56%), 16 addressed mood disorders (26%), and 11 addressed well-being or other mental health issues (18%). Apps described mental health problems as being psychological symptoms, a risk state, or lack of life achievements. Mental health problems were framed as present in everyone, but everyone was represented as employed, white, and in a family. Explanations about mental health focused on abnormal responses to mild triggers, with minimal acknowledgment of external stressors. Therapeutic strategies included relaxation, cognitive guidance, and self-monitoring. Apps encouraged frequent use and promoted personal responsibility for improvement. CONCLUSIONS: Mental health apps may promote medicalization of normal mental states and imply individual responsibility for mental well-being. Within the health care clinician-patient relationship, such messages should be challenged, where appropriate, to prevent overdiagnosis and ensure supportive health care where needed.