Optimization and Validation of a Custom-Designed Perfusion Bioreactor for Bone Tissue Engineering: Flow Assessment and Optimal Culture Environmental Conditions.

Various perfusion bioreactor systems have been designed to improve cell culture with three-dimensional porous scaffolds, and there is some evidence that fluid force improves the osteogenic commitment of the progenitors. However, because of the unique design concept and operational configuration of each study, the experimental setups of perfusion bioreactor systems are not always compatible with other systems. To reconcile results from different systems, the thorough optimization and validation of experimental configuration are required in each system. In this study, optimal experimental conditions for a perfusion bioreactor were explored in three steps. First, an in silico modeling was performed using a scaffold geometry obtained by microCT and an expedient geometry parameterized with porosity and permeability to assess the accuracy of calculated fluid shear stress and computational time. Then, environmental factors for cell culture were optimized, including the volume of the medium, bubble suppression, and medium evaporation. Further, by combining the findings, it was possible to determine the optimal flow rate at which cell growth was supported while osteogenic differentiation was triggered. Here, we demonstrated that fluid shear stress up to 15 mPa was sufficient to induce osteogenesis, but cell growth was severely impacted by the volume of perfused medium, the presence of air bubbles, and medium evaporation, all of which are common concerns in perfusion bioreactor systems. This study emphasizes the necessity of optimization of experimental variables, which may often be underreported or overlooked, and indicates steps which can be taken to address issues common to perfusion bioreactors for bone tissue engineering.

Digital health for the End TB Strategy: developing priority products and making them work.

In 2014, the World Health Organization (WHO) developed the End TB Strategy in response to a World Health Assembly Resolution requesting Member States to end the worldwide epidemic of tuberculosis (TB) by 2035. For the strategy's objectives to be realised, the next 20 years will need novel solutions to address the challenges posed by TB to health professionals, and to affected people and communities. Information and communication technology presents opportunities for innovative approaches to support TB efforts in patient care, surveillance, programme management and electronic learning. The effective application of digital health products at a large scale and their continued development need the engagement of TB patients and their caregivers, innovators, funders, policy-makers, advocacy groups, and affected communities.In April 2015, WHO established its Global Task Force on Digital Health for TB to advocate and support the development of digital health innovations in global efforts to improve TB care and prevention. We outline the group's approach to stewarding this process in alignment with the three pillars of the End TB Strategy. The supplementary material of this article includes target product profiles, as developed by early 2016, defining nine priority digital health concepts and products that are strategically positioned to enhance TB action at the country level.

Patients direct costs to undergo TB diagnosis.

BACKGROUND: A major impediment to the treatment of TB is a diagnostic process that requires multiple visits. Descriptions of patient costs associated with diagnosis use different protocols and are not comparable. METHODS: We aimed to describe the direct costs incurred by adults attending TB diagnostic centres in four countries and factors associated with expenditure for diagnosis. Surveys of 2225 adults attending smear-microscopy centres in Nigeria, Nepal, Ethiopia and Yemen. Adults >18 years with cough >2 weeks were enrolled prospectively. Direct costs were quantified using structured questionnaires. Patients with costs >75(th) quartile were considered to have high expenditure (cases) and compared with patients with costs <75(th) quartile to identify factors associated with high expenditure. RESULTS: The most significant expenses were due to clinic fees and transport. Most participants attended the centres with companions. High expenditure was associated with attending with company, residing in rural areas/other towns and illiteracy. CONCLUSIONS: The costs incurred by patients are substantial and share common patterns across countries. Removing user fees, transparent charging policies and reimbursing clinic expenses would reduce the poverty-inducing effects of direct diagnostic costs. In locations with limited resources, support could be prioritised for those most at risk of high expenditure; those who are illiterate, attend the service with company and rural residents.

Investing to end epidemics: the role of the Global Fund to control TB by 2030.

The Global Fund to fight AIDS, Tuberculosis and Malaria provides over three-quarters of all international financing towards TB programs with US$4.7 billion disbursed, supporting provision of treatment for 13.2 million patients with smear-positive TB and 210 000 patients with multidrug-resistant TB in over 100 countries since 2002. In 2013, the Global Fund launched a new funding model that, among others, is advancing strategic investments to maximize impact, addressing 'missing' TB cases, enhancing a synergistic response to TB/HIV dual epidemics, and building resilient and sustainable systems for health. A new Global Fund Strategy is under development through consultation with various stakeholders, with which the Global Fund will work to play a more catalytic role and foster innovations to end the TB epidemic.

Patient and community experiences of tuberculosis diagnosis and care within a community-based intervention in Ethiopia: a qualitative study.

BACKGROUND: The Ethiopian TB control programme relies on passive case finding of TB cases. The predominantly rural-based population in Ethiopia has limited access to health facilities creating barriers to TB services. An intervention package aimed to bring TB diagnosis and treatment services closer to communities has been implemented through partnership with health extension workers (HEWs). They undertook advocacy, communication and social mobilization (ACSM) activities, identified symptomatic individuals, collected sputum, prepared smears and fixed slides at community level. Field supervisors supported HEWs by delivering smeared slides to the laboratory, feeding back results to the HEWs and following up smear-negative cases. Patients diagnosed with TB initiated treatment in the community, they were supported by supervisors and HEWs through the local health post. Case notification increased from 64 to 127/100,000 population/year. METHODS: This qualitative study assessed community members' treatment seeking behaviour and their perceptions of the intervention. In-depth interviews (n=36) were undertaken with participants in six districts. Participants were clients of the community-based intervention, currently on TB treatment or those screened negative for TB. Transcripts were translated to English and a thematic analytical framework was developed guided by the different steps symptomatic individuals take within the intervention package. Coding was done and queries run using NVivo software. RESULTS: Prior to the intervention many patients with chronic cough did not access TB services. Participants described difficulties they faced in accessing district level health facilities that required travel outside their communities. Giving sputum samples and receiving results from within their home communities was appreciated by all participants. The intervention had a high level of acceptability; particularly clear benefits emerged for poor women and men and those too weak to travel. Some participants appeared to prefer a diagnosis of TB, this is likely because receiving a negative smear microscopy result brought further uncertainty and necessitated seeking further investigation. CONCLUSIONS: There is evidence rural populations with high levels of poverty, and in particular women, are at high risk of unmet health needs and undiagnosed TB. Embedding TB services within communities was an acceptable approach for vulnerable groups experiencing poor access to health facilities. In the Ethiopian context this approach can facilitate early diagnosis and improve treatment outcomes.

Barriers to completing TB diagnosis in Yemen: services should respond to patients' needs.

OBJECTIVES AND BACKGROUND: Obtaining a diagnosis of tuberculosis (TB) is a prerequisite for accessing specific treatment, yet one third of estimated new cases are missed worldwide by National Programmes. This study investigated economic, geographical, socio-cultural and health system factors hindering adults' attendance and completion of the TB diagnostic process in Yemen, to inform interventions designed to improve patient access to services. METHODOLOGY: The study employed a mixed methods design comprising a cross-sectional survey and In-Depth-Interviews (IDIs) and Focus Group Discussions (FGDs) among patients abandoning the diagnosis or registering for treatment. Adults with cough of ≥ 2 weeks attending a large governmental referral centre in Sana'a, Yemen, between 2009 and 2010, were eligible to participate. RESULTS: 497 and 446 (89.7%) participants were surveyed the first and second day of attending the services and 48 IDIs and 12 FGDs were also conducted. The majority of patients were disadvantaged and had poor literacy (61% illiterate), had travelled from rural areas (47%) and attended with companions (84%). Key barriers for attendance identified were clinic and transport costs (augmented by companions), distance from home, a preference for private services, strong social stigma and a lack of understanding of the diagnostic process. There were discrepancies between patient- and doctor-reported diagnosis and 46% of patients were unaware that TB treatment is free. Females faced more difficulties to attend than men. The laboratory practice of providing first-day negative smear results and making referrals to the private sector also discouraged patients from returning. Strategies to bring TB diagnostic services closer to communities and address the multiple barriers patients face to attend, will be important to increase access to TB diagnosis and care.

Duration and associated factors of patient delay during tuberculosis screening in rural Cameroon.

OBJECTIVES: (i) To determine patient delay - the time from the onset of symptoms to presentation at a health facility - and its causes in patients undergoing sputum smear examination in Cameroon; and (ii) to compare the results with those of a previous study in Ethiopia. METHODS: A cross-sectional study of 243 consecutive patients using a structured questionnaire. RESULTS: Median (interquartile range) patient delay in Cameroon was 2.0 (1-4) weeks, shorter than the 4.3 (2-13) week delay in Ethiopia. Significantly fewer patients delayed more than 1, 2 and 3 months in Cameroon than in Ethiopia (P < 0.001). Delays in Cameroon were significantly associated with being the main income earner, the belief that TB is stigmatizing, and the use of traditional medicine - the latter being the only factor significant in both studies. CONCLUSION: Engaging traditional healers in TB control programs and reducing stigma through education could help to reduce patient delays, accelerate diagnosis, improve clinical outcomes and reduce disease transmission. These results, when placed in context of national human development indices, suggest that economic development, investment in health care and literacy may all be involved in improving access to TB services in sub-Saharan Africa.