1,251 research outputs found

    A system for rating the stability and strength of medical evidence

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    BACKGROUND: Methods for describing one's confidence in the available evidence are useful for end-users of evidence reviews. Analysts inevitably make judgments about the quality, quantity consistency, robustness, and magnitude of effects observed in the studies identified. The subjectivity of these judgments in several areas underscores the need for transparency in judgments. DISCUSSION: This paper introduces a new system for rating medical evidence. The system requires explicit judgments and provides explicit rules for balancing these judgments. Unlike other systems for rating the strength of evidence, our system draws a distinction between two types of conclusions: quantitative and qualitative. A quantitative conclusion addresses the question, "How well does it work?", whereas a qualitative conclusion addresses the question, "Does it work?" In our system, quantitative conclusions are tied to stability ratings, and qualitative conclusions are tied to strength ratings. Our system emphasizes extensive a priori criteria for judgments to reduce the potential for bias. Further, the system makes explicit the impact of heterogeneity testing, meta-analysis, and sensitivity analyses on evidence ratings. This article provides details of our system, including graphical depictions of how the numerous judgments that an analyst makes can be combined. We also describe two worked examples of how the system can be applied to both interventional and diagnostic technologies. SUMMARY: Although explicit judgments and formal combination rules are two important steps on the path to a comprehensive system for rating medical evidence, many additional steps must also be taken. Foremost among these are the distinction between quantitative and qualitative conclusions, an extensive set of a priori criteria for making judgments, and the direct impact of analytic results on evidence ratings. These attributes form the basis for a logically consistent system that can improve the usefulness of evidence reviews

    Impact of elosulfase alfa in patients with morquio A syndrome who have limited ambulation: An open-label, phase 2 study.

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    Efficacy and safety of elosulfase alfa enzyme replacement therapy (ERT) were assessed in an open-label, phase 2, multi-national study in Morquio A patients aged ≥5 years unable to walk ≥30 meters in the 6-min walk test. Patients received elosulfase alfa 2.0 mg/kg/week intravenously for 48 weeks. Efficacy measures were functional dexterity, pinch/grip strength, mobility in a modified timed 25-foot walk, pain, quality of life, respiratory function, and urine keratan sulfate (KS). Safety/tolerability was also assessed. Fifteen patients received elosulfase alfa, three patients discontinued ERT due to adverse events (two were grade 3 drug-related adverse events, the other was not drug-related), and two patients missed >20% of planned infusions; 10 completed treatment through 48 weeks and received ≥80% of planned infusions (Modified Per Protocol [MPP] population). The study population had more advanced disease than that enrolled in other trials. From baseline to week 48, MPP data showed biochemical efficacy (urine KS decreased 52.4%). The remaining efficacy results were highly variable due to challenges in test execution because of severe skeletal and joint abnormalities, small sample sizes, and clinical heterogeneity among patients. Eight patients showed improvements in one or more outcome measures; several patients indicated improvements not captured by the study assessments (e.g., increased energy, functional ability). The nature of adverse events was similar to other elosulfase alfa studies. This study illustrates the considerable challenges in objectively measuring impact of ERT in very disabled Morquio A patients and highlights the need to examine results on an individual basis. © 2016 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc

    The ideology and discourse of the English Defence League: ‘Not racist, not violent, just no longer silent’

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    The English Defence League (EDL) emerged in 2009 and quickly became a major ‘anti-Islamist’ street protest movement, able to attract thousands to its national demonstrations. Despite the violence and anti-Muslim rhetoric associated with its protests, the group claims to be an anti-racist human rights organisation dedicated to protecting liberal freedoms. This article employs a critical methodology to address these claims, analysing EDL literature alongside strategies identified as typical of racist discourse construction. The representations, narratives and rhetorical strategies used by the group support the analysis of EDL Islamophobia as a form of cultural racism that constructs opposing ‘British’ and ‘Muslim’ subjects and functions to maintain traditional ethno-cultural dominance of the former over the latter

    Rifampicin and clarithromycin (extended release) versus rifampicin and streptomycin for limited Buruli ulcer lesions: a randomised, open-label, non-inferiority phase 3 trial.

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    BACKGROUND: Buruli ulcer is a neglected tropical disease caused by Mycobacterium ulcerans infection that damages the skin and subcutis. It is most prevalent in western and central Africa and Australia. Standard antimicrobial treatment with oral rifampicin 10 mg/kg plus intramuscular streptomycin 15 mg/kg once daily for 8 weeks (RS8) is highly effective, but streptomycin injections are painful and potentially harmful. We aimed to compare the efficacy and tolerability of fully oral rifampicin 10 mg/kg plus clarithromycin 15 mg/kg extended release once daily for 8 weeks (RC8) with that of RS8 for treatment of early Buruli ulcer lesions. METHODS: We did an open-label, non-inferiority, randomised (1:1 with blocks of six), multicentre, phase 3 clinical trial comparing fully oral RC8 with RS8 in patients with early, limited Buruli ulcer lesions. There were four trial sites in hospitals in Ghana (Agogo, Tepa, Nkawie, Dunkwa) and one in Benin (Pobè). Participants were included if they were aged 5 years or older and had typical Buruli ulcer with no more than one lesion (caterories I and II) no larger than 10 cm in diameter. The trial was open label, and neither the investigators who took measurements of the lesions nor the attending doctors were masked to treatment assignment. The primary clinical endpoint was lesion healing (ie, full epithelialisation or stable scar) without recurrence at 52 weeks after start of antimicrobial therapy. The primary endpoint and safety were assessed in the intention-to-treat population. A sample size of 332 participants was calculated to detect inferiority of RC8 by a margin of 12%. This study was registered with ClinicalTrials.gov, NCT01659437. FINDINGS: Between Jan 1, 2013, and Dec 31, 2017, participants were recruited to the trial. We stopped recruitment after 310 participants. Median age of participants was 14 years (IQR 10-29) and 153 (52%) were female. 297 patients had PCR-confirmed Buruli ulcer; 151 (51%) were assigned to RS8 treatment, and 146 (49%) received oral RC8 treatment. In the RS8 group, lesions healed in 144 (95%, 95% CI 91 to 98) of 151 patients, whereas lesions healed in 140 (96%, 91 to 99) of 146 patients in the RC8 group. The difference in proportion, -0·5% (-5·2 to 4·2), was not significantly greater than zero (p=0·59), showing that RC8 treatment is non-inferior to RS8 treatment for lesion healing at 52 weeks. Treatment-related adverse events were recorded in 20 (13%) patients receiving RS8 and in nine (7%) patients receiving RC8. Most adverse events were grade 1-2, but one (1%) patient receiving RS8 developed serious ototoxicity and ended treatment after 6 weeks. No patients needed surgical resection. Four patients (two in each study group) had skin grafts. INTERPRETATION: Fully oral RC8 regimen was non-inferior to RS8 for treatment of early, limited Buruli ulcer and was associated with fewer adverse events. Therefore, we propose that fully oral RC8 should be the preferred therapy for early, limited lesions of Buruli ulcer. FUNDING: WHO with additional support from MAP International, American Leprosy Missions, Fondation Raoul Follereau France, Buruli ulcer Groningen Foundation, Sanofi-Pasteur, and BuruliVac

    Reflections on undertaking the Probation Qualifying Framework scheme during the transforming rehabilitation changes

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    This article reflects upon the author’s experience of undertaking the PQF (Probation Qualifying Framework) training scheme during the chaotic period of Transforming Rehabilitation. The author asserts that the uncertainty and precarious nature of the changes were detrimental to an effective learning environment, which ultimately promoted a practice culture of punitiveness and control and did not allow learners the space to be skilful and confident practitioners, comfortable working autonomously. Furthermore, the author contends there is an emerging culture within the NPS (National Probation Service) increasingly fostered on ‘risk management’, which is reflected in the vocational nature of PQF training and is contributing towards a widening cultural gap that is emerging between the community rehabilitation companies and NPS

    Measurement of the Branching Fraction for B- --> D0 K*-

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    We present a measurement of the branching fraction for the decay B- --> D0 K*- using a sample of approximately 86 million BBbar pairs collected by the BaBar detector from e+e- collisions near the Y(4S) resonance. The D0 is detected through its decays to K- pi+, K- pi+ pi0 and K- pi+ pi- pi+, and the K*- through its decay to K0S pi-. We measure the branching fraction to be B.F.(B- --> D0 K*-)= (6.3 +/- 0.7(stat.) +/- 0.5(syst.)) x 10^{-4}.Comment: 7 pages, 1 postscript figure, submitted to Phys. Rev. D (Rapid Communications

    A Study of Time-Dependent CP-Violating Asymmetries and Flavor Oscillations in Neutral B Decays at the Upsilon(4S)

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    We present a measurement of time-dependent CP-violating asymmetries in neutral B meson decays collected with the BABAR detector at the PEP-II asymmetric-energy B Factory at the Stanford Linear Accelerator Center. The data sample consists of 29.7 fb1{\rm fb}^{-1} recorded at the Υ(4S)\Upsilon(4S) resonance and 3.9 fb1{\rm fb}^{-1} off-resonance. One of the neutral B mesons, which are produced in pairs at the Υ(4S)\Upsilon(4S), is fully reconstructed in the CP decay modes J/ψKS0J/\psi K^0_S, ψ(2S)KS0\psi(2S) K^0_S, χc1KS0\chi_{c1} K^0_S, J/ψK0J/\psi K^{*0} (K0KS0π0K^{*0}\to K^0_S\pi^0) and J/ψKL0J/\psi K^0_L, or in flavor-eigenstate modes involving D()π/ρ/a1D^{(*)}\pi/\rho/a_1 and J/ψK0J/\psi K^{*0} (K0K+πK^{*0}\to K^+\pi^-). The flavor of the other neutral B meson is tagged at the time of its decay, mainly with the charge of identified leptons and kaons. The proper time elapsed between the decays is determined by measuring the distance between the decay vertices. A maximum-likelihood fit to this flavor eigenstate sample finds Δmd=0.516±0.016(stat)±0.010(syst)ps1\Delta m_d = 0.516\pm 0.016 {\rm (stat)} \pm 0.010 {\rm (syst)} {\rm ps}^{-1}. The value of the asymmetry amplitude sin2β\sin2\beta is determined from a simultaneous maximum-likelihood fit to the time-difference distribution of the flavor-eigenstate sample and about 642 tagged B0B^0 decays in the CP-eigenstate modes. We find sin2β=0.59±0.14(stat)±0.05(syst)\sin2\beta=0.59\pm 0.14 {\rm (stat)} \pm 0.05 {\rm (syst)}, demonstrating that CP violation exists in the neutral B meson system. (abridged)Comment: 58 pages, 35 figures, submitted to Physical Review
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