30 research outputs found

    In Situ Cell Signalling of the Hippo-YAP/TAZ Pathway in Reaction to Complex Dynamic Loading in an Intervertebral Disc Organ Culture

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    Recently, a dysregulation of the Hippo-YAP/TAZ pathway has been correlated with intervertebral disc (IVD) degeneration (IDD), as it plays a key role in cell survival, tissue regeneration, and mechanical stress. We aimed to investigate the influence of different mechanical loading regimes, i.e., under compression and torsion, on the induction and progression of IDD and its association with the Hippo-YAP/TAZ pathway. Therefore, bovine IVDs were assigned to one of four different static or complex dynamic loading regimes: (i) static, (ii) “low-stress”, (iii) “intermediate-stress”, and (iv) “high-stress” regime using a bioreactor. After one week of loading, a significant loss of relative IVD height was observed in the intermediate- and high-stress regimes. Furthermore, the high-stress regime showed a significantly lower cell viability and a significant decrease in glycosaminoglycan content in the tissue. Finally, the mechanosensitive gene CILP was significantly downregulated overall, and the Hippo-pathway gene MST1 was significantly upregulated in the high-stress regime. This study demonstrates that excessive torsion combined with compression leads to key features of IDD. However, the results indicated no clear correlation between the degree of IDD and a subsequent inactivation of the Hippo-YAP/TAZ pathway as a means of regenerating the IVD

    National policy-makers speak out: are researchers giving them what they need?

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    The objective of this empirical study was to understand the perspectives and attitudes of policy-makers towards the use and impact of research in the health sector in low- and middle-income countries. The study used data from 83 semi-structured, in-depth interviews conducted with purposively selected policy-makers at the national level in Argentina, Egypt, Iran, Malawi, Oman and Singapore. The interviews were structured around an interview guide developed based on existing literature and in consultation with all six country investigators. Transcripts were processed using a thematic-analysis approach. Policy-makers interviewed for this study were unequivocal in their support for health research and the high value they attribute to it. However, they stated that there were structural and informal barriers to research contributing to policy processes, to the contribution research makes to knowledge generally, and to the use of research in health decision-making specifically. Major findings regarding barriers to evidence-based policy-making included poor communication and dissemination, lack of technical capacity in policy processes, as well as the influence of the political context. Policy-makers had a variable understanding of economic analysis, equity and burden of disease measures, and were vague in terms of their use in national decisions. Policy-maker recommendations regarding strategies for facilitating the uptake of research into policy included improving the technical capacity of policy-makers, better packaging of research results, use of social networks, and establishment of fora and clearinghouse functions to help assist in evidence-based policy-makin

    Influencing policy change: the experience of health think tanks in low- and middle-income countries

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    In recent years there has been a growth in the number of independent health policy analysis institutes in low- and middle-income countries which has occurred in response to the limitation of government analytical capacity and pressures associated with democratization. This study aimed to: (i) investigate the contribution made by health policy analysis institutes in low- and middle-income countries to health policy agenda setting, formulation, implementation and monitoring and evaluation; and (ii) assess which factors, including organizational form and structure, support the role of health policy analysis institutes in low- and middle-income countries in terms of positively contributing to health policy. Six case studies of health policy analysis institutes in Bangladesh, Ghana, India, South Africa, Uganda and Vietnam were conducted including two NGOs, two university and two government-owned policy analysis institutes. Case studies drew on document review, analysis of financial information, semi-structured interviews with staff and other stakeholders, and iterative feedback of draft findings. Some of the institutes had made major contributions to policy development in their respective countries. All of the institutes were actively engaged in providing policy advice and most undertook policy-relevant research. Relatively few were engaged in conducting policy dialogues, or systematic reviews, or commissioning research. Much of the work undertaken by institutes was driven by requests from government or donors, and the primary outputs for most institutes were research reports, frequently combined with verbal briefings. Several factors were critical in supporting effective policy engagement. These included a supportive policy environment, some degree of independence in governance and financing, and strong links to policy makers that facilitate trust and influence. While the formal relationship of the institute to government was not found to be critical, units within government faced considerable difficulties

    Influencing policy change: the experience of health think tanks in low- and middle-income countries

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    In recent years there has been a growth in the number of independent health policy analysis institutes in low- and middle-income countries which has occurred in response to the limitation of government analytical capacity and pressures associated with democratization. This study aimed to: (i) investigate the contribution made by health policy analysis institutes in low- and middle-income countries to health policy agenda setting, formulation, implementation and monitoring and evaluation; and (ii) assess which factors, including organizational form and structure, support the role of health policy analysis institutes in low- and middle-income countries in terms of positively contributing to health policy. Six case studies of health policy analysis institutes in Bangladesh, Ghana, India, South Africa, Uganda and Vietnam were conducted including two NGOs, two university and two government-owned policy analysis institutes. Case studies drew on document review, analysis of financial information, semi-structured interviews with staff and other stakeholders, and iterative feedback of draft findings. Some of the institutes had made major contributions to policy development in their respective countries. All of the institutes were actively engaged in providing policy advice and most undertook policy-relevant research. Relatively few were engaged in conducting policy dialogues, or systematic reviews, or commissioning research. Much of the work undertaken by institutes was driven by requests from government or donors, and the primary outputs for most institutes were research reports, frequently combined with verbal briefings. Several factors were critical in supporting effective policy engagement. These included a supportive policy environment, some degree of independence in governance and financing, and strong links to policy makers that facilitate trust and influence. While the formal relationship of the institute to government was not found to be critical, units within government faced considerable difficulties

    Are vaccination programmes delivered by lay health workers cost-effective? A systematic review

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    <p>Abstract</p> <p>Background</p> <p>A recently updated Cochrane systematic review on the effects of lay or community health workers (LHWs) in primary and community health care concluded that LHW interventions could lead to promising benefits in the promotion of childhood vaccination uptake. However, understanding of the costs and cost-effectiveness of involving LHWs in vaccination programmes remains poor. This paper reviews the costs and cost-effectiveness of vaccination programme interventions involving LHWs.</p> <p>Methods</p> <p>Articles were retrieved if the title, keywords or abstract included terms related to 'lay health workers', 'vaccination' and 'economics'. Reference lists of studies assessed for inclusion were also searched and attempts were made to contact authors of all studies included in the Cochrane review. Studies were included after assessing eligibility of the full-text article. The included studies were then reviewed against a set of background and technical characteristics.</p> <p>Results</p> <p>Of the 2616 records identified, only three studies fully met the inclusion criteria, while an additional 11 were retained as they included some cost data. Methodologically, the studies were strong but did not adequately address affordability and sustainability and were also highly heterogeneous in terms of settings and LHW outcomes, limiting their comparability. There were insufficient data to allow any conclusions to be drawn regarding the cost-effectiveness of LHW interventions to promote vaccination uptake. Studies focused largely on health outcomes and did illustrate to some extent how the institutional characteristics of communities, such as governance and sources of financial support, influence sustainability.</p> <p>Conclusion</p> <p>The included studies suggest that conventional economic evaluations, particularly cost-effectiveness analyses, generally focus too narrowly on health outcomes, especially in the context of vaccination promotion and delivery at the primary health care level by LHWs. Further studies on the costs and cost-effectiveness of vaccination programmes involving LHWs should be conducted, and these studies should adopt a broader and more holistic approach.</p

    Human resources for health care delivery in Tanzania: a multifaceted problem

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    BACKGROUND: Recent years have seen an unprecedented increase in funds for procurement of health commodities in developing countries. A major challenge now is the efficient delivery of commodities and services to improve population health. With this in mind, we documented staffing levels and productivity in peripheral health facilities in southern Tanzania. METHOD: A health facility survey was conducted to collect data on staff employed, their main tasks, availability on the day of the survey, reasons for absenteeism, and experience of supervisory visits from District Health Teams. In-depth interview with health workers was done to explore their perception of work load. A time and motion study of nurses in the Reproductive and Child Health (RCH) clinics documented their time use by task. RESULTS: We found that only 14% (122/854) of the recommended number of nurses and 20% (90/441) of the clinical staff had been employed at the facilities. Furthermore, 44% of clinical staff was not available on the day of the survey. Various reasons were given for this. Amongst the clinical staff, 38% were absent because of attendance to seminar sessions, 8% because of long-training, 25% were on official travel and 20% were on leave. RCH clinic nurses were present for 7 hours a day, but only worked productively for 57% of time present at facility. Almost two-third of facilities had received less than 3 visits from district health teams during the 6 months preceding the survey. CONCLUSION: This study documented inadequate staffing of health facilities, a high degree of absenteeism, low productivity of the staff who were present and inadequate supervision in peripheral Tanzanian health facilities. The implications of these findings are discussed in the context of decentralized health care in Tanzania

    Regional and experiential differences in surgeon preference for the treatment of cervical facet injuries: a case study survey with the AO Spine Cervical Classification Validation Group

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    Purpose: The management of cervical facet dislocation injuries remains controversial. The main purpose of this investigation was to identify whether a surgeon’s geographic location or years in practice influences their preferred management of traumatic cervical facet dislocation injuries. Methods: A survey was sent to 272 AO Spine members across all geographic regions and with a variety of practice experience. The survey included clinical case scenarios of cervical facet dislocation injuries and asked responders to select preferences among various diagnostic and management options. Results: A total of 189 complete responses were received. Over 50% of responding surgeons in each region elected to initiate management of cervical facet dislocation injuries with an MRI, with 6 case exceptions. Overall, there was considerable agreement between American and European responders regarding management of these injuries, with only 3 cases exhibiting a significant difference. Additionally, results also exhibited considerable management agreement between those with ≤ 10 and &gt; 10&nbsp;years of practice experience, with only 2 case exceptions noted. Conclusion: More than half of responders, regardless of geographical location or practice experience, identified MRI as a screening imaging modality when managing cervical facet dislocation injuries, regardless of the status of the spinal cord and prior to any additional intervention. Additionally, a majority of surgeons would elect an anterior approach for the surgical management of these injuries. The study found overall agreement in management preferences of cervical facet dislocation injuries around the globe

    Effect of surgical experience and spine subspecialty on the reliability of the {AO} Spine Upper Cervical Injury Classification System

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    OBJECTIVE The objective of this paper was to determine the interobserver reliability and intraobserver reproducibility of the AO Spine Upper Cervical Injury Classification System based on surgeon experience (&lt; 5 years, 5–10 years, 10–20 years, and &gt; 20 years) and surgical subspecialty (orthopedic spine surgery, neurosurgery, and "other" surgery). METHODS A total of 11,601 assessments of upper cervical spine injuries were evaluated based on the AO Spine Upper Cervical Injury Classification System. Reliability and reproducibility scores were obtained twice, with a 3-week time interval. Descriptive statistics were utilized to examine the percentage of accurately classified injuries, and Pearson’s chi-square or Fisher’s exact test was used to screen for potentially relevant differences between study participants. Kappa coefficients (κ) determined the interobserver reliability and intraobserver reproducibility. RESULTS The intraobserver reproducibility was substantial for surgeon experience level (&lt; 5 years: 0.74 vs 5–10 years: 0.69 vs 10–20 years: 0.69 vs &gt; 20 years: 0.70) and surgical subspecialty (orthopedic spine: 0.71 vs neurosurgery: 0.69 vs other: 0.68). Furthermore, the interobserver reliability was substantial for all surgical experience groups on assessment 1 (&lt; 5 years: 0.67 vs 5–10 years: 0.62 vs 10–20 years: 0.61 vs &gt; 20 years: 0.62), and only surgeons with &gt; 20 years of experience did not have substantial reliability on assessment 2 (&lt; 5 years: 0.62 vs 5–10 years: 0.61 vs 10–20 years: 0.61 vs &gt; 20 years: 0.59). Orthopedic spine surgeons and neurosurgeons had substantial intraobserver reproducibility on both assessment 1 (0.64 vs 0.63) and assessment 2 (0.62 vs 0.63), while other surgeons had moderate reliability on assessment 1 (0.43) and fair reliability on assessment 2 (0.36). CONCLUSIONS The international reliability and reproducibility scores for the AO Spine Upper Cervical Injury Classification System demonstrated substantial intraobserver reproducibility and interobserver reliability regardless of surgical experience and spine subspecialty. These results support the global application of this classification system

    In situ cell signalling of the hippo-YAP/TAZ pathway in reaction to complex dynamic loading in an intervertebral disc

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    Introduction: Intervertebral disc (IVD) degeneration (IDD) is a main contributor to chronic low back pain. Recently, a dysregulation of the Hippo-YAP/TAZ pathway has been correlated with IDD, as it plays a key role in cell proliferation, differentiation, regeneration, and cell survival. Therefore, our aim was to investigate the influence of different mechanical loading profiles in two Degree-of-Freedom (2DoF) loading, i.e., under compression and torsion, on the induction and progression of IDD and in particularly the role and context of the Hippo-YAP/TAZ pathway. Methods: Around one-year old coccygeal IVDs were isolated from bovine tails obtained from a local abattoir. All IVDs were excised and prepared for organ culture as previously established and then randomly assigned to one of four different static or complex mechanical loading regimes for seven days, i.e., i) “static” (0.1 MPa compression), ii) “low stress” (up to 0.2 MPa compression and 2° torsion), iii) “intermediate stress” (up to 0.4 MPa compression and 8° torsion), and iv) “high stress” (up to 0.6 MPa compression and 15° torsion) profile using a bioreactor that allows 2DoF loading. After one week of loading, the tissue and the culture medium of each condition was harvested and analysed for their glycosaminoglycan (GAG) content, relative disc height changes, relative gene expression of anabolic, catabolic, and inflammatory markers, as well as the major players in the Hippo-YAP/TAZ pathway. Results: After one week of organ culture, a significant loss of IVD height was observed in every mechanical loading regime, with the most significant height loss observed in the higher stress regimes (up to 27 ± 5% height loss). Furthermore, the high stress condition showed a significant decrease of GAG in the tissue (232 ± 48 vs. up to 314 ± 14 µg GAG / mg dry weight) and a significant increase of GAG in the culture medium (97 ± 14 vs. 44 ± 22 µg GAG / cm3 freshly isolated tissue). Moreover, a higher upregulation of catabolic (MMP13 up to 1805 ± 2284-fold upregulation) and inflammation-related genes (MCP1 up to 121 ± 201-fold upregulation) was generally observed the more stressed the IVDs were. Finally, a significant upregulation of TAZ (up to 49 ± 73-fold upregulation) was found for the high stress condition. Conclusion: Altogether, this study demonstrated that excessive torsion combined with compression leads to key features of IDD. Furthermore, we were able to show that the Hippo-YAP/TAZ pathway reacted differently depending on the applied mechanical loading profile and the degenerated state of the IVD. Hence, this study showed the potential of targeting the Hippo-YAP/TAZ pathway to counteract IDD
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