Pre-existing invasive fungal infection is not a contraindication for allogeneic HSCT for patients with hematologic malignancies: a CIBMTR study.

Patients with prior invasive fungal infection (IFI) increasingly proceed to allogeneic hematopoietic cell transplantation (HSCT). However, little is known about the impact of prior IFI on survival. Patients with pre-transplant IFI (cases; n=825) were compared with controls (n=10247). A subset analysis assessed outcomes in leukemia patients pre- and post 2001. Cases were older with lower performance status (KPS), more advanced disease, higher likelihood of AML and having received cord blood, reduced intensity conditioning, mold-active fungal prophylaxis and more recently transplanted. Aspergillus spp. and Candida spp. were the most commonly identified pathogens. 68% of patients had primarily pulmonary involvement. Univariate and multivariable analysis demonstrated inferior PFS and overall survival (OS) for cases. At 2 years, cases had higher mortality and shorter PFS with significant increases in non-relapse mortality (NRM) but no difference in relapse. One year probability of post-HSCT IFI was 24% (cases) and 17% (control, P<0.001). The predominant cause of death was underlying malignancy; infectious death was higher in cases (13% vs 9%). In the subset analysis, patients transplanted before 2001 had increased NRM with inferior OS and PFS compared with later cases. Pre-transplant IFI is associated with lower PFS and OS after allogeneic HSCT but significant survivorship was observed. Consequently, pre-transplant IFI should not be a contraindication to allogeneic HSCT in otherwise suitable candidates. Documented pre-transplant IFI is associated with lower PFS and OS after allogeneic HSCT. However, mortality post transplant is more influenced by advanced disease status than previous IFI. Pre-transplant IFI does not appear to be a contraindication to allogeneic HSCT

Compliance with pathology testing guidelines in Australian general practice: Protocol for a secondary analysis of electronic health record data

© 2018 Author(s). Introduction In Australia, general practitioners usually are the first point of contact for patients with non-urgent medical conditions. Appropriate and efficient utilisation of pathology tests by general practitioners forms a key part of diagnosis and monitoring. However overutilisationand underutilisation of pathology tests have been reported across several tests and conditions, despite evidence-based guidelines outlining best practice in pathology testing. There are a limited number of studies evaluating the impact of these guidelines on pathology testing in general practice. The aim of our quantitative observational study is to define how pathology tests are used in general practice and investigate how test ordering practices align with evidence-based pathology guidelines. Methods and analysis Access to non-identifiable patient data will be obtained through electronic health records from general practices across three primary health networks in Victoria, Australia. Numbers and characteristics of patients, general practices, encounters, pathology tests and problems managed over time will be described. Overall rates of encounters and tests, alongside more detailed investigation between subcategories (encounter year, patient's age, gender, and location and general practice size), will also be undertaken. To evaluate how general practitioner test ordering coincides with evidence-based guidelines, five key candidate indicators will be investigated: Full blood counts for patients on clozapine medication; international normalised ratio measurements for patients on warfarin medication; glycated haemoglobin testing for monitoring patients with diabetes; vitamin D testing; and thyroid function testing. Ethics and dissemination Ethics clearance to collect data from general practice facilities has been obtained by the data provider from the RACGP National Research and Evaluation Ethics Committee (NREEC 17-008). Approval for the research group to use these data has been obtained from Macquarie University (5201700872). This study is funded by the Australian Government Department of Health Quality Use of Pathology Program (Agreement ID: 4-2QFVW4M). Findings will be reported to the Department of Health and disseminated in peer-reviewed academic journals and presentations (national and international conferences, industry forums)

Cognitive behaviour therapy versus counselling intervention for anxiety in young people with high-functioning autism spectrum disorders: a pilot randomised controlled trial

The use of cognitive-behavioural therapy (CBT) as a treatment for children and adolescents with autism spectrum disorder (ASD) has been explored in a number of trials. Whilst CBT appears superior to no treatment or treatment as usual, few studies have assessed CBT against a control group receiving an alternative therapy. Our randomised controlled trial compared use of CBT against person-centred counselling for anxiety in 36 young people with ASD, ages 12–18. Outcome measures included parent- teacher- and self-reports of anxiety and social disability. Whilst each therapy produced improvements inparticipants, neither therapy was superior to the other to a significant degree on any measure. This is consistent with findings for adults

COVID-19: protocol for observational studies utilizing near real-time electronic Australian general practice data to promote effective care and best-practice policy—a design thinking approach

Background: Health systems around the world have been forced to make choices about how to prioritize care, manage infection control and maintain reserve capacity for future disease outbreaks. Primary healthcare has moved into the front line as COVID-19 testing transitions from hospitals to multiple providers, where tracking testing behaviours can be fragmented and delayed. Pooled general practice data are a valuable resource which can be used to inform population and individual care decision-making. This project aims to examine the feasibility of using near real-time electronic general practice data to promote effective care and best-practice policy. Methods: The project will utilize a design thinking approach involving all collaborators (primary health networks [PHNs], general practices, consumer groups, researchers, and digital health developers, pathology professionals) to enhance the development of meaningful and translational project outcomes. The project will be based on a series of observational studies utilizing near real-time electronic general practice data from a secure and comprehensive digital health platform [POpulation Level Analysis and Reporting (POLAR) general practice data warehouse]. The study will be carried out over 1.5 years (July 2020–December 2021) using data from over 450 general practices within three Victorian PHNs and Gippsland PHN, Eastern Melbourne PHN and South Eastern Melbourne PHN, supplemented by data from consenting general practices from two PHNs in New South Wales, Central and Eastern Sydney PHN and South Western Sydney PHN. Discussion: The project will be developed using a design thinking approach, leading to the building of a meaningful near real-time COVID-19 geospatial reporting framework and dashboard for decision-makers at community, state and nationwide levels, to identify and monitor emerging trends and the impact of interventions/policy decisions. This will integrate timely evidence about the impact of the COVID-19 pandemic related to its diagnosis and treatment, and its impact across clinical, population and general practice levels

Guillain-Barré syndrome: a century of progress

In 1916, Guillain, Barré and Strohl reported on two cases of acute flaccid paralysis with high cerebrospinal fluid protein levels and normal cell counts — novel findings that identified the disease we now know as Guillain–Barré syndrome (GBS). 100 years on, we have made great progress with the clinical and pathological characterization of GBS. Early clinicopathological and animal studies indicated that GBS was an immune-mediated demyelinating disorder, and that severe GBS could result in secondary axonal injury; the current treatments of plasma exchange and intravenous immunoglobulin, which were developed in the 1980s, are based on this premise. Subsequent work has, however, shown that primary axonal injury can be the underlying disease. The association of Campylobacter jejuni strains has led to confirmation that anti-ganglioside antibodies are pathogenic and that axonal GBS involves an antibody and complement-mediated disruption of nodes of Ranvier, neuromuscular junctions and other neuronal and glial membranes. Now, ongoing clinical trials of the complement inhibitor eculizumab are the first targeted immunotherapy in GBS

Effect of human leukocyte antigen heterozygosity on infectious disease outcome: The need for allele-specific measures

BACKGROUND: Doherty and Zinkernagel, who discovered that antigen presentation is restricted by the major histocompatibility complex (MHC, called HLA in humans), hypothesized that individuals heterozygous at particular MHC loci might be more resistant to particular infectious diseases than the corresponding homozygotes because heterozygotes could present a wider repertoire of antigens. The superiority of heterozygotes over either corresponding homozygote, which we term allele-specific overdominance, is of direct biological interest for understanding the mechanisms of immune response; it is also a leading explanation for the observation that MHC loci are extremely polymorphic and that these polymorphisms have been maintained through extremely long evolutionary periods. Recent studies have shown that in particular viral infections, heterozygosity at HLA loci was associated with a favorable disease outcome, and such findings have been interpreted as supporting the allele-specific overdominance hypothesis in humans. METHODS: An algebraic model is used to define the expected population-wide findings of an epidemiologic study of HLA heterozygosity and disease outcome as a function of allele-specific effects and population genetic parameters of the study population. RESULTS: We show that overrepresentation of HLA heterozygotes among individuals with favorable disease outcomes (which we term population heterozygote advantage) need not indicate allele-specific overdominance. On the contrary, partly due to a form of confounding by allele frequencies, population heterozygote advantage can occur under a very wide range of assumptions about the relationship between homozygote risk and heterozygote risk. In certain extreme cases, population heterozygote advantage can occur even when every heterozygote is at greater risk of being a case than either corresponding homozygote. CONCLUSION: To demonstrate allele-specific overdominance for specific infections in human populations, improved analytic tools and/or larger studies (or studies in populations with limited HLA diversity) are necessary

Lambda and Antilambda polarization from deep inelastic muon scattering

We report results of the first measurements of Lambda and Antilambda polarization produced in deep inelastic polarized muon scattering on the nucleon. The results are consistent with an expected trend towards positive polarization with increasing x_F. The polarizations of Lambda and Antilambda appear to have opposite signs. A large negative polarization for Lambda at low positive x_F is observed and is not explained by existing models.A possible interpretation is presented.Comment: 9 pages, 2 figure

Case report 476

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46788/1/256_2004_Article_BF00351012.pd

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition