Heterogeneity in cancer guidelines: should we eradicate or tolerate?

Background: Heterogeneity in aspects of development, structure and context of oncology guidelines was not evaluated. We analysed and critically examined its implications. Materials and methods: Nine cancer clinical practice guidelines were selected on the basis of popularity among oncologists. The relevant Web sites and publications on three tumours were examined and characteristics grouped in the data domains: producing organisation, methodology, guideline structure and content, implementation and evaluation and scientific agreement. Results: ASCO, ESMO, NICE, SIGN, START, NHMRC, NCI, NCCN and CCO guidelines were examined. Development was initiated by stakeholders or authorised bodies, run by task forces with varying degrees of multidisciplinarity, with rare endorsement of external guidelines. Recommendation formulation was on the basis of evidence, shaped via interactive processes of expert review and public consultation-based modifications. Guidelines varied in comprehensiveness per tumour type, number, size, format, grading of evidence, update and legal issues. Orientation for clinic use or as reference document, end-users and binding or elective nature also varied. Standard dissemination strategies were used, though evaluation of adoption and of impact on health outcomes was implemented with considerable heterogeneity. Conclusions: Heterogeneity in development, structure, user and end points of guidelines is evident, though necessary in order to meet divergent demands. Crucial for their effectiveness are adherence to methodological standards, a clear definition of what the guideline intends to do for whom and a systematic evaluation of their impact on health car

Phosphorus status and cycling in native savanna and improved pastures on an acid low-P Colombian Oxisol

On acid low-phosphorus (P) Colombian Oxisols, improved pastures with acid-soil-tolerant grass and legume varieties have increased beef production by a factor of 10 to 15 with only modest P fertilizer inputs. This indicates that the efficiency of P fertilization could be greater than is commonly expected on such strongly P-sorbing soils. To understand the effect of improved pastures on P cycling and availability, we estimated P budgets, and characterized soil P by sequential fractionation, isotopic exchange and biological activity measurements on soil samples from unfertilized native savanna, and fertilized improved grass-only (Brachiaria decumbens cv. Basilisk) and grass-legume (B. decumbens + Pueraria phaseoloides, Kudzu) pastures established in 1978 on a medium-textured isohyperthermic, tropeptic haplustox. Comparison of calculated P budgets, based on inputs and exports, with total soil P contents showed that fertilization, as part of the improved pasture management, had resulted in a measurable increase of total P in the surface 0-20 cm soil layer of nearly 30 mg kg-1 or about 20% over the savanna level. Sequential soil P fractionation of different seasonal samplings indicated that grass-legume maintained higher organic and available inorganic P levels with less temporal variation than the two other types. The linkage of organic P and available P was also reflected in soil biological activity. Estimates of P in microbial biomass and phosphatase activity were significantly higher in grass-legume than grass-only and savanna. The improvement in soil P availability, as measured by solution P concentration, P sorption and exchangeable P, was much greater in grass-legume than in grass-only. With comparable fertilizer inputs and greater product exports, improved P availability in grass-legume cannot be due to differences in budgets but can be attributed to changes in the overall biological activity in the soil-plant system caused by the presence of legumes in the vegetation cover. Total C, organic P content and macrofaunal activity were all significantly higher in grass-legume soils. Greater turnover of organic litter in grass-legume may provide for steadier organic P inputs and, therefore, higher P cycling and availabilit

Index of pretreatment intensity predicts outcome of high-dose chemotherapy and autologous progenitor cell transplantation in chemosensitive relapse of Hodgkin's disease

Purpose To identify prognostic factors in patients with chemosensitive relapsed Hodgkin's disease treated by high-dose chemotherapy with autologous progenitor cell transplantation (HDC) and to compare the duration of treatment-free remission prior to HDC with the progression-free survival after HDC in individual patients. Patients and methods Forty-five consecutive patients were analyzed retrospectively. We devised an index of pretreatment intensity (IPTI) based number of different chemo- and radio-therapy regimens given between diagnosis and HDC and on the duration of disease. Results With a median follow-up of 47 months the post-transplant event-free survival (EFS) was 44% and the overall survival. (OAS) was 62% at four years. The IPTI allowed to discriminate between a low and a high-risk group with a four-year post-transplant EFS of 66% and 11% and a OAS of 87% and 28%, respectively (P = 0.0001). Of the 39 patients with sufficient follow-up after HDC, post-transplant EFS lasted on average ≥ 18.5 months longer than the pretransplant treatment-free remission. Conclusions HDC with the CBV regimen confers significant benefit to patients with chemosensitive relapsed Hodgkin's disease. The IPTI may help to select patients with a good response to HDC and to identify poor prognosis patients suitable for experimental protocols or palliative care onl

Peroxisome Proliferator-Activated Receptors: “Key” Regulators of Neuroinflammation after Traumatic Brain Injury

Traumatic brain injury is characterized by neuroinflammatory pathological sequelae which contribute to brain edema and delayed neuronal cell death. Until present, no specific pharmacological compound has been found, which attenuates these pathophysiological events and improves the outcome after head injury. Recent experimental studies suggest that targeting peroxisome proliferator-activated receptors (PPARs) may represent a new anti-inflammatory therapeutic concept for traumatic brain injury. PPARs are “key” transcription factors which inhibit NFκB activity and downstream transcription products, such as proinflammatory and proapoptotic cytokines. The present review outlines our current understanding of PPAR-mediated neuroprotective mechanisms in the injured brain and discusses potential future anti-inflammatory strategies for head-injured patients, with an emphasis on the putative beneficial combination therapy of synthetic cannabinoids (e.g., dexanabinol) with PPARα agonists (e.g., fenofibrate)

Bias towards publishing positive results in orthopedic and general surgery: a patient safety issue?

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