Type 2 diabetes mellitus (T2DM) is now one of the leading causes of disease-related deaths globally. India has the world’s second largest number of individuals living with diabetes. Lifestyle change has been proven to be an effective means by which to reduce risk of T2DM and a number of “real world” diabetes prevention trials have been undertaken in high income countries. However, systematic efforts to adapt such interventions for T2DM prevention in low- and middle-income countries have been very limited to date. This research-to-action gap is now widely recognised as a major challenge to the prevention and control of diabetes. Reducing the gap is associated with reductions in morbidity and mortality and reduced health care costs. The aim of this article is to describe the adaptation, development and refinement of diabetes prevention programs from the USA, Finland and Australia to the State of Kerala, India.The Kerala Diabetes Prevention Program (K-DPP) was adapted to Kerala, India from evidence-based lifestyle interventions implemented in high income countries, namely, Finland, United States and Australia. The adaptation process was undertaken in five phases: 1) needs assessment; 2) formulation of program objectives; 3) program adaptation and development; 4) piloting of the program and its delivery; and 5) program refinement and active implementation.The resulting program, K-DPP, includes four key components: 1) a group-based peer support program for participants; 2) a peer-leader training and support program for lay people to lead the groups; 3) resource materials; and 4) strategies to stimulate broader community engagement. The systematic approach to adaptation was underpinned by evidence-based behavior change techniques.K-DPP is the first well evaluated community-based, peer-led diabetes prevention program in India. Future refinement and utilization of this approach will promote translation of K-DPP to other contexts and population groups within India as well as other low- and middle-income countries. This same approach could also be applied more broadly to enable the translation of effective non-communicable disease prevention programs developed in high-income settings to create context-specific evidence in rapidly developing low- and middle-income countries.ACTRN12611000262909. Registered 10 March 2011.Australia and New Zealand Clinical Trials Registry:  Type 2 diabetes mellitus (T2DM) is now one of the leading causes of disease-related deaths globally . India hSeveral large efficacy trials including the Diabetes Prevention Study in Finland (Fin-DPS) , the UniTo date, cultural adaptation of T2DM prevention programs has mainly occurred with ethnic groups or indigenous population within HICs and has included settings such as churches , health To address this critically important evidence-practice gap, our team has developed the Kerala Diabetes Prevention Program (K-DPP), a culturally tailored, community-based and peer-led diabetes prevention intervention for individuals at high risk of developing T2DM in the state of Kerala, India. This paper describes the development and piloting of the program and we discuss the learnings so far and the implications for future program adaptation elsewhere. Although screening and recruitment are important parts of diabetes prevention programs, it is outside the scope of this paper to describe the process undertaken in K-DPP, however, details have been previously published . The desDue to the lack of evidence-based diabetes prevention programs in India and other LMICs , the K-DThe needs assessment phase involved the triangulation of: available evidence from policy and program documents relevant to diabetes prevention in Kerala and India; empirical studies on the prevalence and control of diabetes in India; and lay perceptions of T2DM from focus groups held in communities where the program was to be delivered. The complete detail of the needs assessment has been previously published,  however,Due to the paucity of intervention studies underpinned by socio-behavioral theories in the Indian context, there existed very limited evidence on the application of behavior change theories and determinants of target behaviors. As such, the Health Action Process Approach model  was utilDuring Phase 3, the program objectives along with the findings from the needs assessment were used to inform the development of the K-DPP intervention model and its delivery appropriate to the Keralan context. The suggested behavior change techniques were mapped onto Michie et al.’s Behavior Change Technique (BCT) Taxonomy v1 . The BCTThe program was piloted in one of the communities randomly selected from the trial sampling frame. Participants were selected using the Indian Diabetes Risk Score, the details of which have previously been described . The piln = 500; control arm, n = 507) were recruited directly from the community through home visits. Participants were at high-risk of diabetes , aged 30-60 years (mean age 46.0 ± 7.5 years) and 47.2% were women [The findings from the four developmental phases then informed program implementation as part of a cluster randomized control trial. Participants . All participants had pre-diabetes (fasting blood glucose 110-125 mg/dl) and came from the Thiruvananthapuram District. Content analysis of the FGDs revealed: a general interest to know more about diabetes and its prevention; the commonplace and somewhat ‘normalized’ nature of lifestyle risk factors such as unhealthy diet and physical inactivity; a lack of awareness of T2DM risk; a limited understanding of measures to prevent T2DM; and low self-efficacy regarding the ability to make and sustain lifestyle changes [Three FGDs were held, each with six participants  to share knowledge more broadly, as well as additional community activities to assist in achieving program goals and maintenance see Fig. . Formingn = 12 participants). Male participants had lower attendance rates (2/7) compared to females (10/19). A total of 28 family members also attended the pilot sessions.A total of 26 participants  aged 31- 60 years were enrolled in two separate groups to pilot the program. The mean attendance rate of participants for the four small group sessions was 46.1%  and twelve peer-led small group sessions.Diabetes Education Sessions (DPES 1 and DPES 2) were delivered by local healthcare experts to the program participants from 2 to 3 neighborhoods within close proximity. The aims of the sessions were to increase knowledge of T2DM and its risk factors, targets for behavior change and to highlight the benefits of participating in the small group sessions. DPES 1 provided basic information on T2DM and its management. DPES 2 focused on the rationale behind and means for modifying the risk factors to prevent T2DM. As in the pilot, participants were encouraged to bring their family members along to both DPES 1 and DPES 2.Each K-DPP group comprised 10-20 people recruited from the same community. The small group sessions were delivered at locations convenient for participants, such as community centres, local reading rooms, and schools. The first four sessions took place fortnightly, and subsequent sessions were conducted monthly over the duration of ten months. Each session lasted for 60 to 90 min. The program started with an inaugural small group session, where participants were briefed about the program and provided with the participant resource material. The participants from each group selected two peer-leaders , from within the group. Subsequent small group sessions covered six topics: a) healthy diet ; b) approaches to increase physical activity ; c) weight loss ; d) tobacco control and cessation; e) alcohol consumption reduction; and f) adequate sleep. Various strategies were employed to enhance participants’ knowledge on how to reduce their diabetes risk, such as through information provision, storytelling and problem solving. Sessions were planned to be flexible in style and management. The local resource person informed the participants of the time and venue of the sessions either by home visit or telephone call, and followed up attendance. Participants were encouraged to send another family member to any small group sessions where they were unable to attend themselves. This provided an opportunity for participants to understand what occurred during the sessions they may have missed and to spread the knowledge of the program among family members. If a participant missed two or more consecutive sessions, telephone calls were made to the participant by the K-DPP research team, followed by house visits by the local resource persons. Table 2.Peer-leader training program and ongoing support3.Resource materialsPeer-leaders, both male and female, were nominated from each group based on their level of education, willingness to lead the group, social credibility and acceptance by their group members. Peer-leaders underwent two training blocks of two days duration each. The first training block focused on knowledge and skill building in relation to diabetes prevention and group facilitation. In the second training block, taking place after the fifth small group session, experiences in conducting sessions were shared, and strengths as well as need for support from the K-DPP team and ways to improve the conduct of the sessions were identified. Each of the training blocks were attended by peer-leaders from seven to eight clusters, with at least one peer-leader from each cluster (average number per training block = 12 peer leaders). Peer-leader training was important for the initial building of knowledge and skills, but also provided a platform for sharing and support between the peer-leaders and helped to sustain motivation and confidence. The K-DPP intervention team provided on-going support to peer-leaders via telephone before and after each small group session. Additionally, peer leaders participated in a “peer leader’s follow up session” to brief on the activities conducted in their locality involving potential community stakeholders for knowledge dissemination and community partnership for healthy lifestyle behaviors. These stakeholders included: members from Kudumbashree State Mission ; residents’ associations; arts and sports club members and organizers; and members from religious organizations. Such forums enabled the peer leaders to have varied perspective of integrating the program to the existing community networks.4.Strategies for community engagementEach participant received a Participant Handbook and a Participant Workbook in the local language . The Participant Handbook contained information about T2DM, its risk factors, target behaviors and strategies to assist in behavior change, which the peer-leader or the participants could refer to during the sessions. The Participant Workbook includes tools for self-monitoring of behavior; goal settings for diet, physical activity, tobacco and alcohol use; and goal review. In addition, peer-leaders received a Peer-Leader Handbook, which expanded upon the Participant Handbook and Workbook and has hands-on instructions on how to facilitate the activities guiding the work during each session.The program implementation involved strong collaboration and engagement with the Panchayats . Each Panchayat nominated a local resource person, mostly ASHAs from the State public health services to support implementation. The local resource person was the first point of contact for each community and their role remained strong throughout the program. The involvement of family and community members was also encouraged to support the participants’ lifestyle changes through creating favourable social norms. Engagement of community members was enhanced through community-based activities held in the local neighborhoods. These included events to be conducted separately from the regular group sessions to assist the group members to make their behavioral goals practical such as walking groups, yoga clubs, and kitchen garden training to promote the cultivation and consumption of vegetables. Additionally, the role and reputation of the Indian institution behind the K-DPP project, the Sree Chitra Tirunal Institute for Medical Science and Technology (SCTIMST), was seen as an important contributing factor to program engagement. SCTIMST is an institute of national importance established by an Act of the Indian parliament in 1980 and has a positive reputation in the Kerala society. The Institute has a longstanding history of delivering patient care of high quality, technology development of industrial significance and health research studies of social relevance. The Achutha Menon Centre for Health Science Studies, the public health wing of SCTIMST is recognized as a centre of excellence for public health.While 80% of NCDs occur in LMICs , the majThis study highlights the alignment of implementation science with cultural adaptation, both of which ultimately aim to translate and deliver interventions to improve the use and impact of evidence-based practices in new contexts. Cabassa et al.  states tAs K-DPP originates from programs in Finland , 14, theThe short history of NCD prevention and the paucity of relevant research in India made it crucial for our research group to conduct a comprehensive needs assessment and a more careful, phased program planning and adaptation process than had typically been the case in implementation studies in the HIC’s. The needs assessment showed a high prevalence of the behavioral risk factors and NCDs in the State of Kerala, with lack of services and mechanisms within the health system to curb the rising rates of disease . This phThe pilot study provided insights into the challenges of implementation and enabled suggestions for feasible and effective ways of adapting the program to reflect the community needs. First and foremost, a strong link between prevention and disease management needed to be established to make the program relevant for the participants. Additionally, we encountered problems with male participation. Despite actions such as incorporating male peer-leaders and adjusting session timing to fit working schedules, attendance by male participants remained lower than female’s throughout the program. This challenge may be explained in part by a perception that health related activities are predominately linked with women. Until recently, the only health service delivered at a local level was maternal and child health with women being the major focus . StrategThe implementation of the program highlighted many lessons that are likely transferable to other community-based prevention projects. Firstly, engagement of participants, peer-leaders and local resource persons was crucial. The high reputation of the implementing institute (SCTIMST) was important for raising the profile of the program amongst community members and enhancing engagement. Secondly, strong community links and support was necessary to assist the program to mobilize extra-curricular activities. The involvement of the local leaders, community resource persons and the peer-leaders at each stage was crucial, whilst also challenging to undertake in a way that did not compromise the program fidelity. Thirdly, the program content needed to be relevant to the participants. Finally, the peer-leaders required on-going support to enhance confidence and motivation to run the program. The use of lay peer-leaders over health professionals adds strength to this study as it overcomes the need to rely on resource-intensive health professionals. The resulting program, K-DPP, was built around a core of peer-led, community-based small group sessions supported by expert-led education sessions and extracurricular activities.The development of K-DPP demonstrates the feasibility of adapting evidence-informed prevention programs to LMIC settings such as India. The phased approach to program development and adaptation from HIC employed in this study could be utilized for cultural translation of any program. The process systematically explored the local context and interlinked it with evidence-based behavior change techniques tested elsewhere. The knowledge generated through the process of translation of K-DPP will benefit policy makers, action implementers, service providers, and eventually wider populations in India and similar countries. Lessons learnt from the implementation of K-DPP would also have applicability to other rapidly developing LMICs in the Asia, Pacific and African regions where there is an urgent need of such interventions to control the growing numbers of cases with chronic diseases.


More than one-fourth of Australian adolescents are overweight or obese, with obesity in adolescents strongly persisting into adulthood. Recent evidence suggests that the mid-teen years present a final window of opportunity to prevent irreversible damage to the cardiovascular system. As lifestyle behaviors may change with increased autonomy during adolescence, this life stage is an ideal time to intervene and promote healthy eating and physical activity behaviors, well-being, and self-esteem. As teenagers are prolific users and innate adopters of new technologies, app-based programs may be suitable for the promotion of healthy lifestyle behaviors and goal setting training.This study aims to explore the reach, engagement, user experience, and satisfaction of the new app-based and Web-based Health Online for Teens (HOT) program in a sample of Australian adolescents above a healthy weight  and their parents.HOT is a 14-week program for adolescents and their parents. The program is delivered online through the Moodle app–based and website-based learning environment and aims to promote adolescents’ lifestyle behavior change in line with Australian Dietary Guidelines and Australia’s Physical Activity and Sedentary Behaviour Guidelines for Young People (aged 13-17 years). HOT aims to build parental and peer support during the program to support adolescents with healthy lifestyle behavior change.Data collection for this study is ongoing. To date, 35 adolescents and their parents have participated in one of 3 groups.HOT is a new online-only program for Australian adolescents and their parents that aims to reduce cardiovascular disease risk factors. This protocol paper describes the HOT program in detail, along with the methods to measure reach, outcomes, engagement, user experiences, and program satisfaction.Australian New Zealand Clinical Trials Registry ACTRN12618000465257; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374771DERR1-10.2196/13340 At present, more than one-fourth of Australian adolescents aged 14 to 17 years are overweight or obese, which is significantly higher than 20 years ago . PreviouAdolescence is a period of transition during which autonomy and independence increase. During this life stage, autonomy over food choice  and inflAdolescents are early adopters of technology and generally are innately accepting of innovative methods of communication and learning. In 2015, it was estimated that 65% of Australian teenagers aged 14 to 17 years used a mobile phone to access the internet, 74% used a computer to access the internet, and 80% had a smartphone . MoreoveA new program, Health Online for Teens (HOT), is the first Australian online-only, expert-supported group intervention involving parental and peer support for obesity prevention in adolescents. HOT is underpinned by theories of behavior change and self-determination and recognizes the importance of engagement in lifestyle choices at a critical, yet pliable, period of transition. Covering the key areas of overcoming peer pressure, maintaining a healthy diet, and being physically active as well as emotional well-being, HOT provides opportunities for teens (and their parents) to gain improved lifestyles through goal setting and peer and expert support.The objective of this study is to determine the feasibility of a new online healthy lifestyle program (HOT) to improve lifestyle-related behaviors in a sample of Australian adolescents above a healthy weight. Specifically, this study aims to (1) obtain feedback from a sample of overweight or obese teens who will be asked to discuss the content, features, and design of HOT and (2) determine the feasibility of HOT through pilot testing in a sample of up to 45 adolescents and collecting data on recruitment, retention, and engagement over the course of the 14-week program. This publication describes the study methods and rationale to achieve these research aims.This study is a nonrandomized intervention feasibility trial  that aimThis paper reports the protocol of intervention and evaluation of HOT in line with the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist  26,27].,27.26,27To assess engagement and use of the HOT program and its components and Health Online for Teens chat-bot (HOT-BOT) by teenage participantsTo assess engagement and use of HOT and parent resources by parents or caregivers of the participantsTo determine the reach of HOT recruitment and representativeness of the target populationTo determine the effectiveness of the program to support teenagers to achieve healthy lifestyle goals and improve weight, diet and activity behaviors, and self-perception To determine program satisfaction and process evaluation data from participantsTo conduct focus groups and/or interviews to deeply explore the participants’ HOT experience, thoughts on the content, appearance and design of the program and its elements, and barriers or enablers to engagementAustralian adolescents will be recruited from the community through social media advertising. Adolescent participants express interest to participate in the study through an online survey administered through Qualtrics . Qualtrics is an online survey tool that is supported by the researchers’ host institution. Adolescents expressing an interest to participate will be screened against several inclusion and exclusion criteria. Eligible adolescents include girls and boys, aged between 13 and 17 years at enrollment, who are above a healthy weight for their age and gender, not pregnant or breastfeeding, with access to Wi-Fi at home. Eligible parents or caregivers of included adolescents can be of any age, and typically, 1 to 2 parents or caregivers are anticipated to be included for each adolescent. Adolescent participants will be identified as above a healthy weight  using self-reported height and weight and weight status from BMI  . Groups The online HOT program aims to support overweight or obese adolescents to improve their lifestyle, through setting goals and making sustainable changes to diet and activity patterns. The HOT program aims to improve knowledge on healthy diet, activity, and emotional well-being and build skills and capacity for teens to plan ahead, set their own goals, and reflect and evaluate on their progress. The HOT program encourages participants to seek support from parents and peers to facilitate a home improvement, which is supportive of a healthy lifestyle and self-esteem.The HOT program has a number of principles that inform program targets and strategies that are promoted to achieve the targets . These tGoal setting is a key element of HOT, and although HOT participants set their own goals around diet and activity and monitor their progress, HOT aims to address common adverse behaviors for adolescents, including skipping breakfast, frequent fast food intake, high levels of sedentary behavior, and low levels of physical activity, by encouraging individual goal setting in these areas. HOT employs the use of SMART goals  that areAdolescents participating in HOT will be loaned an iPad Mini for the duration of the project. The iPad is configured with the apps required for the project (Moodle and Facebook Messenger) and will be delivered to the adolescents approximately 1.5 weeks before they start the program. On safe return of equipment at the end of the program, families will receive an Aus $50 gift card for either Apple iTunes/App Store or Coles Myer in recognition of their contribution to this study. Adolescents will be provided with their HOT login and will be able to log in to Moodle from any other device as they wish. Parents will not be loaned any device during HOT but will be given a login to access HOT for themselves using their own personal devices (smartphone or tablet) or computer (desktop or laptop). Parents and adolescents will have access to the same HOT content; however, there will be separate spaces for parents and adolescents to connect with their peers through a discussion forum. In addition to HOT sessions, parents will have access to specifically tailored information including supporting your teen to meet HOT targets, communicating with your teen, your teen and body image, healthy lifestyle guidelines for adults , and a collection of additional parent resources (Web links).A mixed-methods approach comprising quantitative and qualitative evaluation will be used to evaluate the feasibility of HOT. This project aims to evaluate the feasibility of HOT, including population characteristics (program reach), program outcomes (indication of program effectiveness), processes (program implementation), engagement (program use), and acceptability (program satisfaction) measures. A summary of measures and the time of assessment are described in Program outcomes will be determined through pre-post program changes in lifestyle behaviors associated with increased cardiovascular risk and obesity  as well as changes in adolescent self-perception domains and overall self-esteem. Adolescents will be asked to complete online preprogram and postprogram semiquantitative surveys that assess key lifestyle behaviors. Self-reported adolescent height and weight will be used to calculate BMI z-score  and IOTFUsage of the program will be measured using metrics, together with program satisfaction evaluation will inform adolescent engagement with the program elements and its acceptability. Data on program engagement for both parents and teens will be obtained from the online metrics collected by Moodle and Chatfuel, where applicable. Usage metrics will include weekly sessions viewed , total number of hits (n), average number of hits per week , number of individual sessions on Moodle (n), number of forum posts (n), and number of chatbot weekly check-ins completed .Parent and adolescent satisfaction with the HOT program will be explored by a purpose-designed questionnaire that is distributed postprogram.t tests will be used to analyze changes in outcomes over time for parametric data, whereas the Wilcoxon signed-rank test will be used for paired pre-post nonparametric data. The alpha value will be set at .05. The proportion of adolescents meeting recommendations for diet, physical activity, and sedentary time as per Australian Guidelines [Participants will be allocated unique identification (ID) numbers at enrollment, and all data collected will be recorded against this ID number; hence, evaluation data will be deidentified for research purposes. All questionnaires will be completed online through Qualtrics. The collection of evaluation data online has considerable advantages by avoiding manual data entry by research staff, minimizing data entry errors and staff time. Direct data entry also enables the research team immediate access to the data by downloading directly to IBM SPSS v23 (IBM Corp). As there is no control group for this healthy lifestyle intervention, preprogram and postprogram changes in lifestyle measures and child anthropometric data will be reported descriptively. Continuous data will be analyzed in SPSS and reported as means (95% CI lower limit to upper limit) or medians (interquartile range), as appropriate, and categorical data will be reported as n (%). Repeated-measures paired idelines  before aOn completion of HOT, parents and adolescents may be invited to participate in an interview or focus group to more deeply explore user experience in HOT. Qualitative semistructured interviews and/or focus groups will be conducted face-to-face for those living in the Adelaide area or over the phone for rural, remote, and interstate participants. Interview schedules will broadly aim to explore the user experience and usefulness of HOT for both adolescents and their parents. Interview questions will probe experiences for adolescents and their parents and will aim to capture what participants were seeking when they enrolled into HOT (including perception of lifestyle problems and their severity), what changes they have made to their lifestyle as a result of participating in HOT, what challenges to making behavior changes were encountered when participating in HOT, and what additional content and/or support would have helped to get more out of the HOT program, including to make suggested lifestyle behavior changes. A more detailed indicative interview schedule is presented in Qualitative semistructured interviews and/or focus groups will be audio-recorded and transcribed verbatim. Data will be entered and coded in NVivo version 10 qualitative data analysis software  and analyzed thematically. All data, including qualitative data, will be deidentified and stored in a secure, password-protected drive with access only available to the research team members.The authors of this paper comprise the multidisciplinary steering committee for the project that includes an advanced accredited practicing dietitian, accredited practicing dietitians, a registered nutritionist, a physiotherapist, and health psychology and digital health experts. The project governance will also comprise a 4-member Expert Advisory Committee comprising the HOT project manager including 3 Australian experts in the areas of nutrition and dietetics, physical activity, and electronic health and behavior change and are external to the administering institution. Any publications arising from this study will be reviewed by all members of the steering committee before submission, and authorship will be decided according to contribution.Data collection for this study is ongoing. To date, 35 adolescents and their parents have participated in one of 3 groups.Multiple health risk behaviors are recognized to emerge and cluster during the adolescent life stage, including cigarette smoking, alcohol consumption, and drug use . AlthougAdolescent obesity remains a public health concern in Australia and many other Western nations. This study aims to explore the feasibility of the new online program HOT that promotes lifestyle behavior change for adolescents who are above a healthy weight. If this program is deemed to be feasible and acceptable for adolescents and their parents, program effectiveness will be explored in a subsequent randomized controlled trial. It is important to note that while preliminary pre-post outcome measures will be collected in this sample, these data will be used to inform sample size calculations for a larger randomized controlled trial rather than implying intervention effectiveness. Feedback from users will be incorporated in future intervention delivery where possible to improve the experience of future users.


Dengue is an increasing public health concern worldwide and requires efficient laboratory diagnostics. We evaluated three commercially available dengue rapid diagnostic tests—the Humasis Dengue Combo NS1 & IgG/IgM , SD Bioline Dengue Duo NS1 Ag & IgG/IgM , and CareUS Dengue Combo NS1 and IgM/IgG kits —and compared them to reference immunoglobulin M (IgM) or immunoglobulin G (IgG) ELISAs and quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays. In total, 109 dengue-positive samples from children with acute symptomatic dengue and 63 dengue-negative samples from febrile and asymptomatic individuals were collected. For the nonstructural 1 protein (NS1) Ag test, the sensitivity and specificity were in the following order: CareUS (79.82 and 100%), Humasis (63.30 and 100%), and SD Bioline (48.62 and 100%). For IgM and IgG, CareUS had the highest sensitivities and specificities , followed by SD Bioline , and Humasis . The IgM kits were more sensitive than the NS1 Ag or IgG kits; however, combining NS1 Ag and IgM reduced the number of missed cases. Therefore, the NS1 Ag plus IgM dengue kits increase the accuracy of the results. In our study, the CareUS Dengue Combo NS1 and IgM/IgG kit showed higher accuracy in performance with reference to qRT-PCR and ELISA results. Aedes aegypti. Since the end of the 20th century, dengue infection has been found to be common in subtropical areas, and has also been reported in urban areas [Dengue fever is caused by four serotypes of dengue virus (DENV)—DENV1, DENV2, DENV3, and DENV4—and is transmitted mainly by an areas . The Woran areas , resultian areas . In partan areas . Tragicaan areas .The early diagnosis of patients with dengue is critical for timely clinical intervention, etiological investigations, and in disease control . The WHORecently, based on immunochromatographic or immunoblot technologies, commercially available DENV kits have been developed for the rapid detection of dengue infections. Dengue rapid diagnostic test (anti-dengue IgM/ IgG RDT) kits yield results in less than 15 min, are simple to perform and, therefore, are used widely as a point-of-care test in outpatient clinics and emergency departments . These kHere, we selected commercially available Humasis, SD Bioline, and CareUS dengue NS1 and IgM/IgG RDTs. The performances of these three RDT kits were compared and evaluated using samples from children with acute dengue in Myanmar. Moreover, we evaluated the performances of these RDTs in patients with primary and secondary serological profiles and those classified by DENV diagnosis using WHO guidelines and DENV serotypes. The evaluations were performed using existing qRT-PCR- and IgM/IgG ELISA-based diagnostic tests as references.Blood samples were collected from patients with suspected dengue fever at the Yankin Children Hospital in Yangon in Myanmar from October 2015 to August 2016. Clinical diagnoses of dengue were categorized as dengue, dengue with warning signs, or severe dengue, according to the WHO guidelines . A totalThis protocol was designed based on in-house real-time RT-PCR and IgM/IgG ELISA. Dengue-positive and -negative cases were used for the comparative evaluation of the performances of three rapid diagnostic (RDT) kits: Humasis Dengue Combo NS1 and IgM/IgG , SD Bioline Dengue Duo NS1 and IgM/IgG , and CareUS Dengue Combo NS1 & IgM/IgG .The presence of dengue virus and the corresponding serotype was confirmed by qRT-PCR and sequencing. The theoretical specificity of the system was investigated using BLAST against the NCBI nucleotide database. RNA was extracted from the serum sample obtained from each patient with clinically diagnosed with dengue fever using the QIAamp Viral RNA kit  and used as template for qRT-PCR using a DiaStar OneStep Multiplex qRT-PCR Kit . Newly designed DENV 1–4 primers and probes  were useThe blood and serum samples were tested for dengue IgM/IgG using a Dengue IgG and IgM ELISA  according to the manufacturer's instructions. Briefly, dengue serum samples were diluted 1:20 (IgG) and 1:1000 (IgM) in dilution buffer, and then 100 μL of the mixture was added to each well. After incubating for 10 min, the wells were washed and 100 μL of enzyme conjugate (anti-dengue IgM or IgG antibody labeled with peroxidase) was added to each well. After incubating for 10 min, the plates were washed and the conjugated complex was visualized by adding 100 μL of TMB solution to the wells. After incubating for 10 min, the reaction was stopped by adding 100 μL of stop solution, and the plate was then read at 450 nm using a microtiter plate reader. Positive determinations were made against the provided IgM and IgG reference sera .The Dengue Combo NS1 Ag and IgG/IgM Ab Rapid Test is a qualitative membrane-based immunoassay for the detection of NS1 antigen and IgG/IgM antibodies in human serum/plasma/whole blood. The test kit consists of one device for detecting the dengue NS1 antigen, and a second device for the differential detection of dengue IgG/IgM antibodies. All tests were performed in accordance with the manufacturer’s instructions. To detect the dengue NS1 antigen, 100 μL of whole blood, or serum/plasma sample, was added to the sample well of the Humasis Dengue NS1 device. Similarly, for the detection of dengue IgG/IgM, 10 μL of whole blood, or serum/plasma sample, was added to the sample well, followed by the addition of 3 to 4 drops (100–120 μL) of assay buffer to the round assay buffer well. All data were obtained after 15–20 min. Each cassette included a control and a test line, where the appearance of both the control and the test line indicated a positive result, and the appearance of the control line alone indicated a negative result.The SD Bioline Dengue Duo NS1 Ag and IgG/IgM test kit is a one-step immunochromatographic assay designed to detect both dengue virus NS1 antigen and differential IgM/IgG antibodies to detect the presence of dengue virus in human whole blood, serum, and plasma. The SD Bioline Dengue Duo rapid test contains two tests in one device, where the left and right sides are dengue NS1 antigen and IgG/IgM tests, respectively. All tests in this study were carried out in accordance with the manufacturer’s instructions. To detect the dengue NS1 antigen, 100 μL of the test sample was added to the left sample well and the results were read at 15–20 min. To detect dengue IgG/IgM, 10 μL of test sample was added to the right sample well, and 4 drops (90–120 μL) of assay diluent were added to the round assay diluent well, and the results were read 15–20 min later. Each test included a control and a test line, where the appearance of both the control and test line indicated a positive result, while the appearance of only the control line indicated a negative result.CareUS Dengue Combo NS1 and IgM/IgG tests  are designed to diagnose dengue fever in acute to convalescent patients and consist of a dengue NS1 antigen test strip and an anti-dengue immune IgM/IgG test strip in one device. All tests were carried out in accordance with the manufacturer’s instructions. To detect the dengue NS1 antigen, 80 μL of the test sample was added to the left sample well, 1 drop (~40 μL) of the analytical diluent was then added to the same well, and the results were read at 20 min. To detect dengue IgG/IgM, 20 μL of test sample was added to the right sample well, followed by the addition of 1 drop (40 μL) of analytical diluent to the same well, and the results were read at 15–20 min. Each test included control and test lines, where the appearance of both the control and test line indicated a positive result, and the appearance of only the control line indicated a negative result.https://www.medcalc.org/calc/diagnostic_test.php) and the Free Statistics Calculators program .Data were tabulated and analyzed using Microsoft Excel . Confidence intervals for sensitivity and specificity were set at 95% and a two-tailed p < 0.05 indicated significance. Statistical analysis was performed with Stata v13 . The sensitivity and specificity for the assays were calculated based on “true positive dengue samples” (PCR and IgM & IgG positives) using a diagnostic test evaluation calculator program  are shown in Based on the Dengue IgG and IgM ELISA  as a reference, the CareUS Dengue Combo NS1 and IgM/IgG test was found to have the highest sensitivity (89.91%) for IgM antibodies followed by the SD Bioline Dengue Duo NS1 Ag and IgM/IgG test (60.55%), and then the Humasis Dengue Combo NS1 and IgM/IgG test (51.38%). The specificity of the CareUS Dengue Combo NS1 and IgM/IgG and the SD Bioline Dengue Duo NS1 Ag and IgM/IgG tests were 100% for IgM, while the specificity of the Humasis kit for IgM was 98.21%.Based on the Dengue IgG and IgM ELISA  as a reference, the CareUS Dengue Combo NS1 and IgM/IgG test was found to have the highest sensitivity (82.57%) for IgG antibodies, followed by the SD Bioline Dengue Duo NS1 Ag and IgM/IgG test (77.98%), and then the Humasis Dengue Combo NS1 and IgM/IgG test (72.48%). The specificities of the CareUS Dengue Combo NS1 and IgM/IgG and the SD Bioline Dengue Duo NS1 Ag and IgM/IgG tests were 100% for IgG, while the specificity of the Humasis kit for IgG was 95.24%.Since the concentrations of NS1 and DENV IgM/IgG antibodies in the blood depends on whether the infection is primary or secondary, the sensitivities of three DENV RDT kits were determined in patients with primary or secondary serological profiles . For NS1-) or a secondary infection (NS1/IgM/IgG+), the Humasis RDT kit had similar sensitivities for primary (63.64%) and secondary infections (65.52%). However, the sensitivities of the SD Bioline (68.97%) and CareUS (95.40%) RDT kits for secondary infections were higher than for primary infections . Among the three RDT kits, the CareUS RDT kit was the only kit displaying a statistically significant difference between primary and secondary DENV infections (p < 0.05).The sensitivities of all three IgG kits were statistically significantly (p <0.05) higher for secondary infections  than for primary infections . When we analyzed the sensitivity of all biomarkers according to the classification as a primary  than for NS1 antigen-negative cases . Among tThe clinical disease classifications, according to the WHO classifications, consisted of dengue , warning signs , and severe dengue , as shown in The sensitivities of the three RDT kits for the dengue serotypes were compared and evaluated . For theDengue fever is caused by the dengue virus and is a tropical disease transmitted by mosquitoes , 18. SecIn this study, we compared and evaluated the diagnostic usefulness of three RDTs, Humasis, SD Bioline, and CareUS dengue kits based on dengue diagnosis criteria using RT-PCR and single serum for IgM/IgG. When the SD Bioline NS1 and IgM RDT kit results were compared with those from an earlier study , the sen-) and secondary infections (NS1/IgM/IgG+), the CareUS kit had statistically different (p <0.05) sensitivities of 59.09 and 95.40%, respectively. SD IgG kit showed no cross-reactivity with Chikungunya virus infected serum. All three NS1/IgM kits showed no cross reactivity with Chikungunya virus infected serum. However, in cross-reactivity test of three RDT kits against Chikungunya virus infected serum samples (n = 15) among other flavivirus, Humasis and CareUS IgG test showed cross-reactivities 80% and 73.3%, respectively  values reflect the overall amount of viral load in each clinical specimen, and the relative viral load can be estimated from the Ct value of each specimen. For specimens with low Ct values, the three RDT kits showed comparable sensitivities. However, for specimens with higher Ct values, the NS1 antigen and IgM of CareUS kit only detected Dengue viruses. These findings suggest that the CareUS kit detects lower viral loads more precisely than do the two other RDT kits.The limitations of this study are that there were not enough DENV4 samples to analyze test performance and DENV3 samples were not collected. The results for adult samples may also be different, since only samples from children were used in this study. The sensitivity and specificity results in this study may be difference with the results classified by the standard dengue diagnosis (RT-PCR and paired serum for IgM/IgG) recommended by WHO, because dengue and non-dengue cases in this study were classified by using RT-PCR and single serum for IgM/IgG. In addition, the sensitivity of the three tested RDT kits may have decreased slightly because patient blood was stored at -80°C and shipped to Korea from Myanmar for testing.In conclusion, our study suggests that testing for both dengue NS1 and IgM/IgG is more effective for diagnosis than either alone. RDTs are simple, easy to perform, inexpensive, sensitive, and require no sophisticated protocols, and, therefore can be used in any location. Among the kits evaluated, the CareUS RDT kit was the most efficient when confirming dengue infections by capturing the NS1 antigen and detecting DENV-IgG/IgM from infected patients. Moreover, it was the most convenient to use (as the results could be obtained in 15 min), easy to perform, and it did not require special laboratory equipment.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S3 Table(DOCX)Click here for additional data file.S1 Row data(XLSX)Click here for additional data file.


The optimal procedure for maximizing the diagnostic yield and minimizing the procedural complexity of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is controversial. We conducted a prospective randomized controlled trial to determine the optimal procedure of EBUS-TBNA for mediastinal and hilar lymphadenopathy, with a particular focus on the roles of the inner-stylet and suction.Consecutive patients with enlarged mediastinal and hilar lymph nodes (LNs), detected by computed tomography (CT) or positron emission tomography-CT (PET-CT), who underwent EBUS-TBNA were included. Each LN was sampled with three needle passes using suction–stylet, suction–no stylet, and stylet–no suction procedures. The samples were smeared onto glass slides for cytological evaluation. A single, blinded cytopathologist evaluated each set of slides. The primary outcomes were cytological specimen adequacy rate and diagnostic yield of malignant LNs. The secondary outcomes were tissue-core acquisition rate, procedural time, and the amount of bleeding.P <  0.001). The no-stylet procedure decreased the average procedural time by 14 s (P <  0.001). There was no significant difference in the amount of bleeding among the procedures.This study evaluated 97 patients with a total of 255 LNs. The final LN diagnosis was benign in 144, malignant in 104, and inadequate in 7 cases. There were no significant differences among the suction–stylet, suction–no stylet, and stylet–no suction groups in specimen adequacy rate  or diagnostic yield of malignancy . However, the use of suction was associated with an increase in tissue-core acquisition rate . Retrospective registered date: 12th February, 2017.Trial registration: ( Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a technique that is highly effective for diagnosing enlarged mediastinal and hilar lymph nodes (LNs) detected on computed tomography (CT) or positron emission tomography-CT (PET-CT), in patients with benign or malignant conditions. Some clinical studies have demonstrated that EBUS-TBNA is a cost-effective  and safeThe conventional EBUS-TBNA technique requires that a metal stylet within the inner lumen of a fine needle be inserted and removed during every needle pass, which increases the procedural time and complicates the procedure. Therefore, we considered the possibility of omitting the inner-stylet during EBUS-TBNA. In addition, because there is considerable controversy regarding whether it is necessary to apply suction during EBUS-TBNA, we here conducted a prospective randomized controlled trial to determine the optimal EBUS-TBNA procedure for detection of mediastinal and hilar malignant lymphadenopathy, with a particular focus on the effect of using an inner-stylet and suction.www.chictr.org.cn (ChiCTR-IOR-17010616).Consecutive patients with enlarged mediastinal and hilar LNs who underwent EBUS-TBNA between October 2016 and May 2017 were enrolled. An LN with a short-axis diameter > 5 mm on a chest CT image was considered as an enlarged LN. Lymph-node stations were classified in accordance with the international lymph-node map by the International Association for the Study of Lung Cancer . All patTBNA was performed with a 22-gauge needle  under EBUS and real-time color Doppler guidance with a convex-probe echoendoscope. After puncturing an LN, the fine needle was moved to and fro within the LN 10–20 times and then withdrawn. Each LN was sampled with three needle passes using suction–stylet, suction–no stylet, and stylet–no suction procedures (each process was performed once). To adjust for the effects of some potential confounding factors, including passes made using different procedures, the order of the procedure for each target site was randomized by a senior biostatistician from the School of Public Health, Wenzhou Medical University, using SAS 9.4 for Windows .During the conventional EBUS-TBNA procedure (the suction–stylet group), the inner lumen of the fine needle was first occluded with a metal stylet, which was removed after the needle entered the target LN. Once the stylet was withdrawn, a 20-mL syringe was applied to the needle for providing suction. For the no-stylet procedure, the stylet was omitted throughout the procedure, and the syringe was applied to the needle before the latter was inserted into the working channel of the echoendoscope. In the no-suction procedure, after the needle was inserted into the target LN, the stylet was withdrawn by 10 cm without using suction. During each pass, the physician assessed the amount of bleeding from the puncture site on the bronchial wall.Each needle-pass specimen was extruded onto a separate glass slide using a 10-mL air-filled syringe, and a direct smear was made by an experienced EBUS nurse. Rapid on-site cytological evaluation was not performed. The residual contents of the needle from a single LN were flushed into the same container and consolidated by formalin to obtain a single cell block or tissue core for histological examination . After flushing the needle, the outside of the needle and the stylet were vigorously wiped with sterile gauze to reduce cross contamination between passes. A related on-site trial assistant recorded whether or not a visible tissue core was acquired with each needle pass and calculated the procedural time for each pass from the time of insertion of the fine needle through the working channel of the echoendoscope to the retrieval of the needle during each pass, excluding the time for reinsertion of the stylet into the fine needle. If insufficient specimen for a cell block or tissue core was obtained after the third pass, additional passes were permitted, with the choice of procedures and number of passes left to the discretion of the endoscopic physician.The smears on glass slide were alcohol-fixed (95% ethanol) and stained with hematoxylin and eosin. A cytopathologist, who was blinded to the procedural order for EBUS-TBNA, characterized each individual needle pass for cytological specimen adequacy and made a specific diagnosis as follows: malignancy, benign , and inadequate. Specimens with > 40 lymphocytes per high power field  in the mThe final diagnosis of each LN was determined using all available cytological and histological findings from three EBUS-TBNA procedures. The primary outcomes of the trial were the cytological specimen adequacy rate and the diagnostic yield for malignant lymphadenopathy. A sample size of 225 LNs would provide sufficient power for a 10% non-inferiority margin upon performing non-inferiority analysis. The secondary outcomes were tissue-core acquisition rate, procedural time and amount of bleeding during each procedure. The amount of bleeding was categorized on the basis of the following scores: 0 ; 1 ; 2 .P value of < 0.05 was considered to indicate statistical significance.Statistical analysis was performed with the IBM SPSS Statistics Version 22.0 software . The analysis evaluated only the first three passes for each LN. Descriptive statistics were used to summarize the characteristics of all patients and all LNs in the trial. Data on continuous variables were presented as mean ± standard deviation. McNemar tests were performed to determine the difference in specimen adequacy rate, diagnostic yield and tissue-core acquisition rate between suction–stylet and suction–no stylet or suction–stylet and stylet–no suction procedures. The paired t-test was employed to compare procedural time. In addition, the amount of bleeding was analyzed using Wilcoxon’s test. A subgroup analysis was performed to determine the association of different EBUS-TBNA procedures with specimen adequacy rate and diagnostic yield, for LNs >  10 mm or ≤ 10 mm in diameter. A two-sided The trial evaluated 97 patients with a total of 255 mediastinal and hilar LNs. Randomization ensured that each third of the suction–stylet, suction–no stylet, and stylet–no suction passes were first, second, and third passed Fig. . The basTwo or three LNs were sampled for most patients. For the 255 LNs, the mean short-axis diameter on chest CT images was 14.7 mm, and the most common enlarged LN stations were 4R and 7. The final pathologic diagnoses for the 255 LNs were as follows: 104 malignancies, 144 benign diagnoses, and 7 inadequate samples.The cytological specimen adequacy rates were 87.1, 88.2, and 85.9% in the suction–stylet, suction–no stylet, and stylet–no suction groups, respectively; the corresponding values for diagnostic yield of malignancy were 32.2, 31.8, and 31.0%, respectively, which showed no statistically significant difference among the three groups. The results of statistical analysis of specimen adequacy rate and diagnostic yield are detailed in Table P <  0.001). Non-use of the stylet did not decrease or increase the tissue-core acquisition rate . In terms of procedural time, the no-stylet procedure was on average 14 s shorter than the suction–stylet procedure . However, in terms of amount of bleeding, the use or non-use of suction yielded similar scores; similar results were observed for procedures with and without the stylet.Comparison of secondary outcomes among the three procedures Table  revealedThis prospective randomized controlled trial demonstrated that the traditional procedure of applying suction during EBUS-TBNA did not make a statistically significant difference in cytological specimen adequacy or diagnostic yield of malignant lymphadenopathy, although it increased the rate of tissue-core acquisition for histological examination. Compared to procedures performed with a stylet, not using a stylet did not decrease the specimen adequacy or diagnostic yield. Upon comparing EBUS-TBNA procedures with or without suction and with or without stylet for LNs ≤ 10 mm and >  10 mm in short-axis diameter, we found no difference in the adequacy or diagnostic yield of cytological specimens. Although more data may be needed to confirm these specific conclusions, our findings may assist endoscopic physicians in determining the optimal EBUS-TBNA procedure.Mediastinal and hilar lymphadenopathy may be caused by various inflammatory, infectious, or malignant factors, and it is important to ascertain the diagnosis or to determine the disease stage in case of malignancy before deciding on treatment. Mediastinoscopy has long been the reference standard of mediastinal and hilar LN sampling; however, it has several disadvantages, including its relatively high complexity and invasiveness . Over thHowever, EBUS-TBNA has several limitations. Although its median sensitivity for detecting malignant lymphadenopathy (89%)  is betteThe use of an inner-stylet during EBUS-TBNA is somewhat controversial. It has commonly been used because it can theoretically prevent bronchial mucosa and cartilage filling the inner lumen and protect the fine needle by increasing its stiffness upon entry into the target LN. However, the inner-stylet has to be inserted and removed through the fine needle during every needle pass, which increases the procedural time and complicates the EBUS-TBNA procedure. Moreover, conventional TBNA is performed without an inner-stylet in the fine needle. Evaluation of the use of the inner-stylet in EBUS-TBNA has been limited to a single recent study. Scholten and colleagues  found noApplication of suction during FNA has been a standard practice for many decades in various medical specialties, including pathology and gastroenterology. However, there is considerable controversy about the need to apply suction during EBUS-TBNA. Some clinicians believe that suction might increase tissue trauma at the biopsy site and result in more bleeding into the specimen, thus decreasing the diagnostic yield of EBUS-TBNA. Others have argued that suction helps to acquire more specimen material. Wallace et al.  reportedRapid advances in oncologic therapy have necessitated further ancillary studies, including immunohistochemical and molecular analyses for subtyping and genotyping of lung cancer, during the diagnostic workup of small tissue specimens. A guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology, states that tissue samples should be prioritized for molecular analysis and that cytological samples are also suitable for studies, with cell blocks being preferred over smeared material . In our The most frequent complication associated with EBUS-TBNA is hemorrhage; other rare complications of the procedure are infection, pneumothorax, and device breakage . In 2014An advantage of the present prospective trial, which involved randomization of the procedure order and blinding of the cytopathologist, is its self-contrast design, which could control for the effects of size, location, density, and pathological type of different LNs, as well as other unknown factors. Furthermore, in our trial, an on-site assistant recorded the procedural time for each pass; this has not been evaluated in other previous studies.A limitation of our trial, however, is its single-centre and single-operator design. A multicentre trial would be ideal to confirm the statistical significance of the results obtained with different EBUS-TBNA procedures. Additionally, we compared tissue-core acquisition rate among different procedures but, regrettably, failed to analyze the specimen quality for cell block or tissue histological examination, which might have decreased the chance of identifying differences among the procedures.In summary, the use of suction or non-use of the inner-stylet does not make a significant difference in cytological specimen adequacy or diagnostic yield when performing EBUS-TBNA. Omitting the stylet can simplify the procedure, and applying suction can help increase the tissue-core acquisition rate. These findings may assist endoscopic physicians in determining the optimal EBUS-TBNA procedure and warrant clinical verification in a future multicentre study.


Behavioral activation therapy (BAT) directly addresses activities that individuals value most highly, and may be easily applicable to cancer patients. However, there is no established evidence of the use of BAT in this population. In this study, we examined the possibility of a BAT program for depression and anxiety in cancer patients.P = 0.0014; GAD-7: P = 0.0004). CGI-I scores ranged from 1 to 3, and all subjects except the patient who dropped out improved clinically. Among the ten patients, three distinctive cases could be observed as follows. Case 1; a 45-year-old housewife with breast cancer who did not agree to take antidepressants because of concerns about the side effects achieved remission without antidepressants and began to live an active life. Case 4; a 66-year-old housewife was so shocked after endometrial cancer diagnosis that she was absent-minded and her compliance with the assigned homework was poor, therefore, her depression did not improve much. Case 9; a 62-year-old man with laryngeal cancer who had recurrent anxiety. Increased business activity, on which he put great value, gradually allowed him to be able to live his life actively without concerns.We retrospectively reviewed the medical records of cancer patients with each of the following characteristics: 1) were outpatients or inpatients visiting the psycho-oncology division of the National Cancer Center Hospital in Japan; 2) met criteria for Major Depressive Disorder or Adjustment Disorders; and 3) participated in a BAT program. The primary outcome was the program completion percentage. Secondary outcomes were self-reported depression severity  score), anxiety disorder status  score), and clinical improvement  score) after the program. We analyzed both depression and anxiety by the matched paired t-test. Ten patients participated in the program, and nine completed it. One dropped out due to cognitive impairment secondary to brain metastasis. Both the PHQ-9 scores ; post: 5.1 ) and the GAD-7 scores ; post: 4.7 ) significantly improved after the program (PHQ-9: This study suggests that BAT would be effective for the depression and anxiety of cancer patients. Psychiatric disorders such as major depression and adjustment disorders are reported to occur in 30–40% of patients in the oncological setting . Most deThere is evidence that cancer patients may benefit from psychotherapeutic approaches such as cognitive restructuring–based cognitive behavioral therapy (CBT) and problem-solving therapy , 5. HoweBehavioral activation therapy (BAT) directly addresses daily activities that individuals value most highly. The mechanisms underlying BAT are as follows: (i) individuals suffering from depressive or anxiety conditions experience avoidance and decreased participation in normal activities; (ii) this leads to decreased opportunities for them to experience joy; (iii) they feel that they are overwhelmed by hardships; (iv) the value they place on their lives and themselves is diminished; (v) they pay more attention to negative information; (vi) they eventually experience more distress and depression; (vii) BAT facilitates activities they value and breaks this vicious cycle; and (viii) this improves the depressive condition and (ix) leads to improvement in quality of life. Of note, BAT emphasizes identifying values as a part of behavioral change . Thus BAThe effectiveness of BAT for depression and anxiety is well established , 9. HoweThe medical records of the patients were investigated retrospectively. The inclusion criteria were as follows: cancer patients who 1) visited the psycho-oncology division of the National Cancer Center Hospital (NCCH) in Japan, as outpatients or inpatients, from October 2016 to March 2018; 2) met the criteria for Major Depressive Disorder (MDD) or Adjustment Disorders according to the Diagnostic and Statistical Manual of Mental Disorders ; and 3) participated in the NCCH BAT program.This study was approved by our institutional review board. We obtained written consent from all participants.The primary outcome was the BAT program completion percentage . Secondary outcomes were the self-reported depression severity  score), anxiety disorder status  score), and Clinical Global Impression-Improvement (CGI-I) score after the program.The PHQ-9 is the nine-item depression module from the full PHQ, and a Japanese version has been validated . The ninThe GAD-7 is a seven-item questionnaire developed to identify probable cases of GAD and to measure the severity of GAD symptoms; a Japanese version has been validated . The GADThe CGI-I scale ranges from 1 to 7 points and is scored using the following benchmarks: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; and 7, very much worse . A correThe BAT program was one of the support programs provided by the patient support research and development center in NCCH. The center was opened in September 2016 to provide cancer patients with rehabilitation and social work services, psychological care, nursing consultation, and counseling on nutrition and appearance. The BAT program was a clinical activity available to individuals who met the following criteria: 1) were cancer patients visiting the NCCH in Japan; 2) were over 20 years old; 3) had an Eastern Cooperative Oncology Group performance status (PS) score of 0 to 1, making it easier to modify behaviors; 4) could speak Japanese; and 5) expressed their desire to participate in the program. Exclusion criteria were as follows: 1) serious physical symptoms that prevented participants from finishing the program; 2) cognitive functional disorders and disturbance of consciousness that made it impossible to understand the program content; 3) severe mental symptoms, such as those related to depression, that were accompanied by psychotic symptoms or imminent suicidal ideation, because these indicated the need for more intensive approaches such as pharmacological treatment or electroconvulsive therapy (ECT); and 4) the physicians in charge judged it difficult for their patients to participate in the program.Each patient completed the PHQ-9 and GAD-7  and CBT were prohibited. The outlines of the BAT program are shown in Table The supervisor of the program was a professor specializing in BAT and CBT. He led eight sessions, all of which were attended by a psychiatrist and two psychologists who work at our hospital. All therapists had at least 5 years of clinical experience that included work with cancer patients. After attending the supervisor’s sessions, the psychiatrist and psychologists conducted the program on their own under supervision.We analyzed both demographic data and the completion percentage by descriptive statistics, and both depression and anxiety by the matched paired t-test.Ten patients participated in the BAT program during the study period. Of them, nine ) completed the program, resulting in a completion percentage of 90%. One patient dropped out of the program due to cognitive impairment secondary to brain metastasis.Patient characteristics are shown in Table The clinical course varied among the ten patients who participated in the BAT program. Most cases showed clinical improvement, however, there was one case with poor clinical improvement. Here, we report three cases with distinctive results.A 45-year-old housewife who lived with her husband and two children who was diagnosed as having breast cancer (Stage II) and received a surgical resection. After surgery, she was told that she would need adjuvant chemotherapy. She became anxious about the possible recurrence of her breast cancer and side effects of chemotherapy such as hair loss and nausea. Consequently, she could not go out and stayed home all day long. She gradually became depressive, so she visited the psycho-oncology division of our hospital. She was diagnosed as having an MDD and prescribed antidepressant. However, she was unable to continue the medication because of nausea and fatigue. Though another antidepressant was proposed, she did not agree to use it because of concerns about the side effects. Therefore, she participated in the BAT program. At the beginning of the program, her depression was considered to be moderately severe by HRSD. However, she achieved remission of depression by the end of the program, without antidepressants, and began to live an active life.A 66-year-old housewife who lived with her husband was found during a biannual medical checkup to have endometrial cancer (Stage III). She was so shocked that she became seriously depressed. She repeatedly thought, “why do I have cancer despite a biannual medical checkup”“I should have had more medical checkups, if I had, I might have no cancer.” She became very nervous and anxious about the possible recurrence of her cancer and its development into a serious physical disease. Her psychiatrist prescribed an antidepressant. She subsequently began participating in the BAT program. However, she was absent-minded during much of every session, and her compliance with the assigned daily homework was poor. Although antidepressant was increased, her depression did not improve much.A 62-year-old man who lived with her wife and had his own business was diagnosed as having laryngeal cancer recurrence and had an operation 2 years previously. He was only given followed up care and had no symptoms. However, he became nervous about the possible recurrence of his cancer. He repeatedly thought, “cancer may spread to other parts of my body”, “if so, I may die” and he kept to his room all day long. He gradually became depressive, so he visited the psycho-oncology division of our hospital. He was diagnosed as having an MDD and prescribed antidepressant. He subsequently began participating in the BAT program. After taking part in the program, increased business activity, on which he placed great value, gradually allowed him to live his life actively without concerns.The completion percentage in the BAT program was 90% (nine out of 10 patients), and the only patient who did not complete it dropped out due to cognitive impairment secondary to brain metastasis. These results suggest that the program is feasibly for use with cancer patients.All patients except the one who dropped out demonstrated clinical improvement according to the CGI-I. Furthermore, both PHQ-9 and GAD-7 scores were significantly improved after the program. These results suggest that the BAT program is effective for patients with cancer.From the cases with good clinical courses (Case 1 and Case 9), we are of the view the BAT program would be effective in cases where patient has recurrent anxiety and rumination and their activity decreases due to them. BAT facilitates activities they value and brings about positive reinforcement for the patients. As a result, BAT breaks the vicious cycle which occurs from recurrent anxiety and rumination and leads to improvement of the depressive condition. Both cases suggest that BAT can lead patients to live independent and active lives after their cancer diagnosis. Furthermore, Case 1 suggests that BAT can be adapted particularly well to cancer patients who do not want to take antidepressants because of concerns about side effects.Questionnaire results of the patient with poor clinical improvement (Case No. 4) showed slight decreases in cancer-related distress and anxiety about the possibility of recurrence, but overall the effect of the program was not significant. Given her inadequate response to the program, as well as previous findings that the effects of BAT are poor in patients with severe depression and poor compliance , BAT pron = 10). According to one report, pilot studies should have sample sizes of at least 30 [This study has several limitations. First, it used a retrospective design that may have caused several systematic biases. Second, it was conducted at a single cancer center, raising the question of institutional bias, and the results may not be applicable to other settings. Third, there is a possibility of assessment bias. Although psychiatric diagnoses were made using DSM-V criteria, this method is not robust because our diagnoses were clinical in nature and were not based on the Structured Clinical Interview for DSM-5 (SCID-5). Moreover, the CGI-I is a subjective scale and does not have a specific anchor point. Fourth, the study sample was small (least 30 . The BATDespite its limitations, this case series study suggests that BAT is potentially effective for the depression and anxiety of cancer patients. To establish further evidence for BAT use with cancer patients, randomized controlled trials are needed.


Rwanda is the only African country to use the pediatric International In-Training Examination (I-ITE). The objectives of this study were to use the scores from the I-ITE to outline the baseline level of knowledge of Rwandan residents entering the pediatric residency and the trends in knowledge acquisition from 2012 to 2018, during the Human Resources for Health (HRH) Program, an education partnership between the Rwanda Ministry of Health and a consortium of US universities.A retrospective descriptive analysis of the I-ITE exam scores, taken by all Rwandan pediatric residents for five of the six academic years of the study period. Individual resident scores were weighted using the non-Rwandan I-ITE sites to minimise confounding from annual variations in exam difficulty. Statistical analysis included descriptives with ANOVA to compare variation in annual mean scores.p < 0.001) in 2018. The 32-point gap between the mean US-ITE and Rwandan I-ITE score in 2012–2013 was reduced to a 16-point gap in 2017–2018. First year resident (PG1) scores, which likely reflect the knowledge level of undergraduate medical students entering the residency program, increased from 34.8 to 44.3% (p = 0.002) between 2013 and 2018.Eighty-four residents took 213 I-ITE exam sittings over the five exam cycles. The mean weighted I-ITE score of all residents increased from 34% in 2013 to 49% (The I-ITE is an independent, robust tool, measuring both learners and the institutional factors supporting residents. This is the first study to demonstrate that the I-ITE can be used to monitor resident knowledge acquisition in resource-limited settings, where assessment of resident knowledge can be a major challenge facing the academic medicine community. The significant increase in I-ITE scores between 2012 and 18 reflects the substantial curricular reorganisation accomplished through collaboration between Rwandan and US embedded faculty and supports the theory that programs such as HRH are highly effective at improving the quality of residency programs and undergraduate medical education. Twenty-three African countries offered paediatric postgraduate training programs in 2013 [In the United States (US) monitoring this knowledge acquisition among pediatric residents has been accomplished over the last four decades through the use of an annual In-Training Examination (ITE) as a formative self-assessment instrument . AlthougInternational In-Training Examination (I-ITE) is offered annually by the American Board of Pediatrics (ABP) to training institutions outside of North America. The I-ITE is a subset of 200 multiple-choice questions (MCQs) developed by board-certified subject matter experts [The  experts . ABP psyRwanda is a small country in East Africa with a population of 10.5 million people according to the last census in 2012, a GDP of 787 USD per capita in 2018 . There iWithin paediatrics, the US institution faculty making up the HRH team has included general paediatricians and paediatric subspecialists who have worked alongside local University of Rwanda (UR) academic and Ministry of Health clinical staff to develop and support the educational, research and administrative activities of the Department of Paediatrics , 13. DurThis study aimed to use a completely independent high-quality tool, the I-ITE, to measure the baseline level of paediatric knowledge of new residents entering the paediatric residency, and the trends in knowledge acquisition by Rwandan paediatric residents, from 2012 to 2018.We performed a retrospective analysis of I-ITE scores of all Postgraduate (PG) paediatric residents enrolled from 2012 to 2018 in the University of Rwanda (UR), the only university in Rwanda with a paediatric residency program. Our reporting of this observational study is in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist [No Rwandan resident had previously taken the I-ITE before the HRH Program. We contracted with the American Board of Pediatrics to utilise the I-ITE in Rwanda for five of the six academic years of the study period, namely: November 2012, March 2014, April 2016, March 2017 and May 2018. However, we were unable to administer the I-ITE in 2015 due to financial and organisational barriers.All Postgraduate (PG) paediatric residents enrolled in the program from 2012 to 2018 sat the I-ITE.Following standard ABP protocol, we administered the best-of-five MCQ I-ITE electronically using password protected computers connected to the internet and proctored by faculty. The ABP provided us with summary data for the US ITE and non-Rwandan International-ITE scores in electronic format along with raw scores for all the Rwandan PG residents, and data was password protected in an Excel spreadsheet.No sample size calculation was undertaken as all residents in the program sat the I-ITE throughout the study period, and we analysed all results.p < 0.0001, Table We weighted exam scores for variation in difficulty. Although the difficulty of the questions in the I-ITE are relatively stable, there is still statistically significant variation year-to-year . The ABPWe used the Statistical Package for the Social Sciences (SPSS) . In order to analyse increases in weighted scores and z-scores during the five sittings, we conducted an ANOVA and used a repeated-measures ANOVA to analyse if there was an increase in scores within each class.. No incentives were offered, no potential risks were identified, and participation was deemed as consent. The Institutional review board (IRB) of the University of Rwanda (UR) approved the project proposal. Ref: 027/CMHS_IRB/2018.We paid particular attention to potential ethical issues and resident confidentiality. Faculty discussed the rationale and context for the exam before providing each resident with their score and ABP-provided subject breakdown. Residents’ results are otherwise only available to faculty and used for resident development and advising purposesEighty-four residents completed a total of 213 I-ITE sittings (Table p < 0.0001) in the mean scores from these sites. Therefore, we used the mean non-Rwandan I-ITE score to weight each Rwandan resident’s I-ITE score  in 2018 (Table p = 0.002).We demonstrate a significant increase in the performance of residents during the period of the HRH program with mean weighted-scores of all the residents increasing from 34.3 in 2013 to 48.6 (p < 0.001). We also demonstrate a greater progression in the increase of scores among residents who began residency in 2012 and later, while HRH was present.In order to analyse progression throughout time in the program, we created resident cohorts that were “tracked” by year of predicted graduation Table . We obseOur objective was to use a globally available, independent monitoring tool of high quality that could objectively measure trends in knowledge acquisition by Rwandan paediatric residents from 2012 to 2018. With this study, we demonstrate a significant increase in I-ITE scores during this period, along with a decrease in the gap between the mean US US ITE score and mean Rwandan I-ITE score. In addition to overall improvement of the mean scores for all Rwandan residents, we find that the mean Rwandan PG1 I-TE results has increased from − 2 z-scores to − 0.98 z-score, below the non-Rwandan International PG1 scores. This means that the top performing Rwandan post-graduates are now performing at the level of 16% of the other International post-graduates taking the I-ITE. If the rate of improvement was sustained, equity with these other international countries could be obtained within 5–6 years.US residency programs have implemented different strategies for improving ITE and board performance by residents, including web-based curriculum , email-bPrior to the HRH program, residents were taught primarily by means of week-long clusters of lectures delivered a few times per year in an ad-hoc fashion according to local, and primarily Belgian, lecturer availability. Subsequently, a formal curriculum based on the Global Pediatrics Education Consortium was developed and implemented by the HRH and UR faculty during the 2012–2013 academic year . This cuAdditionally, other modalities of teaching were implemented both at the hospital and university level and included daily morning reports, daily bedside teaching rounds, simulation sessions, practical skill teaching, morbidity, and mortality meetings, research training, and leadership development workshops.The mean score of PG1 residents increased during this period. Though PGs sit the I-ITE late in the academic year, the PG1 score is also a surrogate marker for the level of knowledge of residents entering into the residency program. The PG1’s increased level of knowledge suggests that undergraduate education has improved during the period of this study. Implementation of a structured educational curriculum during clinical clerkship has been shown to improve medical student performance on end-of-clerkship shelf exams . In addiKinyarwanda, English, French, and Kiswahili are the current official languages of Rwanda. English became an official language in Rwanda in 2008. Until then, Kinyarwanda and French were the primary languages of instruction in primary, secondary, and tertiary education. Most of the residents first encountered English as the language of instruction at the tertiary university level. This is similar in Saudi Arabia where most high schools are instructed in Arabic, but the language of instruction in Saudi medical schools is English. A study of Saudi students enrolled in a premedical preparatory course found a correlation between English examination scores and performance on medical written and oral examinations . TherefoLongitudinal exposure to MCQ testing has been shown to improve ITE performance . The firPrior to the start of the HRH program in 2012, there were15 paediatricians in the Rwandan public sector. During the program, there have been 36 expatriate paediatricians working full time, in-country for periods between of 2–3 months  to multiple years . HRH faculty are integrated as members of the Department of Pediatrics, to work full time in the training environment, supporting clinical and didactic activities at both the undergraduate and postgraduate level. I-ITE scores increased most significantly for the classes that had more years of exposure to the curriculum and teaching and curriculum developed by the Department of Paediatrics Faculty and their embedded HRH colleagues.The I-ITE is administered in an online, secure, and proctored manner. The individual questions are of uniformly high quality and are standardised by trained question writers following a standardised curriculum. The entire I-ITE is analysed and modified by skilled psychometric analysts. Therefore, we believe that the I-ITE should be highly attractive to paediatric residencies internationally as few paediatric departments have the infrastructure or the faculty with this breadth of technical skills.The I-ITE can, therefore, be used to provide consistent and detailed formative feedback to individual residents on their pediatric knowledge throughout their residency. The I-ITE is independent of faculty group, in contrast to programs where local faculty design end-of-year internal exams which determine promotion to the next year of training. This lack of reliance on local design leads to recognition of the I-ITE as a tool to monitor the ability of a residency program in general to meet its training requirements over time.These results are highly suggestive that residency organisation and restructuring, through collaborative efforts between local and international faculty, can significantly improve the knowledge competency of residents. The HRH Program aims not only to create a larger, diversified health workforce capable of providing the people of Rwanda with high quality healthcare, but also, through strengthening of academic institutions to develop capacity within Rwanda to carry forward with their own high-quality programs. This study demonstrates that the HRH Program can have an impact on narrowing the gap between resource rich countries and low-resource countries that are facing a shortage of healthcare workforce (including Faculty). However, other competencies cannot be measured with a standardised computer-based testing mechanism and must still be assessed on site. Most importantly, whether and how the increase in scores ultimately impacts clinical practice and patient care remains to be studied.This is the first study to report the use the I-ITE to measure performance in a resource-limited setting. The results are based on a standardised assessment and therefore void of local bias.There are several limitations to our study. The I-ITE is best taken in the first few months of the academic calendar in order to more closely match scores with US counterparts: this was never accomplished due to organisational and financial constraints. Because of administrative and financial issues, we were unable to implement the I-ITE in the 2014–15 academic year, and therefore one data cycle is absent.The I-ITE only assesses medical knowledge, which is only one of the competencies assessed in a high-quality residency training program. However, the I-ITE has given us a standardised format within which to measure resident medical knowledge. Our personal experience is that clinical skills, attitudes, communication, etc. have also seen parallel improvements during the course of the HRH program.It is unclear how improved I-ITE scores will impact patient care or residents in the long run. In the US and Canada, ITE scores are used as a predictor of passing internal medicine speciality and subspecialty board examinations , 30–33. We demonstrate that the use of a standardised, well-designed, and independent exam available globally can be a powerful tool to monitor the knowledge acquisition of individual residents throughout training. Moreover, we believe it can reflect the capability of residency programs to provide the requisite training. Rwandan pediatric residents improved their pediatric knowledge scores on the I-ITE over a six-year period, both upon entry to residency and throughout their training, possibly reflecting the significant curricular reorganisation accomplished through the HRH Program.