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Partnership working in public health
'Partnership Working in Public Health' presents the findings from a detailed study of public health partnerships in England. The lessons from the research are used to explore the governent's changes in public health, their likely impact and the implications for the future of public health partnerships.
Book
Uncertainty in the Era of Precision Medicine
Far from ushering in an age of diagnostic and prognostic certainty, precision-medicine tools will demand a greater tolerance of uncertainty and greater facility for calculating and interpreting probabilities than we have been used to as physicians and patients.
A National Research Council report on “precision medicine” explains that the term “refers to the tailoring of medical treatment to the individual characteristics of each patient.” The report goes on to say, “It should be emphasized that in ‘precision medicine’ the word ‘precision’ is being used in a colloquial sense, to mean both ‘accurate’ and ‘precise.’”
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In the colloquial sense, “precision” also implies a high degree of certainty of an outcome, as in “precision-guided missile” or “at what precise time will you arrive?” So will precision medicine usher in an age of diagnostic and prognostic certainty?
In fact, the opposite . . .
Journal Article
The individual and socioeconomic impact of osteoarthritis
Osteoarthritis (OA) is an important cause of disability worldwide, and its impact is growing rapidly. In this Opinion article, the authors draw attention to the current and projected burden of OA for individuals and for health-care systems, and call for a shift in the approach to the disease.
Osteoarthritis (OA) is a highly prevalent, disabling disease, with a commensurate tremendous individual and socioeconomic burden. This Perspectives article focuses on the burden of OA for the individual, the health-care system and society, to draw attention to the magnitude of the current problem with some reference to projected figures. We have an urgent opportunity to make fundamental changes to the way we care for individuals with OA that will have an effect upon the direct and indirect costs of this disease. By focusing on the burden of this prevalent, disabling, and costly disease, we hope to highlight the opportunity for shifts in health-care policy towards prevention and chronic-disease management.
Journal Article
Pharmacologic therapy for osteoarthritis—the era of disease modification
Current therapeutic strategies for osteoarthritis (OA) are mostly palliative; modifying the structural progression of OA has, therefore, become a focus of drug development. This Review discusses the challenges involved in the discovery and development of disease-modifying OA drugs, and describes specific agents that have shown promise in phase II and III trials.
Osteoarthritis (OA) is a prevalent and disabling condition for which few safe and effective therapeutic options are available. Current approaches are largely palliative and in an effort to mitigate the rising tide of increasing OA prevalence and disease impact, modifying the structural progression of OA has become a focus of drug development. This Review describes disease modification and discusses some of the challenges involved in the discovery and development of disease-modifying OA drugs (DMOADs). A variety of targeted agents are in mature phases of development; specific agents that are beyond preclinical development in phase II and III trials and show promise as potential DMOADs are discussed. A research agenda with respect to disease modification in OA is also provided, and some of the future challenges we face in this field are discussed.
Key Points
Current therapeutic approaches for osteoarthritis (OA) are largely palliative
Modifying the structural progression of OA has become a focus of drug development
Numerous challenges face those involved in disease-modifying OA drugs (DMOADs) development
A number of DMOADs are currently in phase II and III clinical trials
Journal Article
Priorities for cancer research in low- and middle-income countries: a global perspective
Cancer research currently is heavily skewed toward high-income countries (HICs), with little research conducted in, and relevant to, the problems of low- and middle-income countries (LMICs). This regional discordance in cancer knowledge generation and application needs to be rebalanced. Several gaps in the research enterprise of LMICs need to be addressed to promote regionally relevant research, and radical rethinking is needed to address the burning issues in cancer care in these regions. We identified five top priorities in cancer research in LMICs based on current and projected needs: reducing the burden of patients with advanced disease; improving access and affordability, and outcomes of cancer treatment; value-based care and health economics; quality improvement and implementation research; and leveraging technology to improve cancer control. LMICs have an excellent opportunity to address important questions in cancer research that could impact cancer control globally. Success will require collaboration and commitment from governments, policy makers, funding agencies, health care organizations and leaders, researchers and the public.
Radical rethinking is needed to address the burning issues in cancer care in low- and middle-income countries. In this Perspective, the authors outline the main challenges and top priorities for cancer research now and into the future.
Journal Article
The Development of Disease-Modifying Therapies for Osteoarthritis (DMOADs): The Evidence to Date
Osteoarthritis (OA) is a complex heterogeneous articular disease with multiple joint tissue involvement of varying severity and no regulatory-agency-approved disease-modifying drugs (DMOADs). In this review, we discuss the reasons necessitating the development of DMOADs for OA management, the classifications of clinical phenotypes or molecular/mechanistic endotypes from the viewpoint of targeted drug discovery, and then summarize the efficacy and safety profile of a range of targeted drugs in Phase 2 and 3 clinical trials directed to cartilage-driven, bone-driven, and inflammation-driven endotypes. Finally, we briefly put forward the reasons for failures in OA clinical trials and possible steps to overcome these barriers.
Journal Article
Post-traumatic osteoarthritis: from mouse models to clinical trials
In this Review, Little and Hunter discuss the use of animal models in osteoarthritis (OA) research, focusing on their importance in understanding post-traumatic OA, the human form of the disease that the models most accurately reflect. The authors also outline the approach necessary for the successful translation of scientific data into clinically useable drugs.
Osteoarthritis (OA), the most common of all arthropathies, is a leading cause of disability and has a large (and growing) worldwide socioeconomic cost. Despite its burgeoning importance, translation of disease-modifying OA therapies from the laboratory into clinical practice has slowed. Differences between the OA models studied preclinically and the disease evaluated in human clinical trials contribute to this failure. Most animal models of OA induce disease through surgical or mechanical disruption of joint biomechanics in young individuals rather than the spontaneous development of age-associated disease. This instability-induced joint disease in animals best models the arthritis that develops in humans after an injurious event, known as post-traumatic OA (PTOA). Studies in genetically modified mice suggest that PTOA has a distinct molecular pathophysiology compared with that of spontaneous OA, which might explain the poor translation from preclinical to clinical OA therapeutic trials. This Review summarizes the latest data on potential molecular targets for PTOA prevention and modification derived from studies in genetically modified mice, and describes their validation in preclinical therapeutic trials. This article focuses on how these findings might best be translated to humans, and identifies the potential challenges to successful implementation of clinical trials of disease-modifying drugs for PTOA.
Key Points
The translational value of animal models is primarily determined by how well they correspond with the human condition, and major improvements might be achieved by aligning preclinical and clinical disease
Preclinical research and drug development primarily uses models of post-traumatic osteoarthritis (OA) in young individuals; its molecular pathophysiology could be different than the age-associated OA most commonly targeted in clinical trials
Post-traumatic OA in mice is a valid model of the human disease, and using genetically engineered strains has identified disease-modifying targets that have been validated in preclinical therapeutic studies
Issues remain in study design for therapeutic clinical trials of post-traumatic OA, and the development of predictive biomarkers is critical to drug development for this common and costly disease
Journal Article