Walton – Acute Pulmonary Oedema: Not Always Cardiogenic

Author(s): Bonello M.; Pullicino R.; Larner A.J.

Source: Journal of the Royal College of Physicians of Edinburgh; 2017; vol. 47 (no. 1); p. 57-59

Publication Date: 2017

Publication Type(s): Article

Available in full text at Journal of the Royal College of Physicians of Edinburgh –  from Directory of Open Access Journals

Abstract:A patient presented with fulminant pulmonary oedema and required acute intubation and ventilation. There was no history of a prior cardiac disorder. As he was weaned from sedation, following stabilisation of his pulmonary status, neurological signs suggestive of brainstem dysfunction became apparent. Investigations showed infarcts in the posterior cerebral circulation secondary to a vertebral artery dissection. Neurogenic pulmonary oedema needs to be considered in any patient with fulminant pulmonary oedema without overt evidence or history of cardiac disease.

Copyright © Royal College of Physicians of Edinburgh.

Database: EMBASE

Walton – Autologous Haemopoietic Stem-Cell Transplantation for Aggressive Multiple Sclerosis

Author(s): Pomeroy I.

Source: Journal of the Royal College of Physicians of Edinburgh; 2017; vol. 47 (no. 1); p. 62-64

Publication Date: 2017

Publication Type(s): Article

Available in full text at Journal of the Royal College of Physicians of Edinburgh –  from Directory of Open Access Journals

Database: EMBASE

Walton – Altered Theta Oscillations in Resting EEG of Fibromyalgia Syndrome Patients

Author(s): Fallon N.; Stancak A.; Chiu Y.; Nurmikko T.

Source: European Journal of Pain (United Kingdom); 2017

Publication Date: 2017

Publication Type(s): Article In Press

Abstract:Background: Fibromyalgia syndrome (FM) is a chronic pain disorder characterized by widespread pain, sleep disturbance, fatigue and cognitive/affective symptoms. Functional imaging studies have revealed that FM and other chronic pain syndromes can affect resting brain activity. This study utilized electroencephalographic (EEG) recordings to investigate the relative power of ongoing oscillatory activity in the resting brain. Methods: A 64-channel EEG was recorded at rest in 19 female FM patients and 18 healthy, age-matched, control subjects. The Manual Tender Point Scale (MTPS) examination was performed to quantify tonic pain and tenderness on the day of testing along with measures of mood, arousal and fatigue. Oscillations in delta, theta, alpha, beta and gamma frequency bands were analysed using Standardised Low-Resolution Brain Electromagnetic Tomography to evaluate sources of spectral activity throughout the whole brain. Results: FM patients exhibited greater pain, tiredness and tension on the day of testing relative to healthy control participants and augmented theta activity in prefrontal and anterior cingulate cortices. No significant differences were seen in other frequency bands. Augmented frontal theta activity in FM patients significantly correlated with measures of tenderness and mean tiredness scores. Conclusions: The findings indicate that alterations to resting-state oscillatory activity may relate to ongoing tonic pain and fatigue in FM, and manifest in brain regions relevant for cognitive-attentional aspects of pain processing and endogenous pain inhibition. Enhanced low-frequency oscillations were previously seen in FM and other chronic pain syndromes, and may relate to pathophysiological mechanisms for ongoing pain such as thalamocortical dysrhythmia. Significance: Increased prefrontal theta activity may contribute to persistent pain in fibromyalgia or represent the outcome of prolonged symptoms. The findings point to the potential for therapeutic interventions aimed at normalizing neural oscillations, while further research utilizing quantitative analysis of resting EEG could benefit our understanding of fibromyalgia pathophysiology.

Copyright © 2017 European Pain Federation – EFIC.

Database: EMBASE

Aintree – Patient Centered Approach to Disease Modification in Scleroderma: Results from the Fasscinate Trial of Tocilizumab Compared to Placebo in Active Diffuse Cutaneous Systemic Sclerosis

Author(s): Arnold M.; Khanna D.; Denton C.; Lin C.; Van Laar J.; Frech T.; Anderson M.; Baron M.; Chung L.; Fierlbeck G.; Allanore Y.; Riemekasten G.; Steen V.; Muller-Ladner U.; Burke L.; Spotswood H.; Jahreis A.; Siegel J.; Furst D.; Pope J.

Source: Journal of Rheumatology; 2017; vol. 44 (no. 6); p. 881

Publication Date: 2017

Publication Type(s): Conference Abstract

Available in print  at Edge Hill Aintree LIRC –  from JOURNAL OF RHEUMATOLOGY

Abstract:Objectives: Patient Acceptable Symptom State (PASS) as an absolute state of well-being and has shown promise as an outcome measure in many rheumatologic conditions. We assessed whether PASS may be an effective in active diffuse cutaneous SSc. Methods: Data from the faSScinate trial were used, which compared tocilizumab vs placebo over 48 weeks followed by an open-label tocilizumab period to 96 weeks. Three different types of PASS questions were evaluated at weeks 8, 24, 48 and 96 including would a current state be acceptable over time as yes vs no response, and Likert scales about how acceptable a current state is if remaining over time. Additional outcomes assessed included mRSS, HAQ-DI, MD and Pt global VAS, CRP and ESR. PASS question #1: “Considering all of the ways your scleroderma has affected you over the last week, how acceptable would you rate your level of symptoms?” PASS question #2: “Think about all the ways that your scleroderma has affected you during the last week. If you were to remain for the next few months as you were in the last week, would this be acceptable to you?” PASS question #3: “Has there been a change in how you would describe your level of functional impairment since you started the study?” Results: At baseline, the placebo group consisted of 44 patients, and tocilizumab group had 43 patients. At baseline, 33% achieved PASS for all three PASS questions, with the proportion increasing to 69%, 71% and 78%, respectively at 96 weeks. Changes in PASS scores showed a moderately negative correlation with HAQ-DI, Pt and MD global VAS. PASS asking “Considering all of the ways your scleroderma has affected you how acceptable would you rate your level of symptoms?” showed significant correlations with patient-reported outcomes and differentiating placebo vs tocilizumab at 48 weeks (P = 0.023). Conclusion: PASS may be used as patient-centered outcome in SSc especially as a 7-point Likert scale. Further validation through larger clinical trials is required before being able to apply this concept to clinical practice.

Database: EMBASE

Aintree – The Molecular Heterogeneity of Sporadic Colorectal Cancer with Different Tumor Sites in Chinese Patients

Author(s): Peng J.; Ma X.; Wang R.; Cai S.; Huang D.; Sheng W.; Zhou X.; Zhu X.; Poston G.

Source: Oncotarget; 2017; vol. 8 (no. 30); p. 49076-49083

Publication Date: 2017

Publication Type(s): Article

Abstract:Purpose: To assess the biological variability of clinical meaningful molecular markers and their clinical correlations in Chinese patients with colorectal cancer (CRC). Materials and methods: In this prospective observational study, frequencies and clinico-pathological features of RAS and BRAFV600E mutations, deficiency of DNA mismatch repair (dMMR) were evaluated in patients with colorectal cancer staged I-IV. The molecular heterogeneity between right-sided and left-sided colorectal cancers was studied in our series by classifying patients with different mutations and dMMR status. Results: Among 400 evaluable patients, mutations in KRAS exon 2, exon 3 or 4, NRAS and BRAFV600E were detected in 36%, 7.5%, 3.5% and 2.5%, respectively. RAS mutations were significantly higher in metastatic CRCs (56.4% vs. 43.1%, p=0.015) and right-sided CRCs (62.5% vs 41.7%, p=0.003). In 212 RAS wild-type patients, V600E mutation was higher in older patients (9.5% vs. 2.2%, p=0.017), women (9.2% vs. 2.2%, p=0.021) and right-sided CRCs (10.5% vs. 3.4%, p=0.06). dMMR was detected in 7.75% of all stages of CRCs, with the highest dMMR rate of 40% in stage II right-sided colon cancer. Conclusions: By assessing the mutations and clinical correlations of RAS and BRAF genes, and dMMR status, similar RAS mutation, dMMR frequency and lower BRAF mutation was observed in Chinese patients compared to western patients. A distinct molecular heterogeneity was found between patients with right-sided and left-sided CRCs.

Copyright © Peng et al.

Database: EMBASE

Aintree – The Association of Tidal EFL with Exercise Performance, Exacerbations, and Death in COPD

Author(s): Aarli B.B.; Eeagan T.M.L.; Bakke P.S.; Hardie J.A.; Calverley P.M.A.; Jensen R.L.; Dellaca R.

Source: International Journal of COPD; Jul 2017; vol. 12 ; p. 2179-2188

Publication Date: Jul 2017

Publication Type(s): Article

Available in full text at International Journal of Chronic Obstructive Pulmonary Disease –  from National Library of Medicine

Available in full text at International Journal of COPD –  from Directory of Open Access Journals

Abstract:Background: Tidal expiratory flow limitation (EFLT) is frequently found in patients with COPD and can be detected by forced oscillations when within-breath reactance of a single-breath is >=0.28 kPa.s.L-1. The present study explored the association of within-breath reactance measured over multiple breaths and EFLT with 6-minute walk distance (6MWD), exacerbations, and mortality. Methods: In 425 patients, spirometry and forced oscillation technique measurements were obtained on eight occasions over 3 years. 6MWD was assessed at baseline and at the 3-year visit. Respiratory symptoms, exacerbations, and hospitalizations were recorded. A total of 5-year mortality statistics were retrieved retrospectively. We grouped patients according to the mean within-breath reactance (DELTA(Formula Presented.)), measured over several breaths at baseline, calculated as mean inspiratory-mean expiratory reactance over the sampling period. In addition to the established threshold of EFLT, an upper limit of normal (ULN) was defined using the 97.5th percentile of DELTA(Formula Presented.) of the healthy controls in the study; 6MWDs were compared according to DELTA(Formula Presented.), as normal, >= ULN T, or >= EFLT. Annual exacerbation rates were analyzed using a negative binomial model in the three groups, supplemented by time to first exacerbation analysis, and dichotomizing patients at the ULN. Results: In patients with COPD and baseline DELTA(Formula Presented.) below the ULN (0.09 kPa.s.L-1), 6MWD was stable. 6MWD declined significantly in patients with DELTA(Formula Presented.) >= ULN. Worse lung function and more exacerbations were found in patients with COPD with DELTA(Formula Presented.) >= ULN, and patients with DELTA(Formula Presented.) >= ULN had shorter time to first exacerbation and hospitalization. A significantly higher mortality was found in patients with DELTA(Formula Presented.) >= ULN and FEV1.50%. Conclusion: Patients with baseline DELTA(Formula Presented.) >= ULN had a deterioration in exercise performance, more exacerbations, and greater hospitalizations, and, among those with moderate airway obstruction, a higher mortality. DELTA(Formula Presented.) is a novel independent marker of outcome in COPD.

Copyright © 2017 Aarli et al.

Database: EMBASE

Walton Centre – Clinical Outcomes Following Traumatic Brain Injury in a Combined Multidisciplinary Neurotrauma Clinic: Experiences from a Tertiary Centre

Author(s): Bell C.; Hackett J.; Hall B.; Pulhorn H.; McMahon C.J.; Bavikatte G.

Source: Brain Injury; 2017; vol. 31 (no. 6); p. 796-797

Publication Date: 2017

Publication Type(s): Conference Abstract

Available in full text at Brain Injury –  from Informa Healthcare

Abstract:Objectives: The Walton Centre NHS Foundation Trust is part of the major trauma centre collaborative for the North West of England, UK. Of the 2.4 million patients under the remit of this collaborative, the Walton Centre as a specialist neuroscience institution provides surgical intervention and rehabilitation services for those admitted following traumatic brain injury (TBI). TBI specifically accounts for 3.4% of emergency department admissions in the UK. Main Outcome Measure: A broad spectrum of physical, cognitive and psychological sequelae occurring in patients with TBI has been identified as late as 2 years post injury. These symptoms have been found in patients regardless of the severity of their original brain injury. Indeed, those with mild injury may often fare worse due to oversights in management early on, as early rehabilitation has been shown to be associated with better outcomes. To aid in the management of such patients, a combined, multidisciplinary neurotrauma clinic led by a neurosurgeon and specialist in neurorehabilitation has been initiated at The Walton Centre. The clinic provides specialist management for the wide range of problems that follow TBI. The primary objective of this study is to describe outcomes of patients following TBI who attended a multidisciplinary neurotrauma clinic at a tertiary centre. Methods: All patients who had attended the clinic since its inception were eligible. The following data was collected for each patient: basic demographics, mechanism and severity of injury, initial CT findings, information on hospital stay and discharge, symptomatology in clinic, and outcomes (including further investigations, referral to other specialties or services and return to employment). Results: 305 patients (98.1%) had clinic notes available and were included in the study. Mean age was 47.5 and the majority of patients were male (72.1%). The commonest mechanism of injury was falls (53.1%). 17.4% of injuries were classed as mild, 68.2% as moderate, and 14.1% as severe. Frontal (21.6%) and temporal (16.1%) injuries were the commonest locations with contusions (37.4%) and subdural haematomas (27.9%) the commonest type of injury found on initial CT scan. In clinic the most frequent physical complaints were headache (47.9%), memory problems (42.0%) and loss of driver’s licence (28.5%). 41.6% were referred to further services or other specialties, the commonest being psychology (19.3%) and neuropsychiatry (18.4%). Of 184 patients known to be in employment before their injury, only 48.4% of these had returned to work before their last appointment. Further analysis of the data is ongoing. Conclusions: The information gathered in this study about the characteristics of the TBI population and their outcomes should allow for better targeting of suitable patients for referral to a multidisciplinary clinic. This kind of data is essential for planning of health care provision, and improving efficiency and ultimately patient outcome.

Database: EMBASE

Walton Centre – Growing Pains: Understanding the Needs of Emerging Adults with Chronic Pain

Author(s): Twiddy H.; Hanna J.; Haynes L.

Source: British Journal of Pain; Aug 2017; vol. 11 (no. 3); p. 108-118

Publication Date: Aug 2017

Publication Type(s): Article

Available in full text at British Journal of Pain –  from Highwire Press

Abstract:Background: Emerging adulthood (18-30 years), in the Western world, is often a time of identity development and exploration, focusing on areas of work, relationships and education. Individuals with chronic illnesses, such as chronic pain, may be more vulnerable to facing challenges during this time. This study aims to investigate the needs of young adults (YAs) attending a tertiary level National Health Service (NHS) Pain Management Programme (PMP) Service in the United Kingdom; exploring how these needs may translate on to clinical assessment and the delivery of rehabilitation interventions. Method: This is a descriptive qualitative study influenced by phenomenological approaches. YA with a diagnosis of chronic pain were recruited and assigned to one of four focus groups facilitated by a clinical psychologist and occupational therapist. A semi-structured interview guide was used to help facilitate the group discussion. Results: Qualitative analysis identified four key themes in understanding the needs of YAs with chronic pain: (1) thwarted opportunities, (2) peer separation, (3) perceived illness validity in the context of age and (4) dependency/parental enmeshment. Conclusions: The emerging adulthood literature provides a valuable framework for examining a normal developmental trajectory and highlights the relevance of age-related processes in YAs with chronic pain. The idealisation of opportunity and the role of perception in this developmental phase both appear relevant. It is significant that emotional stability is not yet established in emerging adulthood and links to unhelpful management strategies that may be differentiated from older populations are identified.

Copyright © 2017, © The British Pain Society 2017.

Database: EMBASE

Walton Centre – The Use of Rechargeable or Non-Rechargeable Deep Brain Stimulation Devices in Parkinson’s Disease (PD) and Dystonia: A Cost Analysis

Author(s): Eggington S.; Autiero S.W.; Stromberg K.; Weaver T.; Eldridge P.R.

Source: Stereotactic and Functional Neurosurgery; 2017; vol. 95 ; p. 227

Publication Date: 2017

Publication Type(s): Conference Abstract

Abstract:Objectives: Deep brain stimulation (DBS) is a recommended option for the treatment of movement disorders in well-selected patients. Both rechargeable and non-rechargeable devices are available; one of the advantages of a rechargeable DBS device may lie in the avoidance of costs for battery replacements and associated risks and hospitalisations. The objective of this study was to evaluate the economic impact of using a rechargeable DBS device over a non-rechargeable device in patients treated for either Parkinson’s Disease (PD) or Dystonia. Methods: An economic model (Markov Model) was built to follow a group of dystonia and PD DBS patients over time comparing two scenarios, one assuming a rechargeable and one assuming a non-rechargeable device, for first implant and replacements. The model captures patients’ replacement surgeries, hospitalisations, adverse events and deaths. Data for the model were sourced from the Medtronic product surveillance registry (PSR; patient characteristics, adverse events and consequences associated with implant and replacement surgeries) and non-rechargeable device longevity data from Medtronic performance registry based modelling analyses. For the rechargeable device longevity, current longevity (9 years) and a hypothetical longevity scenario (15 years) were tested. Clinical expert advice was used to inform model assumptions. Costs were estimated from a UK health care perspective. Sensitivity analyses were undertaken to test for parameter uncertainty, including time horizon. Results: Results of the base case analysis (16 year time horizon) show:For PD,an average of 3.68 battery replacements in the non-rechargeable vs 0.62 in the rechargeable group; for Dystonia, 5.08 and 0.74 replacements in the non-rechargeable vs the rechargeable group(15-year hypothetical device longevity). Over 16 years,the model suggests cost savings of 15,564 (PD) and 27,954 (Dystonia) using the 9 year device longevity, and 20,418 and 32,060, respectively, for a 15-year hypothetical device longevity. Sensitivity analyses showed that over a patient’s life time, cost savings were 28,450(PD) and 65,413(dystonia)(15-year hypothetical device longevity). Conclusion: The use of a rechargeable DBS device in this model is cost saving in the long-term compared to a nonrechargeable device. Prolonging rechargeable device life to 15 years is predicted to reduce DBS treatment costs and would thus improve DBS therapy cost-effectiveness, for both PD and dystonia. This analysis was funded by Medtronic. Simon Eggington, Katherine Stromberg, Silke Walleser Autiero and Todd Weaver are employees of Medtronic. Professor Paul Eldridge received compensation for his work providing clinical advice and review on this project.

Database: EMBASE

 

Walton Centre – Outcomes of a Prospective, Multicenter International Registry of Deep Brain Stimulation for Parkinson’s Disease

Author(s): Vesper J.; Witt K.; Deuschl G.; Mehdorn H.M.; Kuhn A.; Barbe M.T.; Visser-Vandewalle V.; Potter-Nerger M.; Hamel W.; Buhmann C.; Eldridge P.; Jain R.; Wang A.; Scholtes H.

Source: Stereotactic and Functional Neurosurgery; 2017; vol. 95 ; p. 29

Publication Date: 2017

Publication Type(s): Conference Abstract

Abstract:Objective: The effectiveness and safety of the use of DBS to reduce motor complications of PD patients has been substantiated by several randomized controlled trials (Schuepbach et al., 2013). Motor improvement following DBS is sustained for up to 10 years as reported by Deuschl et al. 2013. An in-depth evaluation of real world outcomes following DBS will add to the existing database of knowledge and be a useful tool for physicians. As part of an on-going, large scale registry study, we investigated the effectiveness and safety-related real-world outcomes of a multiple independent current source control (MICC) Deep Brain Stimulation (DBS) System for use in the management of motor symptoms of levodopa-responsive Parkinson’s disease (PD). Methods: This is a prospective, on-label, multi-center, international registry sponsored by Boston Scientific Corporation. Patients were implanted with a CE-marked, MICC-based DBS system (Vercise, Boston Scientific). Subjects will be followed up at 6 and 12 months and up to 3 years post-implantation where their overall improvement in quality of life and PD motor symptoms will be evaluated. Clinical endpoints will be evaluated at baseline and during study follow up that include Unified Parkinson’s disease Rating Scale (UPDRS), MDS-UPDRS, Parkinson’s disease Questionnaire (PDQ-39), and Global Impression of Change. Adverse events are also collected. Results: Preliminary data suggests an overall improvement in Quality of life at 6 months post implant as compared with Baseline as measured by a 17.6% (n = 89) improvement in PDQ-39 Summary Index. Over 90% of patients, caregivers and clinicians reported improvement as compared with Baseline. This report will provide the safety and effectiveness outcomes of the first cohort of subjects analyzed at 6 (N=150) and 12 months (N=100) post-implantation as compared with baseline. Conclusion: Deep Brain stimulation (DBS) of the subthalamic nucleus (STN) is an established treatment option for patients with advanced Parkinson’s disease (PD). A device that enables fractionalization of current using a multiple source mode of delivery (MICC) can permit the application of a well-defined, shaped electrical field. This registry represents the first comprehensive, large scale collection of real-world outcomes and includes evaluation of the safety and effectiveness of the Vercise DBS System up to 12 months post lead placement.

Database: EMBASE