bluuebunny/crossref_metadata_2025_split huggingface dataset:
Linkage to care among adults being investigated for tuberculosis in South Africa: pilot study of a case manager intervention
Authors: Maraba Noriah , Chihota Violet , McCarthy Kerrigan , Churchyard Gavin J , Grant Alison D 
Published: May 2018

ObjectivesWe piloted an intervention to determine if support from a case manager would assist adults being investigated for tuberculosis (TB) to link into TB and HIV care.DesignPilot interventional cohort study.Participants and settingPatients identified by primary healthcare clinic staff in South Africa as needing TB investigations were enrolled.InterventionParticipants were supported for 3 months by case managers who facilitated the care pathway by promoting HIV testing, getting laboratory results, calling patients to return for results and facilitating treatment initiation.Outcomes measuredLinkage to TB care was defined as starting TB treatment within 28 days in those with a positive test result; linkage to HIV care, for HIV-positive people, was defined as having blood taken for CD4 count and, for those eligible, starting antiretroviral therapy within 3 months. Intervention implementation was measured by number of attempts to contact participants.ResultsAmong 562 participants (307 (54.6%) female, median age: 36 years (IQR 29–44)), most 477 (84.8%) had previously tested for HIV; of these, 328/475 (69.1%) self-reported being HIV-positive. Overall, 189/562 (33.6%) participants needed linkage to care (132 HIV care linkage only; 35 TB treatment linkage only; 22 both). Of 555 attempts to contact these 189 participants, 407 were to facilitate HIV care linkage, 78 for TB treatment linkage and 70 for both. At the end of 3-month follow-up, 40 participants had not linked to care (29 of the 132 (22.0%) participants needing linkage to HIV care only, 4 of the 35 (11.4%) needing to start on TB treatment only and 7 of the 22 (31.8%) needing both).ConclusionMany people testing for TB need linkage to care. Despite case manager support, non-linkage into HIV care remained higher than desirable, suggesting a need to modify this intervention before implementation. Innovative strategies to enable linkage to care are needed.
Idylla assay and next generation sequencing: an integrated EGFR mutational testing algorithm
Authors: De Luca Caterina , Rappa Alessandra G , Gragnano Gianluca , Malapelle Umberto , Troncone Giancarlo , Barberis Massimo 
Published: May 2018

AimsAny reference laboratory testing non-small cell lung cancer samples for predictive biomarkers needs to develop and validate a wide range of different molecular techniques, each with a specific time requirement and application. Updated international guidelines suggest that next generation sequencing (NGS) to be the initial procedure. However, in a non-negligible subset of cases, library generation may fail or amplicon coverage may be insufficient. In these NGS ‘invalid’ cases, the Idylla system may represent a viable option for rapid epidermal growth factor receptor (EGFR) genotyping.MethodsThis retrospective study included 68 archival DNA samples previously processed by Ion Torrent NGS assay. Out of these, 43 cases, including 24EGFRmutant samples, had a valid NGS result, whereas 25/68 (37%) were invalid. All samples were retested by directly pipetting the DNA inside theEGFRIdylla assay cartridge.ResultsIn all 43 cases with a valid NGS result, Idylla confirmed theEGFRmutational status. In particular, 24/24 (100%) ofEGFRmutant samples as detected by NGS were confirmed by Idylla. Moreover, a large portion of cases (20/25; 80%) whose assessment by NGS was invalid were adequately processed by Idylla. Noteworthy, in 4/25 (16%) of cases, Idylla detected actionableEGFRmutations.ConclusionsIdylla assay could be very useful to quickly process cases for which NGS does not allow genotyping.
102 Alemtuzumab associated thrombocytopenia: a case series
Authors: Gaekwad Aaron , Lee Andrew 
Published: May 2018

IntroductionAlemtuzumab is a humanised anti-CD52 monoclonal antibody for the early treatment of relapsing remitting multiple sclerosis (RRMS) that works by inducing T-cell depletion.1 Alemtuzumab has shown benefit in reducing disease activity, relapse, and MRI lesion activity in clinical trials.2 There is emerging evidence of autoimmune related adverse effects that include thyroid disease, nephropathy, and thrombocytopenia.3 Thrombocytopenia secondary to alemtuzumab has been associated with mortality. The pathophysiological mechanism of alemtuzumab-associated thrombocytopenia is yet to be elucidated and treatment efficacy for patients with thrombocytopenia is unclear, ranging from watchful waiting to intravenous immunoglobulin (IVIG). We discuss a four patient case series in regards to alemtuzumab-associated thrombocytopenia.MethodsA retrospective review of a random sample of four patients at one institution with RRMS who had been treated with alemtuzumab and developed thrombocytopenia requiring intervention with either prednisolone, IVIG or romiplostim.ResultsWe describe four patients with varying degrees of alemtuzumab-associated thrombocytopenia. Patient 1 developed mild thrombocytopenia with response to prednisolone. Patient 2 developed moderate thrombocytopenia and responded to methylprednisolone and prednisolone. Patient 3 developed fluctuating thrombocytopenia that required prednisolone. This patient then developed severe thrombocytopenia with clinical evidence of purpura. A bone marrow biopsy was undertaken and romiplostim was started with platelet recovery. Patient 4 developed severe thrombocytopenia refractory to prednisolone and IVIG. Romiplostim was initiated with platelet recovery.ConclusionThe pathophysiology of alemtuzumab-associated thrombocytopenia is incompletely understood and may include both a central immune tolerance checkpoint failure of platelet self-antigens and potentially peripheral immune mechanisms.4 Treatment of alemtuzumab-associated thrombocytopenia under the assumption that the mechanism is primarily similar to immune thrombocytopenic purpura may be incorrect, and thrombopoietin receptor agonists may have a role.References. Sprenger, et al. Alemtuzumab: who and when to treat?Comment in the Lancet 2012;380:1795–1797.. Cohen, et al. Alemtuzumab versus interferon beta 1a as first line treatment for patients with relapsing-remitting multiple scleorsis: A randomised controlled phase 3 trial.The Lancet 2012;380:1819–28.. Havroda, et al. Understanding the positive benefit: risk profile of alemtuzumab in relapsing multiple sclerosis: perspectives from the Alemtuzumab Clinical development program. Therapeutics and Clinical Risk management 2017:13:1423–1437.. Fogarty, et al. ITP: Tolerance Lost. Blood 2011;118(24):6232–6233.
104 Severe unilateral optic neuritis in multiple sclerosis
Authors: Gerbis Natasha , Parratt John 
Published: May 2018

IntroductionOptic neuritis (ON) results in acute loss of vision with pain on eye movement. It may be the first manifestation of multiple sclerosis (MS) and usually follows a resolving course. Here we describe five patients with MS who developed severe unilateral ON resulting in persistent visual loss without significant resolution.MethodsA retrospective clinical review of five cases identified from a database of 550 patients with MS.ResultsAll patients were female and the mean age was 30 years at onset (range 25–40). All patients had no light perception at diagnosis, and received treatment with high dose intravenous methylprednisolone. Two patients also had plasma exchange. All of the patients were subsequently treated with immunomodulatory therapy. The patients were followed for a mean period of 13.3 years (range 2 months to 31 years). None of the patients had significant improvement in their visual acuity, with most achieving vision of 6/60. The mean retinal nerve fibre layer thickness was 66.33 microns (range 46–98 microns) in the affected eye, compared to 86.7 microns (69–105 microns) in the unaffected eye. All patients were aquaporin-4 antibody negative and oligoclonal band positive, with the MRI brain and spine being diagnostic for MS. Interestingly, none of the patients developed significant symptoms in the contralateral eye with vision of 6/5. All patients had an EDSS score of 4.0 predominantly due to visual impairment.ConclusionSevere unilateral ON is rarely seen in MS. This case series highlights a phenotypically distinct group of female MS patients with severe unilateral ON, and no improvement in visual acuity after prolonged follow-up and despite treatment with steroids and potent immune therapies. In such patients, where the diagnosis of MS is confirmed by MRI and CSF analysis, the patient might be reassured that visual loss in the fellow eye is unlikely.References. Wilhelm H, Schabet M. The diagnosis and treatment of optic neuritis. Deutsches Arzteblatt International2015;112(37):616–626.. Dachsel RM, et al. Optic neuropathy after retrobulbar neuritis in multiple sclerosis: Are optical coherence tomography and magnetic resonance imaging useful and necessary follow-up parameters?Der Nervenarzt2015;86(2):187–96.
108 Longitudinally extensive transverse myelitis as the sole manifestation of sarcoidosis
Authors: Fontes-Villalba Ariadna , Parratt John 
Published: May 2018

IntroductionNeurosarcoidosis is a rare disease with variable clinical and radiological manifestations. We report a case of longitudinally extensive transverse myelitis mimicking NMO that was pathologically confirmed to be sarcoidosis.Case a 50 year old Caucasian man presented with left arm paraesthesia, sensory and gait disturbance. Spinal MRI showed a swollen longitudinally extensive cord lesion (6 spinal segments) with peripheral enhancement. Brain MRI was normal. The CSF protein was 0.51 g/L and oligoclonal bands were restricted to the CSF. AQP-4 and MOG antibodies were negative. Serum ACE, vasculitis, and infectious screens were negative. The patient was administered a four day course of 1 g of iv methylprednisolone once daily, and improved clinically and radiologically. However, subsequent deterioration prompted treatment with plasma exchange (6 courses) and rituximab, which was ineffective. The peripheral nature of the enhancement pattern and steroid responsiveness prompted a whole body PET, showing FDG avid mediastinal lymph nodes, and a biopsy demonstrated non-necrotizing granulomas. Mycobacteria were absent. The diagnosis of sarcoidosis was made and the patient was initiated on intravenous infliximab (500 mg at 0, 2, 6 and 8 weeks). The patients gait and sensation improved.ConclusionNeurosarcoidosis should be included in the differential of longitudinally extensive transverse myelitis, particularly in AQP4-IgG seronegative patients.References1. Tavee JO, Stern BJ. Neurosarcoidosis. Continuum (Minneap Minn)2014Jun;20(3 Neurology of Systemic Disease):545–59.2. Sohn M, Culver DA, Judson MA, Scott TF, Tavee J, Nozaki K. Spinal cord neurosarcoidosis. Am J Med Sci2014Mar;347(3):195–8.3. Flanagan EP, Kaufmann TJ, Krecke KN, Aksamit AJ, Pittock SJ, Keegan BM, Giannini C, Weinshenker BG. Discriminating long myelitis of neuromyelitis optica from sarcoidosis. Ann Neurol2016Mar;79(3):437–47.
113 Rituximab and maintenance mycophenolate mofetil for treatment of refractory ANTI-N-METHYL-D-ASPARTATE-receptor (NMDAR) encephalitis
Authors: Edwards Leon S , Barnett Michael H , Kiernan Matthew C 
Published: May 2018

IntroductionNMDAR encephalitis is an autoimmune condition with antibodies to the NR1 subunit of the NMDAR. It has a variable clinical presentation with behavioural and psychiatric symptoms. There is frequently a relapsing course. A known association exists with tumours, particularly ovarian teratoma. Cases which are not associated with tumour often fail first line therapy. As such, therapy for this disease can be challenging and involves a spectrum of immunotherapy. Rituximab is widely considered to be second line treatment for this illness. We present two cases of refractory anti-NMDAR encephalitis.CasesBoth patients were confirmed antibody positive in the serum and cerebral spinal fluid. There was no tumour identified on whole body positron emission tomography and transvaginal pelvic ultrasound. Each patient was initially treated with first line therapy of intravenous immunoglobulin, plasmapheresis and methylprednisolone with limited symptomatic improvement. Second line therapy of two doses of rituximab was administered intravenously two weeks apart at a dose of 1000 mg. Mycophenolate mofetil was used at a dose of 1000 mg twice daily to minimise B-cell reconstitution. Response to treatment was monitored with measurement of CD 19+ Pan B cells in peripheral blood and clinical assessment by the consultant liaison psychiatry service. Both patients demonstrated significant response with undetectable CD 19+ Pan B cells on serial testing and sustained clinical improvement in initial behavioural symptoms.ConclusionIn patients with anti-NMDAR encephalitis, rituximab combined with maintenance mycophenolate mofetil may be an effective treatment.
013 Lipid metabolism and body composition in frontotemporal dementia-amyotrophic lateral sclerosis spectrum: effect on survival and disease progression
Authors: Ahmed Rebekah M , Highton-Williamson Elizabeth , Caga Jashelle , Thornton Nicollette , Ramsey Eleanor , Zoing Margaret , Piguet Olivier , Hodges John , Halliday Glenda , Farooqi Sadaf , Kiernan Matthew C 
Published: May 2018

IntroductionPatients with Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) exhibit changes in eating behaviour that could potentially affect lipid levels and body composition. This study aimed to document changes in lipid metabolism and body composition across the ALS-FTD spectrum to identify potential relationships to eating behaviour (including fat intake), cognitive change, body mass index (BMI) and effect on survival.MethodsOne hundred and twenty eight participants were recruited: 37 ALS patients, 15 ALS patients with cognitive and behavioural change (ALS-Plus), and 13 ALS-FTD, 31 behavioural variant FTD, and 32 healthy controls. Fasting total cholesterol, low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL) and triglyceride levels were measured and correlated to eating behaviour (caloric, fat intake), cognitive change, and BMI; effect on survival was examined using cox regression analyses. In a cohort of 60 patients, changes in body composition and fat deposition was examined using Dual energy X-ray absorptiometry scans (DEXA), a technique used in obesity research.ResultsThere was a spectrum of lipid changes from ALS to FTD with increased triglyceride (p<0.001), total cholesterol/HDL ratio (p<0.001), and lower HDL levels (p=0.001) in all patient groups compared to controls. Whilst there was no increase in total cholesterol levels, a higher cholesterol level was found to correlate with 3.25 times improved survival (p=0.031). Triglyceride and HDL cholesterol correlated to fat intake, BMI, and measures of cognition andConclusionA spectrum of changes in lipid metabolism and body composition has been identified in ALS-FTD, with total cholesterol levels found to potentially impact on survival. These changes were mediated by changes in fat intake, and BMI, and may also be mediated by the neurodegenerative process, offering the potential to modify these factors to slow disease progression and improve survival.
019 Correlation of visual field loss with mri findings in patients with pituitary tumours
Authors: Lueck Christian J , Kane Emily , Ashton David , Mews Peter , Reid Kate , Neely Andrew J 
Published: May 2018

IntroductionThe exact mechanism that gives rise to bi-temporal hemianopia in chiasmal compression by pituitary tumours is currently unknown. One theory suggests that, because crossing fibres cross each other and therefore have less contact area, they experience greater stress from compressive forces than those experienced by uncrossed fibres (which have a larger contact area). Finite element modelling has been used has been used to investigate this in silico but the hypothesis needs testing in vivo. This study aimed to determine whether extrinsic chiasmal compression was associated with patterns of visual field loss which supported the ‘crossing hypothesis’ or not.MethodsSubjects with chiasmal compression secondary to pituitary tumours who also had clear visual field abnormalities were identified from the Canberra Hospital database. Visual fields were analysed to derive ‘temporality’ and ‘bi-temporality’ indices. MRI scans were analysed to determine the relative elevations of centre and peripheral portions of the optic chiasm and, in turn, the eccentricity of compression. Temporality indices were plotted against central chiasmal elevation, and both temporal and nasal hemi-field abnormalities were plotted against eccentricity.Results122 patients were identified but only 12 were suitable for analysis. Both temporality and bi-temporality indices were significantly correlated with central chiasmal elevation (p=0.004). Hemi-field studies demonstrated patterns of visual loss with increasing eccentricity that were more consistent with the ‘crossing hypothesis’ though the correlations failed to reach significance.ConclusionThis study provides tentative support for the ‘crossing hypothesis’. The information will be used to inform further finite element models of chiasmal compression. A larger, prospective study is warranted.
002 Persistent improvement in door-to-needle times after implementation of the helsinki protocol for routine acute stroke care
Authors: Silsby Matthew , Duma Stephen R , Fois Alessandro F , Koryzna Joanna , Mahant Neil , Evans Andrew , Fung Victor SC 
Published: May 2018

IntroductionIntravenous thrombolysis for acute ischaemic stroke is a time-critical intervention. Time to treatment may be reduced by implementing measures known as the Helsinki protocol. We aimed to investigate the effectiveness of implementing the Helsinki protocol at a large tertiary teaching hospital.MethodsThe protocol for treatment of acute stroke at Westmead hospital was modified to mirror the Helsinki protocol. Focus was placed on reducing time factors after patient arrival to hospital, without changes to the existing infrastructure. This included:education of triage staff to improve stroke recognition;transferring patients directly from the ambulance to CT;intravenous contrast administration as standard CT imaging; andtissue plasminogen activator preparation in CT.The primary endpoints were ‘door-to-CT’ time (DCT) and ‘door-to-needle’ time (DNT).ResultsData from stroke calls made in-hours were compared from 2016–2017. In the 12 months prior to implementation, 156 stroke calls occurred and 26 patients received thrombolysis. In the initial ten-week study, 49 stroke calls occurred and seven patients received thrombolysis. Median DNT was significantly reduced (77.5 vs 28 min, p=0.0477). In the following six months, 93 stroke calls occurred and eight patients received thrombolysis. Median DNT remained significantly reduced (77.5 vs 39 min, p=0.012). DCT was unchanged across the eight-month period (26 vs 23 min, p=0.646). Post-implementation, fewer patients received thrombolysis (17% vs 11%), but the number of calls increased (13 vs 18 per month).ConclusionIntroduction of the Helsinki protocol for acute stroke calls resulted in a significant reduction in DNT. The changes persisted notwithstanding routine changes in junior staff. Fewer patients received thrombolysis, despite the focus on minimising delays. This might be because there were more calls, reflecting the preference for sensitivity over specificity. Reduction in DNT has significant implications for patient recovery and the effects of simple process changes persist beyond a dedicated study period.
029 Multiple-acyl-coa dehydrogenase deficiency (MADD): a rare but treatable genetic metabolic myopathy
Authors: Hooi Wai Foong , Kyndt Christopher , Faragher Mark , Day Bruce 
Published: May 2018

IntroductionMultiple-acyl-CoA dehydrogenase deficiency or MADD is a rare autosomal recessive disorder caused by deficiency of electron transfer flavoprotein. Late onset form of MADD typically present with slowly progressive proximal weakness, myalgia, lethargy, vomiting, hypoglycaemia and metabolic acidosis. This condition is highly variable in age and symptoms at onset. The mean delay between onset of symptoms and diagnosis was 3.9 years. Confirmation of the diagnosis requires relatively complicated tests including muscle biopsy, Acylcarnitine profiling, urinary organic acid analysis and molecular gene testing. MADD responds dramatically to riboflavin supplementation and dietary treatment i.e. high carbohydrate, low fat and low protein diet. We report of a case of Multiple-Acyl-CoA Dehydrogenase Deficiency (MADD) and a review of the literature.CaseA 22 year old female presented with 3 year history of slowly progressive muscle weakness, fatigue and dyspnea on minimal exertion. Clinical examination revealed profound neck extension weakness (‘dropped head syndrome’), proximal muscle weakness (winged scapula and positive Gower’s sign), mild dysphagia and dysarthria. There was no obvious facial weakness, ptosis or ophthalmoplegia. Muscle biopsy showed prominent lipid and generalised hypotrophy of type I fibres. The diagnosis of MADD was suspected on the basis of clinical presentation. The patient was commenced on riboflavin, carnitine supplementation and low protein, low fat diet. Her symptoms improved significantly over 2 months (improvement in muscle strength and respiratory function, FVC improved from 42% to 89%). Acylcarnitine and amino acid screen results came back later showing elevated levels of C6, C8, C10 and C12 in keeping with the diagnosis of MADD.ConclusionMultiple-acyl-CoA dehydrogenase deficiency is a rare genetic metabolic myopathy. It is under-recognised and diagnosis of the adult onset form is often challenging. The majority of patients respond well to riboflavin and dietary modifications with excellent clinical outcome.References. Sharp LJ, Haller RG. Metabolic and mitochondrial myopathies. Neurol Clin2014Aug;32:777–99.. Grunert SC. Clinical and genetical heterogeneity of late-onset multiple acyl-coenzyme: A dehydrogenase deficiency. Orphanet J Rare Dis2014Jul 22;9:117.. Angelini C. Spectrum of metabolic myopathies. Biochem Biophys Acta2015Apr;1852(4):615–21.. Yee WC. Two eminently treatable genetic metabolic myopathies. Neurol India2008Jul–Sep;56(3):333–8.