Serum Immunoglobulin in Scabies **From the Rupert Hallam Department of Dermatology. Hallamshire Hospital, and † the Department of Immunology, hallamshire Hospital Medical School. Sheffield, England. (Reprint requests to: Dr. Ward, Deapartment of Immunology, Hallamshire Hospital Medical School. Sheffield, S10 2RX, England.

Serum immunoglobulin levels were measured in 100 patients with scabies. White cell counts and erythrocyte sedimentation rates were measured in 62 of these patients and were normal in 59. The patients were divided into two groups according to whether their symptoms had been present for more or less than 3 weeks. The values for IgA were significantly lower in both early and late groups than in the normal. IgE levels were normal in both groups. The relationship between raised IgG and IgM and systemic infection and scabies sensitization is discussed. It is postulated that the low serum IgA may correlate with low secretory IgA in skin secretions, and may predispose to scabies infestation

Computed tomography chest imaging offers no advantage over chest X-ray in the initial assessment of gestational trophoblastic neoplasia

Background The International Federation of Gynaecology and Obstetrics (FIGO) score identifies gestational trophoblastic neoplasia (GTN) patients as low- or high-risk of single-agent chemotherapy resistance (SACR). Computed tomography (CT) has greater sensitivity than chest X-ray (CXR) in detecting pulmonary metastases, but effects upon outcomes remain unclear. Methods Five hundred and eighty-nine patients underwent both CXR and CT during GTN assessment. Treatment decisions were CXR based. The number of metastases, risk scores, and risk category using CXR versus CT were compared. CT-derived chest assessment was evaluated as impact upon treatment decision compared to patient outcome, incidence of SACR, time-to-normal human chorionic gonadotrophin hormone (TNhCG), and primary chemotherapy resistance (PCR). Results Metastasis detection (p < 0.0001) and FIGO score (p = 0.001) were higher using CT versus CXR. CT would have increased FIGO score in 188 (31.9%), with 43 re-classified from low- to high-risk, of whom 23 (53.5%) received curative single-agent chemotherapy. SACR was higher when score (p = 0.044) or risk group (p < 0.0001) changed. Metastases on CXR (p = 0.019) but not CT (p = 0.088) lengthened TNhCG. Logistic regression analysis found no difference between CXR (area under the curve (AUC) = 0.63) versus CT (AUC = 0.64) in predicting PCR. Conclusions CT chest would improve the prediction of SACR, but does not influence overall treatment outcome, TNhCG, or prediction of PCR. Lower radiation doses and cost mean ongoing CXR-based assessment is recommended

Red flags to screen for malignancy and fracture in patients with low back pain: Systematic review

Abstract Objective To review the evidence on diagnostic accuracy of red flag signs and symptoms to screen for fracture or malignancy in patients presenting with low back pain to primary, secondary, or tertiary care. Design Systematic review. Data sources Medline, OldMedline, Embase, and CINAHL from earliest available up to 1 October 2013. Inclusion criteria Primary diagnostic studies comparing red flags for fracture or malignancy to an acceptable reference standard, published in any language. Review methods Assessment of study quality and extraction of data was conducted by three independent assessors. Diagnostic accuracy statistics and post-test probabilities were generated for each red flag. Results We included 14 studies (eight from primary care, two from secondary care, four from tertiary care) evaluating 53 red flags; only five studies evaluated combinations of red flags. Pooling of data was not possible because of index test heterogeneity. Many red flags in current guidelines provide virtually no change in probability of fracture or malignancy or have untested diagnostic accuracy. The red flags with the highest post-test probability f

Murchison Widefield Array rapid-response observations of the short GRB 180805A

Abstract Here we present stringent low-frequency (185 MHz) limits on coherent radio emission associated with a short-duration gamma-ray burst (SGRB). Our observations of the short gamma-ray burst (GRB) 180805A were taken with the upgraded Murchison Widefield Array (MWA) rapid-response system, which triggered within 20s of receiving the transient alert from the Swift Burst Alert Telescope, corresponding to 83.7 s post-burst. The SGRB was observed for a total of 30 min, resulting in a $3\sigma$ persistent flux density upper limit of 40.2 mJy beam–1. Transient searches were conducted at the Swift position of this GRB on 0.5 s, 5 s, 30 s and 2 min timescales, resulting in $3\sigma$ limits of 570–1 830, 270–630, 200–420, and 100–200 mJy beam–1, respectively. We also performed a dedispersion search for prompt signals at the position of the SGRB with a temporal and spectral resolution of 0.5 s and 1.28 MHz, respectively, resulting in a $6\sigma$ fluence upper-limit range from 570 Jy ms at DM $=3\,000$ pc cm–3 ( $z\sim 2.5$ ) to 1 750 Jy ms at DM $=200$ pc cm–3 ( $z\sim 0.1)$ , corresponding to the known redshift range of SGRBs. We compare the fluence prompt emission limit and the persistent upper limit to SGRB coherent emission models assuming the merger resulted in a stable magnetar remnant. Our observations were not sensitive enough to detect prompt emission associated with the alignment of magnetic fields of a binary neutron star just prior to the merger, from the interaction between the relativistic jet and the interstellar medium (ISM) or persistent pulsar-like emission from the spin-down of the magnetar. However, in the case of a more powerful SGRB (a gamma-ray fluence an order of magnitude higher than GRB 180805A and/or a brighter X-ray counterpart), our MWA observations may be sensitive enough to detect coherent radio emission from the jet-ISM interaction and/or the magnetar remnant. Finally, we demonstrate that of all current low- frequency radio telescopes, only the MWA has the sensitivity and response times capable of probing prompt emission models associated with the initial SGRB merger event.</jats:p

PRECISE - pregabalin in addition to usual care for sciatica: Study protocol for a randomised controlled trial

Background: Sciatica is a type of neuropathic pain that is characterised by pain radiating into the leg. It is often accompanied by low back pain and neurological deficits in the lower limb. While this condition may cause significant suffering for the individual, the lack of evidence supporting effective treatments for sciatica makes clinical management difficult. Our objectives are to determine the efficacy of pregabalin on reducing leg pain intensity and its cost-effectiveness in patients with sciatica.Methods/Design: PRECISE is a prospectively registered, double-blind, randomised placebo-controlled trial of pregabalin compared to placebo, in addition to usual care. Inclusion criteria include moderate to severe leg pain below the knee with evidence of nerve root/spinal nerve involvement. Participants will be randomised to receive either pregabalin with usual care (n = 102) or placebo with usual care (n = 102) for 8 weeks. The medicine dosage will be titrated up to the participant's optimal dose, to a maximum 600 mg per day. Follow up consultations will monitor individual progress, tolerability and adverse events. Usual care, if deemed appropriate by the study doctor, may include a referral for physical or manual therapy and/or prescription of analgesic medication. Participants, doctors and researchers collecting participant data will be blinded to treatment allocation. Participants will be assessed at baseline and at weeks 2, 4, 8, 12, 26 and 52. The primary outcome will determine the efficacy of pregabalin in reducing leg pain intensity. Secondary outcomes will include back pain intensity, disability and quality of life. Data analysis will be blinded and by intention-to-treat. A parallel economic evaluation will be conducted from health sector and societal perspectives.Discussion: This study will establish the efficacy of pregabalin in reducing leg pain intensity in patients with sciatica and provide important information regarding the effect of pregabalin treatment on disability and quality of life. The impact of this research may allow the future development of a cost-effective conservative treatment strategy for patients with sciatica.Trial registration: ClinicalTrial.gov, ACTRN 12613000530729

PRECISE - pregabalin in addition to usual care: Statistical analysis plan

Background: Sciatica is a severe, disabling condition that lacks high quality evidence for effective treatment strategies. This a priori statistical analysis plan describes the methodology of analysis for the PRECISE study. Methods/design: PRECISE is a prospectively registered, double blind, randomised placebo controlled trial of pregabalin compared to placebo, in addition to usual care in patients with sciatica. The aim of this study is to determine the efficacy and cost-effectiveness of pregabalin in reducing leg pain intensity (primary outcome). Secondary outcomes include disability (key secondary), back pain intensity, quality of life, participants' perceived global effect, work absenteeism and health utilisation. Information about medication usage and tolerability are also collected. Outcomes are collected over one year (weeks 2, 4, 8, 12, 26 and 52). Double data entry will be conducted for primary and key secondary outcomes. Other outcomes will be checked using a risk-based approach. Analyses will be consistent with the intention-to-treat principle. Statistical tests will be two-tailed with a p value <0.05 considered significant. Group allocation will remain masked until analyses and interpretation are finalised. Repeated-measure linear mixed models will assess the effect of treatment (pregabalin versus placebo) on primary and secondary outcomes at all time points. Fixed effects will include group allocation, visit as a categorical variable and the interaction between group and visit. Covariates will include baseline leg pain and symptom duration, with an interaction term between baseline leg pain and visit. Pairwise differences between groups will be tested at weeks 8 and 52. The number of serious adverse events and adverse events will be reported, and the proportion of patients per group who have at least one event will be compared using Fisher's exact test. An economic evaluation will be conducted if there is a treatment effect on the primary outcome at week 8. A subgroup analysis will assess whether presenting features of neuropathic pain at baseline modify the treatment effect of leg pain at week 8. Discussion: This statistical analysis plan provides detailed methodology for the analysis of the PRECISE study, which aims to deliver much needed evidence about effective and affordable management of sciatica. Trial registration: Australian and New Zealand Clinical Trials Registry ( ACTRN12613000530729. Registered 13 May 2013

PREDICT-GTN 1: Can we improve the FIGO scoring system in gestational trophoblastic neoplasia?

Gestational trophoblastic neoplasia (GTN) patients are treated according to the eight-variable International Federation of Gynaecology and Obstetrics (FIGO) scoring system, that aims to predict first-line single-agent chemotherapy resistance. FIGO is imperfect with one-third of low-risk patients developing disease resistance to first-line single-agent chemotherapy. We aimed to generate simplified models that improve upon FIGO. Logistic regression (LR) and multilayer perceptron (MLP) modelling (n = 4191) generated six models (M1-6). M1, all eight FIGO variables (scored data); M2, all eight FIGO variables (scored and raw data); M3, nonimaging variables (scored data); M4, nonimaging variables (scored and raw data); M5, imaging variables (scored data); and M6, pretreatment hCG (raw data) + imaging variables (scored data). Performance was compared to FIGO using true and false positive rates, positive and negative predictive values, diagnostic odds ratio, receiver operating characteristic (ROC) curves, Bland-Altman calibration plots, decision curve analysis and contingency tables. M1-6 were calibrated and outperformed FIGO on true positive rate and positive predictive value. Using LR and MLP, M1, M2 and M4 generated small improvements to the ROC curve and decision curve analysis. M3, M5 and M6 matched FIGO or performed less well. Compared to FIGO, most (excluding LR M4 and MLP M5) had significant discordance in patient classification (McNemar's test P < .05); 55-112 undertreated, 46-206 overtreated. Statistical modelling yielded only small gains over FIGO performance, arising through recategorisation of treatment-resistant patients, with a significant proportion of under/overtreatment as the available data have been used a priori to allocate primary chemotherapy. Streamlining FIGO should now be the focus

The MLL recombinome of acute leukemias in 2017

Chromosomal rearrangements of the human MLL/KMT2A gene are associated with infant, pediatric, adult and therapy-induced acute leukemias. Here we present the data obtained from 2345 acute leukemia patients. Genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and 11 novel TPGs were identified. Thus, a total of 135 different MLL rearrangements have been identified so far, of which 94 TPGs are now characterized at the molecular level. In all, 35 out of these 94 TPGs occur recurrently, but only 9 specific gene fusions account for more than 90% of all illegitimate recombinations of the MLL gene. We observed an age-dependent breakpoint shift with breakpoints localizing within MLL intron 11 associated with acute lymphoblastic leukemia and younger patients, while breakpoints in MLL intron 9 predominate in AML or older patients. The molecular characterization of MLL breakpoints suggests different etiologies in the different age groups and allows the correlation of functional domains of the MLL gene with clinical outcome. This study provides a comprehensive analysis of the MLL recombinome in acute leukemia and demonstrates that the establishment of patient-specific chromosomal fusion sites allows the design of specific PCR primers for minimal residual disease analyses for all patients