bluuebunny/crossref_metadata_2025_split huggingface dataset:
Psychometric properties of the St George’s Respiratory Questionnaire in patients with idiopathic pulmonary fibrosis: insights from the INPULSIS trials
Authors: Swigris Jeffrey J , Wilson Hilary , Esser Dirk , Conoscenti Craig S , Stansen Wibke , Kline Leidy Nancy , Brown Kevin K 
Published: May 2018

IntroductionWe evaluated the psychometric properties of the St George’s Respiratory Questionnaire (SGRQ) in patients with idiopathic pulmonary fibrosis (IPF) using data from the two INPULSIS trials.MethodsData from 1061 patients treated with nintedanib or placebo were pooled. Internal consistency, test–retest reliability, construct validity, known-groups validity, responsiveness and responder thresholds were examined.ResultsCronbach’s α was 0.93 for SGRQ total score and >0.75 for domain scores. In patients with stable disease based on change in forced vital capacity (FVC) ≤5% predicted or ‘no change’ on Patient’s Global Impression of Change, intraclass correlation coefficients for the SGRQ total score were 0.72 or 0.76, respectively. Moderate to strong correlations were observed between SGRQ total and domain scores and the Cough and Sputum Assessment Questionnaire cough domains (−0.34 to −0.65), University of California San Diego Shortness of Breath Questionnaire (0.56 to 0.83) and EuroQol 5-Dimensional Quality of Life Questionnaire Visual Analogue Scale (−0.41 to −0.55); correlations with FVC % predicted were weak (−0.24 to −0.30). Longitudinal correlations between changes in SGRQ total score and these patient-reported outcomes over 52 weeks were moderate. Changes in SGRQ total, impact and activity scores were sensitive to detecting improvement or deterioration in FVC >10% predicted at week 52. Collectively, distribution-based and anchor-based approaches suggested using a change of 4–5 points in SGRQ total score as a starting point for responder analyses.ConclusionsThe psychometric properties of the SGRQ support its use as a measure of health-related quality of life in patients with IPF.
Italian consensus conference on guidelines for conservative treatment on lower limb muscle injuries in athlete
Authors: Bisciotti Gian Nicola , Volpi Piero , Amato Maurizio , Alberti Giampietro , Allegra Francesco , Aprato Alessandro , Artina Matteo , Auci Alessio , Bait Corrado , Bastieri Gian Matteo , Balzarini Luca , Belli Andrea , Bellini Gianandrea , Bettinsoli Pierfrancesco , Bisciotti Alessandro , Bisciotti Andrea , Bona Stefano , Brambilla Lorenzo , Bresciani Marco , Buffoli Michele , Calanna Filippo , Canata Gian Luigi , Cardinali Davide , Carimati Giulia , Cassaghi Gabriella , Cautero Enrico , Cena Emanuele , Corradini Barbara , Corsini Alessandro , D'Agostino Cristina , De Donato Massimo , Delle Rose Giacomo , Di Marzo Francesco , Di Pietto Francesco , Enrica Drapchind , Eirale Cristiano , Febbrari Luigi , Ferrua Paolo , Foglia Andrea , Galbiati Alberto , Gheza Alberto , Giammattei Carlo , Masia Francesco , Melegati Gianluca , Moretti Biagio , Moretti Lorenzo , Niccolai Roberto , Orgiani Antonio , Orizio Claudio , Pantalone Andrea , Parra Federica , Patroni Paolo , Pereira Ruiz Maria Teresa , Perri Marzio , Petrillo Stefano , Pulici Luca , Quaglia Alessandro , Ricciotti Luca , Rosa Francesco , Sasso Nicola , Sprenger Claudio , Tarantola Chiara , Tenconi Fabio Gianpaolo , Tosi Fabio , Trainini Michele , Tucciarone Agostino , Yekdah Ali , Vuckovic Zarko , Zini Raul , Chamari Karim 
Published: May 2018

Provide the state of the art concerning (1) biology and aetiology, (2) classification, (3) clinical assessment and (4) conservative treatment of lower limb muscle injuries (MI) in athletes. Seventy international experts with different medical backgrounds participated in the consensus conference. They discussed and approved a consensus composed of four sections which are presented in these documents. This paper represents a synthesis of the consensus conference, the following four sections are discussed: (i) The biology and aetiology of MIs. A definition of MI was formulated and some key points concerning physiology and pathogenesis of MIs were discussed. (ii) The MI classification. A classification of MIs was proposed. (iii) The MI clinical assessment, in which were discussed anamnesis, inspection and clinical examination and are provided the relative guidelines. (iv) The MI conservative treatment, in which are provided the guidelines for conservative treatment based on the severity of the lesion. Furthermore, instrumental therapy and pharmacological treatment were discussed. Knowledge of the aetiology and biology of MIs is an essential prerequisite in order to plan and conduct a rehabilitation plan. Another important aspect is the use of a rational MI classification on prognostic values. We propose a classification based on radiological investigations performed by ultrasonography and MRI strongly linked to prognostic factors. Furthermore, the consensus conference results will able to provide fundamental guidelines for diagnostic and rehabilitation practice, also considering instrumental therapy and pharmacological treatment of MI. Expert opinion, level IV.
Prehospital emergency anaesthesia: an updated survey of UK practice with emphasis on the role of standardisation and checklists
Authors: Burgess Mark R , Crewdson Kate , Lockey David J , Perkins Zane B 
Published: May 2018

IntroductionPrehospital emergency anaesthesia (PHEA or ‘prehospital rapid sequence intubation’) is a high-risk procedure. Standard operating procedures (SOPs) and checklists within healthcare systems have been demonstrated to reduce human error and improve patient safety. We aimed to describe the current practice of PHEA in the UK, determine the use of checklists for PHEA and describe the content, format and layout of any such checklists currently used in the UK.MethodA survey of UK prehospital teams was conducted to establish the incidence and conduct of PHEA practice. Results were grouped into systems delivering a high volume of PHEA per year (>50 PHEAs) and low volume (≤50 PHEAs per annum). Standard and ‘crash’ (immediate) induction checklists were reviewed for length, content and layout.Results59 UK physician-led prehospital services were identified of which 43 (74%) participated. Thirty services (70%) provide PHEA and perform approximately 1629 PHEAs annually. Ten ‘high volume’ services deliver 84% of PHEAs per year with PHEA being performed on a median of 11% of active missions. The most common indication for PHEA was trauma. 25 of the 30 services (83%) used a PHEA checklist prior to induction of anaesthesia and 24 (80%) had an SOP for the procedure. 19 (76%) of the ‘standard’ checklists and 5 (50%) of the ‘crash’ induction checklists used were analysed. On average, standard checklists contained 169 (range: 52–286) words and 41 (range: 28–70) individual checks. The style and language complexity varied significantly between different checklists.ConclusionPHEA is now performed commonly in the UK. The use of checklists for PHEA is relatively common among prehospital systems delivering this intervention. Care must be taken to limit checklist length and to use simple, unambiguous language in order to maximise the safety of this high-risk intervention.
A simple technique to construct tissue macroarrays
Authors: Dias Eliane P , Picciani Bruna L S , Santos Vanessa de C B dos , Cunha Karin S 
Published: May 2018

AimsIn the diagnostic or research field, there is a need that the histopathological evaluation provides as much information as possible, with the shortest time and lowest cost. The development of the tissue microarray (TMA) technology has significantly facilitated and accelerated studies with tissue analyses using in situ technologies. Nevertheless, one of the most recognised limitations of TMA is that the small cores used to construct a TMA may not accurately represent characteristics of the whole tissue specimen. The aim is to present the technical aspects of a simple system to construct tissue macroarrays (TMaAs), its advantages and limitations, and some results of its use in for research purposes.MethodsThe study presents three possibilities of preparing the specimens with up to 6 mm diameter to be included into the TMaA paraffin block using our method.ResultsWith this technique, it was possible to obtain glass slides with multiple whole fragments, which were used in five different studies.ConclusionsWe presented a method for construction of multi-TMaA paraffin blocks, which is very simple for optimising laboratory techniques requiring paraffin-embedded tissue sections and can be easily implemented in any institution with a histology laboratory.
011 Ex-vivo generation of plasmin from patients with acute ischaemic stroke is predictive of successful thrombolysis
Authors: Levi Chris , Lillicrap Thomas , Harman Stevi , Draxler Dominik , Niego Be’Eri , Ho Heidi , McCutcheon Fiona , Kleinig Timothy , Koblar Simon , Hamilton-Bruce Monica Anne , Garcia-Esperon Carlos , Lincz Lisa , Bivard Andrew , Attia John , Maguire Jane , Holliday Elizabeth , Medcalf Robert 
Published: May 2018

IntroductionThrombolysis with recombinant tissue-type plasminogen activator (rt-PA) fails in more than 60% of patients with acute ischaemic stroke (AIS). Simultaneously, there are risks associated with the use of rt-PA, including the risk of symptomatic intracranial haemorrhage (sICH) even in patients who do re-canalise. While thrombus location, aetiology and infarct size can affect the likelihood of successful thrombolysis, other factors distinguishing patients who re-canalise from those who don’t have yet to be fully elucidated. The ability of rt-PA to promote thrombolysis is dependent upon its capacity to generate plasmin, and we set out to test this capacity ex-vivo. We hypothesised that patients with low plasmin generating capacity are less likely to re-canalise following rt-PA treatment.MethodsPlasma was obtained from 90 AIS patients up to 1 hour before thrombolysis and screened for baseline levels of plasminogen, anti-plasmin, and plasmin-anti-plasmin (PAP) complexes. The degree of inducible plasmin generation was determined using amidolytic assays following ex-vivo addition of rt-PA for 1 hour. ELISA assays were also used to quantitate the fold-increase in PAP complex levels after rt-PA treatment.Resultsrt-PA inducible PAP levels, a surrogate for the capacity to generate plasmin from plasminogen, varied dramatically between patients. The ratio of post-thrombolysis PAP to pre-thrombolysis PAP ranged from 3.4 to 105.9 within the cohort examined for this study. Multivariate regression analyses revealed that each fold increase in PAP levels was associated with a 4.2% increase in the odds of recanalisation (p=0,035) when corrected for blood glucose levels.ConclusionThis is the first report of ex vivo-inducible plasmin generation as a predictor of thrombolysis. The predictive power of this screening assay for sICH is still under investigation.
014 The diagnostic odyssey for fabry disease: ten years experience in testing
Authors: Dobbins Julia , Fuller Maria , Pyragius Tim , Brion Kristian , Chin Sharon , Gurner Melissa , Pacyna Janina , Stark Samantha , Fletcher Janice M 
Published: May 2018

IntroductionFabry disease is an X-linked disorder of glycosphingolipid metabolism arising from a deficiency of the enzyme, α-galactosidase A (AGA). In the absence of a family history, biochemical diagnosis is conferred by reduced activity in dried filter paper blood spots (DBS), elevations in globotriaosylsphingosine (lyso-Gb3) and/or identification of a mutation within the GLA gene.MethodsFrom 2008 to 2012, AGA determinations were performed on leucocytes and in 2012, DBS testing was introduced. A mass spectrometric method to quantify lyso-Gb3 in plasma was added to our repertoire of testing in 2016. Mutation analysis was performed using either Sanger or Next Generation Sequencing, the latter confirmed by sequencing.ResultsBetween 2008 and 2012, approximately 1000 samples were screened for Fabry disease using AGA determinations in leucocytes and 29 patients were confirmed positive (diagnosis rate of 2.9%). Since 2012, approximately 4000 samples have been screened from DBS, with 126 patients being confirmed positive (diagnosis rate of 3.2%). There were 24 patients with AGA deficiency and a GLA gene variant which did not have elevated lyso-Gb3 (approximately 20% of positives).DiscussionFabry disease is a relatively complicated disease to diagnose and requires significant interpretation of results from all three tests. As an X-linked disease, classically affected males are easier to identify, but females are more difficult to diagnose as their DBS can be normal, even when symptomatic. Further testing via lyso-Gb3 and mutation analysis is required to make a final biochemical diagnosis. The ease of submitting a DBS for testing has contributed to an increase in test requests.
032 Neurological sequelae of immune checkpoint inhibitors: a case series
Authors: Silsby Matthew , Duma Stephen R , Mahant Neil , Vucic Steve , Henderson Andrew 
Published: May 2018

IntroductionMonoclonal antibodies directed against co-stimulatory molecules on T cells (checkpoint inhibitors, CIs) are used to treat solid organ malignancies. Neurological complications are an increasingly recognised consequence of their use. We present three patients referred to the Neurology service at Westmead Hospital in 2017 with new neurological complaints following CI therapy.CasesPatient 1, a 54 year old woman with stage IV non-small cell lung cancer treated with pembrolizumab (anti-PD-1), presented with cerebral vasculitis causing bilateral ACA territory cerebral infarction. Patient 2, a 59 year old woman with metastatic melanoma treated with ipilimumab (anti-CTLA4) and nivolumab (anti-PD-1), presented with ataxia, diplopia and ptosis consistent with Miller Fisher syndrome. Patient 3, a 77 year old woman with metastatic colorectal adenocarcinoma treated with nivolumab (anti-PD-1), presented with ocular myasthenia manifesting as fatigable ptosis and complex ophthalmoplegia.The diagnoses were made by clinical assessment with imaging and neurophysiological investigations where possible. Antibodies relevant to the neurological condition were negative, in keeping with previous reports. CIs were discontinued in all patients. Treatment included intravenous pulsed methylprednisolone followed by high dose oral taper in all patients. Additionally, Patient 1 was treated with infliximab and rituximab; Patients 2 and 3 received intravenous immunoglobulin followed by monthly maintenance therapy; Patient 2 underwent plasma exchange. Patients 1 and 2 recovered independent ambulation. Patient 3 died two months after presentation due to underlying malignancy.ConclusionCheckpoint inhibitors block co-stimulatory molecules on T-cells, allowing the immune system to mount an anti-tumour response. The resulting immune dysregulation can also lead to organ-specific inflammatory and immune complications, of which neurological sequelae are increasingly recognised. The three reported patients highlight the spectrum of disease that can arise. Their occurrence within one year suggests an increasing incidence, and a need for increased vigilance. Early recognition is paramount as treatment with high dose corticosteroids, even in conditions that would not normally respond, is recommended.
039 Rates of lymphopenia in years 1–4 in patients with relapsing multiple sclerosis treated annually with cladribine tablets
Authors: Cook Stuart , Comi Giancarlo , Giovannoni Gavin , Rieckmann Peter , Sorensen Per Soelberg , Vermersch Patrick , Dangond Fernando , King John , Hicking Christine 
Published: May 2018

IntroductionThe CLARITY and CLARITY Extension studies demonstrated the efficacy of cladribine tablets in patients with relapsing multiple sclerosis. The most common adverse event was lymphopenia, consistent with the mechanism of action of cladribine tablets. Objective was to evaluate whether lymphopenia persists following annual treatment with cladribine tablets.MethodsLymphopenia by grade (NCI CTCAE v3.0) for patients randomised to cladribine tablets 3.5 mg/kg in CLARITY and re-randomised to cladribine tablets 3.5 mg/kg in CLARITY Extension (7 mg/kg cumulative dose over 4 years; n=186) are reported. Patients with Grade 0 lymphopenia (≥1.0×109 cells/L) before the first course of cladribine tablets and Grade 0/1 (≥0.8×109 cells/L) prior to administration in Years 2, 3 and 4 were included in the analysis.Results176 patients were Grade 0 at CLARITY baseline and 167 were Grade 0/1 at CLARITY Extension baseline. Grade 3 lymphopenia was observed in 1% of patients at Week 13 in Year 1, and in 7%, 11% and 12% at Week 12 in Years 2, 3 and 4, respectively. By Week 24 in Years 1, 2, 3 and 4, Grade 3 lymphopenia was observed in 1%, 4%, 4% and 4% of patients, respectively. By Week 36 in Years 1, 2, 3 and 4, Grade 3 lymphopenia was observed in 1%, 2%, 2% and 2% of patients, respectively. Grade 3 lymphopenia was only observed in Week 48 of Year 2 (1% of patients). Grade 3 lymphopenia was reported in <18% of patients at any time point. No patients had Grade 4 lymphopenia at the end of any years.ConclusionNo patients included in this analysis experienced Grade 4 lymphopenia at the end of any treatment year. Grade 3 lymphopenia was uncommon. This study demonstrates the effectiveness of lymphocyte-based treatment criteria in minimising the incidence of severe, sustained lymphopenia during treatment with cladribine tablets.
048 Large pseudo-meningocele causing severe papilledema, retinal haemorrhages and recurrent positional syncope
Authors: Hooi Wai Foong , Waterston John 
Published: May 2018

IntroductionPseudo-meningocele is an abnormal collection of cerebrospinal fluid in the extradural space that occurs due to leakage from the CSF-filled spaces surrounding the brain and spinal cord. Pseudo-meningocele may result after spinal surgery. We report a case of a young woman with pseudo-meningocele post lumbar spinal surgery. She subsequently developed recurrent syncope, headaches and clinical signs of raised intracranial pressure (severe papilledema and retinal haemorrhages).CaseA 34 year old woman with spina bifida occulta and a large lipoma at the lumbar spinal level of L5 presented with urinary retention, worsening right leg pain, numbness and foot drop. She subsequently underwent L4-S1 laminectomy, debulking of lipoma and detethering of the cord. Her neurological deficits resolved post-surgery. One month later, the patient re-presented with recurrent syncope and intermittent headaches. She was admitted to the hospital for further investigations. Detailed neurological examination revealed grade IV papilledema and retinal haemorrhages. MRI of the brain showed distended optic nerve sheaths and narrowed distal transverse sinuses, in keeping with intracranial hypertension. MRI spine showed a large CSF collection posterior to the spinal canal at the L4-L5 level, measuring 77×53 mm in trans axial plane and 98 mm in craniocaudal dimension. Her symptoms improved with insertion of external ventricular drain. The symptoms resolved completely after a ventriculo-peritoneal shunt was inserted. She was commenced on acetazolamide. She remained well and asymptomatic. Repeat fundus photography a month later showed complete resolution of papilledema.ConclusionPostoperative pseudo-meningocele is uncommon and the exact incidence is unknown as most of these patients are asymptomatic. This case illustrates that pseudo-meningocele can cause raised intracranial pressure leading to recurrent syncope. It is important for clinician to recognise the varied clinical presentations of meningocele and pseudo-meningocele.References. Marlin A, Epstein F, Rovid R. Positional headache and syncope associated with a pseudomeningocele. Arch Neurol1980;37(11):736–737.. Bekavac I, Hollaran J. Meningocele-induced positional syncope and retinal haemorrhages. AJNR Am J NeuroradiolMay 2003;24:838–839.. Arseni C, Maretsis M. Tumours of the lower spinal cord associated with increased intracranial pressure and papilloedema. J Neurosurg1967;27:105–110.
049 Lower stimulus contrast is associated with stronger multifocal visual evoked potential signals
Authors: Barton Joshua L , Barnett Michael H , Klistorner Alexander 
Published: May 2018

IntroductionVisual evoked potentials (VEPs) are used to assess the visual system in neuro-ophthalmological diseases such as multiple sclerosis (MS). Axonal damage, and subsequent reduction of VEP amplitude, is considered central to the development of disability. To obtain the strongest signal possible, high contrast (HC) pattern-reversing checkboard stimuli are routinely used to induce cortical electrical potentials. Low contrast (LC) visual acuity assessment is better than HC visual acuity testing in detecting MS-related visual impairment. This study aims to determine if the use of LC stimuli in multifocal VEPs improves detection visual dysfunction in patients with MS.Methods14 MS patients (8 with history of optic neuritis) and 12 healthy controls had HC (Michelson 98%) and LC (Michelson 22%) multifocal VEP performed. The VEP signal from the 56 individual sectors was transformed into absolute values and averaged. The area under the curve (AUC) for each individual’s mfVEP was determined for HC and LC stimuli. Subsequently, 5 healthy controls with best-corrected vision ≥20/20 underwent mfVEP assessment at 8 different contrast levels (Michelson contrast 8%, 15%, 22%–31% 41%, 53%, 64%, 98%).ResultsThere was no significant difference in the mfVEP AUC between MS patients (including 10 ON eyes only) and controls for HC, LC or the difference between HC and LC stimuli. Part 2 of the study demonstrated the relationship between stimulus contrast and signal strength. All subjects had a roughly parabolic relationship with AUC greatest at mid-level contrast. Averaged data of all subjects showed a parabolic relationship characterised by y=-2834.1x2 – 2127.1x+3144.2, R²=0.911.ConclusionAssessing reduction in mfVEP signal strength with LC stimuli requires an appropriate HC comparator stimulus. This study may also provide rationale for clinical mfVEP studies to use lower contrast stimuli to increase the signal strength of the study.
052 Diagnostic accuracy of the CT angiographic ‘spot sign’ for predicting intracerebral haematoma growth
Authors: Krishnadas Natasha , Phan Thanh G , Lai Vivian WY , Batt Michael J , Chandra Ronil V , Srikanth Velandai , Ma Henry 
Published: May 2018

IntroductionTo study the predictive value of the ‘spot sign’ in predicting spontaneous intracerebral haemorrhage (ICH) expansion.MethodPubMed, Medline, conference proceedings and manuscript references up to June 2017 were searched for studies reporting “computed tomography angiography” and “spot sign” or “intracerebral haemorrhage” and “spot sign”. The positive (PLR) and negative (NLR) likelihood ratios were calculated using MetaDisc. The PLR needs to be ≥5 and NLR ≤0.1 for a test to be clinically useful.ResultsThere were 36 studies describing 6888 patients. This current analysis includes 23 studies that were not used in previous meta-analyses. The frequency of haematoma growth was 21%. The PLR and NLR for the CTA spot sign indicating haematoma growth were 4.25 (95%CI 3.52–5.13) and 0.48 (95%CI 0.41–0.56) respectively. The sensitivity analyses show a plateau in PLR and NLR of 4.3 and 0.48. The heterogeneity chi square was 214.36–250.24 (p<0.001) and inconsistency I2 was 83.7%–86%.ConclusionThe PLR for the CTA spot sign did not reach the desired threshold of 5 to be clinically useful. The heterogeneity around this estimate adds to uncertainty. The high NLR suggest that the absence of the CTA spot sign does not guarantee a lack of ICH growth.