bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic variation in arthropod vectors of disease-causing organisms: obstacles and opportunities
Authors: Gooding R H
Published: October 2018

An overview of the genetic variation in arthropods that transmit pathogens to vertebrates is presented, emphasizing the genetics of vector-pathogen relationships and the biochemical genetics of vectors. Vector-pathogen interactions are reviewed briefly as a prelude to a discussion of the genetics of susceptibility and refractoriness in vectors. Susceptibility to pathogens is controlled by maternally inherited factors, sex-linked dominant alleles, and dominant and recessive autosomal genes. There is widespread interpopulation (including intercolony) and temporal variation in susceptibility to pathogens. The amount of biochemical genetic variation in vectors is similar to that found in other invertebrates. However, the amount varies widely among species, among populations within species, and temporally within populations. Biochemical genetic studies show that there is considerable genetic structuring of many vectors at the local, regional, and global levels. It is argued that genetic variation in vectors is critical in understanding vector-pathogen interactions and that genetic variation in vectors creates both obstacles to and opportunities for application of genetic techniques to the control of vectors.
Avian gut-associated lymphoid tissues and intestinal immune responses to Eimeria parasites
Authors: Lillehoj H S , Trout J M
Published: October 2018

Coccidiosis, an intestinal infection caused by intracellular protozoan parasites belonging to several different species of Eimeria, seriously impairs the growth and feed utilization of livestock and poultry. Host immune responses to coccidial infection are complex. Animals infected with Eimeria spp. produce parasite-specific antibodies in both the circulation and mucosal secretions. However, it appears that antibody-mediated responses play a minor role in protection against coccidiosis. Furthermore, there is increasing evidence that cell-mediated immunity plays a major role in resistance to infection. T lymphocytes appear to respond to coccidial infection through both cytokine production and a direct cytotoxic attack on infected cells. The exact mechanisms by which T cells eliminate the parasites, however, remain unclear. Although limited information is available on the intestinal immune system of chickens, gut lymphoid tissues have evolved specialized features that reflect their role as the first line of defense at mucosal surfaces, including both immunoregulatory cells and effector cells. This review summarizes our current understanding of the avian intestinal immune system and mucosal immune responses to Eimeria spp., providing an overview of the complex cellular and molecular events involved in intestinal immune responses to enteric pathogens.
Varicella-zoster virus
Authors: Arvin A M
Published: October 2018

Varicella-zoster virus (VZV) is a ubiquitous human alphaherpesvirus that causes varicella (chicken pox) and herpes zoster (shingles). Varicella is a common childhood illness, characterized by fever, viremia, and scattered vesicular lesions of the skin. As is characteristic of the alphaherpesviruses, VZV establishes latency in cells of the dorsal root ganglia. Herpes zoster, caused by VZV reactivation, is a localized, painful, vesicular rash involving one or adjacent dermatomes. The incidence of herpes zoster increases with age or immunosuppression. The VZV virion consists of a nucleocapsid surrounding a core that contains the linear, double-stranded DNA genome; a protein tegument separates the capsid from the lipid envelope, which incorporates the major viral glycoproteins. VZV is found in a worldwide geographic distribution but is more prevalent in temperate climates. Primary VZV infection elicits immunoglobulin G (IgG), IgM, and IgA antibodies, which bind to many classes of viral proteins. Virus-specific cellular immunity is critical for controlling viral replication in healthy and immunocompromised patients with primary or recurrent VZV infections. Rapid laboratory confirmation of the diagnosis of varicella or herpes zoster, which can be accomplished by detecting viral proteins or DNA, is important to determine the need for antiviral therapy. Acyclovir is licensed for treatment of varicella and herpes zoster, and acyclovir, valacyclovir, and famciclovir are approved for herpes zoster. Passive antibody prophylaxis with varicella-zoster immune globulin is indicated for susceptible high-risk patients exposed to varicella. A live attenuated varicella vaccine (Oka/Merck strain) is now recommended for routine childhood immunization.
Detection of infection or infectious agents by use of cytologic and histologic stains
Authors: Woods G L , Walker D H
Published: October 2018

A wide variety of stains are useful for detection of different organisms or, for viruses, the cytopathologic changes they induce, in smears prepared directly from clinical specimens and in tissue sections. Other types of stains, such as hematoxylin and eosin, are used routinely to stain tissue sections and are most valuable for assessing the immunologic response of the host to the invading pathogen. In many cases, the pattern of inflammation provides important clues to diagnosis and helps to guide the selection of additional "special" stains used predominantly for diagnosis of infectious diseases. A stain may be nonspecific, allowing detection of a spectrum of organisms, as do the Papanicolaou stain and silver impregnation methods, or detection of only a limited group of organisms, as do the different acid-fast techniques. Some nonspecific stains, such as the Gram stain, are differential and provide valuable preliminary information concerning identification. Immunohistochemical stains, on the other hand, are specific for a particular organism, although in some cases cross-reactions with other organisms occur. Despite the wealth of information that can be gleaned from a stained smear or section of tissue, however, the specific etiology of an infection often cannot be determined on the basis of only the morphology of the organisms seen; culture data are essential and must be considered in the final diagnosis.
Identification methods for campylobacters, helicobacters, and related organisms
Authors: On S L
Published: October 2018

The organisms which are referred to as campylobacteria are associated with a diverse range of diseases and habitats and are important from both clinical and economic perspectives. Accurate identification of these organisms is desirable for deciding upon appropriate therapeutic measures, and also for furthering our understanding of their pathology and epidemiology. However, the identification process is made difficult because of the complex and rapidly evolving taxonomy, fastidious nature, and biochemical inertness of these bacteria. These problems have resulted in a proliferation of phenotypic and genotypic methods for identifying members of this group. The purpose of this review is to summarize the problems associated with identifying campylobacteria, critically appraise the methods that have been used for this purpose, and discuss prospects for improvements in this field.
Rotavirus vaccines: an overview
Authors: Midthun K , Kapikian A Z
Published: October 2018

Rotavirus vaccine development has focused on the delivery of live attenuated rotavirus strains by the oral route. The initial "Jennerian" approach involving bovine (RIT4237, WC3) or rhesus (RRV) rotavirus vaccine candidates showed that these vaccines were safe, well tolerated, and immunogenic but induced highly variable rates of protection against rotavirus diarrhea. The goal of a rotavirus vaccine is to prevent severe illness that can lead to dehydration in infants and young children in both developed and developing countries. These studies led to the concept that a multivalent vaccine that represented each of the four epidemiologically important VP7 serotypes might be necessary to induce protection in young infants, the target population for vaccination. Human-animal rotavirus reassortants whose gene encoding VP7 was derived from their human rotavirus parent but whose remaining genes were derived from the animal rotavirus parent were developed as vaccine candidates. The greatest experience with a multivalent vaccine to date has been gained with the quadrivalent preparation containing RRV (VP7 serotype 3) and human-RRV reassortants of VP7 serotype 1, 2, and 4 specificity. Preliminary efficacy trial results in the United States have been promising, whereas a study in Peru has shown only limited protection. Human-bovine reassortant vaccines, including a candidate that contains the VP4 gene of a human rotavirus (VP4 serotype 1A), are also being studied.
Mycobacterium haemophilum: microbiology and expanding clinical and geographic spectra of disease in humans
Authors: Saubolle M A , Kiehn T E , White M H , Rudinsky M F , Armstrong D
Published: October 2018

Reports of the association of Mycobacterium haemophilum with disease in humans have greatly increased. At least 64 cases have now been reported, with symptoms ranging from focal lesions to widespread, systemic disease. The organism is now known to cause primarily cutaneous and subcutaneous infection, septic arthritis, osteomyelitis, and pneumonitis in patients who are immunologically compromised and lymphadenitis in apparently immunocompetent children. Underlying conditions in the compromised patients have included AIDS; renal, bone marrow, and cardiac transplantation; lymphoma; rheumatoid arthritis; marrow hypoplasia; and Crohn's disease. Reports have originated from diverse geographic areas worldwide. The epidemiology of M. haemophilum remains poorly defined; there appears to be a genetic diversity between strains isolated from different regions. The organism is probably present in the environment, but recovery by sampling has not been successful. M. haemophilum has several unique traits, including predilection for lower temperatures (30 to 32 degrees C) and requirement for iron supplementation (ferric ammonium citrate or hemin). These may in the past have compromised recovery in the laboratory. Therapy has not been well elucidated, and the outcome appears to be influenced by the patient's underlying immunosuppression. The organisms are most susceptible to ciprofloxacin, clarithromycin, rifabutin, and rifampin. Timely diagnosis and therapy require communication between clinician and the laboratory.
Epidemiology of nosocomial fungal infections
Authors: Fridkin S K , Jarvis W R
Published: October 2018

This paper briefly reviews the current knowledge of the epidemiology and modes of transmission of nosocomial fungal infections and some of the therapeutic options for treating these diseases. In the mid-1980s, many institutions reported that fungi were common pathogens in nosocomial infections. Most, if not all, hospitals care for patients at risk for nosocomial fungal infections. The proportion in all nosocomial infections reportedly caused by Candida spp. increased from 2% in 1980 to 5% in 1986 to 1989. Numerous studies have identified common risk factors for acquiring these infections, most of which are very common among hospitalized patients; some factors act primarily by inducing immunosuppression (e.g., corticosteroids, chemotherapy, malnutrition, malignancy, and neutropenia), while others primarily provide a route of infection (e.g., extensive burns, indwelling catheter), and some act in combination. Non-albicans Candida spp., including fluconazole-resistant C. krusei and Torulopsis (C.) glabrata, have become more common pathogens. Newer molecular typing techniques can assist in the determination of a common source of infection caused by several fungal pathogens. Continued epidemiologic and laboratory research is needed to better characterize these pathogens and allow for improved diagnostic and therapeutic strategies.
Carrier effects on biological activity of amphotericin B
Authors: Brajtburg J , Bolard J
Published: October 2018

Amphotericin B (AmB), the drug of choice for the treatment of most systemic fungal infections, is marketed under the trademark Fungizone, as an AmB-deoxycholate complex suitable for intravenous administration. The association between AmB and deoxycholate is relatively weak; therefore, dissociation occurs in the blood. The drug itself interacts with both mammalian and fungal cell membranes to damage cells, but the greater susceptibility of fungal cells to its effects forms the basis for its clinical usefulness. The ability of the drug to form stable complexes with lipids has allowed the development of new formulations of AmB based on this property. Several lipid-based formulations of the drug which are more selective in damaging fungal or parasitic cells than mammalian cells and some of which also have a better therapeutic index than Fungizone have been developed. In vitro investigations have led to the conclusion that the increase in selectivity observed is due to the selective transfer of AmB from lipid complexes to fungal cells or to the higher thermodynamic stability of lipid formulations. Association with lipids modulates AmB binding to lipoproteins in vivo, thus influencing tissue distribution and toxicity. For example, lipid complexes of AmB can be internalized by macrophages, and the macrophages then serve as a reservoir for the drug. Furthermore, stable AmB-lipid complexes are much less toxic to the host than Fungizone and can therefore be administered in higher doses. Experimentally, the efficacy of AmB-lipid formulations compared with Fungizone depends on the animal model used. Improved therapeutic indices for AmB-lipid formations have been demonstrated in clinical trials, but the definitive trials leading to the selection of an optimal formulation and therapeutic regimen have not been done.
Blastocystis hominis revisited
Authors: Stenzel D J , Boreham P F
Published: October 2018

Blastocystis hominis is a unicellular organism found commonly in the intestinal tract of humans and many other animals. Very little is known of the basic biology of the organism, and controversy surrounds its taxonomy and pathogenicity. There morphological forms (vacuolar, granular, and ameboid) have been recognized, but recent studies have revealed several additional forms (cyst, avacuolar, and multivacuolar). The biochemistry of the organism has not been studied to any extent, and organelles and structures of unknown function and composition are present in the cells. Several life cycles have been proposed but not experimentally validated. The form used for transmission has not been defined. Infections with the organism are worldwide and appear in both immunocompetent and immunodeficient individuals. Symptoms generally attributed to B. hominis infection are nonspecific, and the need for treatment is debated. If treatment appears warranted, metronidazole is suggested as the drug of choice, although failures of this drug in eradicating the organism have been reported. Infection is diagnosed by light microscopic examination of stained smears or wet mounts of fecal material. Most laboratories identify B. hominis by observing the vacuolar form, although morphological studies indicate that other forms, such as the cyst form and multivacuolar form, also should be sought for diagnosis.
Biology of Oral Streptococci
Authors: Abranches J. , Zeng L. , Kajfasz J. K. , Palmer S. R. , Chakraborty B. , Wen Z. T. , Richards V. P. , Brady L. J. , Lemos J. A.
Published: October 2018

Bacteria belonging to the genus
Streptococcus
are the first inhabitants of the oral cavity, which can be acquired right after birth and thus play an important role in the assembly of the oral microbiota. In this article, we discuss the different oral environments inhabited by streptococci and the species that occupy each niche. Special attention is given to the taxonomy of
Streptococcus
, because this genus is now divided into eight distinct groups, and oral species are found in six of them. Oral streptococci produce an arsenal of adhesive molecules that allow them to efficiently colonize different tissues in the mouth. Also, they have a remarkable ability to metabolize carbohydrates via fermentation, thereby generating acids as byproducts. Excessive acidification of the oral environment by aciduric species such as
Streptococcus mutans
is directly associated with the development of dental caries. However, less acid-tolerant species such as
Streptococcus salivarius
and
Streptococcus gordonii
produce large amounts of alkali, displaying an important role in the acid-base physiology of the oral cavity. Another important characteristic of certain oral streptococci is their ability to generate hydrogen peroxide that can inhibit the growth of
S. mutans
. Thus, oral streptococci can also be beneficial to the host by producing molecules that are inhibitory to pathogenic species. Lastly, commensal and pathogenic streptococci residing in the oral cavity can eventually gain access to the bloodstream and cause systemic infections such as infective endocarditis.
Retinal oxygen saturation is an independent risk factor for the severity of diabetic retinopathy
Authors: Bek Toke , Stefánsson Einar , Hardarson Sveinn Hákon
Published: October 2018

Background

The oxygen saturation in larger retinal vessels has been shown to increase with increasing diabetic retinopathy (DR) grade and to help predict the effect of antivascular endothelial growth factor treatment in patients with diabetic maculopathy. However, it is unknown to what extent the increased oxygen saturation co-varies with other risk factors and whether it is an independent risk factor for the severity of DR.

Methods

Seven hundred and twenty-two successive patients referred for specialist evaluation of diabetic retinopathy including retinal oximetry were studied. Multiple regression analysis was used to investigate whether oxygen saturation in the larger retinal arterioles and venules contributed to the severity of diabetic retinopathy, independently of gender, age, diabetes duration, diabetes type, body mass index, blood pressure, haemoglobin A1c, visual acuity and central retinal thickness.

Results

The included parameters could explain less than 15% of the variation in retinopathy grade. Approximately, one-third of the explained variation was related to the retinal oxygen saturation.

Conclusions

Prospective studies are needed to evaluate whether retinal oxygen saturation is predictive for the development of diabetic retinopathy and how it interacts with other biomarkers and risk factors over time.
Evaluation of guideline-endorsed red flags to screen for fracture in patients presenting with low back pain
Authors: Parreira Patricia C S , Maher Christopher G , Traeger Adrian C , Hancock Mark J , Downie Aron , Koes Bart W , Ferreira Manuela L
Published: October 2018

Objectives

(1) Describe the evolution of guideline-endorsed red flags for fracture in patients presenting with low back pain; (2) evaluate agreement between guidelines; and (3) evaluate the extent to which recommendations are accompanied by information on diagnostic accuracy of endorsed red flags.

Design

Systematic review.

Data sources

MEDLINE and PubMed, PEDro, CINAHL and EMBASE electronic databases. We also searched in guideline databases, including theNational Guideline ClearinghouseandCanadian Medical Association Infobase.

Eligibility criteria for selecting studies

Evidence-based clinical practice guidelines.

Data extraction

Two review authors independently extracted the following data: health professional association or society producing guideline, year of publication, the precise wording of endorsed red flag for vertebral fracture, recommendations for diagnostic workup if fracture is suspected, if the guidelines substantiate the recommendation with citation to a primary diagnostic study or diagnostic review, if the guideline provides any diagnostic accuracy data.

Results

78 guidelines from 28 countries were included. A total of 12 discrete red flags were reported. The most commonly recommended red flags were older age, use of steroids, trauma and osteoporosis. Regarding the evolution of red flags, older age, trauma and osteoporosis were the first red flags endorsed (in 1994); and previous fracture was the last red flag endorsed (in 2003). Agreement between guidelines in endorsing red flags was only fair; kappa=0.32. Only 9 of the 78 guidelines substantiated their red flag recommendations by research and only nine provided information on diagnostic accuracy.

Summary/conclusion

The number of red flags endorsed in guidelines to screen for fracture has risen over time; most guidelines do not endorse the same set of red flags and most recommendations are not supported by research or accompanied by diagnostic accuracy data.
Help-seeking behaviour outside office hours in Denmark, the Netherlands and Switzerland: a questionnaire study exploring responses to hypothetical cases
Authors: Huibers Linda , Keizer Ellen , Carlsen Anders Helles , Moth Grete , Smits Marleen , Senn Oliver , Christensen Morten Bondo
Published: October 2018

Objectives

We aim to study the preferred behaviour among individuals from different age groups in three countries when acute health problems occur outside office hours and thereby to explore variations in help-seeking behaviour.

Design

A questionnaire study exploring responses to six hypothetical cases describing situations with a potential need for seeking medical care and questions on background characteristics.

Setting

General population in Denmark, the Netherlands and Switzerland.

Population

Danish, Dutch and Swiss individuals from three age groups (0–4, 30–39, 50–59 years).

Main outcome measures

Distribution of intended help-seeking preferences per case per age group, compared between countries. Differences in percentage of help-seeking outside office hours per age group and country, crude and adjusted for background characteristics.

Results

Danish and Dutch parents of children aged 0–4 years differed in intended help-seeking behaviour for five out of six cases (abdominal pain, red eyes, rash, relapse fever, chickenpox); Danish parents significantly more often chose to contact out-of-hours (OOH) care than Dutch parents. For adults aged 30–39 years, no significant difference between the three countries was found for contacting OOH care. Swiss adults aged 50–59 years had the highest percentage of OOH contacts (38.3%), followed by the Danish (33.4%) and the Dutch (32.5%).

Conclusion

Some differences in help-seeking behaviour outside office hours exist between Danish, Dutch and Swiss individuals, particularly for parents of young children. The question remains whether these differences result from individual preferences, cultural disparities and/or health services variations. Future research should focus on identifying explanations for these differences to reduce undesirable use of OOH care.
Brief intervention on Smoking, Nutrition, Alcohol and Physical (SNAP) inactivity for smoking relapse prevention after release from smoke-free prisons: a study protocol for a multicentre, investigator-blinded, randomised controlled trial
Authors: Jin Xingzhong , Kinner Stuart A , Hopkins Robyn , Stockings Emily , Courtney Ryan J , Shakeshaft Anthony , Petrie Dennis , Dobbins Timothy , Dolan Kate
Published: October 2018

Introduction

Smoking remains the leading risk factor for disease burden and mortality worldwide. Heavy Smoking is often associated with poor Nutrition, Alcohol abuse and Physical inactivity (known as ‘SNAP’). Australia’s first prison smoking ban was introduced in the Northern Territory in July 2013. However, relapse to smoking after release from prison is normative. Holistic and cost-effective interventions are needed to maintain post-release abstinence to realise the potential public health impact of smoke-free prison policies. Rigorous, large-scale trials of innovative and scalable interventions are crucial to inform tobacco control policies in correctional settings.

Methods and analysis

This multicentre, investigator-blinded, randomised parallel superiority trial will evaluate the effectiveness of a brief intervention on SNAP versus usual care in preventing smoking relapse among people released from smoke-free prisons in the Northern Territory, Australia. A maximum of 824 participants will be enrolled and randomly assigned to either SNAP intervention or usual care at a 1:1 ratio at baseline. The primary endpoint is self-reported continuous smoking abstinence three months after release from prison, verified by breath carbon monoxide test. Secondary endpoints include seven-day point prevalence abstinence, time to first cigarette, number of cigarettes smoked post release, Health Eating Index for Australian Adults, Alcohol Use Disorder Identification Test-Consumption and International Physical Activity Questionnaire scores. The primary endpoint will be analysed on an intention-to-treat basis using a simple log binomial regression model with multiple imputation for missing outcome data. A cost-effectiveness analysis of the brief intervention will be conducted subsequently.

Ethics and dissemination

This study was approved by the University of New South Wales Human Research Ethics Committee (HREC), Menzies HREC and Central Australia HREC. Primary results of the trial and each of the secondary endpoints will be submitted for publication in a peer-review journal.

Trial registration number

ACTRN12617000217303; Pre-results.
Prevention of early ventilation-acquired pneumonia (VAP) in comatose brain-injured patients by a single dose of ceftriaxone: PROPHY-VAP study protocol, a multicentre, randomised, double-blind, placebo-controlled trial
Authors: Dahyot-Fizelier Claire , Frasca Denis , Lasocki Sigismond , Asehnoune Karim , Balayn Dorothée , Guerin Anne-Laure , Perrigault Pierre-François , Geeraerts Thomas , Seguin Philippe , Rozec Bertrand , Elaroussi Djilali , Cottenceau Vincent , Guyonnaud Clément , Mimoz Olivier
Published: October 2018

Introduction

Ventilator-associated pneumonia (VAP) is the first cause of healthcare-associated infections in intensive care units (ICUs) and brain injury is one of the main risk factors for early-onset VAP. Antibiotic prophylaxis has been reported to decrease their occurrence in brain-injured patients, but a lack of controlled randomised trials and the risk of induction of bacterial resistance explain the low level of recommendations. The goal of this study is to determine whether a single dose of ceftriaxone within the 12 hours postintubation after severe brain injury can decrease the risk of early-onset VAP.

Methods and analysis

The PROPHY-VAP is a French multicentre, randomised, double-blind, placebo-controlled, clinical trial. Adult brain-injured patients (n=320) with a Glasgow Coma Scale ≤12, requiring mechanical ventilation for more than 48 hours, are randomised to receive either a single dose of ceftriaxone 2 g or a placebo within the 12 hours after tracheal intubation. The primary endpoint is the proportion of patients developing VAP from the 2nd to the 7th day after mechanical ventilation. Secondary endpoints include the proportion of patients developing late VAP (>7 days after tracheal intubation), the number of ventilator-free days, VAP-free days and antibiotic-free days, length of stay in the ICU, proportion of patients with ventilator-associated events and mortality during their ICU stay.

Ethics and dissemination

The initial research project was approved by the Institutional Review Board of OUEST III (France) on 20 October 2014 (registration No 2014-001668-36) and carried out according to the principles of the Declaration of Helsinki and the Clinical Trials Directive 2001/20/EC of the European Parliament relating to the Good Clinical Practice guidelines. The results of this study will be presented in national and international meetings and published in an international peer-reviewed journal.

Trial registration number

NCT02265406; Pre-results.
Comparative efficacy and safety of oral or transdermal opioids in the treatment of knee or hip osteoarthritis: a systematic review and Bayesian network meta-analysis protocol
Authors: Wang Jun , Wang Yin , Zhang Hui , Lu Ming , Gao Weilu , Yin Li , Yin Zongsheng
Published: October 2018

Introduction

Osteoarthritis is a common degenerative joint disease that eventually leads to disability and poor quality of life. The main symptoms are joint pain and mobility disorders. If the patient has severe pain or other analgesics are contraindicated, opioids may be a viable treatment option. To evaluate and compare the efficacy and safety of opioids in the treatment of knee or hip osteoarthritis, we will integrate direct and indirect evidence using a Bayesian network meta-analysis to establish hierarchies of these drugs.

Methods and analysis

We will search the Medical Literature Analysis and Retrieval System Online, Excerpta Medica database, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, Web of Science and PsycINFO databases as well as published and unpublished research in international registries and regulatory agency websites for osteoarthritis reports published prior to 5 January 2018. There will be no restrictions on the language. Randomised clinical trials that compare oral or transdermal opioids with other various opioids, placebo or no treatment for patients with knee or hip osteoarthritis will be included. The primary outcomes of efficacy will be pain and function. We will use pain and function scales to evaluate the main outcomes. The secondary outcomes of safety will be defined as the proportion of patients who have stopped treatment due to side effects. Pairwise meta-analyses and Bayesian network meta-analyses will be performed for all related outcome measures. We will conduct subgroup analyses and sensitivity analyses to assess the robustness of our findings. The Grading of Recommendations, Assessment, Development and Evaluations framework will be used to assess the quality of the evidence contributing to each network assessment.

Ethics and dissemination

This study does not require formal ethical approval because individual patient data will not be included. The findings will be disseminated through peer-reviewed publications or conference presentations.

PROSPERO registration number

CRD42018085503.
Study protocol for investigating physician communication behaviours that link physician implicit racial bias and patient outcomes in Black patients with type 2 diabetes using an exploratory sequential mixed methods design
Authors: Hagiwara Nao , Mezuk Briana , Elston Lafata Jennifer , Vrana Scott R , Fetters Michael D
Published: October 2018

Introduction

Patient-physician racial discordance is associated with Black patient reports of dissatisfaction and mistrust, which in turn are associated with poor adherence to treatment recommendations and underutilisation of healthcare. Research further has shown that patient dissatisfaction and mistrust are magnified particularly when physicians hold high levels of implicit racial bias. This suggests that physician implicit racial bias manifests in their communication behaviours during medical interactions. The overall goal of this research is to identify physician communication behaviours that link physician implicit racial bias and Black patient immediate (patient-reported satisfaction and trust) and long-term outcomes (eg, medication adherence, self-management and healthcare utilisation) as well as clinical indicators of diabetes control (eg, blood pressure, HbA1c and history of diabetes complication).

Methods and analysis

Using an exploratory sequential mixed methods research design, we will collect data from approximately 30 family medicine physicians and 300 Black patients with type 2 diabetes mellitus. The data sources will include one physician survey, three patient surveys, medical interaction videos, video elicitation interviews and medical chart reviews. Physician implicit racial bias will be assessed with the physician survey, and patient outcomes will be assessed with the patient surveys and medical chart reviews. In video elicitation interviews, a subset of patients (approximately 20–40) will watch their own interactions while being monitored physiologically to identify evocative physician behaviours. Information from the interview will determine which physician communication behaviours will be coded from medical interactions videos. Coding will be done independently by two trained coders. A series of statistical analyses (zero-order correlations, partial correlations, regressions) will be conducted to identify physician behaviours that are associated significantly with both physician implicit racial bias and patient outcomes.

Ethics and dissemination

Ethics approval was obtained from the Virginia Commonwealth University IRB. Study results will be disseminated through publications in peer-reviewed journals and presentations at conferences. A novelMedical Interaction involving Black Patients Coding Systemfrom this project will be made publicly available.
Provider interruptions and patient perceptions of care: an observational study in the emergency department
Authors: Schneider Anna , Wehler Markus , Weigl Matthias
Published: October 2018

Background

Interruptions are endemic in healthcare work environments. Yet, they can have positive effects in some instances and negative in others, with their net effect on quality of care still poorly understood. We aimed to distinguish beneficial and detrimental forms of interruptions of emergency department (ED) providers using patients’ perceptions of ED care as a quality measure.

Methods

An observational design was established. The study setting was an interdisciplinary ED of an academic tertiary referral hospital. Frequencies of interruption sources and contents were identified in systematic expert observations of ED physicians and nurses. Concurrently, patients rated overall quality of care, ED organisation, patient information and waiting times using a standardised survey. Associations were assessed with hierarchical linear models controlling for daily ED workload. Regression results were adjusted for multiple testing. Additionally, analyses were computed for ED physicians and nurses, separately.

Results

On 40 days, 160 expert observation sessions were conducted. 1418 patients were surveyed. Frequent interruptions initiated by patients were associated with higher overall quality of care and ED organisation. Interruptions relating to coordination activities were associated with improved ratings of ED waiting times. However, interruptions containing information on previous cases were associated with inferior ratings of ED organisation. Specifically for nurses, overall interruptions were associated with superior patient reports of waiting time.

Conclusions

Provider interruptions were differentially associated with patient perceptions of care. Whereas coordination-related and patient-initiated interruptions were beneficial to patient-perceived efficiency of ED operations, interruptions due to case-irrelevant communication were related to inferior patient ratings of ED organisation. The design of resilient healthcare systems requires a thorough consideration of beneficial and harmful effects of interruptions on providers’ workflows and patient safety.
Altered cerebral blood flow in the anterior cingulate cortex is associated with neuropathic pain
Authors: Watanabe Keisuke , Hirano Shigeki , Kojima Kazuho , Nagashima Kengo , Mukai Hiroki , Sato Takatoshi , Takemoto Minoru , Matsumoto Koji , Iimori Takashi , Isose Sagiri , Omori Shigeki , Shibuya Kazumoto , Sekiguchi Yukari , Beppu Minako , Amino Hiroshi , Suichi Tomoki , Yokote Koutaro , Uno Takashi , Kuwabara Satoshi , Misawa Sonoko
Published: October 2018

Objective

To assess the cerebral blood flow (CBF) in patients with diabetic neuropathic pain, and its changes after duloxetine therapy.

Methods

Using iodine-123-N-isopropyl-p-iodoamphetamine single-photon emission computed tomography (IMP-SPECT), we performed a cross-sectional study of 44 patients with diabetes, and compared CBF in those with (n = 24) and without neuropathic pain (n = 20). In patients with neuropathic pain, we also longitudinally assessed changes in CBF 3 months after treatment with duloxetine.

Results

IMP-SPECT with voxel-based analyses showed a significant increase in cerebral blood flow in the right anterior cingulate cortex and a decrease in the left ventral striatum in patients with neuropathic pain, compared with those without pain. After duloxetine treatment, volume of interest analyses revealed a decrease in cerebral blood flow in the anterior cingulate cortex in patients with significant pain relief but not in non-responders. Furthermore, voxel-based whole brain correlation analyses demonstrated that greater baseline CBF in the anterior cingulate cortex was associated with better pain relief on the numerical rating scale.

Conclusions

Our results suggest that the development of neuropathic pain is associated with increased activity in the anterior cingulate cortex, and greater baseline activation of this region may predict treatment responsiveness to pharmacological intervention.

Trial registration number

UMIN000017130;Results.
THUR 199 MS DMT monitoring according to abn guidelines & product specification
Authors: Carter E , Macleod MA , Visser E
Published: October 2018

Aim

Retrospective audit monitoring Multiple Sclerosis (MS) patients on Disease Modifying Therapies (DMT’s) according to Association of British Neurologists (ABN) guidelines (2015) and product specifications. This requires blood tests prior and during treatment and reviews by MS professionals.

Methods

MS nurse database identified patients, records were reviewed and data extracted including bloods, JC virus (JCV) testing, imaging, specialist tests and counselling. Analysis was presented to the MS team. Protocols and referral pathways were designed, and new patients were re-audited.

Results

The first cycle comprised of 280 patients, representing 325 individual DMT regimens. Prior to commencing treatments 90.7% blood tests, 58% imaging, and 60% JCV testing was completed on average. At 12 months, this decreased to 88.7% bloods, 30% imaging, and 25% JCV testing. Electronic records revealed that counselling documentation was sometimes incomplete. The second cycle analysed 55 patients showing improvement in Progressive multifocal leukoencephalopathy counselling and annual imaging.

Conclusion

Monitoring of bloods is done at a high standard, imaging and JCV testing less frequently meet monitoring guidelines. Factors influencing this include rural locations, variation in practice, and changing guidelines. Further work will include yearly follow-up, documentation of stopping criteria and regular review of monitoring guidelines. Patient involvement should be considered.
THUR 220 To c or not to c
Authors: Pipis Menelaos , Jaunmuktane Zane , Brandner Sebastian , D’Sa Shirley , Marafioti Teresa , Shah Sachit , Fuller Geraint , Reilly Mary M
Published: October 2018

Peripheral T-cell lymphomas (PTCLs) are rare and heterogeneous haematological malignancies that can rarely develop first in the peripheral nervous system, or more commonly, invade nerves from more usual primary locations. Patients with PTCLs usually respond poorly to treatment and have a poor clinical outcome.

We report a patient with multiple skin lesions, multifocal mononeuropathies and constitutional symptoms all suggestive of a lymphoproliferative disorder, in whom repeat skin biopsies and clonality studies failed to achieve a diagnosis. Neurophysiological studies confirmed severe post-ganglionic lesions in the lower limbs including the sciatic, femoral, obturator, tibial and sural territories. Based on this neurotropic presentation we undertook a sural nerve biopsy, despite the clinical and neurophysiological presence of a nerve lesion more proximal to the biopsy site, and this allowed us to establish a final diagnosis of PTCL. The patient was treated successfully with chemotherapy and an autologous stem cell transplant.

In our case PET imaging and MR neurography provided radiological evidence of widespread lesions in the subcutaneous and nerve tissues, and there is emerging evidence for the importance of PET imaging in the diagnostic work-up of PTCLs. Furthermore, a post-treatment PET scan confirmed the complete metabolic remission, highlighting its usefulness as a surveillance tool.
WED 223 Predicting disease activity in inflammatory neuropathies
Authors: Mahima Kapoor , Aisling Carr , Michael Lunn , Mary M Reilly
Published: October 2018

Background

There is currently no accurate way to determine who will need long-term immunoglobulin (IVIg) treatment in chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN).

Aims

Retrospectively compare clinical, investigational and treatment factors in patients who have successfully ceased IVIg with patients who have active disease.

Methods

15 patients who have successfully suspended IVIg infusions were compared with 15 in whom decreasing the IVIg dose was unsuccessful.

Results

30 patients (12 with CIDP and 3 with MMN in both groups) were diagnosed 39.5 months from onset of symptoms in the successful group vs 40.7 months in the unsuccessful group (p=0.953). There was a significant difference in the summed upper limb sensory amplitudes on electrophysiology prior to starting IVIg between the patients with CIDP (17.4 mV vs 9.8 mV p=0.007). There was no difference between the average doses between the groups. A successful cessation trial was attempted at a mean of 60.5 months post starting treatment, compared with 60 months in the unsuccessful patients.

Conclusion

Other than the differences in initial upper limb amplitudes, other factors did not help predict a successful cessation trial of IVIg. This reinforces the need for an objective biomarker to measure disease activity.
WED 224 Building causality networks for inherited neuropathies
Authors: Yung Tiet May , R Barnes Michael
Published: October 2018

Background

Inherited neuropathies are genetic conditions affecting the peripheral motor and sensory nerves. The number of causative genes are continuing to expand. As more genes are being discovered, more phenotypes are attributed. Despite our rapidly growing knowledge, inherited neuropathies remain incurable diseases.

With the wealth of information now available, bioinformatic platforms are available to visualise functional enrichment of genes and gene-phenotype annotations to enhance our understanding of the mechanism of disease and support hypothesis-driven research.

Methods

The interactors of inherited neuropathy genes were explored using the Search Tool for Recurring Incidences of Neighbouring Genes (STRING) database. Drug-phenotype interactions were assessed using PhenogramViz, human phenotype ontology terms (HPO). We used the Drug Gene Interaction Database (DGIdb) to find drug-gene interactions then used DoGSiteScorer to view potential drug binding pockets.

Results

Inherited neuropathy genes were associated with gene ontology terms related to axonal transport. A total of 380 HPO terms were annotated to the genes which shared a phenotypic spectrum with neurodegenerative disorders. We identified 221 drug-gene interactions.

Conclusion

Bioinformatic platforms are available to rapidly visualise and explore large gene-sets. Platforms to annotate drug-gene interactions need to be developed to assist drug discovery and identify potential agents that can be repurposed.
THUR 229 Inertial sensors improve traditional gait monitoring in HSP patients
Authors: Mary McNamara , Ruta Segamogaite , Pamela Shaw , Christopher McDermott , Claudia Mazzá , Channa Hewamadduma
Published: October 2018

Background

HSP is characterised by spasticity and progressive gait impairment. There’s no reliable way to monitor gait deterioration during clinics. Optoelectronic systems have demonstrated differing characteristics between gait of HSP patients and controls. They’re expensive and impractical for use in clinic settings. Inertial sensors haven’t been used to characterise HSP gait

Objectives

Study use of inertial sensors to identify gait characteristics that differentiate mild HSP patients from controls. To identify a gait based biomarker which can be used to monitor disease progression in a longitudinal study.

Methods

Neurological examination, SPRS, Modified Ashworth score, brief pain inventory were undertaken. Instrumented timed up and go (iTUG) and instrumented 10 metre walk tests (i10) wearing an inertial sensor during clinic appointments at 6 month intervals.

Results

Gait variables differentiating between patients and controls, including those with mild disease, were identified. Parameters differentiating between patients with SPG4 and SPG7 mutations were found. 8 patients were re-assessed after 6 months. Analysis did not show gait deterioration.

Conclusion

Inertial sensors can detect differences between HSP patients and controls, including those mildly affected. They can also differentiate between patients with different mutations. Further follow up data is needed to assess whether inertial sensors can predict future gait deterioration.
THUR 018 Advice and guidance: not so quick and easy
Authors: Christopher Kipps , Sarah Delves , Georgina Burke , Christopher Halfpenny , Joanna Kitley , Jonathan Frankel , Sean Slaght , William Gibb
Published: October 2018

Background

Waiting times for outpatient consultations are consistently under pressure, and delivery of the mandatory 18 week target from referral to completed review remains challenging. An Advice and Guidance scheme offers an opportunity to access neurological advice while reducing face-to-face consultation needs. We designed this project to develop the requirements, methods, audit and costing of sustainable neurological advice.

Methods

A DGH Neurology service worked with a local CCG comprising 18 GP practices. All 176 referrals and advice requests received during a 6 month pilot were considered for A and G instead of a clinic appointment.

Results

Advice was offered in 37% of cases overall (48 patients), but a net increase of 12% in face-to-face consultations was observed, as 28 (16%) of advice requests required clinic review. Headache and alteration of consciousness were common, and cases with an established diagnosis the most tractable for the ‘Advice Only’ option. GP referral quality was judged good, neurology satisfaction was reasonable, and a cost of at least £68 per episode was indicated.

Discussion

This pilot showed an increase in the number of face-to-face clinic reviews required. We suggest that other reported schemes may have not included advice requests that resulted in referrals in their metrics.
WED 243 Enhancing our knowledge of leptomeningeal disease – a case of DL-GNT
Authors: Marc Edwards , Alistair Lammie , Chirag Patel , Stefan Schwarz , Mark Wardle
Published: October 2018

A 57-year-old woman presented with several weeks of headache associated with neck stiffness, drowsiness and nausea. She developed diplopia with right-sided 6th nerve palsy and subsequently developed a complex ophthalmoplegia and right-sided ptosis.

Repeated lumbar punctures showed high opening pressures of up to 60 cm H2O and high protein levels up to 2.48 g/L. She developed episodes of marked loss of responsiveness but EEGs showed only generalised slowing. Brain imaging was essentially normal. An MRI Spine showed an enhancing intramedullary hyperintensity T8-T10 with overlying meningeal enhancement. A CT-PET scan revealed uptake along the cord consistent with diffuse infiltration or a meningitis – biopsy was inconclusive but macroscopically the dura was thickened with calcification observed on the spinal cord surface. A brain biopsy did not aid diagnosis and unfortunately the patient deteriorated with increasing severity of headaches and drowsiness. She died after a number of cardiorespiratory arrests.

At post-mortem, thickened meninges showed a glioneuronal cell infiltrate and a diagnosis of diffuse leptomeningeal glioneuronal tumour (DL-GNT). WHO recently described DL-GNT in the 2016 update of CNS tumour classification. Previous case reports of this rare disease have concerned adults and children. DL-GNT should be considered in cases of radiological leptomeningeal enhancement and high CSF protein levels.