396 research outputs found

    Impact of question order on prioritisation of outcomes in the development of a core outcome set: a randomised controlled trial

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    BACKGROUND: Core outcome set (COS) developers increasingly employ Delphi surveys to elicit stakeholders' opinions of which outcomes to measure and report in trials of a particular condition or intervention. Research outside of Delphi surveys and COS development demonstrates that question order can affect response rates and lead to 'context effects', where prior questions determine an item's meaning and influence responses. This study examined the impact of question order within a Delphi survey for a COS for oesophageal cancer surgery. METHODS: A randomised controlled trial was nested within the Delphi survey. Patients and health professionals were randomised to receive a survey including clinical and patient-reported outcomes (PROs), where the PRO section appeared first or last. Participants rated (1-9) the importance of 68 items for inclusion in a COS (ratings 7-9 considered 'essential'). Analyses considered the impact of question order on: (1) survey response rates; (2) participants' responses; and (3) items retained at end of the survey. RESULTS: In total, 116 patients and 71 professionals returned completed surveys. Question order did not affect response rates among patients, but fewer professionals responded when clinical items appeared first (difference = 31.3%, 95% confidence interval [CI] = 13.6-48.9%, P = 0.001). Question order led to different context effects within patients and professionals. While patients rated clinical items highly, irrespective of question order, more PROs were rated essential when appearing last rather than first (difference = 23.7%, 95% CI = 10.5-40.8%). Among professionals, the greatest impact was on clinical items; a higher percentage rated essential when appearing last (difference = 11.6%, 95% CI = 0.0-23.3%). An interaction between question order and the percentage of PRO/clinical items rated essential was observed for patients (P = 0.025) but not professionals (P = 0.357). Items retained for further consideration at the end of the survey were dependent on question order, with discordant items (retained by one question order group only) observed in patients (18/68 [26%]) and professionals (20/68 [29%]). CONCLUSIONS: In the development of a COS, participants' ratings of potential outcomes within a Delphi survey depend on the context (order) in which the outcomes are asked, consequently impacting on the final COS. Initial piloting is recommended with consideration of the randomisation of items in the survey to reduce potential bias. TRIAL REGISTRATION: The randomised controlled trial reported within this paper was nested within the development of a core outcome set to investigate processes in core outcome set development. Outcomes were not health-related and trial registration was not therefore applicable

    Holographic three-point functions of semiclassical states

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    We calculate the holographic three-point functions in N = 4 super-Yang-Mills theory in the case when two of the operators are semiclassical and one is dual to a supergravity mode. We further discuss the transition to the regime when all three operators are semiclassical.Comment: 17 pages, 3 figures; v2: refs. added, discussion in sec. 2.1 expanded; v3: misprint in (2.28) corrected, published versio

    Prioritisation of Clinical Research by the Example of Type 2 Diabetes: A Caregiver-Survey on Perceived Relevance and Need for Evidence

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    BACKGROUND: The Cochrane Collaboration aims at providing the best available evidence for interventions in health care. We wished to examine to which extent treatments considered relevant by caregivers in type 2 diabetes are covered by Cochrane systematic reviews. METHODOLOGY/PRINCIPAL FINDINGS: 130 different interventions in type 2 diabetes were identified based on a review of clinical practice guidelines and expert opinion (Table S1). 459 members of the German Diabetes Society (diabetologists, general practitioners, diabetic nurses, nutritionists, podologists, others) were surveyed via e-mail-list to rank a) the perceived clinical relevance and b) the perceived need for evidence of interventions, based on an internet survey. In the Cochrane Library, there were, at the time of this evaluation, 56 reviews on interventions in diabetes. Generally, coverage of topics by Cochrane reviews reflected the perceived clinical relevance and perceived need for evidence. As an example, highly ranked treatments such as lifestyle changes or oral antidiabetics were well covered, while low rank treatments such as complementary approaches were not covered. Discrepancies occurred with new treatments such as amylin-analogues (low relevance, high need for evidence, review not yet completed) and interventions with immediate and dramatic effects such as treating hypoglycemia (high relevance, low need for evidence, no review). Also, there was a relative scarcity of reviews concerning specific problems, in particular, treatment of late diabetic complications. CONCLUSIONS/SIGNIFICANCE: For most interventions, perceived relevance and perceived need for evidence are reflected by the evidence already available. Prioritizing should aim at improving immediacy and consideration of the treatment of complications

    Meta-analysis: Neither quick nor easy

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    BACKGROUND: Meta-analysis is often considered to be a simple way to summarize the existing literature. In this paper we describe how a meta-analysis resembles a conventional study, requiring a written protocol with design elements that parallel those of a record review. METHODS: The paper provides a structure for creating a meta-analysis protocol. Some guidelines for measurement of the quality of papers are given. A brief overview of statistical considerations is included. Four papers are reviewed as examples. The examples generally followed the guidelines we specify in reporting the studies and results, but in some of the papers there was insufficient information on the meta-analysis process. CONCLUSIONS: Meta-analysis can be a very useful method to summarize data across many studies, but it requires careful thought, planning and implementation

    Assessment of the multidisciplinary education for a major change in clinical practice; a prospective cohort study

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    Background: New approaches are often introduced to the neonatal intensive care unit (NICU) and other areas of the health service in either a haphazard or cataclysmic fashion. The needs of staff education are often addressed incompletely or too late. Rarely is education assessed after the introduction of a major change. We changed the basis of our NICU respiratory support. We conducted a major educational and support program before this intervention. This study documented and assessed the educational components of this change in our health service provision. Methods: Senior medical and nursing staff attended training abroad and an education program was applied for one year prior to the change. Multidisciplinary educational support for doctors, nurses and allied health was continued after the change. Assessment was by anonymous questionnaire, prior to change, at one and at nine months. Our hypothesis was that dissatisfaction with education would be greatest at one month. Results: Both theory education and practical education aspects of the new approach were rated as good to very good and this did not change with time. Difficulty of applying the technique was rated as ambivalent initially but decreased significantly over 9 months until it was rated easy to very easy (p < 0.001). Over all, the change was rated by staff as beneficial, both at the end of the education period and at nine months, with no decrease at one month. Conclusion: If education and training reaches all staff, with a system of mutual and continued support, even large changes in clinical practice can be achieved without the dissatisfaction with the educational process that is often otherwise seen

    The citation of relevant systematic reviews and randomised trials in published reports of trial protocols

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    Background It is important that planned randomised trials are justified and placed in the context of the available evidence. The SPIRIT guidelines for reporting clinical trial protocols recommend that a recent and relevant systematic review should be included. The aim of this study was to assess the use of the existing evidence in order to justify trial conduct. Methods Protocols of randomised trials published over a 1-month period (December 2015) indexed in PubMed were obtained. Data on trial characteristics relating to location, design, funding, conflict of interest and type of evidence included for trial justification was extracted in duplicate and independently by two investigators. The frequency of citation of previous research including relevant systematic reviews and randomised trials was assessed. Results Overall, 101 protocols for RCTs were identified. Most proposed trials were parallel-group (n = 74; 73.3%). Reference to an earlier systematic review with additional randomised trials was found in 9.9% (n = 10) of protocols and without additional trials in 30.7% (n = 31), while reference was made to randomised trials in isolation in 21.8% (n = 22). Explicit justification for the proposed randomised trial on the basis of being the first to address the research question was made in 17.8% (n = 18) of protocols. A randomised controlled trial was not cited in 10.9% (95% CI: 5.6, 18.7) (n = 11), while in 8.9% (95% CI: 4.2, 16.2) (n = 9) of the protocols a systematic review was cited but did not inform trial design. Conclusions A relatively high percentage of protocols of randomised trials involves prior citation of randomised trials, systematic reviews or both. However, improvements are required to ensure that it is explicit that clinical trials are justified and shaped by contemporary best evidence

    A phase I study of the safety and tolerability of olaparib (AZD2281, KU0059436) and dacarbazine in patients with advanced solid tumours

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    BACKGROUND: Poly adenosine diphosphate (ADP)-ribose polymerase (PARP) is essential in cellular processing of DNA damage via the base excision repair pathway (BER). The PARP inhibition can be directly cytotoxic to tumour cells and augments the anti-tumour effects of DNA-damaging agents. This study evaluated the optimally tolerated dose of olaparib (4-(3--4-fluorophenyl) methyl-1(2H)-one; AZD2281, KU0059436), a potent PARP inhibitor, with dacarbazine and assessed safety, toxicity, clinical pharmacokinetics and efficacy of combination treatment. PATIENTS AND METHODS: Patients with advanced cancer received olaparib (20-200 mg PO) on days 1-7 with dacarbazine (600-800 mg m(-2) IV) on day 1 (cycle 2, day 2) of a 21-day cycle. An expansion cohort of chemonaive melanoma patients was treated at an optimally tolerated dose. The BER enzyme, methylpurine-DNA glycosylase and its substrate 7-methylguanine were quantified in peripheral blood mononuclear cells. RESULTS: The optimal combination to proceed to phase II was defined as 100 mg bd olaparib with 600 mg m(-2) dacarbazine. Dose-limiting toxicities were neutropaenia and thrombocytopaenia. There were two partial responses, both in patients with melanoma. CONCLUSION: This study defined a tolerable dose of olaparib in combination with dacarbazine, but there were no responses in chemonaive melanoma patients, demonstrating no clinical advantage over single-agent dacarbazine at these doses
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