Conceptualisation of a region-based group of musculoskeletal pain conditions as 'tibial loading pain' and systematic review of effects of load-modifying interventions.

OBJECTIVES: Conceptualisation of a clinically-relevant group of conditions as a region-based, load-related musculoskeletal pain condition ('tibial loading pain') to enable identification of evidence of treatment effect from load-modifying interventions. DESIGN: Systematic review and evidence synthesis based on a developed and justified theoretical position. METHODS: Musculoskeletal pain localised to the tibial (shin) region and consistent with clinical presentations of an exercise/activity-related onset mechanism, was conceptualised as a group of conditions ('tibial loading pain') that could be reasoned to respond to load modifying interventions. Five databases were searched for randomized controlled studies investigating any load-modifying intervention for pain in the anterior-anteromedial lower leg (shin). Study quality was evaluated (Risk of Bias Tool Version 2) and level of certainty for the findings assessed. RESULTS: Six studies reporting seven comparisons were included. Interventions included braces, anti-pronation taping, compression stocking and a stretch + strengthening programme. All included studies were assessed as having unclear or high risk of bias. The review found no evidence of beneficial effect from any of the load-modifying interventions on symptoms, physical performance or biomechanical measures, apart from a possible benefit of anti-pronation 'kinesio' taping. There was very low certainty evidence that kinesio taping improves pain and pain-free hopping distance after one week. The braces were associated with minor adverse effects and problems with acceptability. CONCLUSIONS: None of the treatments investigated by the included studies can be recommended. Conceptualisation of the problem as regional, primarily loading-related pain rather than as multiple distinct pathoanatomically-based conditions, and clearer load-modifying hypotheses for interventions are recommended.

Author Correction: New paradigms for understanding and step changes in treating active and chronic, persistent apicomplexan infections.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

New paradigms for understanding and step changes in treating active and chronic, persistent apicomplexan infections.

Toxoplasma gondii, the most common parasitic infection of human brain and eye, persists across lifetimes, can progressively damage sight, and is currently incurable. New, curative medicines are needed urgently. Herein, we develop novel models to facilitate drug development: EGS strain T. gondii forms cysts in vitro that induce oocysts in cats, the gold standard criterion for cysts. These cysts highly express cytochrome b. Using these models, we envisioned, and then created, novel 4-(1H)-quinolone scaffolds that target the cytochrome bc1 complex Qi site, of which, a substituted 5,6,7,8-tetrahydroquinolin-4-one inhibits active infection (IC50, 30 nM) and cysts (IC50, 4 µM) in vitro, and in vivo (25 mg/kg), and drug resistant Plasmodium falciparum (IC50, <30 nM), with clinically relevant synergy. Mutant yeast and co-crystallographic studies demonstrate binding to the bc1 complex Qi site. Our results have direct impact on improving outcomes for those with toxoplasmosis, malaria, and ~2 billion persons chronically infected with encysted bradyzoites.

Development of EASY-Care, for brief standardized assessment of the health and care needs of older people; with latest information about cross-national acceptability.

INTRODUCTION: The EASY-Care system has been developed in the past 20 years in the United States and Europe as a brief standardized method for assessing the perceptions of older people about their health and care needs and priorities for a service response. More recently, it has been adapted and tested for use in poor, middle-income, and rich countries across the world. In this article we review its development and report the latest data for cross-cultural acceptability to older people and their clinicians in 6 countries across 4 continents. METHOD: We used a multicenter, mixed-method (quantitative and qualitative) approach to assess clinician (n = 37) and patient (n = 115) perspectives of acceptability of the EASY-Care Standard (2010) instrument. Data were collected between 2008 and 2012 in Iran, Colombia, India, Lesotho, Tonga, and the United Kingdom. RESULTS: Key strengths identified included high levels of acceptability from both clinician and patient perspectives, with the tools seen as useful for identification of unmet need. Key recommendations included enhancing clarity in certain questions, ensuring it is not too long. Recommendations included minor context-specific adaptations, effective use of the screening questionnaire, and use of context-specific interviewer prompts. CONCLUSIONS: The EASY-Care Standard has high levels of acceptability from both clinicians and patients across poor, middle-income, and rich countries and has the potential to become a global gold standard for holistic person-centered assessment.