bluuebunny/crossref_metadata_2025 huggingface dataset:
Kawasaki Syndrome
Authors: Rowley Anne H. , Shulman Stanford T.
Published: October 2018

Kawasaki syndrome (KS) is an acute, sometimes fatal vasculitis of young children. KS has replaced acute rheumatic fever as the most common cause of acquired heart disease in children in the United States. The illness is manifested by prolonged fever, conjunctival injection, enanthem, exanthem, erythema and swelling of the hands and feet, and cervical adenopathy. These acute features of illness are self-limiting, but coronary artery abnormalities occur in 20% of untreated patients. The etiology of the illness is unknown, but its clinical and epidemiologic features are most consistent with an infectious cause. Common cardiovascular manifestations of the illness include myocarditis, pericardial effusion, and coronary artery aneurysm formation. Treatment with intravenous gamma globulin (IVGG) and aspirin within the first 10 days of illness reduces the prevalence of coronary artery abnormalities from 20% in those treated with aspirin alone to 4%. Patients who develop coronary artery aneurysms, particularly those who develop giant coronary artery aneurysms, may suffer myocardial infarction secondary to thrombosis or stenosis in the abnormal vessel. Additional research to determine the cause of KS is urgently needed to allow for improved diagnosis, more specific therapy, and prevention of the disorder.
Serum Therapy for Tuberculosis Revisited: Reappraisal of the Role of Antibody-Mediated Immunity againstMycobacterium tuberculosis
Authors: Glatman-Freedman Aharona , Casadevall Arturo
Published: October 2018

Fifty years after the introduction of the first effective antimicrobial agents against Mycobacterium tuberculosis, this pathogen continues to be a tremendous public health problem. The rise in the number of resistant strains and the difficulties involved in the therapy of tuberculosis in immunocompromised AIDS patients have renewed the interest in the development of effective vaccines. To evaluate whether a potential vaccine against tuberculosis could prevent infection by eliciting a protective antibody response, we reviewed the history of antibody-mediated immunity against tuberculosis. Review of the literature of the past 100 years demonstrates that there is sufficient evidence to conclude that antibody-mediated immunity can modify the course of infection in certain situations. Based on our findings and on what is known in other systems, we propose that the role of antibody-mediated immunity to M. tuberculosis be reexamined, using advanced technology.
The Evolutionary Biology and Population Genetics Underlying Fungal Strain Typing
Authors: Taylor John W. , Geiser David M. , Burt Austin , Koufopanou Vassiliki
Published: October 2018

Strain typing of medically important fungi and fungal population genetics have been stimulated by new methods of tapping DNA variation. The aim of this contribution is to show how awareness of fungal population genetics can increase the utility of strain typing to better serve the interests of medical mycology. Knowing two basic features of fungal population biology, the mode of reproduction and genetic differentiation or isolation, can give medical mycologists information about the intraspecific groups that are worth identifying and the number and type of markers that would be needed to do so. The same evolutionary information can be just as valuable for the selection of fungi for development and testing of pharmaceuticals or vaccines. The many methods of analyzing DNA variation are evaluated in light of the need for polymorphic loci that are well characterized, simple, independent, and stable. Traditional population genetic and new phylogenetic methods for analyzing mode of reproduction, genetic differentiation, and isolation are reviewed. Strain typing and population genetic reports are examined for six medically important species: Coccidioides immitis, Histoplasma capsulatum, Candida albicans, Cryptococcus neoformans, Aspergillus fumigatus, and A. flavus. Research opportunities in the areas of genomics, correlation of clinical variation with genetic variation, amount of recombination, and standardization of approach are suggested.
Intranasal Antibody Prophylaxis for Protection against Viral Disease
Authors: Weltzin Richard , Monath Thomas P.
Published: October 2018

For more than a century, antibody has been used for passive parenteral immunization against viral and bacterial pathogens. This approach has been successful for prevention of viral respiratory infection and has led to testing of intranasal or aerosol delivery of antibody to passively immunize the respiratory tract mucosal surface. Mucosal delivery may be advantageous because it allows the antibody to neutralize the virus particles before they initiate infection and because it concentrates the antibody where viral replication takes place. Animal studies have shown the feasibility of passive intranasal immunization against a number of respiratory tract viruses. Development of nasal antibody treatments for humans is under way, and early clinical studies have confirmed that this approach is safe and can be used to prevent respiratory tract disease. Polyclonal human immunoglobulin from pooled plasma preparations can be used to provide broad protection against a number of different pathogens, while monoclonal antibodies or their fragments can be used to target specific viruses.
Cellular Biology of Prion Diseases
Authors: Harris David A.
Published: October 2018

Prion diseases are fatal neurodegenerative disorders of humans and animals that are important because of their impact on public health and because they exemplify a novel mechanism of infectivity and biological information transfer. These diseases are caused by conformational conversion of a normal host glycoprotein (PrP
C
) into an infectious isoform (PrP
Sc
) that is devoid of nucleic acid. This review focuses on the current understanding of prion diseases at the cell biological level. The characteristics of the diseases are introduced, and a brief history and description of the prion hypothesis are given. Information is then presented about the structure, expression, biosynthesis, and possible function of PrP
C
, as well as its posttranslational processing, cellular localization, and trafficking. The latest findings concerning PrP
Sc
are then discussed, including cell culture systems used to generate this pathogenic isoform, the subcellular distribution of the protein, its membrane attachment, proteolytic processing, and its kinetics and sites of synthesis. Information is also provided on molecular models of the PrP
C
→PrP
Sc
conversion reaction and the possible role of cellular chaperones. The review concludes with suggestions of several important avenues for future investigation.
Developments in Fungal Taxonomy
Authors: Guarro Josep , Gené Josepa , Stchigel Alberto M.
Published: October 2018

Fungal infections, especially those caused by opportunistic species, have become substantially more common in recent decades. Numerous species cause human infections, and several new human pathogens are discovered yearly. This situation has created an increasing interest in fungal taxonomy and has led to the development of new methods and approaches to fungal biosystematics which have promoted important practical advances in identification procedures. However, the significance of some data provided by the new approaches is still unclear, and results drawn from such studies may even increase nomenclatural confusion. Analyses of rRNA and rDNA sequences constitute an important complement of the morphological criteria needed to allow clinical fungi to be more easily identified and placed on a single phylogenetic tree. Most of the pathogenic fungi so far described belong to the kingdom Fungi; two belong to the kingdom Chromista. Within the Fungi, they are distributed in three phyla and in 15 orders (Pneumocystidales, Saccharomycetales, Dothideales, Sordariales, Onygenales, Eurotiales, Hypocreales, Ophiostomatales, Microascales, Tremellales, Poriales, Stereales, Agaricales, Schizophyllales, and Ustilaginales).
Antifungal Activities of Antineoplastic Agents:Saccharomyces cerevisiaeas a Model System To Study Drug Action
Authors: Cardenas Maria E. , Cruz M. Cristina , Del Poeta Maurizio , Chung Namjin , Perfect John R. , Heitman Joseph
Published: October 2018

Recent evolutionary studies reveal that microorganisms including yeasts and fungi are more closely related to mammals than was previously appreciated. Possibly as a consequence, many natural-product toxins that have antimicrobial activity are also toxic to mammalian cells. While this makes it difficult to discover antifungal agents without toxic side effects, it also has enabled detailed studies of drug action in simple genetic model systems. We review here studies on the antifungal actions of antineoplasmic agents. Topics covered include the mechanisms of action of inhibitors of topoisomerases I and II; the immunosuppressants rapamycin, cyclosporin A, and FK506; the phosphatidylinositol 3-kinase inhibitor wortmannin; the angiogenesis inhibitors fumagillin and ovalicin; the HSP90 inhibitor geldanamycin; and agents that inhibit sphingolipid metabolism. In general, these natural products inhibit target proteins conserved from microorganisms to humans. These studies highlight the potential of microorganisms as screening tools to elucidate the mechanisms of action of novel pharmacological agents with unique effects against specific mammalian cell types, including neoplastic cells. In addition, this analysis suggests that antineoplastic agents and derivatives might find novel indications in the treatment of fungal infections, for which few agents are presently available, toxicity remains a serious concern, and drug resistance is emerging.
Methods for Subtyping and Molecular Comparison of Human Viral Genomes
Authors: Arens Max
Published: October 2018

The development over the past two decades of molecular methods for manipulation of RNA and DNA has afforded molecular virologists the ability to study viral genomes in detail that has heretofore not been possible. There are many molecular techniques now available for typing and subtyping of viruses. The available methods include restriction fragment length polymorphism analysis, Southern blot analysis, oligonucleotide fingerprint analysis, reverse hybridization, DNA enzyme immunoassay, RNase protection analysis, single-strand conformation polymorphism analysis, heteroduplex mobility assay, nucleotide sequencing, and genome segment length polymorphism analysis. The methods have certain advantages and disadvantages which should be considered in their application to specific viruses or for specific purposes. These techniques are likely to become more widely used in the future for epidemiologic studies and for investigations into the pathophysiology of virus infections.
Molecular Typing ofBorrelia burgdorferiSensu Lato: Taxonomic, Epidemiological, and Clinical Implications
Authors: Wang Guiqing , van Dam Alje P. , Schwartz Ira , Dankert Jacob
Published: October 2018

Borrelia burgdorferi sensu lato, the spirochete that causes human Lyme borreliosis (LB), is a genetically and phenotypically divergent species. In the past several years, various molecular approaches have been developed and used to determine the phenotypic and genetic heterogeneity within the LB-related spirochetes and their potential association with distinct clinical syndromes. These methods include serotyping, multilocus enzyme electrophoresis, DNA-DNA reassociation analysis, rRNA gene restriction analysis (ribotyping), pulsed-field gel electrophoresis, plasmid fingerprinting, randomly amplified polymorphic DNA fingerprinting analysis, species-specific PCR and PCR-based restriction fragment length polymorphism (RFLP) analysis, and sequence analysis of 16S rRNA and other conserved genes. On the basis of DNA-DNA reassociation analysis, 10 different Borreliaspecies have been described within the B. burgdorferi sensu lato complex: B. burgdorferi sensu stricto, Borrelia garinii, Borrelia afzelii, Borrelia japonica, Borrelia andersonii, Borrelia valaisiana, Borrelia lusitaniae, Borrelia tanukii, Borrelia turdi, and Borrelia bissettii sp. nov. To date, only B. burgdorferi sensu stricto, B. garinii, and B. afzelii are well known to be responsible for causing human disease. Different Borrelia species have been associated with distinct clinical manifestations of LB. In addition, Borrelia species are differentially distributed worldwide and may be maintained through different transmission cycles in nature. In this paper, the molecular methods used for typing of B. burgdorferi sensu lato are reviewed. The current taxonomic status of B. burgdorferi sensu lato and its epidemiological and clinical implications, especiallly correlation between the variable clinical presentations and the infecting Borrelia species, are discussed in detail.
Punctal occlusion for dry eye syndrome: summary of a Cochrane systematic review
Authors: Ervin Ann-Margret , Law Andrew , Pucker Andrew D
Published: October 2018

Dry eye disease is a disorder of the tear film associated with ocular signs and symptoms. Punctal occlusion aids the preservation of natural tears. We conducted a Cochrane systematic review to assess the effectiveness of punctal plugs for managing dry eye. Randomised and quasi-randomised trials were included. The primary outcome was symptomatic improvement (SI) at 2–12 months. Nine databases were searched with no date or language restrictions. Two authors assessed trial quality and extracted data. Summary risk ratios and mean differences were calculated. Ten trials were included. In two trials of punctal plugs versus observation, there was less dryness with punctal plugs. The mean difference (MD) in the dry eye symptom score at 2 months was −28.20 points (95% CI –33.61 to −22.79, range 0 to 105, one trial). Three trials compared punctal plugs with artificial tears. In a pooled analysis of two trials, punctal plug participants reported more SI at 3 months than artificial tear participants (MD −4.20 points, 95%  CI −5.87 to −2.53, scales varied from 0 to 6). In the remaining five trials comparing punctal plug placement, acrylic and silicone plugs, or comparing plugs with cyclosporine or pilocarpine, none of the investigators reported a clinically or statistically meaningful difference in symptomatic improvement at 2–12 months. The effectiveness of punctal plugs for treating dry eye symptoms and common signs are inconclusive. Heterogeneity in the type of punctal plug, type and severity of dry eye being treated, and trial methodology confounds the ability to make decisive statements regarding the effectiveness of punctal plugs.
Women’s psychological experiences of physiological childbirth: a meta-synthesis
Authors: Olza Ibone , Leahy-Warren Patricia , Benyamini Yael , Kazmierczak Maria , Karlsdottir Sigfridur Inga , Spyridou Andria , Crespo-Mirasol Esther , Takács Lea , Hall Priscilla J , Murphy Margaret , Jonsdottir Sigridur Sia , Downe Soo , Nieuwenhuijze Marianne J
Published: October 2018

Objective

To synthesise qualitative studies on women’s psychological experiences of physiological childbirth.

Design

Meta-synthesis.

Methods

Studies exploring women’s psychological experiences of physiological birth using qualitative methods were eligible. The research group searched the following databases: MEDLINE, CINAHL, PsycINFO, PsycARTICLES, SocINDEX and Psychology and Behavioural Sciences Collection. We contacted the key authors searched reference lists of the collected articles. Quality assessment was done independently using the Critical Appraisal Skills Programme (CASP) checklist. Studies were synthesised using techniques of meta-ethnography.

Results

Eight studies involving 94 women were included. Three third order interpretations were identified: ‘maintaining self-confidence in early labour’, ‘withdrawing within as labour intensifies’ and ‘the uniqueness of the birth experience’. Using the first, second and third order interpretations, a line of argument developed that demonstrated ‘the empowering journey of giving birth’ encompassing the various emotions, thoughts and behaviours that women experience during birth.

Conclusion

Giving birth physiologically is an intense and transformative psychological experience that generates a sense of empowerment. The benefits of this process can be maximised through physical, emotional and social support for women, enhancing their belief in their ability to birth and not disturbing physiology unless it is necessary. Healthcare professionals need to take cognisance of the empowering effects of the psychological experience of physiological childbirth. Further research to validate the results from this study is necessary.

PROSPERO registration number

CRD42016037072.
Comparative efficacy of treatment strategies for hepatocellular carcinoma: systematic review and network meta-analysis
Authors: Tian Guo , Yang Shigui , Yuan Jinqiu , Threapleton Diane , Zhao Qiyu , Chen Fen , Cao Hongcui , Jiang Tian’an , Li Lanjuan
Published: October 2018

Objective

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. We conducted network meta-regression within a Bayesian framework to compare and rank different treatment strategies for HCC through direct and indirect evidence from international studies.

Methods and analyses

We pooled the OR for 1-year, 3-year and 5-year overall survival, based on lesions of size ˂ 3 cm, 3–5 cm and ≤5 cm, using five therapeutic options including resection (RES), radiofrequency ablation (RFA), microwave ablation (MWA), transcatheter arterial chemoembolisation (TACE) plus RFA (TR) and percutaneous ethanol injection (PEI).

Results

We identified 74 studies, including 26 944 patients. After adjustment for study design, and in the full sample of studies, the treatments were ranked in order of greatest to least benefit as follows for 5 year survival: (1) RES, (2) TR, (3) RFA, (4) MWA and (5) PEI. The ranks were similar for 1- and 3-year survival, with RES and TR being the highest ranking treatments. In both smaller (<3 cm) and larger tumours (3–5 cm), RES and TR were also the two highest ranking treatments. There was little evidence of inconsistency between direct and indirect evidence.

Conclusion

The comparison of different treatment strategies for HCC indicated that RES is associated with longer survival. However, many of the between-treatment comparisons were not statistically significant and, for now, selection of strategies for treatment will depend on patient and disease characteristics. Additionally, much of the evidence was provided by non-randomised studies and knowledge gaps still exist. More head-to-head comparisons between both RES and TR, or other approaches, will be necessary to confirm these findings.
Impact of using eHealth tools to extend health services to rural areas of Nigeria: protocol for a mixed-method, non-randomised cluster trial
Authors: Ebenso Bassey , Allsop Matthew John , Okusanya Babasola , Akaba Godwin , Tukur Jamilu , Okunade Kehinde , Akeju David , Ajepe Adegbenga , Dirisu Osasuyi , Yalma Ramsey , Sadeeq Abubakar Isa , Okuzu Okey , Ors Tolga , Jagger Terence , Hicks Joseph Paul , Mirzoev Tolib , Newell James Nicholas
Published: October 2018

Introduction

eHealth solutions that use internet and related technologies to deliver and enhance health services and information are emerging as novel approaches to support healthcare delivery in sub-Saharan Africa. Using digital technology in this way can support cost-effectiveness of care delivery and extend the reach of services to remote locations. Despite the burgeoning literature on eHealth approaches, little is known about the effectiveness of eHealth tools for improving the quality and efficiency of health systems functions or client outcomes in resource-limited countries. eHealth tools including satellite communications are currently being implemented at scale, to extend health services to rural areas of Nigeria, in Ondo and Kano States and the Federal Capital Territory. This paper shares the protocol for a 2-year project (‘EXTEND’) that aims to evaluate the impact of eHealth tools on health system functions and health outcomes.

Methodology and analysis

This multisite, mixed-method evaluation includes a non-randomised, cluster trial design. The study comprises three phases—baseline, midline and endline evaluations—that involve: (1) process evaluation of video training and digitisation of health data interventions; (2) evaluation of contextual influences on the implementation of interventions; and (3) impact evaluation of results of the project. A convergent mixed-method model will be adopted to allow integration of quantitative and qualitative findings to achieve study objectives. Multiple quantitative and qualitative datasets will be repeatedly analysed and triangulated to facilitate better understanding of impact of eHealth tools on health worker knowledge, quality and efficiency of health systems and client outcomes.

Ethics and dissemination

Ethics approvals were obtained from the University of Leeds and three States’ Ministries of Health in Nigeria. All data collected for this study will be anonymised and reports will not contain information that could identify respondents. Study findings will be presented to Ministries of Health at scientific conferences and published in peer-reviewed journals.

Trial registration number

ISRCTN32105372; Pre-results.
Availability, prices and affordability of essential medicines for children: a cross-sectional survey in Jiangsu Province, China
Authors: Sun Xiaoluan , Wei Jing , Yao Yuan , Chen Qiutong , You Daiting , Xu Xinglu , Dai Jing , Yao Yanping , Sheng Jingyi , Li Xin
Published: October 2018

Objective

China has undertaken several initiatives to improve the accessibility of safe and effective medicines for children. The aim was to determine the availability, price and affordability of essential medicines for children.

Design

Cross-sectional survey.

Setting

Six cities of Jiangsu Province, China.

Participants

30 public hospitals and 30 retail pharmacies.

Primary and secondary outcome measures

The WHO/Health Action International standardised methodology was used to collect the availability and price data for 40 essential medicines for children. Availability was measured as the percentage of drug outlets per sector where the individual medicine was found on the day of data collection, and prices were measured as median price ratios (MPRs). Affordability was measured as the number of days’ wages required for the lowest paid unskilled government worker to purchase standard treatments for common conditions.

Results

The mean availabilities of originator brands (OBs) and lowest priced generics (LPGs) were 7.5% and 34.2% in the public sector and 8.9% and 29.4% in the private sector. The median MPRs of LPGs in both sectors ranged from 1.41 to 2.12 and 1.10 to 2.24, respectively. However, the patient prices of OBs far exceeded the critical level in both sectors, with median MPRs ranging from 2.47 to 8.22. More than half of these LPGs were priced at 1.5 times their international reference prices in the public sector. Most LPGs were affordable for treatment of common conditions in both public and private sectors, as they each cost less than the daily wage for the lowest paid unskilled government worker.

Conclusions

Access to essential medicines for children is hampered by low availability. Further measures to enhance access to paediatric essential medicines should be taken, such as developing a national essential medicine list for children and mobilising the enthusiasm of pharmaceutical firms to develop and manufacture paediatric medicines.
Trial protocol: a multicentre randomised trial of first-line treatment pathways for newly diagnosed immune thrombocytopenia: standard steroid treatment versus combined steroid and mycophenolate. The FLIGHT trial
Authors: Pell Julie , Greenwood Rosemary , Ingram Jenny , Wale Katherine , Thomas Ian , Kandiyali Rebecca , Mumford Andrew , Dick Andrew , Bagot Catherine , Cooper Nichola , Hill Quentin , Bradbury Charlotte Ann
Published: October 2018

Introduction

Immune thrombocytopenia (ITP) is an autoimmune condition that may cause thrombocytopenia-related bleeding. Current first-line ITP treatment is with high-dose corticosteroids but frequent side effects, heterogeneous responses and high relapse rates are significant problems with only 20% remaining in sustained remission with this approach. Mycophenolate mofetil (MMF) is often used as the next treatment with efficacy in 50%–80% of patients and good tolerability but can take up to 2 months to work.

Objective

To test the hypothesis that MMF combined with corticosteroid is a more effective first-line treatment for immune thrombocytopenia (ITP) than current standard of corticosteroid alone.

Methods and analysis

Design

Multicentre, UK-based, open-label, randomised controlled trial.

Setting

Haematology departments in secondary care.

Participants

We plan to recruit 120 patients >16 years old with a diagnosis of ITP and a platelet count <30x109/L who require first-line treatment. Patients will be followed up for a minimum of 12 months following randomisation.

Primary outcome

Time from randomisation to treatment failure defined as platelets <30x109/L and a need for second-line treatment.

Secondary outcomes

Side effects, bleeding events, remission rates, time to relapse, time to next therapy, cumulative corticosteroid dose, rescue therapy, splenectomy, socioeconomic costs, patient-reported outcomes (quality of life, fatigue, impact of bleeding, care costs).

Analysis

The sample size of 120 achieves a 91.5% power to detect a doubling of the median time to treatment failure from 5 to 10 months. This will be expressed as an HR with 95% CI, median time to event if more than 50% have had an event and illustrated with Kaplan-Meier curves. Cost-effectiveness will be based on the first 12 months from diagnosis.

Ethics and dissemination

Ethical approval from NRES Committee South West (IRAS number 225959). EudraCT Number: 2017-001171-23. Results will be submitted for publication in peer-reviewed journals.

Trial registration number

NCT03156452
A randomised controlled trial of long-chain omega-3 polyunsaturated fatty acids in the management of rotator cuff related shoulder pain
Authors: Sandford Fiona M , Sanders Thomas A , Wilson Hannah , Lewis Jeremy S
Published: October 2018

Study design

Multicentre, double-blind, placebo-controlled randomised clinical trial.

Objectives

To compare the effectiveness of long chain omega-3 polyunsaturated fatty acids (PUFAs) as part of the management for people diagnosed with rotator cuff related shoulder pain (RCRSP).

Summary of background

Although there is no robust evidence to support their use, omega-3 PUFAs have been recommended for those with tendinopathy due to their potential to moderate inflammation.

Methods

Participants with RCRSP (n=73) were randomised to take either nine MaxEPA capsules providing 1.53 g eicosapentaenoic acid, 1.04 g docosahexaenoic acid or nine matching placebo capsules containing oleic acid per day for 8 weeks. In addition, participants attended an exercise/education programme for 8 weeks. Participants were assessed at prerandomisation, 8 weeks (primary outcome point), 3 months, 6 months and 12 months (secondary outcome point). Primary outcome was the Oxford Shoulder Score (OSS). Secondary outcomes included the Shoulder Pain and Disability Index (SPADI), Patient Specific Functional Score, Euro Qol 5D-3L, Short Form 36, global rating of change and impairment measurements. Analysis was by intention to treat.

Results

Difference in the change in the OSS between the two groups at 2 months was –0.1 (95% CI −2.6 to 2.5, p=0.95). The change in SPADI scores was −8.3 (95% CI −15.6 to −0.94, p=0.03, analysed by analysis of covariance adjusted for baseline) at 3 months.

Conclusion

 Omega-3 PUFA supplementation may have a modest effect on disability and pain outcomes in RCRSP.
Depression increases the risk of inflammatory bowel disease, which may be mitigated by the use of antidepressants in the treatment of depression
Authors: Frolkis Alexandra D , Vallerand Isabelle A , Shaheen Abdel-Aziz , Lowerison Mark W , Swain Mark G , Barnabe Cheryl , Patten Scott B , Kaplan Gilaad G
Published: October 2018

Objective

Depression is associated with IBD, but the effect of antidepressants on IBD has been sparsely studied. We assessed the impact of depression and antidepressant therapies on the development of IBD.

Design

The Health Improvement Network (THIN) was used to identify a cohort of patients with new-onset depression from 1986 to 2012. THIN patients who did not meet the defining criteria for depression were part of the referent group. The outcome was incident Crohn’s disease (CD) or ulcerative colitis (UC). Cox proportional hazards modelling was performed to evaluate the rate of Crohn’s disease or UC development among patients with an exposure of depression after controlling for age, sex, socioeconomic status, comorbid conditions, smoking, anxiety and antidepressant use including atypical antidepressants, mirtazapine, monoamine oxidase inhibitors (MAOI), serotonin norepinephrine reuptake inhibitors (SNRI), selective serotonin reuptake inhibitors (SSRI), serotonin modulators; and tricyclic antidepressants (TCA).

Results

We identified 403 665 (7.05%) patients with incident depression. Individuals with depression had a significantly greater risk of developing CD (adjusted HR=2.11, 95% CI 1.65 to 2.70) and UC (adjusted HR=2.23, 95% CI 1.92 to 2.60) after controlling for demographic and clinical covariates. SSRI and TCA were protective against CD, whereas mirtazapine, SNRI, SSRI, serotonin modulators and TCA were protective for UC.

Conclusion

Patients with a history of depression were more likely to be diagnosed with IBD. In contrast, antidepressant treatments were selectively protective for Crohn’s disease and UC. These results may impact counselling and management of depression and IBD.
Cost-effectiveness of raising alcohol excise taxes to reduce the injury burden of road traffic crashes
Authors: Cobiac Linda J , Mizdrak Anja , Wilson Nick
Published: October 2018

Background

Alcohol is an important risk factor for road transport injuries. We aimed to determine if raising alcohol taxes would be a cost-effective intervention strategy for reducing this burden.

Methods

We modelled the effect of a one-off increase in alcohol excise tax (NZ$0.15 (US$0.10)/standard drink) on alcohol consumption in New Zealand, using price elasticities to determine change in on-trade and off-trade sales of beer, cider, wine, spirits and ready-to-drink products. We simulated change in alcohol-attributable motor vehicle and motorcycle injuries, by age, sex and ethnicity, over the lifetime of the current population, and from changes in injuries, we determined changes in costs of health care, productivity, crime and vehicle damage.

Results

The modelled increase in tax led to a net 4.3% reduction in pure alcohol consumption and a 27% increase in excise tax revenue. Lifetime population health improved by 640 quality-adjusted life years (95% uncertainty interval: 450 to 860) and costs of treating transport injuries reduced by NZ$3.6 million ($0.88 million to $6.8 million), although this was countered by a $3.8 million ($2.9 million to $4.8 million) increase in costs of treating other diseases. Health care costs were far outweighed by a $240 million ($130 to $370 million) reduction in lost productivity, crime and vehicle damage costs. Cost-effectiveness was not highly sensitive to price elasticity values, discount rates or time horizons for measurement of outcomes.

Conclusion

Raising alcohol excise tax in this high-income country would be highly cost-effective and could lead to substantial cost-savings for society.
Low-impact strategy for capturing better emergency department injury surveillance data
Authors: Brubacher Jeffrey R , Shih Yuda , Weng Jian Ting , Verma Rahul , Evans David , Grafstein Eric
Published: October 2018

Objectives

Injury prevention should be informed by timely surveillance data. Unfortunately, most injury surveillance only captures patients with severe injuries and is not available in real time, hampering prevention efforts. We aimed to develop and pilot a simple injury surveillance strategy that can be integrated into routine emergency department (ED) workflow to collect more robust mechanism of injury information at time of visit for all injured ED patients with minimal impact on workflow.

Methods

We reviewed ED injury surveillance systems and considered ED workflow. Forms were developed to collect injury-related information on ED patients and refined to address workload concerns raised by key stakeholders. Research assistants observed ED staff as they registered injured patients and noted the time required to collect data and any ambiguities or concerns encountered. Interobserver agreement was recorded.

Results

Injury surveillance questions were based on a modification of the International Classification of External Causes of Injury. Research assistants observed 222 injured patients being admitted by registration clerks. The mean time required to complete the surveillance form was 64.9 s (95% CI 59.9 s to 69.9 s) for paper-based forms (120 cases) and 44.5 s (95% CI 41.7s to 47.4s) with direct electronic data entry (102 cases). Interobserver agreement (26 cases) was 100% for intent (kappa=1.0) of injury and 96% for mechanism of injury (kappa=0.74).

Conclusions

We report a simple injury surveillance strategy that ED staff can use to collect meaningful injury data in real time with minimal impact on workflow. This strategy can be adapted to enhance regional injury surveillance efforts.
Molecular diagnosis of unexplained haemolytic anaemia using targeted next-generation sequencing panel revealed (p.Ala337Thr) novel mutation in GPI gene in two Indian patients
Authors: Kedar Prabhakar S , Gupta Vinod , Dongerdiye Rashmi , Chiddarwar Ashish , Warang Prashant , Madkaikar Manisha R
Published: October 2018

Glucose-6-phosphate isomerase (GPI) deficiency is an autosomal recessive genetic disorder causing congenital haemolytic anaemia (CHA). Diagnosis of GPI deficiency by the biochemical method is unpredicted. Molecular diagnosis by identifying genetic mutation is the gold standard method for confirmation of disease, but causative genes involved in CHA are numerous, and identifying a gene-by-gene approach using Sanger sequencing is also cumbersome, expensive and labour intensive. Recently, next-generation targeted sequencing is more useful in the diagnosis of unexplained haemolytic anaemia. We used targeted next-generation sequencing (NGS) clinical panel for diagnosis of unexplained haemolytic anaemia in two Indian patients which were pending for a long time. All possible causes of haemolytic anaemia were found within normal limit. NGS by clinical exome panel revealed homozygous novel missense mutation in exon 12, c.1009G>A (p.Ala337Thr) in both patients. We further confirm by measuring red blood cell GPI activity in the patients and showed deficiency whereas parents were having intermediate activity. c.1009G>A mutation was also confirmed by Sanger sequencing of exon 12 of GPI gene. The structural–functional analysis by bioinformatics software like Swiss PDB, PolyPhen-2 and PyMol suggested that this pathogenic variant has a direct impact on the structural rearrangement at the region near the active site of the enzyme. This rapid and high-performance targeted NGS assay can be configured to detect specific CHA mutations unique to an individual defect, making it a potentially valuable method for diagnosis of unexplained haemolytic anaemia.
Outcomes from stereotactic surgery for essential tremor
Authors: Dallapiazza Robert Francis , Lee Darrin J , De Vloo Philippe , Fomenko Anton , Hamani Clement , Hodaie Mojgan , Kalia Suneil K , Fasano Alfonso , Lozano Andres M
Published: October 2018

There are several different surgical procedures that are used to treat essential tremor (ET), including deep brain stimulation (DBS) and thalamotomy procedures with radiofrequency (RF), radiosurgery (RS) and most recently, focused ultrasound (FUS). Choosing a surgical treatment requires a careful presentation and discussion of the benefits and drawbacks of each. We conducted a literature review to compare the attributes and make an appraisal of these various procedures. DBS was the most commonly reported treatment for ET. One-year tremor reductions ranged from 53% to 63% with unilateral Vim DBS. Similar improvements were demonstrated with RF (range, 74%–90%), RS (range, 48%–63%) and FUS thalamotomy (range, 35%–75%). Overall, bilateral Vim DBS demonstrated more improvement in tremor reduction since both upper extremities were treated (range, 66%–78%). Several studies show continued beneficial effects from DBS up to five years. Long-term follow-up data also support RF and gamma knife radiosurgical thalamotomy treatments. Quality of life measures were similarly improved among patients who received all treatments. Paraesthesias, dysarthria and ataxia were commonly reported adverse effects in all treatment modalities and were more common with bilateral DBS surgery. Many of the neurological complications were transient and resolved after surgery. DBS surgery had the added benefit of programming adjustments to minimise stimulation-related complications. Permanent neurological complications were most commonly reported for RF thalamotomy. Thalamic DBS is an effective, safe treatment with a long history. For patients who are medically unfit or reluctant to undergo DBS, several thalamic lesioning methods have parallel benefits to unilateral DBS surgery. Each of these surgical modalities has its own nuance for treatment and patient selection. These factors should be carefully considered by both neurosurgeons and patients when selecting an appropriate treatment for ET.
WED 201 A novel KIF1A mutation causing a neurodevelopmental disorder
Authors: Jacob Day , Peter Turnpenny , Nick Gutowski
Published: October 2018

The KIF1A gene encodes a protein in the kinesin-3 family which drives movement along microtubules and is important for transport of synaptic vesicles. Biallelic mutations have been identified in autosomal recessive hereditary spastic paraplegia (HSP30) and hereditary sensory and autonomic neuropathy type 1A. More recently dominant heterozygous mutations have been found in people with a more severe phenotype that includes developmental delay, spastic paraplegia, neuropathy, optic nerve hypoplasia and progressive cerebellar hypoplasia.

We report a female, now 22 years old, who has severe developmental delay, septo-optic dysplasia (requiring growth hormone and hydrocortisone replacement), sensorimotor axonal neuropathy, optic atrophy (now registered blind), non-progressive cerebellar hypoplasia, periodic limb movements and upper limb spasticity. She is extremely sensitive to gabapentin. A de novoKIF1A variant, c.814A>G, was identified. This is a novel missense variant (p.N272D) in the kinesin-motor domain.

This case shows a phenotype consistent with previously described heterozygous KIF1A mutations and we believe represents a unifying diagnosis for her neurological disabilities. No previous cases describe non-progressive cerebellar hypoplasia nor septo-optic dysplasia requiring pituitary hormone replacement. This novel mutation therefore expands the phenotype associated with KIF1A mutations. We hypothesize that her sensitivity to gabapentin may be due to the KIF1A mutation.
WED 202 Lamb-shaffer syndrome: importance of snp array in diagnosing neurodevelopmental syndromes
Authors: Akay Ela M , Schofield Ian S , Lai Ming H , Thomas Rhys H
Published: October 2018

We describe the seizure phenotype of a 26 year old lady who presented with a probable photic-induced convulsion on a background of mild intellectual disability, facial dysmorphia, fused cervical vertebrae and ventricular septal defect. There was no prior history of seizures.

Routine EEG was polyrhythmic with a prominent photoparoxysmal response at 14 Hz and 40 Hz. CT head was normal. A SNP array demonstrated a rare 51 kb deletion at 12 p12.1 which disrupts the SOX5 gene.

SOX5 is a developmentally important gene encoding a transcription factor that plays a role in multiple developmental pathways including of the nervous system. Loss of function of this gene is associated with Lamb-Shaffer syndrome, first characterised in 2012 with global developmental delay, intellectual disability, mild dysmorphic facies, language impairment and variable skeletal abnormalities.

3 of the original cohort of 16 patients described experienced seizures and the nature of their epilepsy was not further defined. Only a further 7 cases have been reported to date, none of whom experienced seizures. Our case helps to broaden the phenotype of Lamb-Shaffer syndrome, highlights the importance of looking for copy number variation and poses questions regarding the neurobiology of photo-sensitivity.
WED 203 Vanishing white matter disease due to variant mutations in the EIF2B- 1 gene
Authors: Priya Bangalore , R Berry Ian , John Livingston , Dan Warren , J Nicholl David , Mary O’ Driscoll , Tom Hayton
Published: October 2018

This otherwise fit and well 25 year old gentleman presented with new onset intermittent stabbing headaches associated with generalised tiredness and one nocturnal seizure. His neurological examination was normal and there were no dysmorphic features. He continues to remain intact neurologically.

Initial CT Brain showed periventricular low attenuation changes bilaterally associated with bi-frontal atrophy. MRI Brain confirmed extensive periventricular White Matter T2 high signal changes in keeping with Leukomalacia and generalised cerebral atrophy.

Genetic testing revealed 2 variant mutations in the EIF2B1 gene, of which one has been previously reported pathogenic and the other is a frame shift variant – likely pathogenic consistent with a diagnosis of vanishing White Matter Leukodystrophy.

VWM leukodystrophy is an autosomal recessive disorder characterized by variable neurologic features, including progressive cerebellar ataxia, spasticity, and cognitive impairment associated with WM lesions on brain imaging. The prevalence is unknown; and age at onset can range from early infancy to adulthood. Rapid neurological deterioration can occur following minor head trauma, infections and stress. Mutations in EIF2B1, EIF2B2, EIF2B3, EIF2B4 and EIF2B5 genes cause leukoencephalopathy with Vanishing White Matter.
THUR 213 An unusual case of cluster acetylcholine receptor antibody positive myasthenia gravis
Authors: Conor Kavanagh , James Lilleker , Rajiv Mohanraj , Thomas Smith
Published: October 2018

A 73-year-old builder presented with fatigable ptosis and ophthalmoplegia. He was started on pyridostigmine for presumed ocular myasthenia gravis (MG). Despite making an initial improvement he subsequently developed dysarthia, dysphonia and a head drop within 3 weeks. At this time, he also had mild proximal weakness and marked asymmetrical distal weakness of the upper limbs and mild distal lower limb weakness.

Conventional serological screening for acetylcholine receptor (AChR) and muscle specific kinase antibodies were negative. However, extended testing using a cell-based cluster assays demonstrated AChR antibody positivity. Repetitive nerve stimulation demonstrated significant decrement more prominent in distal muscles.

Despite high dose prednisolone, azathioprine, several courses of IV Immunoglobulins and plasma exchange the patient has had frequent admissions to the high dependency and intensive care setting with respiratory failure.

Cluster AChR antibody positive MG has been described only within the last decade and is usually mild and treatment responsive. This is the first case reported to have required intubation and ventilation due to respiratory failure. This case highlights the importance of extending the routine panels for antibody testing in patients with ‘seronegative’ MG and the need to remain vigilant in patients with cluster-AChR positive disease.
THUR 216 Myasthenia gravis, thymoma and good’s syndrome
Authors: Sophie Elands , Gordon Ingle
Published: October 2018

Myasthenia gravis (MG) is in 15% of cases a paraneoplastic phenomenon secondary to a thymoma. A subset of these will have both a thymoma and associated immunodeficiency known as Good’s syndrome. Immunological features include hypogammaglobulinaemia, a reduction in peripheral B cells, CD4+ lymphopenia, and reversal of CD4/CD8 ratio.

We present two cases followed by a literature review:

52 year–old man presented with dysphagia, diagnosed as MG. He was found to have a stage 4a thymoma (histology B2), subsequently resected. He was noted to have a reduction in peripheral B cells and CD4+ lymphopenia suggestive of Good’s syndrome. He has also had chronic diarrhoea and recurrent pulmonary infections with Pseudomonas, Klebsiella and Mycobacterium abscessus. Current immunotherapy includes prednisolone.

42 year–old woman presented with a myasthenic crisis requiring ITU admission. She was found to have a thymoma (histology B3), treated with resection and adjuvant radiotherapy. Peripheral B cell reduction led to a diagnosis of Good’s syndrome. She is currently in remission on prednisolone, mycophenolate mofetil and 6–weekly immunoglobulin infusions.

These cases illustrate that Good’s syndrome is an important differential when managing patients with myasthenia gravis, especially as the immunodeficiency may precede or occur after the diagnosis of a thymoma.
THUR 217 Salmonella gives you wings
Authors: Mahima Kapoor , Mary M Reilly , Michael J Devine , Aisling Carr
Published: October 2018

A 35-year-old British man based in Pakistan presented with a febrile illness, associated with hepatosplenomegaly. Salmonella paratyphi A was isolated from blood cultures and he was treated with oral and intravenous cephalosporins. 3 weeks later, he developed polyarthralgia and right scapular winging. 5 weeks after the initial episode, fevers recurred with new right upper limb neuropathic pain. Examination showed weakness of right serratus anterior, deltoid and triceps, and reduced sensation in left lateral cutaneous nerve of forearm (LCNF) distribution. Neurophysiology showed abnormal sensory responses in the left LCNF and right superficial peroneal nerve, and abnormal EMG in right serratus anterior and right pronator teres. MRI brachial plexus showed no abnormal enhancement in the plexus. CSF was normal. Salmonella paratyphi A was again cultured from blood and he was re-treated. 10 months’ later, he has residual, mild weakness of right deltoid.

Salmonella typhi has been associated with Guillain-Barre syndrome, and can have neuropsychiatric manifestations. The association with a post-infectious polyneuropathy has not previously been reported.
WED 222 Hawkes sign: a novel test for carpal tunnel syndrome
Authors: Christopher Hawkes
Published: October 2018

Background

In carpal tunnel syndrome (CTS) patients often report symptoms when elevating the arms, as in driving or phoning.

In Hawkes test both forearms are squeezed firmly about 50 mm (2 inches) proximal to the patient’s wrist while simultaneously elevating the subject’s hands just above shoulder height. When positive there is tingling in a median nerve distribution within a few seconds.

Methods

Fifteen patients with suspected CTS were evaluated by a) Tinel’s, Phalen’s and Hawkes’ manoeuvres b) routine nerve conduction tests (NCT) then graded positive or negative and compared with NCT.

Results

Positive signs were present for Tinel in 14/15; Phalen in 8/10 and Hawkes in 15/15. NCT supported CTS in 9/15. Where NCT were abnormal Tinel and Hawkes signs were always positive but Phalen was negative in 2/7. Where NCT was normal (6/15) the negative/positive rates were: Tinel 1/5; Phalen 3/3; Hawkes 0/6.

Conclusion

All three procedures, particularly Tinel and Hawkes had a high positive rate for CTS, but confirmed by NCT in only 6/15. However, NCT may be falsely negative especially in mild cases. The proposed arm elevation/compression test permits useful initial assessment of CTS although the false positive rate is probably high.