Medicine (RMH) - Research Publications
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ItemNo Preview AvailableEndoscopic features of buried Barrett's mucosa: visible to the trained eye?(Wiley, 2019-12-01)
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ItemExamining maintenance care following infliximab salvage therapy for acute severe ulcerative colitis(WILEY, 2018-01)BACKGROUND AND AIM: Data supporting the optimal maintenance drug therapy and strategy to monitor ongoing response following successful infliximab (IFX) induction, for acute severe ulcerative colitis (ASUC), are limited. We aimed to evaluate maintenance and monitoring strategies employed in patients post-IFX induction therapy. METHODS: Patients in six Australian tertiary centers treated with IFX for steroid-refractory ASUC between April 2014 and May 2015 were identified via hospital IBD and pharmacy databases. Patients were followed up for 1 year with clinical data over 12 months recorded. Analysis was limited to patient outcomes beyond 3 months. RESULTS: Forty one patients were identified. Five of the 41 (12%) patients underwent colectomy within 3 months, and one patient was lost to follow-up. Six of 35 (17%) of the remaining patients progressed to colectomy by 12 months. Maintenance therapy: Patients maintained on thiopurine monotherapy (14/35) versus IFX/thiopurine therapy (15/35) were followed up. Two of 15 (13%) patients who received combination maintenance therapy underwent a colectomy at 12 months, compared with 1/14 (7%) patients receiving thiopurine monotherapy (P = 0.610). Monitoring during maintenance: Post-discharge, thiopurine metabolites were monitored in 15/27 (56%); fecal calprotectin in 11/32 (34%); and serum IFX levels in 4/20 (20%). Twenty of 32 (63%) patients had an endoscopic evaluation after IFX salvage with median time to first endoscopy of 109 days (interquartile range 113-230). CONCLUSION: Following IFX induction therapy for ASUC, the uptake of maintenance therapy in this cohort and strategies to monitor ongoing response were variable. These data suggest that the optimal maintenance and monitoring strategy post-IFX salvage therapy remains to be defined.
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ItemIs our current understanding and management of nocturia allowing improved care? International Consultation on Incontinence-Research Society 2018(WILEY, 2019-12)AIMS: Nocturia or waking at night, to urinate is a common cause of awakenings and may lead to sleep disturbance, impaired somatic health, impaired quality of life, and increased mortality. The aim of this report is to point out and discuss the aspects and issues that need to be addressed to improve the care of nocturia. METHODS: This paper is a report of the presentations and subsequent discussion of a Think Tank session at the annual International Consultation on Incontinence-Research Society (ICI-RS) in June 2018 in Bristol. RESULTS AND CONCLUSION: Nocturia is a known risk factor for in-hospital falls. Unfortunately, its assessment in acutely hospitalized (older) people is not the current practice and ward-based care plans are not tailored to this symptom. A new care pathway for hospitalized patients who have nocturia should be considered. More research into the relation of cardiovascular disorders and nocturnal polyuria (NP) is warranted and management of NP patients may be improved by involving a cardiologist in their management. There is definitely a need for phenotyping nocturia in relation to bladder capacity, filling phase, and emptying phase symptoms and how to treat the different phenotypes. In the near future, smart automated monitoring devices and applications might help us to diagnose and treat nocturia with less efforts.
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ItemA case of actinic granuloma responding to oral retinoids(WILEY, 2019-05)
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ItemAnti-inflammatory disease-modifying treatment and disability progression in primary progressive multiple sclerosis: a cohort study(WILEY, 2019-02)BACKGROUND AND PURPOSE: Treatment options in primary progressive multiple sclerosis (PPMS) are scarce and, with the exception of ocrelizumab, anti-inflammatory agents have failed to show efficacy in ameliorating disability progression. The aim of this study was to investigate a potential effect of anti-inflammatory disease-modifying treatment on disability outcomes in PPMS. METHODS: Using MSBase, a large, international, observational database, we identified patients with PPMS who were either never treated or treated with a disease-modifying agent. Propensity score matching was used to select subpopulations with similar baseline characteristics. Expanded Disability Status Scale (EDSS) outcomes were compared with an intention-to-treat and an as-treated approach in paired, pairwise-censored analyses. RESULTS: Of the 1284 included patients, 533 were matched (treated, n = 195; untreated n = 338). Median on-study pairwise-censored follow-up was 3.4 years (quartiles 1.2-5.5). No difference in the hazard of experiencing 3-month confirmed EDSS progression events was observed between the groups [hazard ratio (HR), 1.0; 95% confidence interval (CI), 0.6-1.7, P = 0.87]. We did not find significant differences in the hazards of confirmed EDSS improvement (HR, 1.0; 95% CI, 0.6-1.6, P = 0.91) or reaching a confirmed EDSS step ≥7 (HR, 1.1; 95% CI, 0.7-1.6, P = 0.69). CONCLUSION: Our pooled analysis of disease-modifying agents suggests that these therapies have no substantial effect on short- to medium-term disability outcomes in PPMS.
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ItemClinical course, therapeutic responses and outcomes in relapsing MOG antibody-associated demyelination(BMJ PUBLISHING GROUP, 2018-02)OBJECTIVE: We characterised the clinical course, treatment and outcomes in 59 patients with relapsing myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelination. METHODS: We evaluated clinical phenotypes, annualised relapse rates (ARR) prior and on immunotherapy and Expanded Disability Status Scale (EDSS), in 218 demyelinating episodes from 33 paediatric and 26 adult patients. RESULTS: The most common initial presentation in the cohort was optic neuritis (ON) in 54% (bilateral (BON) 32%, unilateral (UON) 22%), followed by acute disseminated encephalomyelitis (ADEM) (20%), which occurred exclusively in children. ON was the dominant phenotype (UON 35%, BON 19%) of all clinical episodes. 109/226 (48%) MRIs had no brain lesions. Patients were steroid responsive, but 70% of episodes treated with oral prednisone relapsed, particularly at doses <10 mg daily or within 2 months of cessation. Immunotherapy, including maintenance prednisone (P=0.0004), intravenous immunoglobulin, rituximab and mycophenolate, all reduced median ARRs on-treatment. Treatment failure rates were lower in patients on maintenance steroids (5%) compared with non-steroidal maintenance immunotherapy (38%) (P=0.016). 58% of patients experienced residual disability (average follow-up 61 months, visual loss in 24%). Patients with ON were less likely to have sustained disability defined by a final EDSS of ≥2 (OR 0.15, P=0.032), while those who had any myelitis were more likely to have sustained residual deficits (OR 3.56, P=0.077). CONCLUSION: Relapsing MOG antibody-associated demyelination is strongly associated with ON across all age groups and ADEM in children. Patients are highly responsive to steroids, but vulnerable to relapse on steroid reduction and cessation.
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ItemNo Preview AvailablePathophysiology of MS tremor: an fMRI study(SAGE PUBLICATIONS LTD, 2017-10)
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ItemNo Preview AvailableSubclinical speech signs correlate with MS disease severity and differentiates patients with and without clinical cerebellar dysfunction(SAGE PUBLICATIONS LTD, 2017-10-01)Background: Dysarthria is highly prevalent in Multiple Sclerosis (MS). The relationship between dysarthria, MS disease severity and other cerebellar manifestations (such as tremor) is poorly understood. Aim: To examine the relationship between objective markers of speech, disease severity and upper limb tremor in relapsing-remitting and secondary progressive MS. Method: An experienced neurologist determined A) the presence of upper limb tremor, B) the Expanded Disability Status Scale (EDSS) score and C) the degree of dysarthria (from 0, no disturbance to 4, unintelligible). We used acoustic analysis to investigate 4 speech domains: 1) stability of vocal pitch, in sustained utterance of the vowel /a/; 2) stability of loudness, in the same sustained vowel; 3) diadochokinetic speed, in fast repetition of the meaningless word /pa/ta/ka/ and 4) maximum speed of vocal tract movement (i.e. change in pharynx and mouth cavity shape), measured through change in the second formant frequency in the word “always”, from reading of the “Grandfather Passage”. After adjustment for multiple comparisons, a p< 0.0125 was considered for statistical significance. Results: We assessed 24 MS patients with upper limb tremor (47.2±12.3years, 75% female, EDSS=3.7±1.6) and 24 matched patients without tremor (51.2±10.7years, 75% female, EDSS=3.6±1.7). Clinical dysarthria (median=0, mean=0.375±0.76) moderately correlated with EDSS scores (Spearman's rho =.586, p< .001) and with syllable repetition rates (/pa/ta/ka/ rho=.561, p< .001), marginally correlated with speed of tract movement (rho=.363, p=.012), pitch stability (rho=.37, p=.011), loudness stability (rho=.37, p=.01) but not with upper limb tremor presence (p=.039). Only /pa/ta/ka/ rate correlated with EDSS (rho=.529, p< .001) and speed of tract movement differentiated tremor and non-tremor groups (2-tailed t-test p=0.002, rho=.418). Conclusion: Acoustic speech measurements correlate with MS disease severity and can differentiate overt cerebellar dysfunction. Further study is needed to understand the significance of this relationship longitudinally.
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ItemNo Preview AvailableObjective analysis of speech correlates with disease severity in Multiple Sclerosis and differentiates groups with and without upper limb tremor(SAGE PUBLICATIONS LTD, 2017-11-01)Background: Dysarthria is highly prevalent in Multiple Sclerosis. The relationship between dysarthria, MS disease severity and other cerebellar manifestations (such as tremor) is poorly understood. Objective: To examine the relationship between objective markers of speech, disease severity and upper limb tremor in relapsing-remitting and secondary progressive Multiple Sclerosis. Design Methods: An experienced neurologist determined A) the presence of upper limb tremor, B) the Expanded Disability Status Scale (EDSS) score and C) the degree of dysarthria (from 0, no disturbance to 4, unintelligible). Through acoustic analysis of speech, we investigated: 1) stability of vocal pitch, in sustained utterance of the vowel /a/; 2) stability of loudness, in the same sustained vowel; 3) diadochokinetic speed, in fast repetition of the meaningless word /pa/ta/ka/ and 4) maximum speed of vocal tract movement (i.e. change in pharynx and mouth cavity shape), measured in the word “always” (from a standard reading passage). After adjustment for multiple comparisons, p<0.0125 was considered for statistical significance. Results: We assessed 24 participants with Multiple Sclerosis and upper limb tremor (47.2±12.3years, 75% female, EDSS=3.7±1.6) and 24 matched patients with Multiple Sclerosis without tremor (51.2±10.7years, 75% female, EDSS=3.6±1.7). Clinical dysarthria scores (median=0, mean=0.375±0.76) correlated with all acoustic variables measured: diadochokinetic speed Spearman’s rho=.561 (p<.001); pitch stability rho=.37 (p=.011); loudness stability rho=.37 (p=.01); and maximum speed of vocal tract movement rho=.363 (p=.012). Diadochokinetic speed strongly correlated with EDSS (rho=.529, p<.001). Speed of vocal tract movement correlated with tremor and differentiated tremor and non-tremor groups (2-tailed t-test p=0.002, rho=.418). Conclusions: In a typically non-to-mildly dysarthric cohort, acoustic speech measurements correlate with disease severity and can differentiate overt cerebellar dysfunction in Multiple Sclerosis. Further study is needed to understand the significance of this relationship longitudinally.