‘Trying to pin down jelly’ - exploring intuitive processes in quality assessment for meta-ethnography

Background: Studies that systematically search for and synthesise qualitative research are becoming more evident in health care, and they can make an important contribution to patient care. However, there is still no agreement as to whether, or how we should appraise studies for inclusion. We aimed to explore the intuitive processes that determined the ‘quality’ of qualitative research for inclusion in qualitative research syntheses. We were particularly interested to explore the way that knowledge was constructed. Methods: We used qualitative methods to explore the process of quality appraisal within a team of seven qualitative researchers funded to undertake a meta-ethnography of chronic non-malignant musculoskeletal pain. Team discussions took place monthly between October 2010 and June 2012 and were recorded and transcribed. Data was coded and organised using constant comparative method. The development of our conceptual analysis was both iterative and collaborative. The strength of this team approach to quality came from open and honest discussion, where team members felt free to agree, disagree, or change their position within the safety of the group. Results: We suggest two core facets of quality for inclusion in meta-ethnography - (1) Conceptual clarity; how clearly has the author articulated a concept that facilitates theoretical insight. (2) Interpretive rigour; fundamentally, can the interpretation ‘be trusted?’ Our findings showed that three important categories help the reader to judge interpretive rigour: (ii) What is the context of the interpretation? (ii) How inductive is the interpretation? (iii) Has the researcher challenged their interpretation? Conclusions: We highlight that methods alone do not determine the quality of research for inclusion into a meta-ethnography. The strength of a concept and its capacity to facilitate theoretical insight is integral to meta-ethnography, and arguably to the quality of research. However, we suggest that to be judged ‘good enough’ there also needs to be some assurance that qualitative findings are more than simply anecdotal. Although our conceptual model was developed specifically for meta-ethnography, it may be transferable to other research methodologies

The GRADE System for Rating Clinical Guidelines

Brian Kavanagh critiques the GRADE system of grading guidelines, arguing that even though it has evolved through the Evidence-Based Medicine movement, there is no evidence that GRADE itself is reliable

Is EGFR expression altered following postoperative chemotherapy for colorectal adenocarcinoma?

BACKGROUND: There is immunohistochemical evidence to suggest that expression of epidermal growth factor receptor (EGFR) in primary colorectal adenocarcinoma predicts its expression in recurrent disease. This study investigates whether postoperative chemotherapy affects the degree of concordance between EGFR statuses of the two tumors. METHODS: Thirty-three patients were identified from the files of Sunnybrook Health Sciences Center from July 1994 to June 2005. All patients had resection of their primary tumors and their distant recurrences. Eighteen patients received postoperative chemotherapy, 3 of which also received postoperative radiation therapy. Representative primary and recurrent tumor sections were stained using mouse anti-EGFR antibodies and only membranous staining of malignant cells was recorded. Results were reported as negative (no staining), 1+ (positivity in <50% of cells) or 2+ (positivity in >50% of cells). RESULTS: EGFR immunostaining in the 15 patients, who received no postoperative chemotherapy, was decreased in 3 recurrences, remained the same in 10 and increased in 2. In the group of 18 patients who received postoperative chemotherapy, EGFR immunostaining was decreased in 6 recurrences, remained the same in 9 and increased in 3 (p = 0.6598). In patients who received postoperative chemotherapy, the odds ratio for a recurrence to show lower levels of EGFR immunostaining compared to its originally resected primary was 4.75 (CI = 0.94 – 26.73). CONCLUSION: These preliminary data suggest that recurrences following postoperative chemotherapy are likely to have lower levels of EGFR expression compared to cases who receive no chemotherapy. Although the difference of immunostaining profiles between the two groups was not statistically significant, this observation might impact the management of these patients by targeted biologic therapies and its practical implications need further validation in larger series

Phase II trial of the regulatory T cell-depleting agent, denileukin diftitox, in patients with unresectable stage IV melanoma

<p>Abstract</p> <p>Background</p> <p>We previously found that administration of an interleukin 2/diphtheria toxin conjugate (DAB/IL2; Denileukin Diftitox; ONTAK) to stage IV melanoma patients depleted CD4⁺CD25^HIFoxp3⁺regulatory T cells and expanded melanoma-specific CD8⁺T cells. The goal of this study was to assess the clinical efficacy of DAB/IL2 in an expanded cohort of stage IV melanoma patients.</p> <p>Methods</p> <p>In a single-center, phase II trial, DAB/IL2 (12 μg/kg; 4 daily doses; 21 day cycles) was administered to 60 unresectable stage IV melanoma patients and response rates were assessed using a combination of 2-[¹⁸F]-fluoro-2-deoxy-glucose (FDG)-positron emission tomography (PET) and computed tomography (CT) imaging.</p> <p>Results</p> <p>After DAB/IL2 administration, 16.7% of the 60 patients had partial responses, 5% stable disease and 15% mixed responses. Importantly, 45.5% of the chemo/immuno-naïve sub-population (11/60 patients) experienced partial responses. One year survival was markedly higher in partial responders (80 ± 11.9%) relative to patients with progressive disease (23.7 ± 6.5%; <it>p </it>value < 0.001) and 40 ± 6.2% of the total DAB/IL2-treated population were alive at 1 year.</p> <p>Conclusions</p> <p>These data support the development of multi-center, randomized trials of DAB/IL2 as a monotherapy and in combination with other immunotherapeutic agents for the treatment of stage IV melanoma.</p> <p>Trial registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT00299689">NCT00299689</a></p

New targets for therapy in breast cancer: Mammalian target of rapamycin (mTOR) antagonists

Mammalian target of rapamycin (mTOR) is a serine-threonine kinase member of the cellular phosphatidylinositol 3-kinase (PI3K) pathway, which is involved in multiple biologic functions such as transcriptional and translational control. mTOR is a downstream mediator in the PI3K/Akt signaling pathway and plays a critical role in cell survival. In breast cancer this pathway can be activated by membrane receptors, including the HER (or ErbB) family of growth factor receptors, the insulin-like growth factor receptor, and the estrogen receptor. There is evidence suggesting that Akt promotes breast cancer cell survival and resistance to chemotherapy, trastuzumab, and tamoxifen. Rapamycin is a specific mTOR antagonist that targets this pathway and blocks the downstream signaling elements, resulting in cell cycle arrest in the G(1 )phase. Targeting the Akt/PI3K pathway with mTOR antagonists may increase the therapeutic efficacy of breast cancer therapy

Credible knowledge: A pilot evaluation of a modified GRADE method using parent-implemented interventions for children with autism

Abstract Background Decision-making in child and youth mental health (CYMH) care requires recommendations that are developed through an efficient and effective method and are based on credible knowledge. Credible knowledge is informed by two sources: scientific evidence, and practice-based evidence, that reflects the "real world" experience of service providers. Current approaches to developing these recommendations in relation to CYMH will typically include evidence from one source or the other but do not have an objective method to combine the two. To this end, a modified version of the Grading Recommendations Assessment, Development and Evaluation (GRADE) approach was pilot-tested, a novel method for the CYMH field. Methods GRADE has an explicit methodology that relies on input from scientific evidence as well as a panel of experts. The panel established the quality of evidence and derived detailed recommendations regarding the organization and delivery of mental health care for children and youth or their caregivers. In this study a modified GRADE method was used to provide precise recommendations based on a specific CYMH question (i.e. What is the current credible knowledge concerning the effects of parent-implemented, early intervention with their autistic children?). Results Overall, it appeared that early, parent-implemented interventions for autism result in positive effects that outweigh any undesirable effects. However, as opposed to overall recommendations, the heterogeneity of the evidence required that recommendations be specific to particular interventions, based on the questions of whether the benefits of a particular intervention outweighs its harms. Conclusions This pilot project provided evidence that a modified GRADE method may be an effective and practical approach to making recommendations in CYMH, based on credible knowledge. Key strengths of the process included separating the assessments of the quality of the evidence and the strength of recommendations, transparency in decision-making, and the objectivity of the methods. Most importantly, this method combined the evidence and clinical experience in a more timely, explicit and simple process as compared to previous approaches. The strengths, limitations and modifications of the approach as they pertain to CYMH, are discussed

Effects of luteectomy in early pregnancy on the maintenance of gestation and plasma progesterone concentrations in the viviparous temperate lizard Barisia imbricata imbricata

<p>Abstract</p> <p>Background</p> <p>Several studies have shown that the corpus luteum is the principal source of progesterone during the gravidity period in reptiles; however, its participation in the maintenance of gestation in the viviparous squamata is in dispute. The effects of ovariectomy or luteectomy vary according to the species and the time at which the procedure is performed. In this paper, we describe the effects of luteectomy during early pregnancy on the maintenance of gestation and progesterone concentrations in the temperate Mexican viviparous lizard <it>Barisia imbricata imbricata.</it></p> <p>Methods</p> <p>Twenty-four lizards were subjected to three different treatments: luteectomy, sham luteectomy or non-surgical treatment, and blood samples were obtained before and after surgical treatment at different stages of gestation to determine the effects of luteectomy on the maintenance of gestation and progesterone concentrations.</p> <p>Results</p> <p>Spontaneous abortion was not observed in any of the females. However, luteectomy provoked abnormal parturition and a significant reduction in the number of young born alive. Parturition was normal in untreated females as well as those submitted to sham luteectomy. The surgical treatment also caused a significant reduction in progesterone concentrations in luteectomised females during early and middle gestation. However, no significant differences in hormone concentrations were observed among the three groups during late gestation or immediately post-parturition.</p> <p>Conclusions</p> <p>Our observations indicate that the presence of the corpus luteum is not necesary for the maintenance of gestation, but that it does participate in parturition control. Moreover, the corpus luteum of the viviparous lizard <it>B. i. imbricata</it> produces progesterone, at least during the first half of pregnancy, and that an extra-ovarian source of progesterone must maintain gestation in the absence of luteal tissue.</p

The Src inhibitor dasatinib accelerates the differentiation of human bone marrow-derived mesenchymal stromal cells into osteoblasts

The proto-oncogene Src is an important non-receptor protein tyrosine kinase involved in signaling pathways that control cell adhesion, growth, migration and differentiation. It negatively regulates osteoblast activity, and, as such, its inhibition is a potential means to prevent bone loss. Dasatinib is a new dual Src/Bcr-Abl tyrosine kinase inhibitor initially developed for the treatment of chronic myeloid leukemia. It has also shown promising results in preclinical studies in various solid tumors. However, its effects on the differentiation of human osteoblasts have never been examined.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Demographics of extra-articular calcaneal fractures: Including a review of the literature on treatment and outcome

Introduction: Extra-articular calcaneal fractures represent 25-40% of all calcaneal fractures and an even higher percentage of up to 60% is seen in children. A disproportionately small part of the literature on calcaneal fractures involves the extra-articular type. The aim of this study was to investigate the incidence of extra-articular calcaneal fractures in a Level 1 trauma centre, define the distribution of the various types of fractures and compare patient demographics between extra- and intra-articular calcaneal fractures. In addition the literature was reviewed for the most common types of extra-articular calcaneal fractures with regard to incidence, treatment and clinical outcome. Methods: The radiological records between 2003 and 2005 were reviewed for intra- and extra-articular calcaneal fractures. Patient gender-distribution and age were compared. A literature search was conducted for the treatment of extra-articular calcaneal fractures. Results: In this 3-year study period a total of 49 patients with 50 extra-articular calcaneal fractures and 91 patients with 101 intra-articular fractures were identified. The median age for the first group was 32.7 years, and for the second group 40.3 years; P = 0.04. Male predominance was significantly less pronounced for extra-articular (63%) compared with intra-articular fractures (79%; P = 0.04). Conclusion: One-third of all calcaneal fractures are extra-articular. Significant differences exist between the intra- and extra-articular groups, in terms of lower age and male-female ratio. The literature study shows inconsistencies in treatment options, but most extra-articular fractures are well manageable conservatively