Background: Warfarin is a leading anticoagulant in the management of atrial fibrillation (AF) and deep vein thrombosis (DVT). Drug interactions influence the safety of warfarin use and while extensive literature exists regarding the effect on warfarin control and bleeding incidence with many medicines, there is little evidence on the influence of complementary medicines. The aim of this study was to assess the influence of fish and krill oil supplementation on warfarin control and bleeding incidence in AF and DVT patients. Methods: A retrospective analysis was conducted utilising patient information from a large private pathology clinic. AF and DVT patients receiving long-term warfarin therapy (>30 days) at the clinic and taking fish and krill oil supplements were eligible for study inclusion. Results: Of the 2081 patients assessed, a total of 573 warfarin users met the inclusion criteria with 145 patients in the fish and krill oil group (supplement group) and 428 patients in the control group. Overall, it was found that fish and krill oils did not significantly alter warfarin time in therapeutic range (TTR) or bleeding incidence, even when compared by gender. Conclusion: Omega-3 supplementation with fish and krill oil does not significantly affect long-term warfarin control and bleeding and thromboembolic events when consumed concurrently in patients managed at an anticoagulation clinic. Warfarin is an anticoagulant commonly used in indications such as the prevention of stroke in patients with atrial fibrillation (AF) and the treatment or prevention of deep vein thrombosis (DVT) . WarfariThere are many factors that have been shown to influence warfarin control. Patient-specific factors, such as being female and being aged less than 50 years have been proposed to cause a decrease in TTR and warfarin control . FurtherEuphausia superba [Fish and krill oil products are among the many complementary medicines which has been flagged as having a potential interaction with warfarin . Fish oi superba . Contain superba . Due to  superba . The phy superba ,20,21 re superba  and mult superba  includin superba . Austral superba . Supplem superba ,27. It i superba  has alreAlthough several studies have been conducted assessing the change in incidence of bleeding events associated with fish and krill oil use ,29, the A retrospective cohort analysis was conducted of patients receiving warfarin management from a large private pathology practice in Queensland. AF (any form) and DVT patients receiving long-term warfarin therapy enrolled at the private pathology clinic were eligible for study inclusion. Data collection included current medications, comorbidities, INR test results, reported bleeding and thromboembolic incidences, and patient demographics including age and gender.Data was screened for patients who had consumed fish oil or krill oil supplementation, or both, without the concurrent use of medications identified in the AMH 2015  as havinTime in therapeutic range (TTR) was calculated using the Rosendaal method , which up-value of < 0.05 considered to be statistically significant. An independent Student’s T-Test and Mann-Whitney U test were utilised in the comparison of mean TTR between supplement and control group. The chi-squared test was utilised in the analysis of bleeding incidence per person-year.Subject characteristics were reported as the mean ± the standard deviation for continuous data and number and percentages for nominal or categorical data. Data was analysed using Graph Pad InStat Version 3 , with a Ethics approval for this project was received on 23 June 2014 by Griffith University Ethics Committee, reference number PHM/09/14/HREC.Of the 2081 patients assessed for inclusion into this study, a total of 573 warfarin users met the inclusion criteria after exclusions due to multiple interacting medications (1453 patients), less than 30 days of testing available (30 patients), and no start date of fish oil consumption (25 patients). Four hundred and twenty-eight patients were allocated to the control group, and 145 patients were allocated to the supplement group. As shown in Individual patient data was combined to calculate mean TTR, as shown in A mean TTR comparison by gender identified no differences between males and females in the supplement or control group . In addiOf the 145 fish and krill oil consumers, 24 patients met the inclusion criteria for the additional analysis of mean TTR and adverse incidences of patients before, during, and after fish and krill oil consumption. These 24 patients were assessed for an average of 30 months before, 9.6 months during, and 18 months after consuming fish and krill oil. The mean TTR at various time periods was not significantly different . No signThere has been conflicting evidence regarding the effect of fish and krill oil supplementation on warfarin INR, TTR, and bleeding incidence, placing many concurrent users at potential risk of dangerous therapeutic outcomes or unnecessary cessation of these supplements by their prescriber. The overall aim of this study was to assess the influence of fish and krill oil supplementation on warfarin control in AF and DVT patients. The results of this retrospective cohort study show that fish and krill oil supplementation does not significantly alter warfarin control as measured by TTR in AF and DVT patients, nor does it have an effect on the number of major or minor bleeding incidences in these patients.This study showed no differences in mean TTR and bleeding events between fish and krill oil users and non-users in a cohort of 573 patients taking warfarin for an average of 34 months. These findings are consistent with those of other studies evaluating this interaction. Bender et al.  and BuckIn regards to the incidence of bleeding events, Bender et al.  also recOmega-3 fatty acids, such as EPA and DHA found in fish and krill oil supplementation, exert their effect on the coagulation profile by two different mechanisms. Firstly, EPA and DHA replace arachadonic acid (AA), an omega-6 fatty acid, in the phospholipid membrane of platelets. As a result of less AA available for activation, a decline in thromboxane A2 occurs, causing a decrease in platelet aggregation ,37. A deAlthough there have been in vitro studies that have supported the effect of fish and krill oil supplementation on prolonged bleeding and coagulation factors, the majority of human studies do not support this effect. Previously, there had been conflicting evidence as to whether fish and krill oil increased INR and bleeding incidence when used in conjunction with warfarin. Our study suggests that there is no significant effect on warfarin TTR and bleeding caused by fish and krill oil supplementation, and that it is therefore safe for warfarin users to concurrently consume warfarin and fish and krill oil supplements. However, when taking into consideration the results obtained in our study, it should be noted that all of our patients were managed by a warfarin clinic. Bernaitis et al.  reportedWarfarin is a widely prescribed anticoagulant requiring monitoring with TTR linked to both therapeutic efficacy and adverse effects. Numerous factors are known to influence TTR including drug interactions. However, there is limited information on interactions with complementary and alternative therapies including the widely used fish and krill oils. Fish and krill oil supplementation had no significant influence on both warfarin TTR control, bleeding incidence, or thromboembolic events in AF and DVT patients achieving well controlled warfarin therapy through management at an anticoagulant clinic.


Executive functions (EF) have been conceptualized as a set of higher-level control processes that enable an individual to adapt to diverse situations, inhibit inappropriate responses, formulate, initiate and persevere plans and mediate the organisation of goal-directed thoughts and actions and are commonly reported as being compromised in schizophrenia. Complex measures designed to assess EF suffer from task impurity, activating and reporting on the performance of non-EF processes. The present study examined the potential contribution discrete cognitive subtypes might have on performance on the Wisconsin Card Sorting TestWard’s method hierarchical cluster analysis was performed on the MATRICS Consensus Cognitive Battery (MCCB) and the Wisconsin Card Sorting Test (WCST) collected from 105 healthy controls and 100 patients with schizophrenia/schizoaffective disorder.Two cognitive profiles were identified for general cognition (High/Low) and the WCST (High/Low). For controls, only 53% of low performing participants performed low on the WCST. For patients, 73.5% of patients who performed poorly on the MCCB were found to perform poorly on the WCST.Results indicate that the contribution of general cognitive domains on poor WCST performance differs between patients and control participants. For patients, there appears to be a substantial contribution of impaired general cognition to performance the WCST.


To systematically review the effects of preoperative and postoperative resistance exercise training on the recovery of physical function in patients undergoing abdominal surgery for cancer.A systematic review of English articles using Medline, Physiotherapy Evidence Database, CINAHL and the Cochrane Library electronic databases was undertaken.Studies were included if they used a randomised, quasi-randomised or controlled trial study design and compared the effects of a muscle-strengthening exercise intervention (±other therapy) with a comparative non-exercise group; involved adult participants (≥18 years) who had elected to undergo abdominal surgery for cancer; and used muscle strength, physical function, self-reported functional ability, range of motion and/or a performance-based test as an outcome measure.Following screening of titles and abstracts of the 588 publications retrieved from the initial search, 24 studies met the inclusion criteria and were accessed for review of the full-text version of the article, and 2 eligible studies met the inclusion criteria and were included in the review. One exercise programme was undertaken preoperatively and the other postoperatively, until discharge from hospital. The exercise interventions of the included studies were performed for five and eight sessions, respectively. There were no differences between groups in either study.The only two studies designed to determine whether preoperative or postoperative resistance muscle-strengthening exercise programmes improved or negatively affected physical function outcomes in patients undergoing abdominal surgery for cancer provide inconclusive results. Abdominal and thoracic cancers cause debilitating illness, and surgery is associated with significant decline in physical function.Exercise initiated after completion of active cancer treatment has a beneficial effect on health-related quality of life.There is insufficient evidence that preoperative or postoperative resistance muscle-strengthening exercise improves or negatively affects functional outcomes in patients undergoing abdominal surgery for cancer.Large-scale, well-designed clinical trials are required to determine whether resistance muscle-strengthening exercise is beneficial for patients undergoing abdominal surgery for cancer.et alet alAbdominal and thoracic cancers affect about 12 000 people annually in the UK. Many of these patients will undergo surgery, after which there is a high risk of postoperative complications and significant decline in physical function. A systematic review of exercise for people with cancer by Stevinson While there is growing evidence on the beneficial effects of aerobic exercise, resistance exercise training has received much less attention.Previous reviews, relating to exercise training for patients with cancer, have mostly focused on specific outcomes such as fatigue and quality of life,One of the main challenges in studying the effects of a resistance exercise programme on physical function in cancer surgery patients is in identifying an appropriate outcome measure. The review by Mishra and colleagues found no significant improvement in physical function as evaluated using self-report questionnaires, but they did not measure any index of physical performance.The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines on systematic reviews were followed for this review.The Cochrane Library, EBSCO ), PLOS, PubMed (Medline) and Elsevier (Scopus) electronic databases were searched up to and including December 2014. The search strategy used was exercise OR training OR isometric OR static OR isotonic OR concentric OR eccentric OR resistance OR strengthening exercise OR exercise therapy OR circuit training OR rehabilitation OR physiotherapy; AND neoplasm OR abdominal cancer OR stomach cancer OR gastric cancer OR bowel cancer OR pancreatic cancer OR colorectal cancer OR colon cancer OR rectal cancer OR gastrointestinal cancer OR ovarian cancer OR endometrial cancer OR cervical cancer OR renal cancer OR kidney cancer OR bladder cancer OR uterine cancer OR gynaecological cancer OR urological cancer; AND abdominal surgery OR laparotomy OR laparoscopy OR laparoscopic OR anterior resection OR colectomy OR hemicolectomy; AND clinical trial OR random controlled trial OR quasi-randomised controlled trial OR controlled trial OR comparative trial.All titles and abstracts generated by the search were independently screened for inclusion by three authors . Disagreement between authors was discussed and consensus was reached. The search was restricted to English language and were included if the following criteria were met: (1) randomised, quasi-randomised or controlled trial study design comparing a muscle-strengthening exercise intervention  ± other therapy with a comparative group; (2) included adult participants (≥18 years) who underwent abdominal surgery  for cancer; and (3) included muscle strength, physical function, self-reported functional ability, range of motion and/or performance-based test as an outcome measure.Participants’ age, gender, diagnosis, surgical procedure and sample size were extracted from the included studies, along with a description of the exercise intervention, including muscle group or groups exercised, contraction effort, number of repetitions and frequency, length of programme, length of follow-up, group or individual exercise programme, home or supervised exercise programme, and timing of programme (presurgery and/or postsurgery).The aim of this review was to evaluate the effect of resistance muscle strengthening on physical function in people undergoing abdominal surgery for cancer. For each study, means and SD of outcomes focused on physical function were extracted. Outcomes relating directly to surgery, length of stay, infection and other postsurgical complications were not considered in this review.Assessment was made of the outcome measures for physical function that were used in different studies, before progression to pooling of data for analysis of the most common outcome measure. Treatment effect of individual studies is reported as mean difference and 95% CIs, and the data summarised.Risk of bias was assessed with the Physiotherapy Evidence Database (PEDro) scale.The initial search strategy resulted in 588 publications. Following screening of titles and abstracts, 24 studies met the inclusion criteria and were accessed for review of the full text, of which 2 eligible studieset alet alCharacteristics of the participants and intervention of the two included studies are presented in et alThe preoperative intervention of Dronkers et alThe postoperative intervention of Ahn The methodological quality of the two included studies was rated as moderate according to the GRADE criteria, that is, randomised studies with unclear bias or well-designed observational studies with large, consistent and precise estimates of the magnitude of an intervention effect. Difficulty in blinding trial participants and therapists to the intervention meant studies were not rated as high. Both studies scored 8 out of 11 on the PEDro scale. Block randomisation using prepared envelopes, stratified by age (60–70 and >70) by someone independent of the study, was used in the preoperative study. Randomisation, at a 1-to-1 ratio, into study groups via minimisation to balance prognostic factors between groups (age and gender) was used in the postoperative study. In the preoperative study the gender distribution was similar in the control and intervention groups; however, in the postoperative study, twice as many men were randomised to the exercise group than the control group despite the minimisation procedures to balance gender between groups. In relation to the description of the intervention, some information was lacking in terms of equipment and methodology with regard to the aerobic and functional activity components of the preoperative intervention.et alThe mean difference and upper and lower 95% CI between the control and intervention group in the study by Dronkers et alThe mean difference and upper and lower 95% CI between the control and intervention groups in the study by Ahn Our aim was to systematically review the evidence on the effectiveness of preoperative and postoperative strengthening exercises on short-term and long-term recovery of physical function in patients undergoing abdominal surgery for cancer. Two studies were included, which represented 73 patients (48 men and 25 women) undergoing abdominal surgery for cancer. One exercise programme was undertaken preoperatively and the other postoperatively until discharge from hospital. This represents insufficient evidence to determine whether this type of preoperative or postoperative resistance muscle-strengthening exercise programme improves or negatively affects functional outcomes in patients undergoing abdominal surgery for cancer.et al,The study by Dronkers et alet alet alet al,In contrast, the study by Ahn There are some limitations to our review. We limited our inclusion by study design, only including randomised or quasi-randomised studies where there was a clear resistance muscle strengthening component as part of an exercise programme. It is possible that other studies have included muscle-strengthening exercises or functional exercises that will have an effect on muscle strength that have not been included in this review due to our inclusion criteria, and we advocate the Consensus on Exercise Reporting Template guidelines for reporting exercise intervention studies.Our systematic review suggests that the use of resistance exercise interventions for recovery of physical function in patients undergoing abdominal surgery for cancer must be considered with caution. The small number of included underpowered studies and the inability to pool the results due to the heterogeneity of outcome measures mean that there is a lack of evidence for or against the use of this type of resistance muscle-strengthening exercise programmes to improve functional outcomes in these patients. While the studies give encouraging preliminary evidence that muscle-strengthening programmes may be feasible for abdominal cancer surgery patients, further large-scale, well-designed clinical trials are required to determine whether this type of exercise intervention is beneficial for this group of patients.


With the introduction of direct-acting antiviral drugs, treatment of hepatitis C is both highly effective and tolerable. Access to treatment for patients, however, remains limited in low- and middle-income countries due to the lack of supportive health infrastructure and the high cost of treatment. Poorer countries are being encouraged by international bodies to organize public health responses that would facilitate the roll-out of care and treatment on a national scale. Yet few countries have documented formal plans and policies. Here, we outline the approach taken in Rwanda to a public health framework for hepatitis C control and care within the World Health Organization hepatitis health sector strategy. This includes the development and implementation of policies and programmes, prevention efforts, screening capacity, treatment services and strategic information systems. We highlight key successes by the national programme for the control and management of hepatitis C: establishment of national governance and planning; development of diagnostic capacity; approval and introduction of direct-acting antiviral treatments; training of key personnel; generation of political will and leadership; and fostering of key strategic partnerships. Existing challenges and next steps for the programme include developing a detailed monitoring and evaluation framework and tools for monitoring of viral hepatitis. The government needs to further decentralize care and integrate hepatitis C management into routine clinical services to provide better access to diagnosis and treatment for patients. Introducing rapid diagnostic tests to public health-care facilities would help to increase case-finding. Increased public and private financing is essential to support care and treatment services. It was also one of the few countries in sub-Saharan Africa to achieve most of the health-related millennium development goals.The seroprevalence of HCV antibody has most recently been estimated to be 3.1%In 2011, the Government of Rwanda established its hepatitis control unit under the Division of HIV/AIDS, STIs and Other Blood Borne Infections at the Rwanda Biomedical Centre. The objective was to develop a specific programme for the prevention, care and treatment of hepatitis B and C.In April 2016, a patient chart for hepatitis C care and treatment was developed and implemented in paper form at hospitals receiving HCV patients. This was to support clinical decision-making according to national guidelines and allow proper reporting of patient outcomes. The group also developed patient registers that were implemented to track the overall number of patients enrolled in clinical and laboratory services. As of October 2017, Rwanda Biomedical Centre started developing and reviewing national indicators for hepatitis C to be included in the integrated health management information system in Rwanda.Rwanda began a systematic blood donation screening programme for HIV, HBV and syphilis in 1985, and introduced screening for HCV in 1999.The capacity for HCV testing for patients was first introduced in Rwanda in 2013 and was initially recommended for high-risk groups, including patients with HIV or HBV infection, intravenous drug users, infants of mothers with hepatitis C, individuals who received blood or organ transplants before 1999, individuals with occupational exposure and other patients as clinically indicated.HCV testing guidelines in Rwanda include antibody testing using enzyme-linked immunosorbent assay (ELISA) or a rapid diagnostic test, which is then confirmed with polymerase chain reaction-based viral load quantification. Currently, 11 hospitals nationwide have the capacity to perform ELISA-based testing for HCV. Although several rapid diagnostic tests have been validated in Rwanda, there is no consensus on product selection or procurement, and rapid diagnostic tests are not currently available in public health-care facilities. As part of the well-established health services for HIV, 10 hospitals have the capacity to conduct HCV viral load testing. Using current systems for HIV viral load testing, blood samples for HCV testing are collected at local health centres and district hospitals and delivered to one of the testing sites via a centrally organized transport system, which also delivers results back to the health facilities. Given the predominance of HCV genotypes 1 and 4 in Rwanda,In 2013, the health ministry developed the first national guidelines for hepatitis prevention and treatment, which included guidance on screening, diagnosis and treatment for both hepatitis B and C within the Rwandan context.In August 2015, the health ministry officially authorized the use of sofosbuvir or sofosbuvir with ledipasvir for treatment of hepatitis C in Rwanda. The government was given preferred pricing for these drugs via licensed manufacturers at a cost per 28 days of 300 United States dollars (US$) for sofosbuvir and US$ 400 for sofosbuvir with ledipasvir in 2015 (subsequently reduced to US$ 260 in 2017). A donation of daclatasvir (2000 treatment regimens) was also obtained through the Clinton Health Access Initiative Quick-Start programme. As of June 2017, over 2500 of an estimated 55 000 patients requiring medicationNew Times, a popular newspaper printed in English, published 29 articles about viral hepatitis from 2009–2015, with nine of those articles published in 2015. In 2015, Rwanda officially first commemorated World Hepatitis Day with a public walk advocating for hepatitis prevention and treatment.The health ministry has introduced mass-media campaigns to raise awareness and reduce the general stigma surrounding hepatitis C. The The government has promoted the decentralization of health services to provide a more comprehensive package of health services at provincial hospitals, district hospitals, health centres and at the community level through community health workers. This process was pioneered through the response to the HIV epidemic. The HIV response resulted in 524 facilities providing antiretroviral therapy and 1068 physicians and nurses with the capacity to initiate and maintain patients on therapy.In October 2016, the technical working group developed and approved the Rwanda viral hepatitis national operational plan. The plan demonstrated priority-setting of key national activities and provided cost estimations for different levels of coverage of screening, diagnosis, and treatment of both hepatitis B and C. The annual cost of a comprehensive national viral hepatitis programme was estimated at US$ 168.6 million.As part of the national operational plan, several different costing scenarios were calculated for the prevention, diagnosis and care of hepatitis B and C. In a full intervention scenario ‒ where all screening, diagnosis and treatment options are implemented ‒ the cost for HCV screening of 2.6 million people and treatment of 74 105 people annually was projected to be approximately US$ 128 million. If treatment were reserved for patients with HIV coinfection or advanced disease (aspartate aminotransferase to platelet ratio index > 1.0), then the total annual cost to implement the hepatitis C control programme was projected to be US$ 52 million. In comparison, the estimated annual expenditure for HIV care in Rwanda from 2013‒2018 is around US$ 207 million.Financing for the hepatitis C response to date has largely been through expenditure by the government and there has been a strong commitment from the highest levels of the government to funding hepatitis-C-related programming, operations and consumables.Several key elements have accelerated Rwanda’s success in building a comprehensive framework for the public health response to hepatitis C with resource constrains. Hepatitis C screening, diagnosis and treatment have been integrated into existing programmes and systems for HIV infection. These systems cover policy and guidelines development, laboratory equipment, specimen transport, clinic infrastructure, training platforms, medication supply chain and clinical training and mentorship. This strategy has allowed for rapid implementation of the hepatitis C response. Although a plan for rapid decentralization exists, challenges remain in training adequate numbers of health-care personnel and equipping laboratories to provide maximal access and equitable distribution of services. The involvement of community and hepatitis C patient networks, particularly in advocacy for approval and access to direct-acting antivirals, has been essential in Rwanda’s push to rapidly introduce new diagnostics and therapies. Such networks will continue to play an important role in public awareness efforts. Finally, under the technical working group framework and building on HIV control experiences, partnerships were established between the health ministry and several international organizations, including Stanford University, Maryland University, Duke University, Gilead Sciences, the Clinton Health Access Initiative, Partners In Health, the Centers for Disease Control and Prevention and WHO. These partnerships leverage technical, financial and operational expertise and experience with hepatitis C. The health ministry has been active in building the key partnerships required to develop a rapid, informed and sustainable approach to a national hepatitis C programme. The ministry involved international academic institutions in training and research, insurance companies in the financing of diagnostic testing and medications, pharmaceutical companies in rapid price reductions and procuring direct-acting antivirals, and nongovernmental organizations in securing donations and informing planning and policy.In Rwanda, a robust programme for hepatitis C control has been developed, including key accomplishments in the areas of establishing national governance and planning, developing diagnostic capacity, approving the use of direct-acting antiviral treatment, training key personnel, generating political will and leadership from within the government and fostering key strategic partnerships for technical support . However


The demand for an eHealth-ready and adaptable workforce is placing increasing pressure on universities to deliver eHealth education. At present, eHealth education is largely focused on components of eHealth rather than considering a curriculum-wide approach.This study aimed to develop a framework that could be used to guide health curriculum design based on current evidence, and stakeholder perceptions of eHealth capabilities expected of tertiary health graduates.A 3-phase, mixed-methods approach incorporated the results of a literature review, focus groups, and a Delphi process to develop a framework of eHealth capability statements.Participants (N=39) with expertise or experience in eHealth education, practice, or policy provided feedback on the proposed framework, and following the fourth iteration of this process, consensus was achieved. The final framework consisted of 4 higher-level capability statements that describe the learning outcomes expected of university graduates across the domains of (1) digital health technologies, systems, and policies; (2) clinical practice; (3) data analysis and knowledge creation; and (4) technology implementation and codesign. Across the capability statements are 40 performance cues that provide examples of how these capabilities might be demonstrated.The results of this study inform a cross-faculty eHealth curriculum that aligns with workforce expectations. There is a need for educational curriculum to reinforce existing eHealth capabilities, adapt existing capabilities to make them transferable to novel eHealth contexts, and introduce new learning opportunities for interactions with technologies within education and practice encounters. As such, the capability framework developed may assist in the application of eHealth by emerging and existing health care professionals. Future research needs to explore the potential for integration of findings into workforce development programs. Developing an eHealth-ready workforce ,2 is becSignificant work has been conducted by Gray et al 2014) to identify the educational needs of health professionals necessary for an eHealth-capable workforce . A key f to identMultiple issues need to be addressed when designing strategies for embedding eHealth into undergraduate curricula ,9,16. DrAlthough the tertiary education of health professionals is traditionally framed around a set of specific competency standards decreed by professional associations that allow measurable behaviors to be observed and assessed , competeIn contrast to competency, capability has been defined as “a holistic concept that describes how an individual or organization applies their ability in a confident manner to problems in new and unfamiliar circumstances as well as in familiar situations” . As suchA capabilities approach is, therefore, able to inform and modify competency-based frameworks that better reflect the complexity of real-life environments as is found in the field of using eHealth for health care and wellness ,25. WithA 3-phase approach was used. This consisted of a literature review in the first phase, followed by qualitative studies to identify relevant themes, gain expert opinions, and raise consensus with key stakeholders in the second stage. In the third phase, data from the 2 previous stages were reviewed using a Delphi process to develop a framework of capability statements for guiding health curricula and measurement of workforce readiness in the use of eHealth technologies for health care. The project occurred between October 2016 and November 2017.eHealth, digital health, health professional, workforce readiness, graduate, student, higher education, capability statement, and competency. The fields of health, medicine, nursing, public health, allied health, pharmacy, psychology, physiotherapy, occupational therapy, speech language pathology, dentistry, paramedicine, social work, dietetics, nutrition, radiography, audiology, exercise and sports science, optometry, orthoptics, ophthalmology, and podiatry were included. Researchers also reached out to health and academic communities and reviewed Web pages from a number of professional societies and health organizations to identify the existence of other eHealth readiness competencies and capabilities.A systematic search for literature was undertaken during October 2016 to December 2016 to identify papers related to workforce readiness in the use of eHealth technologies. The databases and search engines used included CINAHL, Medline, ERIC, PsychINFO, Google Scholar, and Google. Databases and search engines were systematically searched for literature on eHealth competencies using combinations and variations of the following key search terms: The search was limited to papers published after 2000 to maximize relevance to current clinical contexts and papers written in English. Research studies and reports were included if they (1) referred to readiness competencies or capabilities for students, graduates, or workforce; (2) referred to the use of digital technologies in health care; and (3) provided empirical support for the capability statements or framework. Included peer-reviewed and gray literature were then reviewed to identify existing core competencies or capability statements relating to eHealth readiness. Data were extracted by 1 author (author 2), analysis and synthesis  conducteFocus groups with key informants from the health workforce and higher education were used to ascertain the perceived eHealth capabilities requirements of new graduates . PurposeThe workshop included 2 focus group sessions: (1) a large focus group  and (2) 4 small breakout focus groups . A semistructured script encouraged topic exploration and included the following questions: (1) What eHealth competencies do you expect health graduates to be able to demonstrate? and (2) Could you provide some examples of how these competencies are taught or applied in your organization? Focus group discussions were facilitated by the researcher team experienced in qualitative research methods. To stimulate discussions, participants were presented with evidence of core eHealth readiness competencies identified via the literature review. Of the focus group participants, 65% (15/23) were female, and 48% (11/23) were University of Sydney faculty representatives. Faculty representatives encompassed the fields of physiotherapy, speech pathology, psychology, nursing, dentistry, pharmacy, medicine, information technology and engineering, and mathematics and statistics. The balance of the participants  included broad representation from health services  and state and national government health agencies , including senior executives, clinicians, and senior health administrators. Participants also included recent health professional graduates  and 1 enrolled student from the University of Sydney. Interviews were transcribed verbatim and thematically analyzed  independThe third phase involved identifying core capability statements by using the Delphi method  to refinAfter duplicates were removed, the search revealed 92 relevant papers. Papers were excluded if they were opinion pieces, provided no empirical support, or reported no specific details regarding eHealth capabilities. This left a total of 30 papers included in this review. Emergent themes from the literature were identified (by authors 1 and 2) and refined through research team discussion at regular meetings.The health, activity, and participation issues identified within the literature were initially arranged into the following 6 categories: (1) health information management (n=24); (2) communication (n=19); (3) professionalism (n=24); (4) information systems and technologies (n=25); (5) patient focus (n=13); and (6) health analytics (n=14). Categorization of the 6 core domains as identified in the literature is presented in Three overarching themes, each with multiple subthemes, emerged from the thematic analyses: (1) reinforce fundamental clinical capabilities, (2) acknowledge and adapt existing capabilities, and (3) introduce and provide opportunities for new learning. Themes and subthemes are presented in At the completion of the fourth round, consensus was achieved. The final capability framework consisted of 4 overarching domains and 40 performance cues . The 4 uThis study aimed to develop a framework of eHealth capabilities that could be used to inform development of higher education curricula for health students and professional development opportunities for the current health workforce. The framework resulting from our literature review, focus groups, and Delphi process describes 4 overarching domains of eHealth capabilities: (1) digital technologies, systems, and policies; (2) clinical practice and applications; (3) data analysis and knowledge creation; and (4) system and technology implementation. Each domain is supported by a capability statement that articulates what learners need to be able to know and do to demonstrate achievement of this capability. Examples of these knowledge and behaviors are provided in the form of performance cues. The key components of the eHealth capability framework are provided in The systematic process for developing the framework was necessary for the successful integration of eHealth and continuous quality improvement at all levels in the health system . CriticaGiven the inherent nature of eHealth as being innovative and transformative, it is critical that we enable our health workforce to be suitably prepared and adaptable. Tertiary education of future health graduates needs to move from a focus on technical skills to encompass broader eHealth capabilities, such as professional competencies and attributes of an adaptable, improvement-minded, and innovative workforce. The eHealth capabilities framework extends beyond this technical proficiency to include the integration of technology into current practice and demonstrating a strong ethos around lifelong learning and transforming care. By re-evaluating traditional resources used in education and incorporating knowledge around eHealth capabilities, educational curriculum will provide greater opportunities to build capability in working with systems undergoing digital transformation . ConsistThis framework is not a curriculum; it is a starting point to guide curriculum development and redesign. Furthermore, the framework is intended to stimulate discussion with industry stakeholders regarding workforce capability with regard to eHealth in practice. As a guide, it will enable further development of both curriculum and competency evaluation . The eHeIt was clear that there is a need to create an eHealth capability framework that accurately reflected the roles and work contexts in the digital age. In addition to moving beyond a focus on the technical skills, this included offering theoretical and practical opportunities for health graduates to integrate eHealth into practice, eg, using technologies to provide new models of care and facilitate consumer empowerment, or to use routinely collected digital health data to inform practice. One of the key challenges for education in this space is the ability for curriculum to adequately address the divide between digitally capable individuals and their capacity to apply digital skills to clinical situations that often use archaic systems . AlthougIn this study, we did not aim to achieve data saturation as this was beyond the scope of this initial work. The participants in this study brought with them a breadth of experience and representation of multiple health professions, but the lack of consumer representation was a study limitation. It is likely that future research incorporating additional participants working across a wider range of contexts, and is inclusive of diverse health care consumers, may provide additional insights into eHealth-enabled interdisciplinary practice. Further research exploring the implications for the existing health care workforce is also warranted, with a focus on identifying the potential relevance and impact of the capability statements on policy and practice, including recruitment, professional development, performance management, and systems improvement activities. Building on the results of this study, the University is undertaking a curriculum mapping process with a commitment to the development of high-quality teaching and learning activities and resources. This will include an analysis of clinical placement experiences, work-based training, and workplace orientation programs to further identify and address gaps in the preparation of our health graduates and workforce for eHealth contexts. We further excluded from the discussion implications of automation and computerization on the actual workforce and their predicted displacement . Thus, tThis framework has direct implications for curriculum redevelopment in health education and professional development opportunities for the current health workforce. The framework could be used to assess which eHealth capabilities are currently being taught in health profession degrees, and how. Exemplars of effective eHealth education could be collated to form resources and professional development for health educators across the sector. Importantly, in using the framework to map current curricular, educators and course coordinators can identify the capabilities not addressed in their programs at present. This provides opportunity for revising the curriculum to better prepare graduates.For the current health workforce, the framework requires further development. At present, the capabilities reflect the knowledge and skills required of a graduate. Further research and development are required to articulate intermediate and advanced levels of capability across the 4 domains of the framework. Once established, this more comprehensive framework could guide professional development opportunities and self-reflection or self-assessment for practicing health professionals.This paper describes the foundational level of eHealth capability expected of tertiary health students at graduation and as they enter the health workforce. Ideally, the eHealth capability framework will inform how tertiary health programs deliver and assess essential eHealth education. The results of this study will inform a cross-faculty eHealth curriculum that aligns with workforce expectations and will be of interest to professional associations, health services, and organizations. Future research needs to explore the potential for integration of findings into workforce development programs, particularly with consideration of intermediate and advanced levels of capability in collaboration with workforce and industry stakeholders.


Zika virus (ZIKV) was first isolated in Africa; decades later, caused large outbreaks in the Pacific, and is considered endemic in Asia. We aim to describe ZIKV disease epidemiology outside the Americas, the importance of travelers as sentinels of disease transmission, and discrepancies in travel advisories from major international health organizations.This descriptive analysis using GeoSentinel Surveillance Network records involves sixty-four travel and tropical medicine clinics in 29 countries. Ill returned travelers with a confirmed or probable diagnosis of ZIKV disease acquired in Africa, Asia and the Pacific seen between 1 January 2012 and 31 December 2016 are included, and the frequencies of demographic, trip, and diagnostic characteristics described. ZIKV was acquired in Asia (18), the Pacific (10) and Africa (1). For five countries , GeoSentinel patients were sentinel markers of recent Zika activity. Additionally, the first confirmed ZIKV infection acquired in Kiribati was reported to GeoSentinel (2015), and a probable case was reported from Timor Leste (April 2016), representing the only case known to date. Review of Zika situation updates from major international health authorities for country risk classifications shows heterogeneity in ZIKV country travel advisories.Travelers are integral to the global spread of ZIKV, serving as sentinel markers of disease activity. Although GeoSentinel data are collected by specialized clinics and do not capture all imported cases, we show that surveillance of imported infections by returned travelers augments local surveillance system data regarding ZIKV epidemiology and can assist with risk categorization by international authorities. However, travel advisories are variable due to risk uncertainties. Zika virus (ZIKV) made global headlines in 2015 when Brazil identified the first cases of confirmed transmission. The alarming association with congenital abnormalities triggered the World Health Organization (WHO) to declare a public health emergency of international concern on 1 February 2016 , 4 and wZIKV is now widely distributed throughout the tropics and sub-tropics, with 75 countries and territories reporting evidence of vector-borne ZIKV transmission between 2015 and 2016 including: three in West and Central Africa , 13 in the Pacific , and 10 in Asia  . In AfriAedes spp. vector.Despite recent advances in knowledge and research regarding ZIKV, a general lack of disease awareness prior to the current outbreak, misdiagnoses due to the clinical similarity of ZIKV infections with other infectious diseases, and limited access to diagnostic testing have resulted in many unresolved questions regarding the distribution and transmission risks outside the Americas. There is also uncertainty regarding the impact of different strains and the potential for obstetric and neurological complications, particularly in Asia and Africa. To date, all reported Pacific and American Zika isolates and associated neurologic or microcephaly complications have been attributed to the expansion of the Asian lineage –21, but To develop a broader understanding of the extent of ZIKV among international travelers from Africa, Asia and the Pacific and the role travelers play in identifying areas of endemicity, we analyzed ZIKV infections reported by the GeoSentinel Surveillance Network and juxtaposed these cases with a review of the published literature and web-based reports of ZIKV cases in select countries outside the Americas. We also examined the level and timing of advisories issued by four major international health authorities: WHO, European Center for Disease Control and Prevention (ECDC), US Centers for Disease Control and Prevention (CDC), and Public Health England’s National Travel Health Network and Centre (NaTHNaC).www.istm.org/geosentinel), currently comprising 64 specialized travel and tropical medicine clinics in 29 countries, the majority being in Europe, America, Australia or New Zealand. To be eligible for inclusion in the GeoSentinel database, patients must have crossed an international border and sought medical advice at a GeoSentinel clinic for a presumed travel-related illness. Data collected include: demographic information, travel data, reason for most recent travel, inpatient or outpatient status, travel duration, and time between the onset of symptoms and presentation at a GeoSentinel clinic. Diagnoses are taken from a list of >500 standardized diagnostic codes. Clinics collect de-identified data on ill travelers for whom they have provided clinical care using a standard form, and report these data to a centralized database [GeoSentinel is a global surveillance network established in 1995  acquirePubMed, ProMED, International SOS reports, WHO situation reports, ECDC situation reports, the CDC website and online news reports were searched (minimum of two co-authors) using the search criteria “Zika” and “Africa or Asia or Pacific”, or “Zika” and each individual country name in these three regions to identify locally acquired or exported cases. Data on the status and timing of international travel advisories were tabulated following a search of the relevant authorities’ websites, including review of weekly situation reports where relevant , 25–27.The first case of ZIKV infection reported to GeoSentinel acquired outside the Americas occurred in a traveler in May 2012 (infection acquired in Indonesia). Since then, two subsequent cases were reported in 2013, five cases in 2014, three in 2015, and 18 cases in 2016 .Sentinel, PCR-positive case from Thailand, exported by a Canadian traveler in 2013  .Only known case reported from Timor Leste, exported by a German traveler in April 2016 .Comparisons of risk classifications and travel advisories issued by the four major international authorities are shown in Travelers are key to the global spread of ZIKV . This reThe GeoSentinel ZIKV case acquired in Indonesia in May 2012 was among the first sporadic cases reported in a traveler , 36. In The role travel-associated cases, including those reported by GeoSentinel, have played as indicator of local ZIKV infections has varied in different regions. ZIKV in South America, the Caribbean and the Pacific led to clinically apparent local outbreaks, with exported cases in travelers also reported . GeoSentDuring 2016, there were significant differences in risk categorizations and in interpretation of data by the four major international authorities, possibly underpinned by political factors, which created marked variability in country stratifications and non-uniformity in both timing and presence of travel advisories Figs . While tIn addition to uncertainties on ZIKV epidemiology, case definitions vary. The current CSTE definitions  are moreCharacteristics of ZIKV transmission can often be best determined in travelers returning from endemic areas, for which the period of exposure may be more easily determined than among local populations. Sexual transmission is best assessed in non-endemic settings where there are no competent mosquito vectors; notably the first detection of sexual transmission occurred in a traveler from Africa . AdditioA limitation of this descriptive report is that surveillance data captured by GeoSentinel include only cases seen at specialized clinics, mostly in developed countries; they do not capture all imported cases and may not be representative of all global travelers. Moreover, GeoSentinel is unable to provide denominator data or absolute risk information. However, GeoSentinel’s deliberate focus to collate data from highly specialized clinics underscores the utility of assessing disease in travelers as a mechanism for identifying geographic areas where emerging diseases may be occurring. Another limitation is that we cannot entirely exclude diagnosis or (unpublished) recognition of additional earlier ZIKV cases, thereby potentially overstating the value of the GeoSentinel reports as index cases. However, given our extensive review of published data and media sources, we nevertheless assert that GeoSentinel reports provide important additive case information.In summary, many uncertainties in ZIKV epidemiology, transmission and risk of adverse outcomes remain, and consensus on diagnostic and definition issues is needed. We have described ZIKV cases among travelers visiting Africa, Asia and the Pacific, highlighted the integral role of travelers as sentinels of ZIKV infection, shown that GeoSentinel assists in the identification of these travelers, and have contextualized GeoSentinel cases with other reported  cases. We have also demonstrated the differential impact of travelers as sentinels in Asia, which likely relates to the lower epidemic potential due to prior flavivirus circulation among the population of this region. Our findings also detail the basis for non-uniformity in travel advisories issued by the four major international authorities. The presence of variable travel advisories may create confusion for health practitioners and individual travelers when determining risks, and the small but non-zero potential for causing devastating fetal outcomes must be discussed. Traveler consultations need to account for overall ZIKV risk assessment, residual risk uncertainties and individual risk tolerance.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.


Compelling evidence has demonstrated that a large proportion of investment in biomedical research is wasted; this waste is avoidable. Academic institutions have, thus far, shown limited response to recommendations for increasing value and reducing waste. We formulated an academic response by (i) achieving consensus across a wide range of stakeholder groups on a comprehensive framework for quality of patient-oriented clinical research and (ii) highlighting first successful examples of its operationalization to facilitate waste-reducing strategies at academic institutions.Based on a systematic review of quality definitions, concepts, and criteria in the medical literature  and on stakeholder websites from 13 countries , we systematically developed a comprehensive framework for the quality of clinical research. We identified websites through personal contacts with experts in clinical research or public health who also suggested, for each country, websites of the following 7 stakeholder groups: patient organizations; academic research infrastructures; governmental bodies; regulatory agencies; ethics committees; the pharmaceutical industry; and funding agencies. In addition, we searched websites of inter- or supranational bodies involved in clinical research until no further insights emerged. After consolidation of the identified definitions, concepts, and criteria of quality in a basic framework structure, we conducted 4 rounds of an adapted online Delphi process among the same 7 stakeholder groups from 16 countries. The Delphi process ultimately achieved consensus on structure and content. The framework addresses 5 study stages  and includes the following dimensions: (i) protection of patient safety and rights, (ii) relevance/patient centeredness and involvement, (iii) minimization of bias , (iv) precision, (v) transparency/access to data, and (vi) generalizability  of study results. These dimensions interact with 2 promoters—infrastructure and sustainability through education—that include a set of factors that may enhance all listed quality dimensions. Each quality dimension contains specific questions and explanatory items that guide quality assessment at each research stage from conceptualization of the research question through reporting and knowledge translation of study results. In the last survey round, Delphi participants from 9 countries  agreed on the structure, content, and wording of the research stages, quality dimensions, specific questions, and descriptive examples of the final framework. In Switzerland, INQUIRE has resulted in a roadmap that guides initiatives to increase value within the Swiss Clinical Trial Organization network and through affiliated researchers.We present a framework based on a consensus of different stakeholder groups guiding the practical assessment of clinical research quality at all stages of a research project. Operationalization of this common structure will support the increase of value by guiding academic institutions and researchers in developing quality enhancement initiatives, from posing the right research question to the transparent publication of results. Belinda von Niederhäusern and colleagues present INQUIRE, a framework based on Delphi-process consensus of stakeholder groups, to guide the practical assessment of quality at all stages of a clinical research project. A large amount of biomedical research is not useful and thus wasteful; academic institutions in particular have failed to take responsive measures to reports of research waste.The lack of a common understanding of the key principles of good clinical research and the lack of practical guidance on how to improve the current situation inhibit efforts to increase value within the academic system.We present INQUIRE , a consensus-based framework that supports academia in developing quality enhancement initiatives and setting research agendas to increase efficiency and quality of patient-oriented research at all study stages, i.e., from conceptualization of the research question to reporting of study results and knowledge translation.In contrast to existing frameworks, 7 international stakeholder groups, including patient representatives, participated in the development of INQUIRE and agreed on the final product. INQUIRE is therefore based on a common understanding of factors contributing to clinical research quality.INQUIRE can support academic institutions and researchers to design quality enhancement initiatives for clinical research. In the future, other stakeholders may adapt INQUIRE for their own environment and specific purposes.In Switzerland, INQUIRE has inspired major stakeholders to agree on a national roadmap to improve clinical research, and is currently undergoing implementation in academia. The Lancet [https://www.thelancet.com/campaigns/efficiency/statement) to increase value, involving stakeholders that include funders, regulators, journal editors, academic institutions, and researchers.Clinical research should generate trustworthy evidence that informs decision-making in clinical practice, health policy, and further research . Evidence Lancet –13 proviA follow-up article in 2016 offered an overview of the initial stimulus of REWARD across stakeholder communities [As a major driving force of patient-oriented clinical research, academia is ideally placed to lead the movement to increase value. Academia not only receives substantial public funds ,16 but aMedical specialties and expert groups, ethics committees, regulatory bodies, funding agencies, industrial partners, and patients all have a say in academic research. Their perceptions on what constitutes “good clinical research” and what is “waste,” however, remain vague and, to the extent they are articulated at all, vary . Lack ofTherefore, we aimed to develop a comprehensive framework for quality of patient-oriented clinical research that is based on the consensus of key major stakeholder groups—and covers key research stages. Here we present the INcreasing QUality In patient-oriented academic clinical REsearch (INQUIRE) framework, describe its development, and highlight examples of its successful operationalization for the purpose of generating more useful clinical research. INQUIRE is intended to guide academic institutions and researchers in developing quality enhancement initiatives. INQUIRE may also be useful for institutions in setting their research agendas, from posing patient-relevant research questions to the transparent publication of results. In the future, the framework and its operationalization may thus provide a possible supporting structure for the REWARD campaign to increase value and reduce waste.http://www.equator-network.org/reporting-guidelines/srqr/) as described in This study is reported according to the Standards for Reporting Qualitative Research  integrating empirical evidence on aspects of quality through a systematic review  informinAs the Delphi process did not include health-related data and was therefore not within the scope of the applicable Swiss Human Research Act , it did not require formal ethical approval, but we obtained a declaration of no obligation (Req-2017-00311) from the Ethics Committee Northwest/Central Switzerland (EKNZ).https://www.surveymonkey.net), we conducted 2 Delphi rounds aimed at (i) identifying any additional quality items that we had not yet considered and (ii) establishing broad consensus across stakeholders on the overall framework structure. After each round, we shared with respondents a summary of the adaptations made based on their suggestions in the previous round and asked for their agreement or further suggestions for improvements on structure and content.The Delphi process took place between September 2015 and June 2017. To allow for broad inclusion of perspectives, we considered the same 7 stakeholder groups to be relevant as in the preceding systematic review [We conducted 2 further Delphi rounds seeking consensus on how to operationalize the framework structure, with a focus on the Swiss academic setting. We invited an additional 33 stakeholder representatives from Switzerland, particularly academics. Specifically, we invited representatives (board members and executive directors) of all 6 Swiss Clinical Trial Units (CTUs) at university hospitals and members of the executive committee and the Quality Working Group at the Swiss Clinical Trial Organization (SCTO). In order to allow for the operationalization of the framework, for these rounds we rephrased the previous “quality items” as “specific quality questions” accompanied by “descriptive examples.” First, we addressed framework structure, content, and wording of specific quality questions and corresponding examples. Second, we provided respondents with all anonymized comments, a response by the authors to each comment, and the overall agreement score on framework structure and specific quality questions. We provide the SurveyMonkey (round 1–3) and email (round 4) questionnaires for all Delphi rounds in We conducted qualitative analysis for open-ended questions and descriptively summarized comments and suggestions for removal, addition, or adaptation of quality dimensions and of individual quality items and key themes based on repetition of concept words. Through discussion, we iteratively adapted the framework structure and content and fed back revisions to the survey participants. We calculated agreement scores in percentages by dividing the number of participants agreeing by the total number of participants who provided an answer to the respective question.This research was designed and conducted with the involvement of 7 stakeholder groups, including patient participants. We actively sought patients’ priorities and preferences. Patients, if required, received plain language explanations of the framework content, and provided their opinion on the structure and content of the framework in the 4 Delphi rounds. After completion of the Delphi process, all stakeholder representatives, including patients, received the final framework.We invited 109 representatives from 7 stakeholder groups and 16 countries to participate in the Delphi process. Response rates ranged from 53.0% in round 1 to 98.1% in round 4, and from 12.5% for governmental participants to 83.3% for pharmaceutical industry participants  in round 4. The final agreement on content ranged from 96.2% (sustainability through education) and 98.1% (planning and feasibility) to 100% for all other stages and the other promoter see :i)6 quality dimensions, with a dimension being defined as an overarching concept of quality containing multiple individual quality questions : (1) proii)5 successive study stages  to which the dimensions apply, andiii)2 quality promoters (infrastructure and sustainability through education), with a promoter being defined as a set of factors that may enhance all quality dimensions at a research institution.Protection of patients’ safety and rights represents the cornerstone of clinical research. It assures that researchers, at all times, respect and protect participants’ safety, rights, and well-being.Research relevance and patient centeredness and involvement reflects the extent to which the research question is scientifically and societally beneficial  and involves patient values and preferences.Minimization of bias—or internal validity—reflects the extent to which the research minimizes systematic error (bias) through selecting an appropriate study design and prespecifying analyses.Precision reflects the extent to which the research minimizes random error  and to what extent authors present precision to facilitate researcher users’ understanding.Transparency and access to data reflects the extent to which study planning, conduct, data collection, and presentation of results are transparent and accessible for the scientific community and the public. This dimension includes the registration of the study in a publicly accessible database, publication of the full study protocol, publication of the study results—independent of their effect size or direction—and explicitly encouraging access to the full patient-level dataset (data sharing).Generalizability—or external validity—reflects the extent to which study results are applicable and generalizable to the wider patient population in real-life circumstances.The first quality promoter, an established research infrastructure, includes well-trained personnel and functional facilities on-site.The second quality promoter, sustainability through education, supports sustainability of a developed infrastructure through effective involvement and hands-on training of young and senior investigators as well as competent mentoring and early career development and continuous education of study personnel to secure a productive clinical research environment in the long term.The framework captures a comprehensive generic set of quality dimensions and 77 specific quality questions accompanied by descriptive examples that can be adapted to different study designs, indications, or treatments. Quality dimensions are not represented hierarchically, and those using the framework may, depending on the setting, apply weights to items or dimensions.Applying the framework in the academic clinical research context requires guidance on its operationalization. In contrast to the existing quality assessment tools or checklists , the INQFor each quality dimension and research stage or promoter, we developed specific quality questions on which the Delphi participants commented, and on which—following revision—they ultimately agreed ?Have crucial feasibility aspects  been piloted?Are recruitment assumptions realistic in a specified timeframe ?Have national/international study registries been checked for studies that could interfere with the planned study?Do anticipated study costs  match with available budget?Are study cost data related to planning, conduct, analysis, and dissemination planned to be collected (if applicable)?Descriptive examples do not constitute a complete list but rather provide guidance on how to interpret the specific quality question.https://www.scto.ch/de/event-calendar/symposium/symposium-2017.html) and a stakeholder event, “From Stumbling Blocks into Stepping Stones: Creating Greater Value and Efficiency in Clinical Research,” in January 2018 . Along with reflections on international initiatives to improve value by 2 authors of The Lancet series and the UK National Institute for Health Research (NIHR), the participants discussed the current situation in Switzerland and the INQUIRE framework. In response, the steering board of the SCTO included INQUIRE into its strategy, is in the process of developing a roadmap, and is taking action on 3 different levels: nationally, through adaptation of its quality policies according to the framework’s dimensions; locally, through the establishment of performance measures and incentives for its network members (CTUs) based on the framework; and individually, through incentivizing academic researchers to evaluate these network activities in Studies Within A Trial—so called SWATs  to increase value and reduce waste. In Switzerland, the framework inspired stakeholders to convene a relevant symposium followed by a stakeholder event, resulting in a roadmap on how to use the INQUIRE framework to guide initiatives to increase value within the SCTO network and through affiliated researchers.We designed the framework to increase value through operationalization of its content. Seventy-seven specific quality questions can guide academic institutions and researchers in developing quality enhancement initiatives that they have, thus far, failed to implement. Mapped to 5 study stages, INQUIRE guides academic institutions and the affiliated research force on how to practically (i) set the right research priorities, (ii) use robust research design, conduct, and analysis, (iii) efficiently assess feasibility and manage research, (iv) make information on research methods and findings accessible, and (v) produce complete, unbiased, and usable research reports. The framework and its operationalization thus provide a possible supporting structure for the REWARD campaign , potentially leading to discipline-specific gaps in the framework’s content. We limited stakeholders to those who were willing to reply in English, German, French, or Italian.While this framework is widely applicable to diverse study designs, its comprehensiveness, with 77 specific questions, might prove challenging. It is possible, however, for institutions to focus on particular parts, or questions, from the framework, and for investigators to focus on sections particularly relevant to their clinical research stage. For example, investigators planning a study may specifically use the quality questions contained within the planning and feasibility section of the framework. At the very least, however, awareness of each of the domains should lead to some consideration of the attendant issues. Similarly, some questions may be applicable to only specific situations . Where this is the case, we phrase these questions in the framework with “if applicable.”https://www.swisstph.ch/en/), to consider what (if any) adaptation of the INQUIRE framework is necessary for lower income settings.Certain criteria or sections of the quality promoters may be difficult to attain in resource-constrained settings and countries. We plan, in collaboration with researchers from the Swiss Public and Tropical Health Institute . Due to the Delphi nature of this study, these items will be considered in future validations and adaptations of the framework.The rapid uptake of the framework in Switzerland has been driven by the broad consensus across Swiss participants of key clinical research stakeholder groups including patients, academia, ethics committees, regulatory and governmental bodies, funding agencies, and the pharmaceutical industry. The development of INQUIRE not only increased stakeholders’ awareness of the “waste issue,” it also represents the conditio sine qua non for any joint future efforts to sustainably increase value. Following up on the national symposium in June and the SCTO roadmap , we willDue to its broad acceptance across international stakeholders and its theoretical underpinning, the framework may further serve as a common structure for other stakeholder groups. We broadly envision 2 categories of operationalization: First, the framework may act as standard criteria—or a common language—for what constitutes high-quality academic clinical research, thereby increasing awareness and stimulating discussions on joint solutions for increasing value and reducing waste across academia and other stakeholder groups. Second, investigators may operationalize the framework at the study level by using the specific questions in https://www.nihr.ac.uk/about-us/our-purpose/principles/adding-value-in-research.htm; cited 2017 Oct 30).“The AViR programme aims to ensure that research funded by the NIHR addresses questions that are relevant to clinicians, patients, and the public; uses appropriate design and methods; is delivered efficiently; results in accessible full publication; and produces unbiased and useable reports. It therefore matches the key goals of the REWARD campaign in tackling waste at every stage of research. Examples of activities promoted by the programme include requiring funding applications for primary research to reference systematic reviews showing what is already known on a topic; ensuring NIHR-funded research is fully reported; and involving patients not only on funding committees, but also in monitoring trials.” Click here for additional data file.S2 Appendix(DOCX)Click here for additional data file.S3 Appendix(DOCX)Click here for additional data file.S4 Appendix(DOCX)Click here for additional data file.S5 Appendix(DOCX)Click here for additional data file.S6 Appendix(DOCX)Click here for additional data file.


Introduction: The rapid and accurate diagnosis of HIV-associated tuberculosis (TB), timely initiation of curative or preventative treatment and assurance of favourable treatment outcomes is a complex process. The current system of monitoring and reporting TB diagnosis and treatment does not include several key aspects of the care cascade, and may obscure systematic bottlenecks, inefficiencies or sources of sub-optimal care.Methods: We critically reviewed the current World Health Organizations recommended system of monitoring and reporting, and identified the following key deficiencies that could limit the ability of healthcare workers to identify structural problems in the provision of TB/HIV care.Results: We identified the following key deficiencies in the current monitoring and evaluation system: (1) an emphasis on national-level reporting and programmatic analysis results in a loss of granularity; (2) the absence of a general framework to anchor indicators in relation to one another as well as the overall goals for TB/HIV collaborative activities; (3) de-linking of TB treatment indicators from those for screening and diagnosis; (4) few indicators are tied to suggested times for completion of an activity. We defined three distinct stages comprising the cascade of HIV-associated TB diagnosis and treatment: (1) Screening & Diagnosis, (2) Treatment and (3) Preventive Therapy. We detailed major steps within each stage, described potential sources of variability, and proposed data elements, process indicators, main outcomes, and retention calculations for each stage.Conclusions: This proposed framework of monitoring is novel in its focus on a cohort experience through the entire scope of the care cascade from screening and TB diagnosis through curative or preventive treatment. This approach can be applied to all settings at clinic, district or national level, and used to identify crucial areas for improvement in order to maximize health outcomes for all those affected by the dual epidemics of TB and HIV. The rapid and accurate diagnosis of HIV-associated tuberculosis (TB), timely initiation of effective treatment (or preventative treatment) and assurance of favourable treatment outcomes is a complex multi-step process, often complicated by inherent resource limitations in the settings where these two epidemics collide. A standardized system for monitoring and reporting of TB diagnosis and treatment was first implemented by the World Health Organization (WHO) in the mid-1990s, as part of the Directly Observed Treatment, Short-course (DOTS) TB control strategy . In respWe critically review the current WHO-recommended tool for monitoring and reporting on HIV-associated TB care and treatment in order to identify gaps. We further explicitly describe the cascade of HIV-associated TB care and propose an enhanced set of indicators for use in routine M&E throughout the diagnostic and treatment pathway of TB/HIV care.The 2015 guide includes 20 core and 16 optional indicators to monitor and report progress at national level. Broadly, these indicators cover TB screening and diagnosis among HIV-infected individuals, HIV testing among TB cases, TB treatment initiation, preventive treatment (PT) and timely start of antiretroviral treatment (ART). The stated goal of the guidance is to assist TB and HIV programme managers, as well as stakeholders and decision-makers in the monitoring and evaluation of collaborative TB/HIV activities by defining a key set of indicators for national  reporting. The emphasis of evaluation is on aggregation of data from individual health facilities at the district, subnational and national levels. Almost all indicators are expressed as a proportion and are defined at the facility level (e.g. proportion of registered new and relapse TB patients with documented HIV status), though some optional indicators are defined in aggregate . Strengths of this guide include the detailed description of each indicator, clearly defined numerators and denominators, as well as the rationale, methodology of data collection, data sources, frequency of measurement, and strengths and limitations. Care has also been taken to avoid double-counting in numerators and denominators, and avoid duplication of efforts in data collection by TB and HIV programmes. The indicators are highly valuable for reporting aggregated statistics and making comparisons between districts and countries on basic metrics.However, several weaknesses exist which reduce the overall potential impact and usefulness of the current M&E system. First, the emphasis on national level reporting and programmatic analysis results in a loss of granularity, which can hinder the identification of the drivers of underperformance or poor outcomes at facility level. For example, a favourable treatment success rate at the national level may obscure high loss to follow-up at individual clinics, where simple interventions such as use of community healthcare workers to trace patients lost to care could be implemented. A second weakness is the absence of a general framework that anchors the indicators in relation to one another as well as the overall goals for TB/HIV collaborative activities. The indicators often “stand alone” from one another, and do not represent the experience of a cohort of individuals along the cascade of diagnosis and care. For example, preventive treatment initiation is often tracked only for individuals with a new HIV diagnosis rather than all patients living with HIV, and a denominator  is rarely recorded. The set of “indicators to measure the cascade of intensified TB case finding” represents an effort to capture the flow from HIV testing, through TB screening, diagnosis and treatment initiation, but key elements of this cascade are simplified. For example, TB diagnosis is treated as a binary event when this is in actuality made up of several key steps, including bacteriological testing, follow-up of test-negative individuals, and drug susceptibility testing (DST). Another weakness is the omission of most indicators of TB treatment, as these are covered in the standard TB programme monitoring. This approach de-links the monitoring of screening and diagnosis from treatment monitoring, for which denominators may not align. Finally, with the exception of the indicator “proportion of HIV-positive new and relapse TB patients having profound immunosuppression (CD4 cell count <50) who are started on ART within 2 weeks of TB diagnosis”, none of the indicators are tied to suggested times for completion of an activity. Timing of events is a crucial component of understanding the flow through the TB/HIV care cascade, and its exclusion may hide suboptimal care, such as lengthy time to TB treatment initiation.In summary, the “Guide to monitoring and evaluation for collaborative TB/HIV activities” offers a valuable set of indicators, particularly at the national and supra-national level. A more holistic approach, with indicators considered as interlinked elements and contextualized within the flow from TB and HIV screening and testing through to treatment (curative or preventive) completion could provide important additional information at facility level.We divided HIV-associated TB care into three stages (1) Screening & Diagnosis, (2) Treatment, and (3) Preventive Therapy . The basIndividuals feeding into the diagnosis stage arise from two sources: individuals living with HIV or of unknown HIV status presenting with symptoms of TB, and individuals screened for TB symptoms during routine HIV care . Major sThe diagnosis stage likely has the most source of variability between settings, as implementation of the four-symptom screen is sub-optimal in most high burden settings , and avaEstimation of overall retention for this stage requires knowledge of the denominators, that is, total number of people presenting with symptoms of TB and total number of HIV-related clinic visits, as well as the numerators, that is, total number classified as TB, stratified as bacteriologically confirmed and clinical, and total number classified as “not TB”, stratified as definite or presumed .Table 1In addition to the estimation of overall retention, various process indicators can be collected, including the proportion of those with presumptive TB providing a sample for bacteriological testing, proportion of sputum results received from the laboratory, proportion of referred patients returning for results, proportion positive by initial diagnostic, proportion smear/Xpert negative followed-up, and proportion receiving knowledge of TB status (TB or “not TB”).The treatment stage encompasses both TB treatment and ART. The starting population consists of individuals who received a TB diagnosis. This stage covers initiation of TB treatment, DST, initiation of ART and cotrimoxazole, and TB treatment monitoring . This stIndividual elements of this treatment stage are likely to vary considerably by country and practice setting. DST may be of limited availability, or may be only be applied to select populations based on background prevalence, limited infrastructure, and budgetary restrictions, among other reasons. Differing treatment algorithms, regimens and availability of treatment for drug resistant TB will cause variability in the timing and length of this stage. Despite these differences in practice, most data elements for DST and drug-resistant TB treatment are already included on TB treatment registers, or could be easily incorporated with little added data capture burden. For simplicity, ART initiation and HIV care including cotrimoxazole preventive therapy, a complex cascade itself , is treaEstimation of overall retention for this stage requires knowledge of the total number of individuals receiving a TB diagnosis at the facility (numerator) and total number of TB patients with known treatment outcomes (inclusive of those not started on treatment) (denominator) .Table 2The preventive therapy stage follows after a diagnosis of “not TB”, or after successful completion of TB treatment PT eligibility is assessed, and duration of PT is determined. This stage ends with documented completion of the PT regimen. Initiation of PT should occur within one month of being assessed as eligible, though the timing of completion will depend on local PT guidelines. Current WHO PT guidelines specify that people living with HIV should be screened for TB at every clinical visit, and that those screening negative should be offered IPT. Ideally, PT should be initiated the same day as a negative screen, but we allow that high patient volumes, clinician shortages and other demands may limit what is accomplished at a single consultation. We therefore chose one month as it represents typical visit spacing, particularly early in HIV care and treatment, and believe that one month represents the maximum amount of time for which a negative symptom screen could be valid, as any longer time period would require a new screen.PT guidelines may vary between settings in terms of eligibility, regimen, and duration. Completion of PT can be based on prescription pick up, but may also incorporate patient self-report of adherence or pharmacy records. As with Stage 2 (Treatment), ART and CPT initiation or continuation are included as a single simplified step.Estimation of overall retention for this stage requires knowing the total number of individuals who are eligible for PT (denominator) and the total number completing their PT regimen (nominator) .Table 3A comprehensive system of monitoring and evaluation such as we have proposed here not only facilitates an understanding of the successes and challenges programmatic implementation and assists in identifying areas which require improvement, but also promotes accountability within the health care system. Ideally, this system would be implemented routinely in settings where TB and HIV care occur, with at least annual standardized analysis of both main outcomes and process indicators. Indeed many of the data elements proposed herein are already routinely captured. Through simple modifications of standardized logs and registers, such as the sputum collection log, additional elements could be added in to systems which are already in place. We acknowledge, however, that collection of good-quality data can be time consuming and burdensome when systems are not seamless, or when duplication occurs through overlapping programs. Further, scarce resources may limit the ability to provide consistent and quality data monitoring in some settings. In these cases, we propose that this system is implemented periodically with the assistance of a dedicated data capturing team, and perhaps targeted only to problematic districts or facilities. Where possible, once problems have been identified, a follow-up round of monitoring can occur in order to measure progress.The WHO recently released ambitious 2025 targets for TB control, including halving TB incidence and reducing TB deaths by 75% . AlthougWe aimed to develop a more holistic, integrated system for monitoring of HIV-associated TB care that draws a focus to the integration of diagnosis, treatment and prevention as related, rather than separate programmatic goals. We hope this will stimulate discussion and debate on the precise data elements and outputs that can enhance monitoring of the process in order to improve patient outcomes, but do not place an undue burden on care providers and public health workers. We envision this framework to be implemented and interpretable at the individual facility level, where setting-specific problems need to be identified and acted upon. Data could then also be aggregated at the district and national level to facilitate comparison between programmes and identify broad areas for investment and improvement.


Geospatial artificial intelligence (geoAI) is an emerging scientific discipline that combines innovations in spatial science, artificial intelligence methods in machine learning , data mining, and high-performance computing to extract knowledge from spatial big data. In environmental epidemiology, exposure modeling is a commonly used approach to conduct exposure assessment to determine the distribution of exposures in study populations. geoAI technologies provide important advantages for exposure modeling in environmental epidemiology, including the ability to incorporate large amounts of big spatial and temporal data in a variety of formats; computational efficiency; flexibility in algorithms and workflows to accommodate relevant characteristics of spatial  processes including spatial nonstationarity; and scalability to model other environmental exposures across different geographic areas. The objectives of this commentary are to provide an overview of key concepts surrounding the evolving and interdisciplinary field of geoAI including spatial data science, machine learning, deep learning, and data mining; recent geoAI applications in research; and potential future directions for geoAI in environmental epidemiology. Spatial science, also referred to as geographic information science, plays an important role in many scientific disciplines as it seeks to understand, analyze, and visualize real-world phenomena according to their locations. Spatial scientists apply technologies such as geographic information systems (GIS) and remote sensing to spatial  data to achieve these objectives – to identify and make sense of patterns in space. Tied to the current era of big data is the real-time generation of spatial big data, which have become ubiquitously available from geotagged social media posts on Twitter to environmental sensors collecting meteorological information . It has The scientific field of geospatial artificial intelligence (geoAI) was recently formed from combining innovations in spatial science with the rapid growth of methods in artificial intelligence (AI), particularly machine learning , data mining, and high-performance computing to glean meaningful information from spatial big data. geoAI is highly interdisciplinary, bridging many scientific fields including computer science, engineering, statistics, and spatial science. The innovation of geoAI partly lies in its applications to address real-world problems. In particular, geoAI applications were showcased at the inaugural 2017 Association of Computing Machinery (ACM) Special Interest Group on Spatial Information (SIGSPATIAL) International Workshop on GeoAI: AI and Deep Learning for Geographic Knowledge Discovery , which included advances in remote sensing image classification and predictive modeling for traffic. Further, the application of AI technologies for knowledge discovery from spatial data reflects a recent trend as demonstrated in other scientific communities including the International Symposium on Spatial and Temporal Databases. These novel geoAI methods can be used to address human health-related problems, for example, in environmental epidemiology . In partThe purpose of this commentary is to provide an overview of key concepts surrounding the emerging field of geoAI; recent advances in geoAI technologies and applications; and potential future directions for geoAI in environmental epidemiology.Several key concepts are currently at the forefront of understanding the geospatial big data revolution. Big data, such as electronic health records and customer transactions, are generally characterized by a high volume of data; large variety of data sources, formats, and structures; and a high velocity of new data creation –7. As a Spatial data science is a niche and still forming field focused on methods to process, manage, analyze, and visualize spatial big data, providing opportunities to derive dynamic insights from complex spatial phenomena . Spatial2 of high-resolution imagery each year as part of its constellation of commercial satellites including the WorldView and GeoEye spacecraft [As spatial data science continues to evolve as a discipline, spatial big data are constantly expanding, with two prominent examples being volunteered geographic information (VGI) and remote sensing. The term VGI encapsulates user-generated content with a locational component . In the acecraft . The U.Sacecraft .Data science involves the application of methods in scientific fields such as artificial intelligence (AI) and data mining. AI refers to machines that make sense of the world, automating processes that create scalable insights from big data , 20. MacGeospatial artificial intelligence (geoAI) is an emerging science that utilizes advances in high-performance computing to apply technologies in AI, particularly machine learning  and data mining to extract meaningful information from spatial big data. geoAI is both a specialized field within spatial science because particular spatial technologies, including GIS, must be used to process and analyze spatial data, and an applied type of spatial data science, as it is specifically focused on applying AI technologies to analyze spatial big data. The first-ever International Workshop on geoAI organized as part of the 2017 ACM SIGSPATIAL International Conference on Advances in Geographic Information Systems brought together scientists across diverse disciplines, including geoscientists, computer scientists, engineers, and entrepreneurs to discuss the latest trends in deep learning for geographical data mining and knowledge discovery. Featured geoAI applications included deep learning architectures and algorithms for feature recognition in historical maps ; multi-sGiven the advances and capabilities on display in recent research, we can begin to connect the dots regarding how geoAI technologies can be specifically applied to environmental epidemiology. To determine the factors to which we may be exposed and thus may influence health, environmental epidemiologists implement direct methods of exposure assessment, such as biomonitoring , and indirect methods, such as exposure modeling. Exposure modeling involves the development of a model to represent a particular environmental variable using various data inputs  and statistical methods  . ExposurgeoAI methods and big data infrastructures  can be applied to address challenges surrounding exposure modeling in environmental epidemiology – including inefficiency in computational processing and time (particularly when big data are compounded with large geographic study areas) and data-related constraints that affect spatial and/or temporal resolution. For example, previous exposure modeling efforts have often been associated with coarse spatial resolutions, impacting the extent to which the exposure model is able accurately estimate individual-level exposure , as well as limitations in temporal resolution which may result in failure to capture exposures during time windows relevant to developing the disease of interest . Advance2.5) in Los Angeles, CA, USA [2.5 concentrations. This spatial data mining approach addresses important issues in air pollution exposure modeling regarding the spatial and temporal variability of the relevant “neighborhood” within which to determine how and which factors influence predicted exposures . Using millions of geographic features available from OSM, the algorithm to create the PM2.5 exposure model first identified U.S. Environmental Protection Agency (EPA) air monitoring stations that exhibited similar temporal patterns in PM2.5 concentrations. The algorithm next trained a random forest model (a popular machine learning method using decision trees for classification and regression modeling) to generate the relative importance of each OSM geographic feature. This was performed by determining the geo-context, or which OSM features and within what distances  are associated with air monitoring stations (and their measured PM2.5 levels) characterized by a similar temporal pattern. Finally, the algorithm trained a second random forest model using the geo-contexts and measured PM2.5 at the air monitoring stations to predict PM2.5 concentrations at unmeasured locations . Prediction errors were minimized through incorporating temporality of measured PM2.5 concentrations in each stage of the algorithm, although modeling would have been improved with time-varying information on predictors. The model predictive performance using measured PM2.5 levels at the EPA air monitoring stations as the gold standard showed an improvement compared to using inverse distance weighting, a commonly used spatial interpolation method [A recent example of geoAI in action for environmental exposure assessment was a data-driven method developed to predict particulate matter air pollution < 2.5 μm in diameter  demonstrates several key advantages for exposure assessment in environmental epidemiology . geoAI aFurther, the flexibility of geoAI workflows and algorithms can address properties of environmental exposures  that are often ignored during modeling such as spatial nonstationarity and anisotropy . Spatial2.5 (irrespective of time and space) is not selected as part of a data-driven method for inclusion into exposure modeling, this may require modifications to the algorithm, evaluation of the input data, etc. Finally, as a currently evolving field, geoAI requires the expertise of multiple disciplines, including epidemiology, computer science, engineering, and statistics, to establish best practices for how to approach environmental exposure modeling given the complexities introduced by the biological, chemical, and physical properties of different environmental exposures, wide-ranging algorithms that can be developed and applied, and heterogeneous spatial big data characterized by varying scales, formats, and quality.Ultimately, geoAI applications for environmental epidemiology move us closer to achieving the goal of providing a highly resolved and more accurate picture of the environmental exposures to which we are exposed, which can be combined with other relevant information regarding health outcomes, confounders, etc., to investigate whether a particular environmental exposure is associated with a particular outcome of interest in an epidemiologic study. However, as with any exposure modeling endeavor, there must be careful scrutiny of data quality and consideration of data costs. In the context of the Lin et al. (2017) study , althouggeoAI is an emerging interdisciplinary scientific field that harnesses the innovations of spatial science, artificial intelligence (particularly machine learning and deep learning), data mining, and high-performance computing for knowledge discovery from spatial big data. geoAI traces part of its roots from spatial data science, which is an evolving field that aims to help organize how we think about and approach processing and analyzing spatial big data. Recent research demonstrates movement towards practical applications of geoAI to address real-world problems from feature recognition to image enhancement. geoAI offers several advantages for environmental epidemiology, particularly for exposure modeling as part of exposure assessment, including the capability to incorporate large amounts of spatial big data of high spatial and/or temporal resolution; computational efficiency regarding time and resources; flexibility in accommodating important features of spatial  processes such as spatial nonstationarity; and scalability to model different environmental exposures in different geographic areas. Potential future geoAI applications for environmental epidemiology should utilize cross-disciplinary approaches to developing and establishing rigorous and best practices for exposure modeling that includes careful consideration of data quality and domain-specific expertise.