Mapping Clinical Barriers and Evidence-Based Implementation Strategies in Low-to-Middle Income Countries (LMICs).

BACKGROUND: Low-to-middle income countries (LMICs) experience a high burden of disease from both non-communicable and communicable diseases. Addressing these public health concerns requires effective implementation strategies and localization of translation of knowledge into practice. AIM: To identify and categorize barriers and strategies to evidence implementation in LMICs from published evidence implementation studies. METHODS: A descriptive analysis of key characteristics of evidence implementation projects completed as part of a 6-month, multi-phase, intensive evidence-based clinical fellowship program, conducted in LMICs and published in the JBI Database of Systematic Reviews and Implementation Reports was undertaken. Barriers were identified and categorized to the Donabedian dimensions of care (structure, process, and outcome), and strategies were mapped to the Cochrane effective practice and organization of care taxonomy. RESULTS: A total of 60 implementation projects reporting 58 evidence-based clinical audit topics from LMICs were published between 2010 and 2018. The projects included diverse populations and were predominantly conducted in tertiary care settings. A total of 279 barriers to implementation were identified. The most frequently identified groupings of barriers were process-related and associated predominantly with staff knowledge. A total of 565 strategies were used across all projects, with every project incorporating more than one strategy to address barriers to implementation of evidence-based practice; most strategies were categorized as educational meetings for healthcare workers. LINKING EVIDENCE TO ACTION: Context-specific strategies are required for successful evidence implementation in LMICs, and a number of common barriers can be addressed using locally available, low-cost resources. Education for healthcare workers in LMICs is an effective awareness-raising, workplace culture, and practice-transforming strategy for evidence implementation.

Transcutaneous electrical nerve stimulation (TENS) reduces chronic hyperalgesia induced by muscle inflammation.

Transcutaneous electrical nerve stimulation (TENS) reduces pain through central mechanisms involving spinal cord and brainstem sites. Since TENS acts through central mechanisms, we hypothesized that TENS will reduce chronic bilateral hyperalgesia produced by unilateral inflammation when applied either ipsilateral or contralateral to the site of muscle inflammation. Sprague-Dawley rats were injected with carrageenan in the left gastrocnemius muscle belly. Mechanical withdrawal threshold was tested bilaterally before and 2 weeks after carrageenan injection. After testing withdrawal thresholds at 2 weeks, rats received TENS treatment either ipsilateral or contralateral to the site of inflammation. In each of these groups, rats were randomized to control (no TENS), low frequency (4 Hz), or high frequency (100 Hz) TENS treatment. TENS was applied for 20 min at sensory intensity under light halothane anesthesia. Mechanical withdrawal thresholds were re-assessed after TENS or 'no TENS' treatment. Unilateral injection of carrageenan to the gastrocnemius muscle significantly reduced the mechanical withdrawal threshold (mechanical hyperalgesia) bilaterally 2 weeks later. Either low or high frequency TENS applied to the gastrocnemius muscle ipsilateral to the site of inflammation significantly reversed mechanical hyperalgesia, both ipsilateral and contralateral to the site of inflammation. Low or high frequency TENS applied to the gastrocnemius muscle contralateral to the site of inflammation also significantly reduced mechanical hyperalgesia, both ipsilateral and contralateral to the site of inflammation. Since ipsilateral or contralateral TENS treatments were effective in reducing chronic bilateral hyperalgesia in this animal model, we suggest that TENS act through modulating descending influences from supraspinal sites such as rostral ventromedial medulla (RVM).

The stem cell marker Bcrp/ABCG2 enhances hypoxic cell survival through interactions with heme.

Our studies demonstrate that the ABC transporter and marker of stem and progenitor cells known as the breast cancer resistance protein (BCRP or ABCG2) confers a strong survival advantage under hypoxic conditions. We show that, under hypoxia, progenitor cells from Bcrp(-)/(-)mice have a reduced ability to form colonies as compared with progenitor cells from Bcrp(+/+) mice. Blocking BCRP function in Bcrp(+/+) progenitor cells markedly reduces survival under hypoxic conditions. However, blocking heme biosynthesis reverses the hypoxic susceptibility of Bcrp(-/-) progenitor cells, a finding that indicates that heme molecules (i.e. porphyrins) are detrimental to Bcrp(-/-) cells under hypoxia. BCRP specifically binds heme, and cells lacking BCRP accumulate porphyrins. Finally, Bcrp expression is up-regulated by hypoxia, and we demonstrate that this up-regulation involves the hypoxia-inducible transcription factor complex HIF-1. Collectively, our findings suggest that cells can, upon hypoxic demand, use BCRP to reduce heme or porphyrin accumulation, which can be detrimental to cells. Our findings have implications for the survival of stem cells and tumor cells in hypoxic environments.