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Abstract Background Cronbach's alpha is widely used as the preferred index of reliability for medical postgraduate examinations. A value of 0.8-0.9 is seen by providers and regulators alike as an adequate demonstration of acceptable reliability for any assessment. Of the other statistical parameters, Standard Error of Measurement (SEM) is mainly seen as useful only in determining the accuracy of a pass mark. However the alpha coefficient depends both on SEM and on the ability range (standard deviation, SD) of candidates taking an exam. This study investigated the extent to which the necessarily narrower ability range in candidates taking the second of the three part MRCP(UK) diploma examinations, biases assessment of reliability and SEM. Methods a) The interrelationships of standard deviation (SD), SEM and reliability were investigated in a Monte Carlo simulation of 10,000 candidates taking a postgraduate examination. b) Reliability and SEM were studied in the MRCP(UK) Part 1 and Part 2 Written Examinations from 2002 to 2008. c) Reliability and SEM were studied in eight Specialty Certificate Examinations introduced in 2008-9. Results The Monte Carlo simulation showed, as expected, that restricting the range of an assessment only to those who had already passed it, dramatically reduced the reliability but did not affect the SEM of a simulated assessment. The analysis of the MRCP(UK) Part 1 and Part 2 written examinations showed that the MRCP(UK) Part 2 written examination had a lower reliability than the Part 1 examination, but, despite that lower reliability, the Part 2 examination also had a smaller SEM (indicating a more accurate assessment). The Specialty Certificate Examinations had small Ns, and as a result, wide variability in their reliabilities, but SEMs were comparable with MRCP(UK) Part 2. Conclusions An emphasis upon assessing the quality of assessments primarily in terms of reliability alone can produce a paradoxical and distorted picture, particularly in the situation where a narrower range of candidate ability is an inevitable consequence of being able to take a second part examination only after passing the first part examination. Reliability also shows problems when numbers of candidates in examinations are low and sampling error affects the range of candidate ability. SEM is not subject to such problems; it is therefore a better measure of the quality of an assessment and is recommended for routine use.

Summary: Management of chronic myeloid leukaemia (CML) has recently undergone dramatic changes, prompting the European LeukemiaNet (ELN) to issue recommendations in 2013; however, it remains unclear whether real‐world CML management is consistent with these goals. We report results of UK TARGET CML, a retrospective observational study of 257 patients with chronic‐phase CML who had been prescribed a first‐line TKI between 2013 and 2017, most of whom received first‐line imatinib (n = 203). Although 44% of patients required ≥1 change of TKI, these real‐world data revealed that molecular assessments were frequently missed, 23% of patients with ELN‐defined treatment failure did not switch TKI, and kinase domain mutation analysis was performed in only 49% of patients who switched TKI for resistance. Major molecular response (MMR; BCR‐ABL1IS ≤0·1%) and deep molecular response (DMR; BCR‐ABL1IS ≤0·01%) were observed in 50% and 29%, respectively, of patients treated with first‐line imatinib, and 63% and 54%, respectively, receiving a second‐generation TKI first line. MMR and DMR were also observed in 77% and 44% of evaluable patients with ≥13 months follow‐up, receiving a second‐generation TKI second line. We found little evidence that cardiovascular risk factors were considered during TKI management. These findings highlight key areas for improvement in providing optimal care to patients with CML. [ABSTRACT FROM AUTHOR]

Background: Cronbach's alpha is widely used as the preferred index of reliability for medical postgraduate examinations. A value of 0.8-0.9 is seen by providers and regulators alike as an adequate demonstration of acceptable reliability for any assessment. Of the other statistical parameters, Standard Error of Measurement (SEM) is mainly seen as useful only in determining the accuracy of a pass mark. However the alpha coefficient depends both on SEM and on the ability range (standard deviation, SD) of candidates taking an exam. This study investigated the extent to which the necessarily narrower ability range in candidates taking the second of the three part MRCP(UK) diploma examinations, biases assessment of reliability and SEM. Methods: a) The interrelationships of standard deviation (SD), SEM and reliability were investigated in a Monte Carlo simulation of 10,000 candidates taking a postgraduate examination. b) Reliability and SEM were studied in the MRCP(UK) Part 1 and Part 2 Written Examinations from 2002 to 2008. c) Reliability and SEM were studied in eight Specialty Certificate Examinations introduced in 2008-9. Results: The Monte Carlo simulation showed, as expected, that restricting the range of an assessment only to those who had already passed it, dramatically reduced the reliability but did not affect the SEM of a simulated assessment. The analysis of the MRCP(UK) Part 1 and Part 2 written examinations showed that the MRCP(UK) Part 2 written examination had a lower reliability than the Part 1 examination, but, despite that lower reliability, the Part 2 examination also had a smaller SEM (indicating a more accurate assessment). The Specialty Certificate Examinations had small Ns, and as a result, wide variability in their reliabilities, but SEMs were comparable with MRCP(UK) Part 2. Conclusions: An emphasis upon assessing the quality of assessments primarily in terms of reliability alone can produce a paradoxical and distorted picture, particularly in the situation where a narrower range of candidate ability is an inevitable consequence of being able to take a second part examination only after passing the first part examination. Reliability also shows problems when numbers of candidates in examinations are low and sampling error affects the range of candidate ability. SEM is not subject to such problems; it is therefore a better measure of the quality of an assessment and is recommended for routine use. [ABSTRACT FROM AUTHOR]

A human complementary DNA clone, designated AML1 because it marks a subtype of acute myeloid leukemia, is the homologue of runt, one of a group of pair-rule genes that determines morphogenesis in the fly Drosophila melanogaster. The area of homology linking the Drosophila and human polypeptide sequences extends to the conserved exon/intron boundary. Further research is needed to establish AML1's effect on human development.

In 2001, reference to the use of imaging in the British Committee for Standards in Haematology guidelines for the diagnosis and management of myeloma was confined to the standard use of plain X-rays in the diagnostic skeletal survey and emergency use of computed tomography (CT) and magnetic resonance (MR) imaging in the setting of cord compression. Since then, there has been a steady rise in interest in the use of various imaging techniques in the management of myeloma. The purpose of imaging in the management of myeloma includes the assessment of the extent and severity of the disease at presentation, the identification and characterisation of complications, and the assessment of response to therapy. Plain radiography, CT, and MR imaging are generally established examination techniques in myeloma whilst positron emission tomography (PET) and 99Technetium sestamibi (MIBI) imaging are promising newer scanning techniques under current evaluation. These stand-alone imaging guidelines discuss recommendations for the use of each modality of imaging at diagnosis and in the follow up of patients with myeloma. [ABSTRACT FROM AUTHOR]

Bilateral internal auditory canal (IAC) tumours are almost exclusively associated with bilateral vestibular schwannomas, and there is very little, if anything, that can mimic this appearance. We present a very rare case of a 75-year-old gentleman who initially presented with bilateral IAC tumours and later diagnosed as an isolated primary CNS myeloma without systemic involvement. This is a very rare presentation and has important diagnostic and therapeutic implications. He was treated with a combination of lenalidomide and dexamethasone. The treatment was well tolerated but with limited response. Although rare, metastasis should be considered as a differential diagnosis of IAC lesions. [ABSTRACT FROM AUTHOR]

A 68-year-old man presented with a 4-day history of worsening knee and arm pain. On examination, there was erythema and swelling of the left knee and both wrists. Joint aspiration grew Neisseria meningitidis. Blood tests showed an unusually high total protein level (100 g/L) and an IgM kappa paraprotein band of 45 g/L on protein electrophoresis. CT showed widespread lymphadenopathy, hepatosplenomegaly and multilevel thoracic vertebral collapse. A bone marrow biopsy revealed a lymphoplasmacytic infiltrate and a lymph node biopsy showed features of nodal marginal zone lymphoma with plasmacytic differentiation. [ABSTRACT FROM AUTHOR]

Objective: Epstein-Barr virus (EBV) encoded latent membrane protein 1 (LMP1) is expressed by the malignant cells of about 30% of cases of Hodgkin''s lymphoma (HL) and is therefore a potential target for immune attack. Given the predominantly immunosuppressive nature of HL infiltrating lymphocytes (HLILs) and the ability of LMP1 to stimulate regulatory T (Treg) responses in healthy donors, we hypothesized that LMP1 was important in the generation of Treg responses in HL. Methods: We compared T helper (Th) 1, Th2, and Treg responses to LMP1 by peripheral blood mononuclear cells (PBMCs) and HLILs from EBV-positive and -negative HL patients. The number of Treg cells in patients'' PBMCs and HLILs was determined by flow cytometry ex vivo. Proliferation (3H-thymidine incorporation) and cytokine (interleukin [IL]-10, IL-4 and γ-interferon) secretion by LMP1-stimulated PBMCs and HLILs was also measured. Results: Ex vivo EBV-positive HL patients had increased numbers of IL-10-secreting/cytotoxic T-lymphocyte-associated antigen-4-expressing cells compared with EBV-negative HL patients. PBMC/HLIL responses to LMP1 from most patients were characterized by IL-10 secretion, although isolated HL patients mounted Th1-like responses. Several responses to LMP1 peptides were made by HLILs, which were otherwise unresponsive to control stimuli. Conclusions: These results suggest that LMP1 epitopes can induce HLIL Treg cells. However, there was no clear evidence of a greater bias toward regulation in EBV-positive HL cases over EBV-negative cases, and thus there are likely to be other mechanisms of Treg cell induction in EBV-negative HL patients. Manipulating the balance of T-helper response to LMP1 might be exploited in immunotherapy of these lymphomas. [Copyright &y& Elsevier]

Myeloma patients presenting with renal failure continue to have a poor prognosis despite significant advances in anti-myeloma therapy. MERIT was a randomised clinical trial (RCT), set up to evaluate if mechanical reduction of elevated free light chain levels (FLC) would result in clinical benefit. Completion of the planned seven plasma exchanges (PEs) in the first 14 days failed to show, for the exchange group, a greater reduction in FLC or any improvement in dialysis independence at 100 days or subsequently. To improve prognosis for these patients requires earlier diagnosis and prompt anti-myeloma therapy with effectiveness guided by frequent FLC monitoring., Competing Interests: Mark Drayson owns shares in Abingdon Health. All other authors report no conflict of interest., (© 2022 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

Background and Objectives: The prognosis in patients with primary refractory or relapsed high grade non-Hodgkin's lymphoma (NHL) is very poor--the 5-year survival being generally reported at 10%., Design and Methods: Multiple salvage regimens have been investigated and, while response rates of 50-80% have been noted in selected patients, the long-term prognosis remains poor. Following the encouraging results in high risk Burkitt's and Burkitt-like lymphoma using the CODOX-M and IVAC protocols, we performed a pilot study using a similar regimen in patients with primary refractory or relapsed high grade NHL., Results: The regimens were modified by a reduction in the intensity of intrathecal therapy. It was planned to mobilize peripheral blood stem cells following the IVAC cycle for use in subsequent autologous peripheral blood stem cell transplantation in chemosensitive patients. The initial plan was to recruit 50 patients, but the study was closed after 8 due to excessive toxicity., Interpretation and Conclusions: We conclude that the CODOX-M/IVAC regimen is too toxic for this group of patients and does not result in better response rates than those to currently available salvage regimens.