Tag: nevin manimala

Statistics (Ber). 2016 Jul 3;50(4):917-929. doi: 10.1080/02331888.2015.1111892. Epub 2016 Jan 8.

ABSTRACT

Copula modelling has in the past decade become a standard tool in many areas of applied statistics. However, a largely neglected aspect concerns the design of related experiments. Particularly the issue of whether the estimation of copula parameters can be enhanced by optimizing experimental conditions and how robust all the parameter estimates for the model are with respect to the type of copula employed. In this paper an equivalence theorem for (bivariate) copula models is provided that allows formulation of efficient design algorithms and quick checks of whether designs are optimal or at least efficient. Some examples illustrate that in practical situations considerable gains in design efficiency can be achieved. A natural comparison between different copula models with respect to design efficiency is provided as well.

PMID:27453616 | PMC:PMC4936440 | DOI:10.1080/02331888.2015.1111892

Statistics (Ber). 2012 Jan 1;46(5):663-671. doi: 10.1080/02331888.2010.545408.

ABSTRACT

We extend the random permutation model to obtain the best linear unbiased estimator of a finite population mean accounting for auxiliary variables under simple random sampling without replacement (SRS) or stratified SRS. The proposed method provides a systematic design-based justification for well-known results involving common estimators derived under minimal assumptions that do not require specification of a functional relationship between the response and the auxiliary variables.

PMID:23645951 | PMC:PMC3640589 | DOI:10.1080/02331888.2010.545408

Statistics (Ber). 2010 Apr 1;44(2):145-153. doi: 10.1080/02331880902986984.

ABSTRACT

Consider a set of order statistics that arise from sorting samples from two different populations, each with their own, possibly different distribution functions. The probability that these order statistics fall in disjoint, ordered intervals and that of the smallest statistics, a certain number come from the first populations is given in terms of the two distribution functions. The result is applied to computing the joint probability of the number of rejections and the number of false rejections for the Benjamini-Hochberg false discovery rate procedure.

PMID:21243084 | PMC:PMC3020799 | DOI:10.1080/02331880902986984

Neurol Neuroimmunol Neuroinflamm. 2023 Aug 7;10(5):e200145. doi: 10.1212/NXI.0000000000200145. Print 2023 Sep.

ABSTRACT

BACKGROUND AND OBJECTIVES: Neural antibodies are detected by tissue-based indirect immunofluorescence assay (IFA) in Mayo Clinic’s Neuroimmunology Laboratory practice, but the process of characterizing and validating novel antibodies is lengthy. We report our assessment of human protein arrays.

METHODS: Assessment of arrays (81% human proteome coverage) was undertaken using diverse known positive samples (17 serum and 14 CSF). Samples from patients with novel neural antibodies were reflexed from IFA to arrays. Confirmatory assays were cell-based (CBA) or line blot. Epitope mapping was undertaken using phage display immunoprecipitation sequencing (PhiPSeq).

RESULTS: Control positive samples known to be reactive with linear epitopes of intracellular antigens (e.g., ANNA-1 [anti-Hu]) were readily identified by arrays in 20 of 21 samples. By contrast, 10 positive controls known to be enriched with antibodies against cell surface protein conformational epitopes (e.g., GluN1 subunit of NMDA-R) were indistinguishable from background signal. Three antibodies, previously characterized by other investigators (but unclassified in our laboratory), were unmasked in 4 patients using arrays (July-December 2022): Neurexin-3α, 1 patient; regulator of gene protein signaling (RGS)8, 1 patient; and seizure-related homolog like 2 (SEZ6L2), 2 patients. All were accompanied by previously reported phenotypes (encephalitis, 1; cerebellar ataxia, 3). Patient 1 had subacute onset of seizures and encephalopathy. Neurexin-3α ranked high in CSF (second ranked neural protein) but low in serum (660th overall). Neurexin-3α CBA was positive in both samples. Patient 2 presented with rapidly progressive cerebellar ataxia. RGS8 ranked the highest neural protein in available CSF sample by array (third overall). RGS8-specific line blot was positive. Patients 3 and 4 had rapidly progressive cerebellar ataxia. SEZ6L2 was the highest ranked neural antigen by arrays in all samples (CSF, 1, serum, 2; Patient 3, ranked 9th overall in CSF, 11th in serum; Patient 4, 6th overall in serum]). By PhIPSeq, diverse neurexin-3α epitopes (including cell surface) were detected in CSF from patient 1, but no SEZ6L2 peptides were detected for serum or CSF samples from Patient 3.

DISCUSSION: Individualized autoimmune neurologic diagnoses may be accelerated using protein arrays. They are optimal for detection of intracellular antigen-reactive antibodies, though certain cell surface-directed antibodies (neurexin-3α and SEZ6L2) may also be detected.

PMID:37550073 | DOI:10.1212/NXI.0000000000200145

Heart. 2023 Aug 7:heartjnl-2023-322463. doi: 10.1136/heartjnl-2023-322463. Online ahead of print.

ABSTRACT

INTRODUCTION: Cardiac troponin (cTn) concentrations above the manufacturer recommended upper limit of normal (ULN) are frequently seen in hospital patients without a clinical presentation consistent with type 1 myocardial infarction, and the significance of this is uncertain. The aim of this study was to assess the relationship between medium-term mortality and cTn concentration in a large consecutive hospital population, regardless of whether there was a clinical indication for performing the test.

METHOD: This prospective observational study included 20 000 consecutive in-hospital and outpatient patients who had a blood test for any reason at a large teaching hospital, and in whom a hs-cTnI assay was measured, regardless of the original clinical indication. Mortality was obtained via NHS Digital.

RESULTS: A total of 20 000 patients were included in the analysis and 18 282 of these (91.4%) did not have a clinical indication for cardiac troponin I (cTnI) testing. Overall, 2825 (14.1%) patients died at a median of 809 days. The mortality was significantly higher if the cTnI concentration was above the ULN (45.3% vs 12.3% p<0.001 log rank). Multivariable Cox analysis demonstrated that the log₁₀ cTnI concentration was independently associated with mortality (HR 1.76 (95% CI 1.65 to 1.88)). Landmark analysis, excluding deaths within 30 days, showed the relationship between cTnI concentration and mortality persisted.

CONCLUSION: In a large, unselected hospital population, in 91.4% of whom there was no clinical indication for testing, cTnI concentration was independently associated with medium-term cardiovascular and non-cardiovascular mortality in the statistical model tested.

PMID:37550072 | DOI:10.1136/heartjnl-2023-322463

Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2023 Aug 8;58:741-746. doi: 10.3760/cma.j.cn115330-20230120-00035. Online ahead of print.

ABSTRACT

Objective: To investigate the value of aspirin challenge tests in the diagnosis of non-steroidal anti-inflammatory drugs-exacerbated respiratory disease (NERD). Methods: Fifty patients (28 females; age, 16-61 years) who were diagnosed with chronic rhinosinusitis with nasal polyps (CRSwNP) with/without asthma, and underwent NERD standardized diagnosis in the Allergy Centre of West China Hospital, Sichuan University from December 2021 to November 2022 were included in the study. The first step was asking about the history of exacerbation respiratory symptoms after intake of any non-steroidal anti-inflammatory drug, including aspirin; the second step was performing intranasal aspirin challenge (IAC); the third step was performing oral aspirin challenge (OAC). The diagnosis of NERD was made if any of the above steps was positive, and the subsequent steps were not performed, otherwise the diagnosis was made to OAC. If OAC was negative, the diagnosis was non-NERD. All patients completed the sino-nasal outcome test 22 (SNOT 22) score, Lund-Kennedy score by nasal endoscopic, allergen skin prick test, blood routine and serum total IgE test. SPSS version 20.0 was used for statistical analysis. Results: The diagnosis of NRED was confirmed in 27 patients (27/50, 54%). Seven (7/50, 14%) of them were diagnosed by clinical history and 20 (20/50, 40%) were diagnosed by aspirin challenge tests, of which 17 (17/20, 85%) were positive to IAC and 3 (3/20, 15%) to OAC. Of the 43 patients who underwent IAC testing, only 2 (2/43, 5%) developed asthma attacks during challenge. Comparing the clinical characteristics of patients in NERD and non-NERD group, there were significant differences between the two groups in gender (P=0.001), hyposmia (P=0.003), history of repeated CRSwNP surgeries (P=0.028), comorbid asthma (P=0.013), SNOT-22 score (P=0.004) and the percentage of peripheral blood eosinophil (P=0.043). Conclusions: Patients may be underdiagnosed if the diagnosis of NERD is made only by medical history, and it is necessary to carry out aspirin challenge tests. IAC is an important means to diagnose NERD with high accuracy and good safety. However, If IAC is negative, further OAC is required.

PMID:37550033 | DOI:10.3760/cma.j.cn115330-20230120-00035

BMJ Open. 2023 Aug 7;13(8):e069208. doi: 10.1136/bmjopen-2022-069208.

ABSTRACT

OBJECTIVES: The emergency department (ED) represents a place and moment of opportunity to provide interventions to improve long-term asthma outcomes, but feasibility, effectiveness and mechanisms of impact are poorly understood. We aimed to review the existing literature on interventions that are delivered in the ED for adults and adolescents, targeting asthma outcomes beyond the ED, and to code the interventions according to theory used, and to understand the barriers and facilitators to their implementation.

METHODS: We systematically searched seven electronic databases and research registers, and manually searched reference lists of included studies and relevant reviews. Both quantitative and qualitative studies that reported on interventions delivered in the ED which aimed to improve asthma outcomes beyond management of the acute exacerbation, for adolescents or adults were included. Methodological quality was assessed using the Mixed Methods Appraisal Tool and informed study interpretation. Theory was coded using the Theoretical Domains Framework. Findings were summarised by narrative synthesis.

RESULTS: 12 articles were included, representing 10 unique interventions, including educational and medication-based changes (6 randomised controlled trials and 4 non-randomised studies). Six trials reported statistically significant improvements in one or more outcome measures relating to long-term asthma control, including unscheduled healthcare, asthma control, asthma knowledge or quality of life. We identified limited use of theory in the intervention designs with only one intervention explicitly underpinned by theory. There was little reporting on facilitators or barriers, although brief interventions appeared more feasible.

CONCLUSION: The results of this review suggest that ED-based asthma interventions may be capable of improving long-term outcomes. However, there was significant variation in the range of interventions, reported outcomes and duration of follow-up. Future interventions would benefit from using behaviour change theory, such as constructs from the Theoretical Domains Framework.

PROSPERO REGISTRATION NUMBER: CRD 42020223058.

PMID:37550032 | DOI:10.1136/bmjopen-2022-069208

BMJ Open. 2023 Aug 7;13(8):e069858. doi: 10.1136/bmjopen-2022-069858.

ABSTRACT

INTRODUCTION: The purpose of TheShinISS-Vax|Flu study is to examine the association between influenza vaccines and adverse events requiring hospital admission or emergency care during the influenza vaccination campaigns 2021/2022 and 2022/2023 in Italy.

METHODS AND ANALYSIS: This is a Self-Controlled Case Series multiregional study using linked routinely collected data from regional healthcare databases of the participating regions. Study participants will be persons aged ≥6 months, unvaccinated or who have received influenza vaccine during the influenza vaccination campaigns in the seasons 2021/2022 and 2022/2023 in Italy and who have experienced the outcome of interest for the first time during the study period (1 September 2021-30 June 2022 and 1 September 2022-30 June 2023 for the first and second vaccination campaigns, respectively). Risk periods will be specifically defined for each outcome and further subdivided into periods of 7 days. The exposures will be the first or second dose of the influenza vaccines administered during the two vaccination campaigns. Statistical analysis will be conducted separately for the data of the two campaigns. Exposure risk period will be compared with baseline risk period defined as any time of observation out of the risk periods. The modified SCCS method will be applied to handle event-dependent exposure and mortality and fitted using unbiased estimating equations to estimate relative incidences and excess of cases per 100 000 vaccinated by dose, age, sex and type of vaccine. Calendar period will be included as time-varying confounder in the model, where appropriate.

ETHICS AND DISSEMINATION: The study received the approval from the National ethics committee for clinical trials of public research bodies and other national public institutions (PRE BIO CE n.0036723, 23/09/2022). Results will be published in peer-reviewed journals and reports in accordance with the publication policies of the Italian National Institute of Health and of the Italian Medicines Agency.

PMID:37550029 | DOI:10.1136/bmjopen-2022-069858

BMJ Open. 2023 Aug 7;13(8):e069176. doi: 10.1136/bmjopen-2022-069176.

ABSTRACT

INTRODUCTION: There is an urgent need to determine the safety, effectiveness and cost-effectiveness of novel antiviral treatments for COVID-19 in vaccinated patients in the community at increased risk of morbidity and mortality from COVID-19.

METHODS AND ANALYSIS: PANORAMIC is a UK-wide, open-label, prospective, adaptive, multiarm platform, randomised clinical trial that evaluates antiviral treatments for COVID-19 in the community. A master protocol governs the addition of new antiviral treatments as they become available, and the introduction and cessation of existing interventions via interim analyses. The first two interventions to be evaluated are molnupiravir (Lagevrio) and nirmatrelvir/ritonavir (Paxlovid).

ELIGIBILITY CRITERIA: community-dwelling within 5 days of onset of symptomatic COVID-19 (confirmed by PCR or lateral flow test), and either (1) aged 50 years and over, or (2) aged 18-49 years with qualifying comorbidities. Registration occurs via the trial website and by telephone. Recruitment occurs remotely through the central trial team, or in person through clinical sites. Participants are randomised to receive either usual care or a trial drug plus usual care. Outcomes are collected via a participant-completed daily electronic symptom diary for 28 days post randomisation. Participants and/or their Trial Partner are contacted by the research team after days 7, 14 and 28 if the diary is not completed, or if the participant is unable to access the diary. The primary efficacy endpoint is all-cause, non-elective hospitalisation and/or death within 28 days of randomisation. Multiple prespecified interim analyses allow interventions to be stopped for futility or superiority based on prespecified decision criteria. A prospective economic evaluation is embedded within the trial.

ETHICS AND DISSEMINATION: Ethical approval granted by South Central-Berkshire REC number: 21/SC/0393; IRAS project ID: 1004274. Results will be presented to policymakers and at conferences, and published in peer-reviewed journals.

TRIAL REGISTRATION NUMBER: ISRCTN30448031; EudraCT number: 2021-005748-31.

PMID:37550022 | DOI:10.1136/bmjopen-2022-069176

Ann Rheum Dis. 2023 Aug 7:ard-2023-224543. doi: 10.1136/ard-2023-224543. Online ahead of print.

ABSTRACT

OBJECTIVES: To update the EULAR recommendations for the use of imaging modalities in primary large vessel vasculitis (LVV).

METHODS: A systematic literature review update was performed to retrieve new evidence on ultrasound, MRI, CT and [¹⁸F]-fluorodeoxyglucose positron emission tomography (FDG-PET) for diagnosis, monitoring and outcome prediction in LVV. The task force consisted of 24 physicians, health professionals and patients from 14 countries. The recommendations were updated based on evidence and expert opinion, iterating until voting indicated consensus. The level of agreement was determined by anonymous votes.

RESULTS: Three overarching principles and eight recommendations were agreed. Compared to the 2018 version, ultrasound is now recommended as first-line imaging test in all patients with suspected giant cell arteritis, and axillary arteries should be included in the standard examination. As an alternative to ultrasound, cranial and extracranial arteries can be examined by FDG-PET or MRI. For Takayasu arteritis, MRI is the preferred imaging modality; FDG-PET, CT or ultrasound are alternatives. Although imaging is not routinely recommended for follow-up, ultrasound, FDG-PET or MRI may be used for assessing vessel abnormalities in LVV patients with suspected relapse, particularly when laboratory markers of inflammation are unreliable. MR-angiography, CT-angiography or ultrasound may be used for long-term monitoring of structural damage, particularly at sites of preceding vascular inflammation.

CONCLUSIONS: The 2023 EULAR recommendations provide up-to-date guidance for the role of imaging in the diagnosis and assessment of patients with LVV.

PMID:37550004 | DOI:10.1136/ard-2023-224543