The synergy between biological and bioengineering advances is critical to developing novel and impactful translational therapies. However, there currently are few opportunities for regenerative scientists to be exposed to the methodologies commonly employed in the clinic by rehabilitation professionals, and most rehabilitation scientists and clinicians are not exposed to the many advances of regenerative medicine. This disconnect has impeded the pace of progress in the field. The Eighth Annual International Symposium on Regenerative Rehabilitation brought together basic scientists, engineers, and rehabilitation clinicians to present scientifically rigorous and cutting-edge research and clinical management, focusing on new and innovative approaches that combine discoveries in tissue engineering, medical devices, and cellular therapies with rehabilitative protocols. However, there currently are few opportunities for regenerative scientists to be exposed to the methodologies commonly employed in the clinic by rehabilitation professionals. Conversely, most rehabilitation scientists and clinicians are not exposed to the many advances of regenerative medicine. This disconnect has impeded the pace of progress in the field. To this end, the International Consortium for Regenerative Rehabilitation—comprised of 16 institutions—aims to increase interdisciplinary interaction. Thus, as technologies are developed and our understanding of regenerative biology progresses, advances may be efficiently translated to the clinic2.Regenerative Rehabilitation seeks to optimize patient outcomes through an integration of two fields: regenerative medicine and rehabilitation science. The former focuses on tissue repair or replacement due to loss from injury, disease, or age. This is achieved primarily through the enhancement of endogenous stem cell function or the transplantation of exogenous stem cells. The latter focuses on the use of mechanical and other stimuli to promote functional recovery. This synergy between biological and bioengineering advances is critical to developing novel and impactful translational therapiesTo address this need, the annual international symposium is designed to propel the translation of regenerative technologies into functionally relevant treatment interventions that have the potential to transform rehabilitative healthcare. The Eighth Annual International Symposium on Regenerative Rehabilitation brought together basic scientists, engineers, and rehabilitation clinicians in order to create a fertile ground for discussion, interaction, and networking across disciplines. The symposium took place on 24–26 October 2019, in Charlottesville, Virginia, and was co-hosted by the University of Virginia and the Uniformed Services University of the Health Sciences.Scientific: to promote the clinical translation of scientific discoveries in the field of regenerative medicine by communicating and disseminating research findings that demonstrate the synergistic relationship between regenerative medicine and rehabilitation; (2) Programmatic: to provide multiple forums in which scientists, rehabilitation clinicians, and trainees may interact, exchange ideas, and identify novel research directions relating to the field of Regenerative Rehabilitation; (3) Mentorship and training: to introduce the concept of Regenerative Rehabilitation to promising graduate students, medical residents, clinical fellows, post-doctoral research fellows, and other junior investigators and clinicians, inspiring and supporting them to embrace and incorporate innovative technologies in their nascent clinical practices and research programs.The symposium held sessions to address three principle objectives: (1) The scientific sessions brought together world-renowned researchers and clinicians to present on scientifically rigorous and cutting-edge research and clinical management. Topics focused on new and innovative approaches that combine discoveries in tissue engineering, medical devices, and cellular therapies with rehabilitative protocols.5. His work has pioneered the use of material-alone, cell-alone, and material+cell approaches to address tissue defects of varying size as well as across all four levels of tissue complexity 6. Dr. Atala highlighted two important lessons learned through his research. First, is the value of a methodical approach. The genesis of each line of investigation is thorough cell biology and materials sciences studies, then transitioning to small, medium, and large animal studies. Only after which does it reach human patients for testing and long-term follow-up. Second, is the necessity of a multidisciplinary team—including cell and molecular biologists, material scientists, biochemists, and physicians—where team science has helped propel this technology from the bench to the bedside. Dr. Atala also discussed work in the cell therapy area, such as the use of skeletal muscle for shoulder cuff injuries, and concluded by sharing his future directions in stem cell therapy, specifically the use of amniotic fluid and placental stem cells7. He emphasized their clinical utility with respect to ease of collection, shared properties with embryonic and adult stem cells, lack of tumor potential and rejection concerns, and storage capabilities.Drs. A. Bobby Chhabra and Fred Epstein from the University of Virginia opened the meeting by emphasizing the importance of interdisciplinary collaborations in research. Opportunities like this symposium do not just highlight existing teamwork but foster new engagement and relationships that are critical to translational success. Picking up on this theme, Dr. Anthony Atala (Wake Forest Institute for Regenerative Medicine) shared his journey through a three-decade long research career in tissue and organ engineering, including the successful implantations of tissue engineered kidneys, bladders, and sexual organs8. Indeed, the new vascular network formation is very sensitive to biomechanical conditions, but the regulatory role of matrix deformations and remodeling during tissue regeneration in vivo needs to be evaluated. He showed how functional loading has a potent time-dependent effect on both mineralization and vascular growth in vivo, with early loading being detrimental whereas delayed loading enhanced outcomes9. Additionally, in a controlled, in vitro model, Dr. Guldberg and his group have demonstrated that allowing the vascular network to develop for 5 days before adding compression plus shear optimized outcomes. Dr. Guldberg’s Regenerative Rehabilitation approach to large bone defect repair nicely demonstrated the clinical relevance of timing and method of stimulation in designing rehabilitation protocols.Plenary speaker Dr. Robert Guldberg (University of Oregon) provided an insightful talk on the preclinical and in vivo models his lab uses to assess vascular and bone growth under different load conditions, with both acute and delayed treatment models. His group has pioneered the integration of implantable wireless sensors to monitor the mechanical environment within the regenerative niche10. As an extension of this pioneering work, Dr. Engler kicked off the session with an engaging presentation on leveraging biomaterials to better approximate extracellular matrix properties to induce cardiomyocyte phenotypes. This disease-in-a-dish approach allows for induction of pathological cardiomyocytes responses to study, identify, and subsequently interrogate signaling pathways, which may ultimately inform clinical interventions. These interesting results suggest that any culture system should require specific dynamic materials that change as the niche does in vivo. Dr. Fabrisia Ambrosio (University of Pittsburgh) then shared her work on extracellular vesicles and the protein Klotho. Understanding how circulating factors affect the mitochondrial function of muscle stem cells provides insight into how muscle loses its ability to heal with increasing age, which could present an interventional target to restore one’s molecular profile to a more “youthful” stage.This session focused on the role of mechanical stimulation for enhancing stem cell function. In 2006, Dr. Adam Engler  and colleagues first demonstrated that stem cells are highly mechanosensitive and that biophysical characteristics of the extrinsic microenvironment is a potent driver of stem cell lineage specification11. The results demonstrated that, although gene therapy alone can improve endurance, muscles in the mdx mouse model treated with gene therapy and combined with exercise are capable of adapting to training and achieving significant gains. Consequently, this Regenerative Rehabilitation therapeutic approach has great clinical potential for development of effective drug and physical therapy treatments of DMD.Dr. Robert Grange (Virginia Tech) talked about the pathogenic mechanisms and treatments for Duchenne muscular dystrophy (DMD), with a focus on rescuing dystrophic muscle so patients can better perform and enjoy activities of daily living. His Regenerative Rehabilitation approach was to use gene therapy in combination with endurance exercise in a rodent model—the mdx mouse—to significantly improve the time-to-fatigue during the final treadmill run at the end of the training period. Dr. Grange has previously shown that mdx muscles can functionally adapt to chronic exercise, but exercise alone is not enough to completely overcome the maladaptive response of dystrophic muscle3T), an NIH-funded resource network established in 2015. The mission of AR3T is to support the expansion of scientific knowledge, expertise, and methodologies across the fields of regenerative medicine, biophysics and rehabilitation. To fully realize this goal, AR3T promotes education, training, research support, and funding opportunities (www.ar3t.pitt.edu). Dr. Rando reiterated AR3T’s support of the Symposium and described the broad range of opportunities that are available through AR3T to help researchers develop and succeed with innovative lines of Regenerative Rehabilitation research. The opportunities include short-term sabbaticals to AR3T sites, consultations with subject matter experts, pilot funding, technology development grants, paired mentoring experiences, and access to diverse educational courses.Co-director Dr. Thomas Rando (Stanford University) shared an overview of the Alliance for Regenerative Rehabilitation Research & Training , Dr. Sunil Gandhi , and Dr. Gunes Uzer (Boise State University) were selected to present on their ARDr. Gandhi discussed his progress in the development of a method for live imaging of somatosensory fibers in cervical spinal cord that can help to determine whether effective human neural stem cell engraftment enhances robotic-assisted therapy after spinal cord injury, thus improving recovery. Dr. Uzer showed a 3D printable, repeatable, adaptable and easy-to-use model of bone marrow that will be useful for studying cell responses in specific mechanical environments.The Department of Defense (DoD) has increasingly relied on the role of Regenerative Rehabilitation to advance the translation of cutting-edge regenerative technologies for the functional recovery of severely wounded soldiers and civilians. This is evidenced by recent funding opportunities such as the RESTORE effort that calls for Regenerative Rehabilitation research and the AFIRM effort to advance regenerative medicine. Along these lines, Colonel Sarah Goldman  illustrated how war has motivated medical advances and she discussed applicable DoD medical research funding opportunities, including opportunities within the Congressionally Directed Medical Research Programs and other DoD Medical Research efforts.12.The plenary speaker of this session was Dr. Robert Mauck (University of Pennsylvania), sharing his translational mechanobiology work. He focused on how to motivate cell migration towards a wound site and how to use mechano-activation to our advantage for improved factor delivery to promote formation and repair of musculoskeletal tissue13. More specifically, demonstrating the importance of a Regenerative Rehabilitation approach, he showed that regeneration of neurons in the cord following SCI was significantly increased with a combination of exercise and cell graft.Dr. John Houle (Drexel University College of Medicine) shared his research on the duality of exercise after spinal cord injury (SCI), which can promote neural plasticity but also block aberrant neuroplasticityDr. David Weiss (University of Virginia) brought a valuable orthopedic surgeon’s perspective to the session. He discussed the challenges in trauma surgery when dealing with volumetric muscle loss (VML), how to evaluate the injury, and the long path ahead to regenerating muscle for massive loss injuries. He described UVA’s collaborative approach for studying VML, which includes working with the Biomedical Engineering Department to quantify the location and magnitude of VML and with the Kinesiology Department to perform functional testing.14. He also shared the multiscale biomechanical approaches currently being used to understand and ideally develop new rehabilitative approaches and therapeutics to reverse it . Drs. Joanne Borg-Stein  and Kenneth Mautner (Emory University) both shared their esteemed insights into bone marrow aspirate and adipose-derived stem cells. There are clinical logistics to consider with respect to the patient and provider, and certain rehabilitation protocols can be used to optimize the precision of regenerative medicine. Gaps in clinical practice using regenerative medicine approaches include identifying the best cell source, correct dose, best route of delivery, and optimal timing and type of rehabilitation. This led to an excellent panel discussion led by Dr. Borg-Stein, Dr. Mautner, Dr. Nelson Hager , and Dr. Quanjun Cui (University of Virginia). Topics included the clinical rationale behind using bone marrow versus adipose, the role of age in deciding treatment approach, what factors may play a role in responding to treatment, and the need to establish standards for stem cell therapeutics. This session’s clinical focus brought home the importance of collaborating in the translational process so that research data can be used to inform rehabilitation protocols to be used in combination with regenerative medicine therapies.This session began with plenary speaker Dr. George Christ (University of Virginia), who focused on volumetric muscle loss and the profound functional deficit that can be disproportionate to the volume lost15. Importantly, he challenged attendees to consider how neural technologies could be combined with regenerative medicine approaches in the brain and spinal cord to enhance stem cell differentiation and the formation of new connections that will result in improved healing.This session provided examples of translational research in the field. Dr. Michael Boninger (University of Pittsburgh) discussed the application of assistive technologies to increase function and participation in individuals with neurological disabilities. This is a very crucial topic that is reported to be of relevant impact in different aspects of neurological patient lives, such as in health, psychological and social status, education, and motor or cognitive learning16. The idea of the AxoMax technology is to use a biodegradable polymer tube containing a drug delivery system to promote the growth of peripheral nerves over large gaps (>3 cm), overcoming the current clinical limitations in nerve repair. One future direction is to add electrical stimulation and exercise to maximize outcomes.Dr. Kacey Marra (University of Pittsburgh) shared her authentic, humorous, and valuable perspective on what the translational research timeline looked like for her AxoMax technology, detailing the 20-year buildup from idea to human clinical trials to forming a companyDr. Silvia Blemker (University of Virginia) shared her collaborative research on 3D muscle modeling, which provides insight into the form, function, and biology of muscle. This work has wide-reaching applications for studying atrophy, injury, and dystrophy, as well as to inform the design and testing of tissue engineering technologies for muscle repair.17. Understanding these altered movement strategies will better inform the design of regenerative and rehabilitation approaches to prevent the development of chronic movement compensations.Dr. Shawn Russell (University of Virginia) spoke on the functional assessment of biomechanics, where the kinematics and kinetics of animal locomotion can be powerful tools for quantifying functional change after volumetric muscle lossOver the past 8 years, the symposium series has evolved to meet the needs of such a disparate audience. While a strength of the symposium is in bringing so many different students, researchers, and clinicians together in one place, there was also a need to program in targeted learning opportunities to meet specific needs.A Clinical Special Interest Group (SIG), formed in response to the growing number of rehabilitation clinicians, provides an opportunity to meet and share experiences related to the treatment of regenerative medicine therapies in the clinic. The Clinical SIG breakfast discussion, led by Drs. Carmen Terzic (Mayo Clinic Rochester) and Quanjun Cui, allowed attendees to share ideas and strategies for clinical approaches following regenerative medicine therapies to optimize outcomes.Held for the first time at the symposium, a breakfast discussion led by the University of Pittsburgh’s Dr. Fabrisia Ambrosio and Mrs. Paula Davis centered on diversity and inclusion. Attendees shared multiple perspectives and thoughts on supporting diversity in the student body and at the faculty level. Recommendations that resulted from the breakfast included that we should all obtain training on diversity and implicit bias, as each one of us can be an ally, and to support diversity across the STEM pipeline.Post-symposium workshops were “Clinical Study Design for Regenerative Rehabilitation” led by Dr. Marcas Bamman (University of Alabama), and “Rehabilitation Strategies in Preclinical Models” led by Dr. Linda Noble-Haeusslein . The goal of Dr. Bamman’s workshop was to address challenges and current opportunities specific to clinical trials in medical rehabilitation. These included trial design, issues in recruitment and retention, funding opportunities, and mobile technology integration into rehabilitation trials. An introduction to clinical trial resources for investigators was given, specifically the REACT Center and the Medical Rehabilitation Research Resource (MR3) Network Coordinating Center. The goals of Dr. Noble-Haeusslein’s workshop were to overview preclinical research design using a rodent model and to cover methods of rehabilitation and outcome measurements. Together, these will help optimize basic regenerative rehabilitation research for more successful translations of basic research to the clinic.A pre-symposium workshop was led by Dr. Rosemarie Hunziker—a former program director of the National Institute of Biomedical Imaging and Bioengineering—on how to maximize success in NIH grant writing. Geared towards trainees, early investigators, and those who may not be familiar with NIH funding, Dr. Hunziker provided an in-depth and entertaining crash course on the tips, tricks, and common challenges of the NIH.A poster session provided an excellent networking opportunity between senior researchers, clinician scientists, and students. A vast spectrum of topics was presented, including implantable sensors, biomaterials, molecular and cellular responses to biophysical signals, and mechanical stimulation in cellular therapeutics and tissue engineering.3T was selected for renewal and received its notice of award July 2020. Due to COVID-19, the AR3T Executive Leadership recently made the difficult decision to postpone the 2020 symposium to 4–6 November 2021 at the University of Texas, Austin. However, a number of virtual options are being planned in the interim that will tap into the pioneering aptitude of our community to deliver world-class education and spotlight Regenerative Rehabilitation innovation.This symposium featured world-renowned researchers and clinicians, focusing on the emerging field of Regenerative Rehabilitation; it succeeded in creating a platform for bridging several areas of expertise in a setting that fosters discussion, interaction, cross-discipline pollination and networking. Drs. Paul George (Stanford University) and Shailly Jariwala  shared a success story of how networking at last year’s Symposium led to their collaborative project, submitted to the Department of Defense, using nerve conduits combined with electrical and chemical stimulation for the treatment of peripheral nerve injury. This session invited attendees to think of innovative approaches and collaborations to continue moving the field of Regenerative Rehabilitation forward. Looking ahead, the P2C grant supporting AR


The increasing burden of Non-Communicable Diseases (NCDs) in Bangladesh underscores the importance of strengthening primary health care systems. In this study, we examined the barriers and facilitators to engaging Community Health Workers (CHWs) for NCDs prevention and control in Bangladesh.a. Situation analyses using a literature review, key personnel and stakeholders’ consultative meetings, and exploratory studies. A grounded theory approach was used for qualitative data collection from health facilities across three districts in Bangladesh. We conducted in-depth interviews with CHWs  (n = 4); key informant interviews with central level health policymakers/ managers (n = 15) and focus group discussions with CHWs . Participants in a stakeholder consultative meeting included members from the government (n = 4), non-government organisations (n = 2), private sector (n = 1) and universities (n = 2). Coding of the qualitative data and identification of themes from the transcripts were carried out and thematic approach was used for data analyses.We used multipronged approaches, including The CHWs in Bangladesh deliver a wide range of public health programs. They also provide several NCDs specific services, including screening, provisional diagnosis, and health education and counselling for common NCDs, dispensing basic medications, and referral to relevant health facilities. These services are being delivered from the sub-district health facility, community clinics and urban health clinics. The participants identified key challenges and barriers, which include lack of NCD specific guidelines, inadequate training, excessive workload, inadequate systems-level support, and lack of logistics supplies and drugs. Yet, the facilitating factors to engaging CHWs included government commitment and program priority, development of NCD related policies and strategies, establishment of NCD corners, community support systems, social recognition of health care staff and their motivation.Engaging CHWs has been a key driver to NCDs services delivery in Bangladesh. However, there is a need for building capacity of CHWs, maximizing CHWs engagement to NCD services delivery, facilitating systems-level support and strengthening partnerships with non-state sectors would be effective in prevention and control efforts of NCDs in Bangladesh.The online version contains supplementary material available at 10.1186/s41256-020-00182-z. Globally, the Non-Communicable Diseases (NCDs) have become the leading cause of death and disability and are the major ongoing public health problems –3. In 20Like other LMICs, Bangladesh is experiencing rapid demographic and epidemiological transitions –8, and sIn recent years, the government of Bangladesh has taken several initiatives to combat NCDs , 26. NatThe Community Health Workers (CHWs) in Bangladesh are those health cadres working in public sector health facilities including Community Health Care Provider (CHCP), Assistant Health Inspector (AHI), Health Inspector (HI) and Family Welfare Assistant (FWA). These CHWs receive some form of formal training. The duration ranged from 12 weeks for CHCP to over three years for HI . The serWhile Bangladesh is committed to offering universal access to health services for NCDs, no options to supplement the existing primary healthcare delivery system has been identified. Information on the training of CHWs, the process to deliver healthcare interventions through CHWs, and the effectiveness of CHW-led intervention are lacking. Identification of the facilitators and barriers to CHW-led implementation of NCD related services can provide policymakers and practitioners with a portfolio of options to address the growing demands for NCD-related healthcare services. Therefore, our study aimed to explore the barriers and facilitators of engaging CHWs in delivering NCD related services in Bangladesh.We used a grounded theory approach , 30 invoSimilarly, the four IDIs  with CHWs were conducted. The FGDs and IDIs were focused on exploring the perceptions of CHWs on NCD, their current workload, capacity in delivering NCD focused preventative care, and the challenges faced by them in the community. The KIIs were conducted in the natural setting of experts (i.e. workplace environment), and these participants were selected based on their current involvement and responsibilities with primary health care service delivery, NCD surveillance, and research background. A stakeholder meeting was organized by the National Heart Foundation Hospital and Research Institute on 31st December 2016 to obtain the views of government and non-government stakeholders on the role of community health workers in combating NCD in Bangladesh.This study was a part of the multi-country study of Asia and Pacific regions , where wn = 9) (ii) four FGDs  with the community clinic service providers and (iii) KII with experts representing the government and non-governmental organizations (n = 15). See Table Purposive sampling was used to choose the participants for this study, and study participants were recruited from three districts. Three main approaches were used for data collection (i) One stakeholders meeting with senior government and non-government officials, researchers, academician and clinicians  General public health programs delivered by CHWs (iii) NCD-specific programs provided by CHWs; and (iv) Facilitating and enabling factors in engaging CHWs in NCD control & prevention. In order to maintain confidentiality, all the data were de-identified and anonymized throughout the transcription and interpretation of the findings.The audio files of the collected data were transcribed verbatim by one of the investigators of the research team (SJ). Two of the team members went through all the transcripts independently, and then coding was done. We adopted an inductive approach in the coding process where two members (SJ and LR) of the researcher team identified the codes by comparing and contrasting the meanings and patterns as expressed by study participants. The identified codes were further checked by another two researchers (SC and AA) for accuracy. All team members reviewed the codes and then finalized the emerging themes from the data. The coding of the transcripts and the identification of emerging themes were carried out using a thematic approach, as recommended by Nowell et al., (2017). Four major themes identified include: (i) Health care delivery around The collection and analysis of data from qualitative interviews adhered to the Standards for Reporting Qualitative Research (SRQR)  and straThe details of the participants’ characteristics are presented in Table “When the patients with the possible non-communicable disease come to our community clinic, we tell them about the risk factors of NCDs, but we realize more awareness and health education needs to motivate the community. We offer BP measurement, Blood sugar test using a glucometer, minor treatment of RTA and some basic biochemical test.” – IDI 1-Medical Officer, Urban Primary Healthcare Centre, DhakaNotably, CHWs said that they usually provide necessary advice and counselling for common NCDs to the people who come to see them. The CHWs provide advice related to dietary habits, the importance of physical activity, health education and healthy behaviour to prevent NCDs when anyone come to consult them. Most of the CCs have limited laboratory facilities available, and the CHWs diagnose hypertension but no other NCDs because of lack of resources and training. Some of those CCs, which have glucometers available to test blood sugar, are most of the time, out of order or the supplies such as glucometer strips or batteries ran out. One participant said:BP machine and glucometer, along with other measuring tools, are available in our CCs. But the problem is we don’t have enough strips here at the CCs, right now because of the shortages of glucometer strips, so I can’t check the blood glucose level using the glucometer.” – FGD1-Health Assistant-Community Clinic, Sylhet district“Community Clinics (CCs) are the grassroots level public sector health facilities in Bangladesh. The services are provided by the Community Health Workers, including CHCP along with FWA and HA. The common NCD and related services provided by these CHWs include a screening of common NCDs such as diabetes and hypertension. However, the services for the detection of other NCDs such as COPD and cancer are not yet available. Basic medication for diabetes and hypertension is also available at the community clinic level. However, for further investigation and confirmatory diagnosis of NCDs and appropriate management, the patients are referred to upper-level health facilities, such as Upazila health complex  or district level health facility, where specialized health services are available. The FGD members reflected this opinion during the FGD.“We don’t have any extensive training on the management of common NCDs, i.e. diabetes, hypertension but these are the very common finding in our regular activity and identified patient wants to get their treatment at the community level” - IDI2 Health Supervisor, Urban PH Clinic, Lalbagh, DhakaTo date, there is no systematic approach in place for a referral and follow up of a patient. These are up to the patient to choose the health facility they want to go for further investigation and management. Suspected patients are referred to UHCs for further investigation, diagnosis and necessary management of NCDs.In general, CHCPs received 12-weeks basic training, mostly focused on maternal and child health and HCPs and AHI/HI received one-day training on NCD prevention and management. The NCD training included a general screening of NCDs, health education, counselling and basic care for common NCDs. One CHCP expressed:“to date, over 29 different types of medicines are supplied to community clinics from the government. They are mostly antibiotic, vitamins, eye ointments, salbutamol, anti-helminths, oral saline and acetaminophen product. These drugs also have more demand for community people. The anti-hypertensive and diabetic drug is not yet available at community clinic though community people are regularly demanding supply for those from CHCP”. KII1 Line Director, (NCD), Director General of Health ServiceIn terms of recording and reporting, participants noted that there is no separate registration for NCDs conditions or related risk factors. The information regarding the patients with NCDs conditions is recorded and reported along with patients of other health conditions.To provide medication, the NCD related drugs are supplied within the regular drug supply schedule, which in general takes longer time, even up to four months once the requisition is made. Also, the uncertainties exist in terms of discrepancy between requisition and actual supply. One of the KIIs shared that:This study identified several challenges and obstacles to engaging CHWs for NCD prevention and control in Bangladesh. The challenges are mainly related to workload, inadequate training, poor system-level support, inadequate remuneration, delivery of services and the availability of resources. The challenging factors are structured in the following key sub-themes:At present, the CHWs job description primarily involves providing services for communicable diseases, MNCH care, nutrition, immunization and health education and counselling services. Participants opined that, to date, no clear job description had been given, which would involve NCD services too. However, in recent years, the health facilities have initiated providing essential preventive and care services for those with NCDs conditions. The CHWs are currently multi-tasking and responsible for both the administrative and technical tasks. One KII opined that:“Our jobs have so far given mainly focused on providing services for communicable, maternal and child health and related services. We still do not have a clear job description on NCD services, however, we know somehow about preventive aspects and also basic NCD services, such as medication for diabetes and hypertension”- KII2, Line Director, Community Based Health Care, Director General of Health ServiceFurther, the CHWs are not yet trained on NCDs screening and providing basic NCD care which hinders them providing NCD services. This may require providing focused training on NCDs and making necessary supplies  available. Inadequate number of health workers at the health facilities often resulted in increased workload on the existing staffs, thus affecting the effective health services delivery, including NCDs services. One health worker expressed that:There are no trained CHCPs, AHI/HI at this CC. Even still now, I have not received any training on NCD. We all received maternal and child health-related training. - FGD2, Community Clinic, Uttar Matlob, Chandpur““ … . but the problem is the staffs need to be involved with their regular activities, and we have staff shortage, especially paramedics. So due to support staff shortage, there is no one to support the dedicatedly NCD patients at the Community Clinic.” – KII3, Principal Scientific Officer, Institute of Epidemiology Disease Control and Research, Director General of Health ServiceAnother participant also added that there had been a shortage of health care providers too:CHWs reported frequent delays in the delivery of medication supplies for common NCDs (i.e. hypertension and diabetes) at the community clinic from the sub-district hospitals. This has hampered their service delivery to the community members and raised dissatisfaction among the public. One participant opined:Yes, we have received glucometer, BP machine, weight and height machine for the CC. But now the problem is, there is a shortage of battery and strips for the glucometer for which we can’t use the glucometers.” -  FGD3 Health inspector, Rakhal Gonj Community Clinic, South Surma, Sylhet“Another participant in the FGD expressed that, once a year, the CCs provide a requisition for medicine. The medicine comes at the CS office, and from where the CCs take what is being allotted for them. The NCD related medicines come with the regular medicine supply, but the supply schedule is uncertain. Also, the amount and types of medicine sent for treating NCD patient is not adequate.“For the outpatients, the type of medicines dispensed depends on the available medicines and supply. We always try to provide whatever medicines are available at the CCs. But for the inpatients, we have medicines required to treat the NCD patients at Upazila level.” – KII4 Upazilla Health and Family Planning Officer South Surma, Sylhet.The CCs are facing many problems. There is a lack of proper instrumental support. At my CC, we received only a BP measurement set. We are waiting for other equipment to arrive. We have no glucometer for screening NCD cases as most of the required blood tests we now advised them to go UHC, but we need available immediate screening and measurement tools.” – FGD4 Zohirbad Nadamodi Community Clinic Uttar Matlab, Chandpur“Coupled with above-described challenges, the participants also identified other key challenges including: inadequate health systems priority and lack of standard operating procedure to NCDs prevention and care, no specific policy documents prioritizing NCDs care and services as core activities of the health facilities, and lack of awareness on NCDs risk factors, NCDs symptoms and delay in seeking care by the patients at the community level.Further, the health facilities, in particularly the CCs, are facing other logistics-related challenges, such as shortages of adequate space, lack of furniture, and inadequate necessary instruments to deliver NCD related services. One FGD participant said:Participants identified following facilitating factors to support engagement of CHWs in NCDs prevention and control.Over the past several years, the government of Bangladesh has initiated several NCD prevention and management related initiatives. Policies and guidelines to NCDs prevention and control at the systems level have been developed, an NCD control program at the DG health services has been created - to primarily looking after the NCD issues. To this end, the NCD corners at the sub-district level health facilities (UHCs) has been introduced, and several efforts to increase NCDs prevention and control measures at the community level have been initiated. One participant opined that:“The government of Bangladesh has given priority for NCDs prevention and control. The government also has established over 300 NCD corners in the country, and we have been able to somehow implement NCD services through these NCD corners in the country” – KII5 Divisional Director, Sylhet Division, Director General of Health Service.Further, in recent years few necessary NCD drugs have been added into the essential drug list and made these essential services drugs (ESDs) freely available at the community health facilities.The CHWs believed that the initiatives taken by the Directorate General of Health Services, Bangladesh, to fulfil the vacant positions in the health facilities will ensure delivery of quality health services in the community level, including NCDs services. They also thought that the retention of health workers is another important aspect of delivering NCD and related services. This is one of the keys facilitating factors the CHWs identified in this study. One participant said:“Government of Bangladesh has taken a good initiative to recruit new positions and fulfil the vacant positions in all health facilities. Retention of health workers to the assigned health facility, in particular, the rural areas is equally important as recruitment and deployment” – KII6, Head of the Department of Epidemiology, National Institute of Preventive and Social Medicine.Despite several challenges the CHWs are facing, they shared that they have a good level of personal satisfaction to the services they are providing. CHWs said that serving people in the community reciprocate the respect and recognition from the community members. One of the participants shared:“I feel great that I have got the opportunity to work at the health facility in my community, and I am serving people in my area. When people tell me that I have done a good job, I feel very proud and happy, and that makes me more responsible” – IDI-4, CHCP, Rakhal Gonj Community Clinic, South Surma, Sylhet.Most of the KIIs, IDIs and the participants of the stakeholder consultation meeting viewed that the CHWs have been playing a vital role for NCDs prevention and management services. One KII emphasized:“Traditionally, the CHWs have been trained and given tasks to deliver communicable diseases and related services. However, the situation in Bangladesh has changed where we are dealing with NCDs rather than communicable diseases. The CHWs have been well recognized to play vital roles in the prevention and management of NCDs. Of course, the CHWs need a range of policy and systems support and guidance, which they have been provided by the government of Bangladesh. KII-7, Manager, Directorate General of Drug AdministrationThe policy level participants  stated that the Ministry of Health and Family Welfare, Bangladesh has given priority to NCDs prevention and control in Bangladesh. There has been a government level commitment. However, there is a need for working together and collaborating with other ministries and non-state sector to optimize the efforts for NCDs prevention and control in Bangladesh. Participants also shared that the non-state sector, in particular, the NGOs and private sector have also taken several initiatives. They also provide NCDs prevention and care services, including screening, early detection, diagnosis, treatment, referral, and health education and counselling services in Bangladesh. One participant highlighted:“The government of Bangladesh have developed a range of NCD related policies and guidelines. We have a dedicated department  to look after NCD related programs in the country. However, there is a need for working together with other ministries, NGOs and private sector” KII-1, Line Director, Community Based Health Care, Director General of Health ServiceLike many other LMICs, Bangladesh has been experiencing the growing burden of NCDs, posing significant threats to the existing weak health care systems in the country –10. In tIn recent years, the government of Bangladesh has taken several initiatives to combat NCDs at systems, institutional and community levels , 26. To In this study, CHWs were highly interested in delivering NCD related services in their community. CHW’s motivation in healthcare delivery can be taken as a key factor in implementing NCD related services and achieving Sustainable Development Goal 3, “Health and Wellbeing” in Bangladesh by 2030 . ResultsThe current healthcare system of Bangladesh is not yet well prepared to mitigate the growing demand of NCDs. A number of key barriers both at systems and service delivery levels were identified. These include (i) lack of appropriate NCD policy guidelines, (ii) insufficient trained human resources, (iii) inadequate logistics, supplies and medications, (iv) lack of laboratory facilities, (v) inefficient referral mechanisms, and (vi) unavailability of systematic recording and reporting systems. These findings corroborate well to the ones reported in the recent studies from Bangladesh , 20, 27 Strengthening primary health care for tackling the burgeoning burden of NCDs in Bangladesh is critically important, where the CHWs who are based at community clinics, union-level health centres and UHCs could play a pivotal role in screening, provisional diagnosis, early management, referral and follow of patients with NCDs . To achiOur study has some limitations. First, we were unable to include participants from more than three sub-districts. Having data available from additional sub-districts and district level could have added extra insights to ensure more generalizable findings. Second, we were unable to collect data from the patients or community members, which could have added insights from the service recipients’ perspective but was out of the scope of this study.We conclude that there is a potential for using CHWs for NCDs prevention and control in Bangladesh. Several barriers and facilitators for CHWs’ potential engagement to deliver NCD related services have been identified. Our results offer suggested options to policymakers and researchers for integrating CHWs in the delivery of community-based interventions for NCDs prevention and control in Bangladesh. Effective integration of CHWs along with policy support for capacity buildings of CHWs, evidence-based practice and referrals and offer flexibility to adapt programs to the local context, are essential to delivering NCD related programs in the country. Further, we recommend developing and testing model interventions to train CHWs and to provide CHW’s-led NCD prevention and control programs in Bangladesh.Additional file 1.


Pofatu, the first online and open-access database to present geochemical compositions and contextual information for archaeological sources and artefacts in a form that can be readily accessed by the scientific community. This relational database currently contains 7759 individual samples from archaeological sites and geological sources across the Pacific Islands. Each sample is comprehensively documented and includes elemental and isotopic compositions, detailed archaeological provenance, and supporting analytical metadata, such as sampling processes, analytical procedures, and quality control.Compositional analyses have long been used to determine the geological sources of artefacts. Geochemical “fingerprinting” of artefacts and sources is the most effective way to reconstruct strategies of raw material and artefact procurement, exchange or interaction systems, and mobility patterns during prehistory. The efficacy and popularity of geochemical sourcing has led to many projects using various analytical techniques to produce independent datasets. In order to facilitate access to this growing body of data and to promote comparability and reproducibility in provenance studies, we designed  Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.12073116 Such material aspects of cultures can be inferred with the help of provenance studies, by reconstructing the movements of materials and artefacts across space. For this purpose, archaeologists have regularly used petrographic and geochemical analyses for more than 40 years for characterising the geological provenance of raw materials and stone artefacts and for reconstructing patterns of exchange based on hard evidence7. Geochemical techniques have proven to be the most efficient and reliable way to fingerprint raw material sources and artefacts thereby providing reproducible and comparable results10. Furthermore, geochemical data are quantitative and can therefore be examined with statistical methods12 or by using, for example, well-known principles of petrogenesis and mantle source evolution.Extracting, transforming, and distributing natural resources and finished goods between individuals and groups has always been an important aspect of technological, economic, and social behaviors in human societies13. Sharing source data compilations facilitates assigning unambiguous provenance to artefacts because it enables a better understanding of geochemical variability of sources throughout a given study region and also shows potential geochemical differences between sources14, especially for artefacts found in either very homogeneous or complex petrogenetic contexts17. Furthermore, accessing large geochemical datasets of archaeological artefacts will lead to more robust and large-scope modelling of prehistoric exchange systems20. However, the current lack of appropriate global data management platform makes it difficult to access and reference relevant archaeological datasets and often induces duplication of individual endeavors.Due to the improvement of analytical techniques and the increasing use of geochemical sourcing, the production and publication of archaeological compositional data have grown exponentially. It is now recognized that using large source data compilations can lead to more efficient and cost-effective research planning24. Furthermore, by using common non-proprietary file formats (CSV) and an open source system for storage and version control (Git and GitHub repository), the Pofatu Database provides an analysis-friendly environment that enables transparency and built-in reproducibility of analytical tasks25.In this data descriptor, we introduce the Pofatu Database, a curated and open-access database of geochemical data on archaeological materials and sources supported by comprehensive contextual information about individual samples and artefacts, including about the archaeological provenance, and a thorough description of analytical procedures. The goals of the database are (i) to provide easy access to published compositional data of archaeological sources and artefacts, (ii) to assemble contextual archaeological information for each individual sample, (iii) to facilitate reuse of existing data and encourage the appropriate crediting of original data sources, and (iv) to ensure reproducibility and comparability by documenting instrumental details, analytical procedures and reference materials used for calibration purposes or quality control. We provide compositional data as well as contextual metadata for 7759 individual samples with a current focus on archaeological sites across the Pacific Islands Fig. . Our vishttps://pofatu.clld.org/). The database was designed to contain geochemical compositional data and extensive contextual metadata , which we compiled to ensure further reuse and reinterpretation of previous provenance analyses  and browsed in the Pofatu web application  as well as the accuracy and reproducibility of published analyses .The compositional data contains all analytical values for major oxide and trace element compositions, radiogenic and stable isotope ratios, and geochronology. Sample metadata involves the creation of unique identifiers, and a description of sample condition and preparation. Archaeological metadata provides information on the geographical, cultural and stratigraphic context of the parent artefacts , the collection origin , and a description of the site and stratigraphic context . The reference metadata lists all bibliographical sources of the data and metadata informationAll data and metadata in the Pofatu Database and included in this data descriptor release are linked with published resources. Geochemical datasets are extracted from peer-reviewed material, while contextual metadata include information gathered from peer-reviewed articles, monographs, book chapters, and publicly available institutional reports. Original sources are coded in the repository and available as a BibTeX database file, suitable for importing into reference management software. Geochemical datasets are associated with a method identifier, which is unique and defined based on the set of available methodological metadata for a specific set of values.The process of data acquisition includes:Data submission: Data and metadata are gathered and stored in normalized tables linked by foreign keys. These interrelated tables each contain sets of information on (i) Data source, (ii) Sample and archaeological provenance, (iii) Compositional data, (iv) Primary analytical and method-specific metadata. The Pofatu Database is frequently curated and updated on a regular basis. New datasets and complementary information on previously documented datasets can be submitted using the Data Submission Template and Guidelines available online (https://pofatu.clld.org/about).Data validation: The content of each table is handled manually but several fields are constrained by ontologies, which are built-in form validation in the submission template. Data is also validated using functionality implemented in the Python package pypofatu, which imposes suitable constraints on data like geographic coordinates.Data output: The manually curated “raw” data undergoes an automated processing workflow (implemented in the Python package pypofatu) to create output formats ready for distribution.https://www.w3.org/TR/json-ld/, accessed January 30, 2020), following the World Wide Web Consortium (W3C) recommendations175. Because the compiled data is exclusively made of line-based text files (in CSV format), it is well-suited for long-term access since it has the lowest requirements on processing software, and provides for a transparent history of changes with the version control software Git .For long-term accessibility, the data is converted to a set of interrelated CSV files, described by metadata encoded as JSON-LD , data consistency can be checked automatically, e.g. detecting multiple conflicting measurements of the same parameter in the same analysis, or conflicting sample metadata.Users feedback: Data and metadata issues can be reported to pofatu@shh.mpg.de. Editors will be contacted if an issue with one of their datasets is reported.178 that enables transparency and built-in reproducibility of analytical tasks that can be achieved through freely available softwares or web browsers25.The Pofatu Database provides an analysis-friendly environmenthttps://sqlite.org/appfileformat.html, accessed January 29, 2020) for the convenience of the users. This SQLite database is contained in a single file document that can be queried with a high-level query language, has accessible content, is cross-platform, performant, and can be used with multiple programming languages.Since the metadata provided with the csv-formatted data files has information about data types as well as relations between the tables making up the dataset, it is automatically loaded into an SQLite database  that enables access and queries of the data with Python programs or the pypofatu API, and facilitates running SQL queries against the SQLite database.using SQL command lineusing SQL browsers such as SQLite manager or SQLite reader180using R, with SQL codes in a notebook or packages such as sqldf or dplyr181using the Datasette toolComplex queries can be created in various ways and with different computing environments:https://github.com/pofatu/pofatu-data, accessed February 6, 2020). A “cookbook” collects shareable pieces of code and how-to instructions to query the relational database , and users are invited to contribute with the “recipes” they used for “cooking” with Pofatu.Data usage instructions are provided in the GitHub repository where the dataset is curated (cf.


Achilles tendinopathy (AT) rehabilitation traditionally includes progressive tendon loading exercises. Recent evidence suggests a biopsychosocial approach that incorporates patient education on psychosocial factors and mechanisms of pain can reduce pain and disability in individuals with chronic pain. This is yet to be examined in individuals with AT.This study aims to compare the effects on movement-evoked pain and self-reported function of pain education as part of a biopsychosocial approach with pathoanatomical education for people with AT when combined with a progressive tendon loading exercise program.A single-site, randomized, double-blind, placebo-controlled clinical trial will be conducted in a university-based hospital in a laboratory setting and/or by telehealth. A total of 66 participants with chronic (>3 months) midportion or insertional AT will be randomized for the Tendinopathy Education of the Achilles (TEAch) study. All participants will complete progressive Achilles tendon loading exercises over 12 weeks and will be encouraged to continue with self-selected exercises as tolerated. All participants will complete 6-7 one-to-one sessions with a physical therapist to progress exercises in a standardized manner over 8 weeks. During the last 4 weeks of the intervention, participants will be encouraged to maintain their home exercise program. Participants will be randomized to 1 of 2 types of education (pain education or pathoanatomic), in addition to exercise. Pain education will focus on the biological and psychological mechanisms of pain within a biopsychosocial framing of AT. Pathoanatomic education will focus on biological processes within a more traditional biomedical framework of AT. Evaluation sessions will be completed at baseline and 8-week follow-up, and self-reported outcome measures will be completed at the 12-week follow-up. Both groups will complete progressive Achilles loading exercises in 4 phases throughout the 12 weeks and will be encouraged to continue with self-selected exercises as tolerated. Primary outcomes are movement-evoked pain during heel raises and self-reported function . Secondary outcomes assess central nervous system nociceptive processing, psychological factors, motor function, and feasibility.Institutional review board approval was obtained on April 15, 2019, and study funding began in July 2019. As of March 2020, we randomized 23 out of 66 participants. In September 2020, we screened 267 individuals, consented 68 participants, and randomized 51 participants. We anticipate completing the primary data analysis by March 2022.The TEAch study will evaluate the utility of pain education for those with AT and the effects of improved patient knowledge on pain, physical function, and clinical outcomes.DERR1-10.2196/19111 Achilles tendinopathy (AT) pain leads to decreased function and participation in work and recreation activities ,2. HowevChronic musculoskeletal pain conditions, such as AT, can be associated with elevated levels of kinesiophobia and catastrophizing . Given t04059146) is a randomized, double-blind, placebo-controlled trial for individuals with chronic AT. The primary outcomes of movement-evoked pain and self-reported function will be represented as a change from baseline to 8-week follow-up  during walking, heel raises, or hopping at evaluation session 1Pain that increases  with increasing load during evaluation session 1Exclusion criteriaYounger than 18 years of ageInability to read and write in EnglishAchilles tendon pain for <3 monthsHistory of Achilles tendon rupture that was verified by surgical or conservative managementHistory of invasive intervention (surgery and Tenex) for Achilles tendinopathy (AT) on more painful sideNoninvasive treatment  for AT in the past 3 monthsDiagnosed with systemic inflammatory conditions , endocrine disorder with complications , and connective tissue disorder Cardiovascular conditions that may be exacerbated by a 90-second submersion of hand in cold water (Raynaud’s and cold contact urticaria)History of taking fluoroquinolones in the past 3 monthsFoot and ankle pain primarily owing to other causes, such as posterior impingement, bursitis, paratendonitis, sural nerve injury, ankle osteoarthritis, and radicular or referred symptoms , from lumbar spine into lower extremitiesFour step square test >15 seconds Cardiovascular condition that prevents participation in an exercise programd≥0.36 for pain  and self-reported function  [The primary outcomes of this study were movement-evoked pain and self-reported function. The sample size is calculated to have sufficient statistical power for each primary outcome using a Bonferroni adjusted type I error rate of 0.025 (0.05/2 for 2 outcomes in aim 1). On the basis of findings by Moseley  for a rares=0.5) . Using tThis is a randomized, double-blind, placebo-controlled trial with individuals who have chronic AT. Participants will be randomized to 1 of 2 groups: pain education or pathoanatomic education. All participants will receive the same progressive tendon loading exercise intervention. Each participant will complete 2 evaluation sessions where primary outcomes will be collected at baseline and 8-week follow-up, 6-7 treatment sessions with a physical therapist, and 1 evaluation session at 12-week follow-up with self-reported measures .Participants will be randomized using a permuted block design with variable block sizes. Randomization will be stratified by sex and AT location . Randomization codes will be stored electronically and printed by a lab assistant and placed into opaque envelopes and sealed. Each envelope will be numbered in sequential order and stored separately from the recruiter, outcome assessor, and treating physical therapist. Immediately before each participant’s first treatment session, the treating physical therapist will either open an envelope or receive an email with the participant’s group allocation. Thus, randomization will occur after baseline assessment and remain concealed from participants for the duration of the study. Following all outcome collections, participants’ planned unmasking will be completed at 12 weeks, where participants will be informed of their group allocation by providing references and resources used for both education groups. Following completion of the study, participants will be offered the option of being sent a copy of the published findings, quarterly newsletters on study progress, and provided with any preliminary findings after study completion.The intervention will occur over 12 weeks. The educational component will take place over the first 8 weeks during individualized treatment visits. The last 4 weeks will include maintenance of a home exercise program (HEP) with a phone call and email follow-up, if not reached by phone, from the physical therapist at 10 weeks to address any questions regarding exercise progression. The education and exercise treatments will be provided to both groups by the same unblinded physical therapist. Although a single treatment provider minimizes confounding social effects between physical therapists, an unblinded provider does allow for the potential of a bias in exercise progression between groups. The education programs, including videos, handouts, and review questions, are similar in length, style, and presentation of content, including the use of a script by a physical therapist to maximize consistency. All educational materials including handouts, weekly exercise records, and questionnaires will be provided through email and completed electronically by participants through an electronic data management system (REDCap). The education programs address participant knowledge on the causes of their pain as well as the overall importance of exercise to address tendon pathology. The main differentiating component will be based on the proposed mechanisms of pain. The pain education group will receive information that addresses concerns about fear of movement and pain catastrophizing, relates these psychosocial factors to their own experience with AT pain, and provides information on how tendon pathology is a potential (but not necessary) contributor to AT pain and that there is evidence that progressive loading is safe . Key resProgressive loading exercises for tendinopathy (same for both groups):Defining the term load for tendon pain rehabilitationTypes of loads placed onto the Achilles tendon during various activitiesUse of symptoms 24 hour after completion of exercises to inform exercise dosageRethinking the role of exercise for Achilles tendinopathy (AT):Achilles tendon load capacity and role of exercise to increase capacityProgressive increase in Achilles tendon exercise intensity and durationDifference between AT and Achilles tendon ruptureCommon tendon adaptations to loading:Common tissue adaptations seen on imaging including bone spurs, tendon calcification, and Haglund deformityLack of correlation between pathology viewed on imaging and clinical presentation of pain/stiffness with ATFactors influencing pain:Pain neurobiological processing including nociceptor activity and signal interpretation by the brain to produce sense of pain to protect from harm or dangerImpact of psychological factors such as stress and context of whole pain experienceUnderstanding pain:Hypersensitivity of the peripheral and central nervous system and persistent painThe role of descending facilitation and inhibition on chronic pain conditionsRecognition that persistent pain is multifactorialBenefits of exercise for chronic musculoskeletal pain:Neurotransmitters and inflammatory mediates present with persistent painRoles of exercise on improving immune system and neurotransmitter function to decrease painPhysical activity guidelines from the Department of Health and Human ServicesProgressive loading exercises for tendinopathy (same for both groups):load for tendon pain rehabilitationDefining the term Types of loads placed onto the Achilles tendon during various activitiesExercise progression and use of symptoms 24 hours after completion of exercises to inform exercise dosageEffects of exercise on Achilles tendon pathology:Collagen tissue composition and common changes with tendinopathyDefining terminology of tendon pathology (tendinitis/tendinosis/tendinopathy)Role of exercise in addressing collagen tissue remodeling through progressive loading exerciseSoft-tissue and boney deformities associated with Achilles tendinopathy (AT):Prevalence and etiology of ATPresentation of radiographic images of common anatomical findings often associated with AT including Haglund deformity, bone spurs, and calcification within the Achilles tendonAnatomical causes of AT pain:AT classification Continuum of mechanical tendon properties from healthy to tendon ruptureIntrinsic and extrinsic factors which predispose tendon to dysfunction Understanding tendinopathy pathophysiology:Pathogenesis of ATCommon imaging techniques used to identify pathologyComponents of clinical evaluation for AT diagnosis including patient history and physical examinationWhole body benefits of exercise:Impact of exercise on multiple systems throughout the body Physical activity guidelines from the Department of Health and Human ServicesIndividualizing exercise goalsEach participant will receive the same standardized therapeutic exercise program where progression will be individualized to each participant based on pain levels, the physical therapist’s clinical judgment, and predetermined physical function criteria . The exeOutcomes are described by the specific aim and timeframe collected in We will use a modified intention-to-treat analysis to examine the treatment effect for all outcome measures on participants based on group randomization. Characteristic comparisons will also be completed for those patients who remained in the study versus those who dropped out to determine if data at subsequent time points were consistent with missing at random data. For aim 1, we will compare differences between education groups for changes in movement-evoked pain and self-reported function from baseline to 8 weeks (primary endpoint) and 12 weeks using a linear mixed model for repeated measures. For aim 2, we will use a linear mixed model for repeated measures for intervention effect within groups on central pain mechanisms from baseline to 8 weeks. Secondary outcomes for pain, function, altered CNS nociceptive processing, psychological factors, motor control, pain, and function will be analyzed with a linear mixed model for repeated measures. Demographics, ultrasound imaging, and treatment history will be used to describe the sample and will be covariates in the analysis if different between groups. Secondary analyses of sex will examine for potential sex-based differences to inform sample size estimates for future clinical trials. Another secondary analysis of AT type  will also be assessed to inform recruitment strategies for future clinical trials.Exploratory aims 1 and 2 will examine whether changes in participant knowledge of pain education and central pain mechanisms, including altered CNS regulation of nociceptive input, changes in fear or pain beliefs, and improved motor function are associated with pain and function. For exploratory aim 1, we will use Pearson correlations between changes in knowledge from baseline to final evaluation (percentage of correct responses to pain education multiple choice questions) and changes in pain and function separately. For exploratory aim 2, we will examine Pearson correlations between changes in central pain mechanisms and changes in pain and function separately.t tests, Wilcoxon rank-sum test for continuous variables, or Chi-square or Fisher exact test for categorical variables, as appropriate.To evaluate the feasibility of future clinical trials, we will use descriptive statistics to assess patient retention, participant recruitment numbers, treatment fidelity, and patient adherence to their exercise program. To evaluate for potential confounders of treatment effect between groups, we will assess differences in duration of treatment sessions, time spent completing their HEP, time participants spent in each phase of their exercise program, percentage of participants who believed they were receiving the education program that the research team believed to be more effective, and the highest level reached within each exercise phase  using two independent samples delayed owing to COVID and rescreened once in-person human subjects research resumed.From March 17 to July 15, 2020, in-person human subjects research was suspended in accordance with the University of Iowa policy related to COVID-19. We conferred with the Data Safety Monitoring Board (DSMB) and the safety officer on protocol changes to continue the clinical trial via telehealth. These protocol changes were approved by the IRB at University of Iowa on March 17, 2020. The intervention content and the primary outcomes of movement-evoked pain and self-reported function were not altered, yet the transition to a virtual format affected screening, evaluation, and mode of delivering treatment as outlined below. Participants who did not pass the additional virtual screening questions were categorized as Modifications to the screening process were included at initiation of intervention delivery via telehealth due to COVID-19 to ensure participant safety during completion of the exercise program:Fall risk was completed using the Stopping Elderly Accidents, Deaths, and Injuries   rather tSymptoms indicating the need for in-person blood pressure monitoring: (1) inconsistent use of hypertension medications and/or (2) any recent/current associated symptoms with uncontrolled hypertension.Unable to successfully complete virtual visits with a webcam and/or prefer only in-person visits.Additional data collected via Zoom was completed to continue primary outcome collection during the telehealth format. The telehealth format did not permit imaging or QST data collection:Two-dimensional kinematics were collected via Zoom instead of 3D kinematics and kinetics.Ultrasound imaging and quantitative sensory testing were not completed.All treatment visits were completed on the web. There were no changes in the educational or exercise program content. The highest level of isometric and heel raise phases of the exercise program requires the use of an externally applied load via a Smith machine or weighted backpacks. Participants without access to a Smith machine in a gym, owing to lack of membership or COVID-19, were offered weighed backpacks.Given that the educational materials  had always been provided to participants via REDCap, the initial design of the intervention facilitated the transition of individualized discussion of materials from in-person to a virtual format. Since July 15, 2020, the option to complete virtual treatment visits remains available to participants who are unable to attend owing to illness, limited transportation, or any other circumstance that may restrict the participants’ ability to complete in-person visits.In addition, the pandemic has had negative effects on mental and physical health. Among adults in the United States, from June 24 to 30, 2020, 31% reported symptoms of anxiety disorder or depressive disorder . A studyThe psychosocial effects of this pandemic and study protocol changes motivated 2 additional exploratory analyses to (1) examine potential confounding effects of a pandemic and virtual participation on outcomes and (2) determine the feasibility of a clinical trial via telehealth. Our study sample can be divided into 3 groups of participants: all in-person visits , all visits via telehealth , and a mix of visits in-person and via telehealth during the pandemic (July 16 to study completion). To evaluate the potential interactions of the pandemic and virtual participation on the intervention, the changes in the primary outcomes (pain and disability) and psychological outcomes  will be compared between the 3 pandemic groups within each treatment arm (pathoanatomic vs pain education). To examine the feasibility of future clinical trials using a virtual format, recruitment rates, retention, adherence to HEP, and AEs will be compared between the 3 pandemic groups .All patient data will be stored in electronic records kept on a network drive of the Department of Physical Therapy and Rehabilitation Science at the University of Iowa and on REDCap. Access will be restricted to only the research team who will comply with the confidentiality of patient information consistent with the Health Insurance Portability and Accountability Act guidelines. An independent safety officer will review all AEs, serious AEs, unanticipated problems, and any protocol deviations affecting safety on a quarterly basis. The DSMB will meet yearly with the study team. The DSMB will convene annually to review the data, recruitment, and safety of subjects. This review will include a discussion of the allocation concealment process to ensure that concealment is done at the last minute and review of records to ensure that the proper random sequence was used. The review will also include reports of AEs, serious AEs, protocol deviations or violations, and unanticipated problems. Recruitment and retention will also be reviewed.Funding for this study was provided by the National Institute of Arthritis Musculoskeletal and Skin Disease research grant R00 AR071517 and the Collaborative Research Grant from the International Association for the Study of Pain (IASP). Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR002537. These funding sources had no role in the study design, collection, analysis/interpretation of data, or decision on submission for publication. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.Institutional review board approval was obtained on March 15, 2019, and study funding began on July 1, 2019. The TEAch study began enrollment on September 17, 2019. As of March 2020, we randomized 23 out of 66 participants. In September 2020, we screened 267 individuals, consented 68 participants, and randomized 51 participants. We anticipate to complete the primary data analysis by March 2022 and will submit the results for primary outcomes no later than 1 year after the primary completion date on ClinicalTrials.gov (NCT: 04059146) and Open Science Framework (JF2XU).In compliance with FAIR  data principles, data will be deposited at the University of Iowa open-access institutional repository, Iowa Research Online. The repository is open access and maintained by the Libraries at the University of Iowa for the preservation and sharing of intellectual work of faculty, students, and staff. The IPD will be available to other researchers for the primary outcomes. Data sets will be accompanied with appropriate descriptive, technical, and administrative metadata to facilitate discovery and scholarly reuse, and will be assigned unique digital object identifiers (DOIs) that can be incorporated into publications and cited in the literature. Metadata will be included in the data records in the repository through readme files and structured information following the DataCite metadata schema.Improved understanding of pain mechanisms and reconceptualization of pain as protective through patient education is recommended for individuals with chronic musculoskeletal conditions -59. Alth


The COVID-19 pandemic has swept across the globe at an unprecedented pace. The first COVID-19 case arrived in Sub-Saharan Africa (SSA) on February 28, 2020, and there are over 600 000 cases spread across the continent . SurgicaThe COVID-19 pandemic has disrupted surgical health care delivery in SSA by reducing surgical delivery, interrupting surgical training, and undermining the political and research priority of surgical health care amidst other global health challenges.Access to EESC is a crucial component of universal health coverage (UHC). A recent modelling study concluded that 866 449 procedures in SSA would be cancelled or postponed during the peak 12 weeks of disruption due to COVID-19, including 737 967 benign, 82 037 cancer and 46 445 obstetric operations [Three Delays Framework, which classifies barriers into seeking, reaching, and receiving care  outlined criteria for the re-escalation of surgical operations which include decreasing new COVID-19 cases daily for two weeks, availability of pre- and postoperative testing, and procurement of a surplus of personal protection equipment (PPE) to prepare for a second COVID-19 wave . HoweverSurgeons, obstetricians, and anaesthesiologists (SOA) are scarce resources in SSA, and their training has been undermined. Due to the shortage of training programs in their home countries, many SSA physicians pursue surgical training in other African countries , EuropeRecent political efforts in 16 southern African countries through the Southern African Development Community, an inter-governmental platform and regional economic zone of the African Union, have established the importance of EESC as regional health and economic priorities, and as significant components of attaining UHC and the Sustainable Development Goals (SDGs) . The COVFinally, research conducted in SSA is needed to inform and translate political support into evidenced-based surgical health care programs that will strengthen health systems based on local specificities. The COVID-19 pandemic has halted surgical research, routine data collection, and quality assessment and improvement. Academic global surgery, a nascent field in global health, is a crucial component of strengthening surgical health care in SSA. Global surgery partnerships are a gateway to additional funding for academic and policy stakeholder meetings, and research to support national health ministries in their efforts to improve surgical delivery. Much of these collaborative efforts have been curtailed [The maintenance of surgical health care services for EESC during the COVID-19 pandemic should be prioritised. First, we stand behind the call for economical and accurate rapid COVID-19 tests for SSA in order to conduct pre- and postoperative patient and staff testing as needed. Second, we support strengthening and expansion of anaesthesia and critical care, crucial components of surgical health services, as part of comprehensive COVID-19 emergency preparedness and response for the evolving COVID-19 surge in SSA. This expanded capacity can be used post-pandemic to improve the quality of surgical health care as a component of UHC and for SDG attainment. Third, we call upon the professional associations, together with academic heads of surgical departments to rapidly develop, implement and scale-up measures that both protect surgical trainees and create an enabling environment for their continued learning and retention within the public sector training programs. Finally, we encourage global surgery academic collaborative partnerships to continue through online platforms to share challenges and solutions throughout SSA on how to deliver surgical health care for emergency and essential surgical conditions during the COVID-19 pandemic.Despite a huge and evolving unmet surgical need in SSA – and the indispensable role of surgery to attain SSA health targets – surgical health care services in SSA are amongst the most inadequate globally in access and quality. The collateral damage of COVID-19 pandemic on surgical health care in SSA will compound an already dire state and are likely to produce enduring consequences for population health, the economy and broader sustainable development; these consequences will be difficult to reverse. The additional barriers to access to care for EESC could result in a tsunami of operative needs in the coming months and increases in avoidable morbidity and mortality. Efforts to increase the surgical workforce have been diminished through limitations in training. Funded research through international collaborative networks to strengthen fragile surgical health care systems and political prioritisation have also been interrupted. We must continue to advocate for equitable access to surgical health care during this unprecedented time, or an excess of lives will be lost.


Public health travel restrictions (PHTR) are crucial measures during communicable disease outbreaks to prevent transmission during commercial airline travel and mitigate cross-border importation and spread. We evaluated PHTR implementation for US citizens on the Diamond Princess during its coronavirus disease (COVID-19) outbreak in Japan in February 2020 to explore how PHTR reduced importation of COVID-19 to the United States during the early phase of disease containment. Using PHTR required substantial collaboration among the US Centers for Disease Control and Prevention, other US government agencies, the cruise line, and public health authorities in Japan. Original US PHTR removal criteria were modified to reflect international testing protocols and enable removal of PHTR for persons who recovered from illness. The impact of PHTR on epidemic trajectory depends on the risk for transmission during travel and geographic spread of disease. Lessons learned from the Diamond Princess outbreak provide critical information for future PHTR use. Public health travel restrictions (PHTR) have been used by the United States to reduce the likelihood of transmission of selected communicable diseases aboard aircraft  infection on the Diamond Princess cruise ship in Japan in February 2020 was the earliest large-scale use of US PHTR applied to a cohort on the basis of a common exposure. A total of 111 individual PHTR were placed in 1 day, compared with 556 during the 10-year period 2007–2016 , informed US citizens and residents that those electing to remain in Japan would be placed on PHTR   and second negative test result (>5 days) and absence of a productive cough  and nasopharyngeal (NP) specimens collected  centers  Figure 1CDC coordinated with USEMB Japan and the cruise line to provide passengers, crew, and hospitals with the criteria and procedures for removal of PHTR  Figure 1https://www.r-project.org). Using a database consolidating data from the cruise ship, the government of Japan, USEMB Japan, and CDC that was originally used for PHTR implementation, we described characteristics of persons subject to PHTR: US state of residence; sex; age; crew or passenger; history of close contact with a case ; number of cabin mates; initial SARS-CoV-2 test result; presence of symptoms at the time of testing (symptomatic or asymptomatic), and disposition . For those with COVID-19, we described their clinical severity and types of samples collected to meet the discharge criteria , comparing proportions of those meeting original CDC criteria for PHTR removal to the modified criteria. We described outcomes, successes, and challenges of the monitoring process to identify lessons learned, based on our professional judgment and expertise on containing infectious diseases. We analyzed data using R  resided in California.From the 111 US citizens and residents remaining in Japan, 44 entered active monitoring after disembarking the ship. Three of these persons were tested for SARS-CoV-2 during the active monitoring period, 1 because of a fever, 1 because of hospitalization for other reasons, and 1 for close contact to a confirmed case; 2 tested positive for SARS-CoV-2. Overall, 69 US citizens had positive test results for SARS-CoV-2 and were hospitalized in 35 hospitals in Japan . Of thesUS citizen and resident passengers disembarked February 19–22 and crew on February 27 . Of the Of the 69 patients with COVID-19, 40 recovered patients were able to meet the original criteria for PHTR removal, and 29 met the modified criteria. The median time from PHTR placement to removal was 17 days (range 7–57 days)  Figure 2The Diamond Princess COVID-19 outbreak represents a unique event in public health history: the quarantine of thousands of persons aboard a cruise ship for a newly identified disease at a time when most countries had few imported cases but the epidemic rapidly became a pandemic. Lessons learned from the experience of implementing PHTR on an unprecedented scale can inform the future use of PHTR in outbreaks with pandemic potential.The first critical lesson is that during a novel disease epidemic, the lack of information about the disease challenges the general practice that ethical use of PHTR requires evidence-based decisions regarding when persons may be contagious or at risk of becoming contagious (As the COVID-19 epidemic unfolded, we observed notable challenges in identifying persons who might transmit SARS-CoV-2 during travel or contribute to cross-border spread of disease . In thisSecond, there are logistical challenges in applying and monitoring travel restrictions on this scale. US government personnel had to identify each person for whom travel restrictions were warranted, verify their identities against federal databases, add them individually to the DNB and PHLO, document that criteria for removal of PHTR were met, and ensure timely removal of PHTR once the criteria were met. Because this situation took place on a cruise ship that kept detailed passenger and crew manifests, it was relatively straightforward to identify, notify, and obtain contact information for the persons at risk. If exposure had occurred in a less well-defined situation, identification would have been particularly challenging. However, the complex process to add >100 persons to the DNB and PHLO in the compressed timeframe of 24–48 hours required substantial federal resources.Typically, documenting criteria for PHTR removal is completed by US jurisdictions or foreign public health authorities (Third, it is critical that travel restrictions do not create undue risk to affected persons. Persons with positive tests or who became ill could access high-quality medical care in Japan; ethics considerations could be different for persons seeking medical care in areas with inadequate medical infrastructure. In such situations, charter travel or medical evacuation may be options for US citizens and residents to return safely to the United States (Limitations of the analysis were incomplete information, including hospital locations and clinical severity, and inability to obtain the specimen collection date. We approximated date of positive test result by the date of notification.As with all decisions, overall costs and benefits should be considered when determining whether to use PHTR. Protection of the public, individual civil liberties, and increasing risk for disease transmission are all considerations that can inform use of PHTR (–PHTR implementation may have prevented transmission via air travel among Diamond Princess travelers under active monitoring and never tested. Transmission on the cruise ship was possible for many days before the vessel quarantine began; it is likely there were many asymptomatic but SARS-CoV-2–positive persons aboard (CDC continues to use individual-level PHTR for persons with known or suspected COVID-19 or high-risk exposures and advises persons who are symptomatic, test positive for SARS-CoV-2, or have been exposed to someone with COVID-19 to delay travel until no longer infectious or at risk of becoming infectious. CDC shares information and considerations for use of PHTR with health authorities of other countries but recognizes that many countries may not have the resources to manage similar systems. Lessons learned from the Diamond Princess outbreak are essential in planning future PHTR use during this pandemic or future outbreaks of novel diseases.Additional information about US public health travel restrictions placed on passengers and crew during the COVID-19 outbreak on the Diamond Princess cruise ship, Japan, February–April 2020.