ORCID Profile
0000-0002-3910-7863
Current Organisation
University of Tasmania
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Publisher: Figshare
Date: 2017
Publisher: Wiley
Date: 09-2017
DOI: 10.1111/CODI.13775
Abstract: This manuscript forms the final of seven that address the surgical management of chronic constipation (CC) in adults. The content coalesces results from the five systematic reviews that precede it and of the European Consensus process to derive graded practice recommendations (GPR). Summary of review data, development of GPR and future research recommendations as outlined in detail in the 'introduction and methods' paper. The overall quality of data in the five reviews was poor with 113/156(72.4%) of included studies providing only level IV evidence and only four included level I RCTs. Coalescence of data from the five procedural classes revealed that few firm conclusions could be drawn regarding procedural choice or patient selection: no single procedure dominated in addressing dynamic structural abnormalities of the anorectum and pelvic floor with each having similar overall efficacy. Of one hundred 'prototype' GPRs developed by the clinical guideline group, 85/100 were deemed 'appropriate' based on the independent scoring of a panel of 18 European experts and use of RAND-UCLA consensus methodology. The remaining 15 were all deemed uncertain. Future research recommendations included some potential RCTs but also a strong emphasis on delivery of large multinational high-quality prospective cohort studies. While the evidence base for surgery in CC is poor, the widespread European consensus for GPRs is encouraging. Professional bodies have the opportunity to build on this work by supporting the efforts of their membership to help convert the documented recommendations into clinical guidelines.
Publisher: Wiley
Date: 09-2017
DOI: 10.1111/CODI.13774
Abstract: This manuscript provides the introduction and detailed methodology used in subsequent reviews to assess the outcomes of surgical interventions with the primary intent of treating chronic constipation in adults and to develop recommendations for practice. PRISMA guidance was adhered to throughout. A literature search was performed in public databases between January 1960 and February 2016. Studies that fulfilled strictly-defined PICOS (patients, interventions, controls, outcome, and study design) criteria were included. The process involved two groups of participants: (i): 'a clinical guidance group' of 18 UK experts (including junior support) who performed the systematic reviews and produced summary evidence statements (SES) based strictly on data synthesis in each review. The same group then produced prototype graded practice recommendations (GPRs) based on coalescence of SES and expert opinion (ii): a European Consensus group of 18 ESCP (European Society of Coloproctology) nominated experts from nine European countries evaluated the appropriateness of each prototype GPR based on published RAND/UCLA methodology. An overview of the search results is provided in this manuscript. A total of 156 studies from 307 full text articles (from 2551 initially screened records) were included, providing data on procedures characterized by: (i) colonic resection (n = 40) (ii) rectal suspension (n = 18) (iii) rectal wall excision (n = 44) (iv) rectovaginal septum reinforcement (n = 47) (v) sacral nerve stimulation (n = 7). The overall quality of evidence was poor with 113/156 (72.4%) studies providing only Oxford level IV evidence. The best evidence was extracted for rectal excisional procedures, where the majority of studies were Oxford level I or II. The five subsequent reviews provide a total of 99 SES (reflecting perioperative variables, efficacy, harms and prognostic variables) that contributed to 100 prototype GPRs covering patient selection, procedural considerations and patient counselling. The final manuscript details the 85/100 GPRs that were deemed appropriate by European Consensus (remaining 15 were all uncertain) and future research recommendations. This manuscript and the following 6 papers suggest that the evidence base for surgical management of chronic constipation is currently poor although some expert consensus exists on best practice. Further studies are required to inform future commissioning of treatments and of research funding.
Publisher: Wiley
Date: 09-2017
DOI: 10.1111/CODI.13773
Abstract: To assess the outcomes of rectal suspension procedures (forms of rectopexy) in adults with chronic constipation. Standardised methods and reporting of benefits and harms were used for all CapaCiTY reviews that closely adhered to PRISMA 2016 guidance. Main conclusions were presented as summary evidence statements with a summative Oxford Centre for Evidence-Based Medicine (2009) level. Eighteen articles were identified, providing data on outcomes in 1238 patients. All studies reported only on laparoscopic approaches. Length of procedures ranged between 1.5 to 3.5 h, and length of stay between 4 to 5 days. Data on harms were inconsistently reported and heterogeneous, making estimates of harm tentative and imprecise. Morbidity rates ranged between 5-15%, with mesh complications accounting for 0.5% of patients overall. No mortality was reported after any procedures in a total of 1044 patients. Although inconsistently reported, good or satisfactory outcome occurred in 83% (74-91%) of patients 86% (20-97%) of patients reported improvements in constipation after laparoscopic ventral mesh rectopexy (LVMR). About 2-7% of patients developed anatomical recurrence. Patient selection was inconsistently documented. As most common indication, high grade rectal intussusception was corrected in 80-100% of cases after robotic or LVMR. Healing of prolapse-associated solitary rectal ulcer syndrome occurred in around 80% of patients after LVMR. Evidence supporting rectal suspension procedures is currently derived from poor quality studies. Methodologically robust trials are needed to inform future clinical decision making.
Publisher: Wiley
Date: 09-2017
DOI: 10.1111/CODI.13772
Abstract: To assess the outcomes of rectal excisional procedures in adults with chronic constipation. Standardised methods and reporting of benefits and harms were used for all CapaCiTY reviews that closely adhered to PRISMA 2016 guidance. Main conclusions were presented as summary evidence statements with a summative Oxford Centre for Evidence-Based Medicine (2009) level. Forty-seven studies were identified, providing data on outcomes in 8340 patients. Average length of procedures was 44 min and length of stay (LOS) was 3 days. There was inadequate evidence to determine variations in procedural duration or LOS by type of procedure. Overall morbidity rate was 16.9% (0-61%), with lower rates observed after Contour Transtar procedure (8.9%). No mortality was reported after any procedures in a total of 5896 patients. Although inconsistently reported, good or satisfactory outcome occurred in 73-80% of patients a reduction of 53-91% in Longo scoring system for obstructive defecation syndrome (ODS) occurred in about 68-76% of patients. The most common long-term adverse outcome is faecal urgency, typically occurring in up to 10% of patients. Recurrent prolapse occurred in 4.3% of patients. Patients with at least 3 ODS symptoms together with a rectocoele with or without an intussusception, who have failed conservative management, may benefit from a rectal excisional procedure. Rectal excisional procedures are safe with little major morbidity. It is not possible to advise which excisional technique is superior from the point of view of efficacy, peri-operative variables, or harms. Future study is required.
Publisher: National Institute for Health and Care Research
Date: 11-2021
DOI: 10.3310/PGFAR09140
Abstract: Chronic constipation affects 1–2% of adults and significantly affects quality of life. Beyond the use of laxatives and other basic measures, there is uncertainty about management, including the value of specialist investigations, equipment-intensive therapies using biofeedback, transanal irrigation and surgery. (1) To determine whether or not standardised specialist-led habit training plus pelvic floor retraining using computer-assisted direct visual biofeedback is more clinically effective than standardised specialist-led habit training alone, and whether or not outcomes of such specialist-led interventions are improved by stratification to habit training plus pelvic floor retraining using computer-assisted direct visual biofeedback or habit training alone based on prior knowledge of anorectal and colonic pathophysiology using standardised radiophysiological investigations (2) to compare the impact of transanal irrigation initiated with low-volume and high-volume systems on patient disease-specific quality of life and (3) to determine the clinical efficacy of laparoscopic ventral mesh rectopexy compared with controls at short-term follow-up. The Chronic Constipation Treatment Pathway (CapaCiTY) research programme was a programme of national recruitment with a standardised methodological framework (i.e. eligibility, baseline phenotyping and standardised outcomes) for three randomised trials: a parallel three-group trial, permitting two randomised comparisons (CapaCiTY trial 1), a parallel two-group trial (CapaCiTY trial 2) and a stepped-wedge (in idual-level) three-group trial (CapaCiTY trial 3). Specialist hospital centres across England, with a mix of urban and rural referral bases. The main inclusion criteria were as follows: age 18–70 years, participant self-reported problematic constipation, symptom onset 6 months before recruitment, symptoms meeting the American College of Gastroenterology’s constipation definition and constipation that failed treatment to a minimum basic standard. The main exclusion criteria were secondary constipation and previous experience of study interventions. CapaCiTY trial 1: group 1 – standardised specialist-led habit training alone ( n = 68) group 2 – standardised specialist-led habit training plus pelvic floor retraining using computer-assisted direct visual biofeedback ( n = 68) and group 3 – standardised radiophysiological investigations-guided treatment ( n = 46) (allocation ratio 3 : 3 : 2, respectively). CapaCiTY trial 2: transanal irrigation initiated with low-volume (group 1, n = 30) or high-volume (group 2, n = 35) systems (allocation ratio 1 : 1). CapaCiTY trial 3: laparoscopic ventral mesh rectopexy performed immediately ( n = 9) and after 12 weeks’ ( n = 10) and after 24 weeks’ ( n = 9) waiting time (allocation ratio 1 : 1 : 1, respectively). The main outcome measures were standardised outcomes for all three trials. The primary clinical outcome was mean change in Patient Assessment of Constipation Quality of Life score at the 6-month, 3-month or 24-week follow-up. The secondary clinical outcomes were a range of validated disease-specific and psychological scoring instrument scores. For cost-effectiveness, quality-adjusted life-year estimates were determined from in idual participant-level cost data and EuroQol-5 Dimensions, five-level version, data. Participant experience was investigated through interviews and qualitative analysis. A total of 275 participants were recruited. Baseline phenotyping demonstrated high levels of symptom burden and psychological morbidity. CapaCiTY trial 1: all interventions (standardised specialist-led habit training alone, standardised specialist-led habit training plus pelvic floor retraining using computer-assisted direct visual biofeedback and standardised radiophysiological investigations-guided habit training alone or habit training plus pelvic floor retraining using computer-assisted direct visual biofeedback) led to similar reductions in the Patient Assessment of Constipation Quality of Life score (approximately –0.8 points), with no statistically significant difference between habit training alone and habit training plus pelvic floor retraining using computer-assisted direct visual biofeedback (–0.03 points, 95% confidence interval –0.33 to 0.27 points p = 0.8445) or between standardised radiophysiological investigations and no standardised radiophysiological investigations (0.22 points, 95% confidence interval –0.11 to 0.55 points p = 0.1871). Secondary outcomes reflected similar levels of benefit for all interventions. There was no evidence of greater cost-effectiveness of habit training plus pelvic floor retraining using computer-assisted direct visual biofeedback or stratification by standardised radiophysiological investigations compared with habit training alone (with the probability that habit training alone is cost-effective at a willingness-to-pay threshold of £30,000 per quality-adjusted life-year gain p = 0.83). Participants reported mixed experiences and similar satisfaction in all groups in the qualitative interviews. CapaCiTY trial 2: at 3 months, there was a modest reduction in the Patient Assessment of Constipation Quality of Life score, from a mean of 2.4 to 2.2 points (i.e. a reduction of 0.2 points), in the low-volume transanal irrigation group compared with a larger mean reduction of 0.6 points in the high-volume transanal irrigation group (difference –0.37 points, 95% confidence interval –0.89 to 0.15 points). The majority of participants preferred high-volume transanal irrigation, with substantial crossover to high-volume transanal irrigation during follow-up. Compared with low-volume transanal irrigation, high-volume transanal irrigation had similar costs (median difference –£8, 95% confidence interval –£240 to £221) and resulted in significantly higher quality of life (0.093 quality-adjusted life-years, 95% confidence interval 0.016 to 0.175 quality-adjusted life-years). CapaCiTY trial 3: laparoscopic ventral mesh rectopexy resulted in a substantial short-term mean reduction in the Patient Assessment of Constipation Quality of Life score (–1.09 points, 95% confidence interval –1.76 to –0.41 points) and beneficial changes in all other outcomes however, significant increases in cost (£5012, 95% confidence interval £4446 to £5322) resulted in only modest increases in quality of life (0.043 quality-adjusted life-years, 95% confidence interval –0.005 to 0.093 quality-adjusted life-years), with an incremental cost-effectiveness ratio of £115,512 per quality-adjusted life-year. Excluding poor recruitment and underpowering of clinical effectiveness analyses, several themes emerge: (1) all interventions studied have beneficial effects on symptoms and disease-specific quality of life in the short term (2) a simpler, cheaper approach to nurse-led behavioural interventions appears to be at least as clinically effective as and more cost-effective than more complex and invasive approaches (including prior investigation) (3) high-volume transanal irrigation is preferred by participants and has better clinical effectiveness than low-volume transanal irrigation systems and (4) laparoscopic ventral mesh rectopexy in highly selected participants confers a very significant short-term reduction in symptoms, with low levels of harm but little effect on general quality of life. All three trials significantly under-recruited [CapaCiTY trial 1, n = 182 (target 394) CapaCiTY trial 2, n = 65 (target 300) and CapaCiTY trial 3, n = 28 (target 114)]. The numbers analysed were further limited by loss before primary outcome. Current Controlled Trials ISRCTN11791740, ISRCTN11093872 and ISRCTN11747152. This project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research Vol. 9, No. 14. See the NIHR Journals Library website for further project information.
Publisher: Springer Science and Business Media LLC
Date: 05-02-2018
Publisher: Figshare
Date: 2018
Publisher: Wiley
Date: 09-2017
DOI: 10.1111/CODI.13779
Abstract: To assess the outcomes of colectomy in adults with chronic constipation (CC). Standardised methods and reporting of benefits and harms were used for all CapaCiTY reviews that closely adhered to PRISMA 2016 guidance. Main conclusions were presented as summary evidence statements (SES) with a summative Oxford Centre for Evidence-Based Medicine (2009) level. Forty articles were identified, providing data on outcomes in 2045 patients. Evidence was derived almost exclusively from observational studies, the majority of which concerned colectomy and ileorectal anastomosis (CIRA) rather than other procedural variations. Average length of stay (LOS) ranged between 7-15 days. Although inconsistent, laparoscopic surgery may be associated with longer mean operating times (210 vs 167 min) and modest decreases in LOS (10-8 days). Complications occurred in approximately 24% of patients. Six (0.4%) procedure-related deaths were observed. Recurrent episodes of small bowel obstruction occurred in about 15% (95%CI: 10-21%) of patients in the long-term, with significant burden of re-hospitalisation and frequent recourse to surgery. Most patients reported a satisfactory or good outcome after colectomy but negative long-term functional outcomes persist in a minority of patients. The influence of resection extent, anastomotic configuration and method of access on complication rates remains uncertain. Available evidence weakly supports selection of patients with an isolated slow-transit phenotype. Colectomy for CC may benefit some patients but at the cost of substantial short- and long-term morbidity. Current evidence is insufficient to guide patient or procedural selection.
Publisher: National Institute for Health and Care Research
Date: 09-2015
DOI: 10.3310/HTA19770
Abstract: Faecal incontinence (FI) is a common condition which is often under-reported. It is distressing for those suffering from it, impacting heavily on their quality of life. When conservative strategies fail, treatment options are limited. Percutaneous tibial nerve stimulation (PTNS) is a minimally invasive outpatient treatment, shown in preliminary case series to have significant effectiveness however, no randomised controlled trial has been conducted. To assess the effectiveness of PTNS compared with sham electrical stimulation in the treatment of patients with FI in whom initial conservative strategies have failed. Multicentre, parallel-arm, double-blind randomised (1 : 1) controlled trial. Eighteen UK centres providing specialist nurse-led (or equivalent) treatment for pelvic floor disorders. Participants aged 18 years with FI who have failed conservative treatments and whose symptoms are sufficiently severe to merit further intervention. PTNS was delivered via the Urgent ® PC device (Uroplasty Limited, Manchester, UK), a hand-held pulse generator unit, with single-use leads and fine-needle electrodes. The needle was inserted near the tibial nerve on the right leg adhering to the manufacturer’s protocol (and specialist training). Treatment was for 30 minutes weekly for a duration of 12 treatments. Validated sham stimulation involved insertion of the Urgent PC needle subcutaneously at the same site with electrical stimulation delivered to the distal foot using transcutaneous electrical nerve stimulation. Outcome measures were assessed at baseline and 2 weeks following treatment. Clinical outcomes were derived from bowel diaries and validated, investigator-administered questionnaires. The primary outcome classified patients as responders or non-responders, with a responder defined as someone having achieved ≥ 50% reduction in weekly faecal incontinence episodes (FIEs). In total, 227 patients were randomised from 373 screened: 115 received PTNS and 112 received sham stimulation. There were 12 trial withdrawals: seven from the PTNS arm and five from the sham arm. Missing data were multiply imputed. For the primary outcome, the proportion of patients achieving a ≥ 50% reduction in weekly FIEs was similar in both arms: 39 in the PTNS arm (38%) compared with 32 in the sham arm (31%) [odds ratio 1.28, 95% confidence interval (CI) 0.72 to 2.28 p = 0.396]. For the secondary outcomes, significantly greater decreases in weekly FIEs were observed in the PTNS arm than in the sham arm (beta –2.3, 95% CI –4.2 to –0.3 p = 0.02), comprising a reduction in urge FIEs ( p = 0.02) rather than passive FIEs ( p = 0.23). No significant differences were found in the St Mark’s Continence Score or any quality-of-life measures. No serious adverse events related to treatment were reported. PTNS did not show significant clinical benefit over sham electrical stimulation in the treatment of FI based on number of patients who received at least a 50% reduction in weekly FIE. It would be difficult to recommend this therapy for the patient population studied. Further research will concentrate on particular subgroups of patients, for ex le those with pure urge FI. Current Controlled Trials ISRCTN88559475. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment Vol. 19, No. 77. See the NIHR Journals Library website for further project information.
Publisher: Springer Science and Business Media LLC
Date: 24-03-2017
Publisher: Figshare
Date: 2017
Publisher: Figshare
Date: 2015
Publisher: Figshare
Date: 2017
Publisher: Elsevier BV
Date: 10-2015
Publisher: Figshare
Date: 2017
Publisher: Figshare
Date: 2018
Publisher: Figshare
Date: 2017
Publisher: Elsevier BV
Date: 12-2017
DOI: 10.1016/J.CGH.2017.06.032
Abstract: A recent randomized, multi-center, phase 3 trial, performed in the United Kingdom (Control of Fecal Incontinence using Distal Neuromodulation Trial), demonstrated no significant clinical benefit of percutaneous tibial nerve stimulation (PTNS) compared to sham stimulation in patients with fecal incontinence (FI). However, this study did not analyze predictors of response. We used data from this trial to identify factors that predict the efficacy of PTNS in adults with FI. The study population comprised 205 patients from the CONtrol of Fecal Incontinence using Distal NeuromodulaTion Trial. The primary outcome was a binary indicator of success (≥50% reduction in weekly FI episodes after 12 weeks of treatment) or failure, as per the original trial characteristics including baseline FI symptom type, defecatory urgency, and co-existent symptoms of baseline liquid stool consistency and obstructive defecation (OD) were defined a priori. Univariable and multivariable analyses were performed to explore these factors as predictors of response to PTNS and sham. In both univariable and multivariable analysis, the presence of OD symptoms negatively predicted outcome in patients who received PTNS (OR, 0.38 95% CI, 0.16-0.91 P = .029), and positively predicted sham response (OR, 3.45 95% CI, 1.31-9.21 P = .012). No other tested variable affected outcome. Re-analysis of the primary outcome excluding patients with OD symptoms (n = 112) resulted in a significant clinical effect of PTNS compared to sham (48.9% vs 18.2% response, P = .002 multivariable OR, 4.71 95% CI, 1.71-12.93 P = .003). Concomitant OD symptoms negatively affected the clinical outcome of PTNS vs sham in a major randomized controlled trial. Future appropriately designed studies could further explore this observation with potential for future stratified patient selection.
Publisher: Figshare
Date: 2017
Publisher: Figshare
Date: 2017
Publisher: figshare
Date: 2018
Publisher: figshare
Date: 2018
Publisher: Figshare
Date: 2015
Publisher: figshare
Date: 2018
Publisher: Elsevier BV
Date: 09-2016
Publisher: Wiley
Date: 09-2017
DOI: 10.1111/CODI.13781
Abstract: To assess the outcomes of recto-vaginal reinforcement procedures in adults with chronic constipation. Standardised methods and reporting of benefits and harms were used for all CapaCiTY reviews that closely adhered to PRISMA 2016 guidance. Main conclusions were presented as summary evidence statements with a summative Oxford Centre for Evidence-Based Medicine (2009) level. Forty-three articles were identified, providing data on outcomes in 3346 patients. Average length of procedures ranged between 20 and 169 min, and length of stay between 1 and 15 days. Complications typically occurred after 7-17% of procedures (range 0-61%). Post-operative bleeding was uncommon (0-4%) as well as haematoma or sepsis (0-2%). Fistulation did not occur in most studies. Two procedure-related deaths were observed for 3209 patients. Although inconsistent, 78% of patients reported a satisfactory or good outcome, with 30-50% experiencing reduced symptoms of straining, incomplete emptying or reduced vaginal digitation. About 17% of patients developed anatomical recurrence. Considering measures of harm and global satisfaction rating scales, there was insufficient evidence to prefer one type of procedure over another. There was no evidence to support better outcomes based on selection of patients with a particular size or grade of rectocoele. Evidence supporting recto-vaginal reinforcement procedures is currently derived from observational studies and comparisons, with only one high quality study. Large trials are needed to inform future clinical decision making.
Publisher: Wiley
Date: 09-2017
DOI: 10.1111/CODI.13780
Abstract: To assess the outcomes of sacral nerve stimulation in adults with chronic constipation. Standardised methods and reporting of benefits and harms were used for all CapaCiTY reviews that closely adhered to PRISMA 2016 guidance. Main conclusions were presented as summary evidence statements with a summative Oxford Centre for Evidence-Based Medicine (2009) level. Seven articles were identified, providing data on outcomes in 375 patients. Length of procedures and length of stay was not reported. Data on harms were inconsistently reported and heterogeneous, making estimates of harm tentative and imprecise. Morbidity rates ranged between 13 and 34%, with overall device removal rate between 8 and 23%. Although inconsistently reported, pooled treatment success was typically 57-87% for patients receiving permanent implants, although there was significant variation between studies. Patient selection was inconsistently documented. No conclusions could be drawn regarding particular phenotypes that responded favourably or unfavourably to sacral nerve stimulation. Evidence supporting sacral nerve stimulation is derived from poor quality studies. Three methodologically robust trials are have reported since this review and all have all urged greater caution.
Publisher: Figshare
Date: 2017
Publisher: BMJ
Date: 10-06-2015
DOI: 10.1136/THORAXJNL-2015-206996
Abstract: Low-dose vitamin D supplementation is already recommended in older adults for prevention of fractures and falls, but clinical trials investigating whether higher doses could provide additional protection against acute respiratory infection (ARI) are lacking. To conduct a clinical trial of high-dose versus low-dose vitamin D3 supplementation for ARI prevention in residents of sheltered-accommodation housing blocks ('schemes') and their carers in London, UK. Fifty-four schemes (137 in idual participants) were allocated to the active intervention (vitamin D3 2.4 mg once every 2 months +10 μg daily for residents, 3 mg once every 2 months for carers), and 54 schemes with 103 participants were allocated to control (placebo once every 2 months +vitamin D3 10 μg daily for residents, placebo once every 2 months for carers) for 1 year. Primary outcome was time to first ARI secondary outcomes included time to first upper/lower respiratory infection (URI/LRI, analysed separately), and symptom duration. Inadequate vitamin D status was common at baseline: 220/240 (92%) participants had serum 25(OH)D concentration <75 nmol/L. The active intervention did not influence time to first ARI (adjusted HR (aHR) 1.18, 95% CI 0.80 to 1.74, p=0.42). When URI and LRI were analysed separately, allocation to the active intervention was associated with increased risk of URI (aHR 1.48, 95% CI 1.02 to 2.16, p=0.039) and increased duration of URI symptoms (median 7.0 vs 5.0 days for active vs control, adjusted ratio of geometric means 1.34, 95% CI 1.09 to 1.65, p=0.005), but not with altered risk or duration of LRI. Addition of intermittent bolus-dose vitamin D3 supplementation to a daily low-dose regimen did not influence risk of ARI in older adults and their carers, but was associated with increased risk and duration of URI. clinicaltrials.gov NCT01069874.
Publisher: Figshare
Date: 2018
Publisher: figshare
Date: 2020
Publisher: figshare
Date: 2018
Publisher: Figshare
Date: 2017
Publisher: BMJ
Date: 14-11-2013
Publisher: Springer Science and Business Media LLC
Date: 03-08-2022
DOI: 10.1186/S13063-022-06526-Z
Abstract: Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease, characterised by oligodendrocyte death and demyelination. Oligodendrocyte progenitor cells can differentiate into new replacement oligodendrocytes however, remyelination is insufficient to protect neurons from degeneration in people with MS. We previously reported that 4 weeks of daily low-intensity repetitive transcranial magnetic stimulation (rTMS) in an intermittent theta-burst stimulation (iTBS) pattern increased the number of new myelinating oligodendrocytes in healthy adult mice. This study translates this rTMS protocol and aims to determine its safety and tolerability for people living with MS. We will also perform magnetic resonance imaging (MRI) and symptom assessments as preliminary indicators of myelin addition following rTMS. Participants ( N = 30, aged 18–65 years) will have a diagnosis of relapsing-remitting or secondary progressive MS. ≤2 weeks before the intervention, eligible, consenting participants will complete a physical exam, baseline brain MRI scan and participant-reported MS symptom assessments [questionnaires: Fatigue Severity Scale, Quality of Life (AQoL-8D), Hospital Anxiety and Depression Scale and smartphone-based measures of cognition (electronic symbol digit modalities test), manual dexterity (pinching test, draw a shape test) and gait (U-Turn test)]. Participants will be pseudo-randomly allocated to rTMS ( n =20) or sham (placebo n =10), stratified by sex. rTMS or sham will be delivered 5 days per week for 4 consecutive weeks (20 sessions, 6 min per day). rTMS will be applied using a 90-mm circular coil at low-intensity (25% maximum stimulator output) in an iTBS pattern. For sham, the coil will be oriented 90° to the scalp, preventing the magnetic field from stimulating the brain. Adverse events will be recorded daily. We will evaluate participant blinding after the first, 10th and final session. After the final session, participants will repeat symptom assessments and brain MRI, for comparison with baseline. Participant-reported assessments will be repeated at 4-month post-allocation follow-up. This study will determine whether this rTMS protocol is safe and tolerable for people with MS. MRI and participant-reported symptom assessments will serve as preliminary indications of rTMS efficacy for myelin addition to inform further studies. Australian New Zealand Clinical Trials Registry ACTRN12619001196134 . Registered on 27 August 2019
Publisher: Figshare
Date: 2017
Publisher: Figshare
Date: 2017
Publisher: Figshare
Date: 2017
Publisher: figshare
Date: 2018
Publisher: figshare
Date: 2018
Publisher: Figshare
Date: 2015
Publisher: Springer Science and Business Media LLC
Date: 26-06-2018
Publisher: Figshare
Date: 2017
Publisher: Springer Science and Business Media LLC
Date: 06-10-2015
Publisher: Figshare
Date: 2017
Publisher: Figshare
Date: 2017
Publisher: figshare
Date: 2018
Publisher: Figshare
Date: 2017
Publisher: Springer Science and Business Media LLC
Date: 16-06-2020
DOI: 10.1186/S13063-020-04388-X
Abstract: Data collection consumes a large proportion of clinical trial resources. Each data item requires time and effort for collection, processing and quality control procedures. In general, more data equals a heavier burden for trial staff and participants. It is also likely to increase costs. Knowing the types of data being collected, and in what proportion, will be helpful to ensure that limited trial resources and participant goodwill are used wisely. The aim of this study is to categorise the types of data collected across a broad range of trials and assess what proportion of collected data each category represents. We developed a standard operating procedure to categorise data into primary outcome, secondary outcome and 15 other categories. We categorised all variables collected on trial data collection forms from 18, mainly publicly funded, randomised superiority trials, including trials of an investigational medicinal product and complex interventions. Categorisation was done independently in pairs: one person having in-depth knowledge of the trial, the other independent of the trial. Disagreement was resolved through reference to the trial protocol and discussion, with the project team being consulted if necessary. Primary outcome data accounted for 5.0% (median)/11.2% (mean) of all data items collected. Secondary outcomes accounted for 39.9% (median)/42.5% (mean) of all data items. Non-outcome data such as participant identifiers and demographic data represented 32.4% (median)/36.5% (mean) of all data items collected. A small proportion of the data collected in our s le of 18 trials was related to the primary outcome. Secondary outcomes accounted for eight times the volume of data as the primary outcome. A substantial amount of data collection is not related to trial outcomes. Trialists should work to make sure that the data they collect are only those essential to support the health and treatment decisions of those whom the trial is designed to inform.
Publisher: Figshare
Date: 2015
Publisher: Figshare
Date: 2015
Publisher: Figshare
Date: 2015
Publisher: Figshare
Date: 2017
Publisher: Elsevier BV
Date: 02-2016
Publisher: Springer Science and Business Media LLC
Date: 19-05-2022
DOI: 10.1007/S10151-022-02633-W
Abstract: The effectiveness of laparoscopic ventral mesh rectopexy (LVMR) in patients with defecatory disorders secondary to internal rectal prolapse is poorly evidenced. A UK-based multicenter randomized controlled trial was designed to determine the clinical efficacy of LVMR compared to controls at medium-term follow-up. The randomized controlled trial was conducted from March 1, 2015 TO January 31, 2019. A stepped-wedge RCT design permitted observer-masked data comparisons between patients awaiting LVMR (controls) with those who had undergone surgery. Adult participants with radiologically confirmed IRP refractory to conservative treatment were randomized to three arms with different delays before surgery. Efficacy outcome data were collected at equally stepped time points (12, 24, 36, 48, 60, and 72 weeks). Clinical efficacy of LVMR compared to controls was defined as ≥ 1.0-point reduction in Patient Assessment of Constipation-Quality of Life and/or Symptoms (PAC-QOL and/or PAC-SYM) scores at 24 weeks. Secondary outcome measures included 14-day diary data, the Generalized Anxiety Disorder scale (GAD-7), the Patient Health Questionnaire-9 (PHQ-9), St Marks incontinence score, the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12), the chronic constipation Behavioral Response to Illness Questionnaire (CC-BRQ), and the Brief Illness Perception Questionnaire (BIPQ). Of a calculated s le size of 114, only 28 patients (100% female) were randomized from 6 institutions (due mainly to national pause on mesh-related surgery). Nine were assigned to the T0 arm, 10 to T12, and 9 to T24. There were no substantial differences in baseline characteristics between the three arms. Compared to baseline, significant reduction (improvement) in PAC-QOL and PAC-SYM scores were observed at 24 weeks post-surgery (– 1.09 [95% CI – 1.76, – 0.41], p = 0.0019, and – 0.92 [– 1.52, – 0.32], p = 0.0029, respectively) in the 19 patients available for analysis (9 were excluded for dropout [ n = 2] or missing primary outcome [ n = 7]). There was a clinically significant long-term reduction in PAC-QOL scores (− 1.38 [− 2.94, 0.19], p = 0.0840 at 72 weeks). Statistically significant improvements in PAC-SYM scores persisted to 72 weeks (− 1.51 [− 2.87, − 0.16], p = 0.0289). Compared to baseline, no differences were found in secondary outcomes, except for significant improvements at 24 and 48 weeks on CC-BRQ avoidance behavior (− 14.3 [95% CI − 23.3, − 5.4], and − 0.92 [− 1.52, − 0.32], respectively), CC-BRQ safety behavior (− 13.7 [95% CI − 20.5, − 7.0], and − 13.0 [− 19.8, − 6.1], respectively), and BIPQ negative perceptions (− 16.3 [95% CI − 23.5, − 9.0], and − 10.5 [− 17.9, − 3.2], respectively). With the caveat of under-powering due to poor recruitment, the study presents the first randomized trial evidence of short-term benefit of LVMR for internal rectal prolapse. ISRCTN Registry (ISRCTN11747152).
Publisher: figshare
Date: 2018
Publisher: Figshare
Date: 2015
Publisher: figshare
Date: 2018
Publisher: Springer Science and Business Media LLC
Date: 31-03-2017
Publisher: Figshare
Date: 2017
Publisher: Figshare
Date: 2015
Publisher: Figshare
Date: 2017
Publisher: Figshare
Date: 2018
Publisher: Springer Science and Business Media LLC
Date: 11-2013
Publisher: American Society for Microbiology
Date: 18-12-2013
DOI: 10.1128/CVI.00121-13
Abstract: Epstein-Barr virus (EBV) is associated with nasopharyngeal carcinoma (NPC). We assess the safety and tolerability of adoptive transfer of autologous cytotoxic T lymphocytes (CTLs) specific for the EBV latent membrane protein (LMP) in a patient with recurrent NPC. After infusion, the majority of pulmonary lesions were no longer evident, although the primary tumor did not regress.
Publisher: Figshare
Date: 2017
Publisher: figshare
Date: 2018
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Natasha Stevens.