ORCID Profile
0000-0001-9210-4082
Current Organisation
University of Warwick
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Publisher: National Institute for Health and Care Research
Date: 07-2021
DOI: 10.3310/PGFAR09070
Abstract: Lewy body dementia, comprising both dementia with Lewy bodies and Parkinson’s disease dementia, is the second commonest cause of neurodegenerative dementia. Existing evidence suggests that it is underdiagnosed and without a consistent approach to management. To improve the diagnosis and management of Lewy body dementia by (1) understanding current diagnostic practice for dementia with Lewy bodies and Parkinson’s disease dementia (2) identifying barriers to and facilitators of diagnosis and management (3) developing evidence-based assessment toolkits to improve diagnosis of dementia with Lewy bodies and Parkinson’s disease dementia (4) producing a management toolkit to facilitate management and (5) undertaking a pilot cluster randomised clinical trial. Work package 1 assessed clinical diagnostic rates from case notes for dementia with Lewy bodies and Parkinson’s disease dementia before and after (work package 1 repeated) introduction of an assessment toolkit. In work package 2, we developed a management toolkit for Lewy body dementia. In work package 3, we developed assessment toolkits for dementia with Lewy bodies and Parkinson’s disease dementia and piloted these and the management toolkit in a clinical service. In work package 4, we undertook a pilot study of 23 services in nine NHS trusts that were cluster randomised to receiving and using the management toolkit or standard care. Work package 5 comprised a series of qualitative studies, examining barriers to and facilitators of diagnosis and management. Secondary care memory assessment and movement disorder services in England. Assessment toolkits for Lewy body dementia consisted of questions for diagnostic symptoms, and management toolkits comprised 161 guidance statements grouped under five symptom domains. The systematic reviews of pharmacological and non-pharmacological management were based on published literature, with meta-analysis when possible, following a search of several electronic databases and the grey literature using terms related to Lewy body dementia, without restriction on time or language. Participants aged ≥ 50 years diagnosed with dementia with Lewy bodies or Parkinson’s disease dementia and, for work package 1 and work package 1 repeated, non-dementia with Lewy bodies and non-Parkinson’s disease dementia controls. The qualitative studies included people with Lewy body dementia, carers and professionals. For work packages 1 and 1 repeated, diagnostic rates for dementia with Lewy bodies and Parkinson’s disease dementia as a proportion of all dementia or Parkinson’s disease. For work packages 2 and 3, the production of diagnostic and management toolkits. For work package 4, feasibility of undertaking a cluster randomised trial of the toolkits, measured by number of participants recruited and use of the toolkits, assessed qualitatively. Work package 1 – 4.6% of dementia cases in secondary care received a dementia with Lewy bodies diagnosis (with significant differences in diagnostic rates between services) and 9.7% of those with Parkinson’s disease had a diagnosis of Parkinson’s disease dementia. There was evidence of delays in diagnosis for both dementia with Lewy bodies and Parkinson’s disease dementia compared with control patients, and the costs of dementia with Lewy bodies and Parkinson’s disease dementia were also greater than those for matched controls ( p 0.01 for both). Work package 2 – we produced 252 statements regarding Lewy body dementia management and, following a Delphi process, 161 statements were included in a management toolkit. Work package 3 – piloting indicated that separate assessment toolkits for use in memory clinic and movement disorder services were preferred, but a single toolkit for Lewy body dementia management was suitable. Work package 4 – we were able to recruit Lewy body dementia patients to target and recruited 131 patients within 6 months (target n = 120), of whom 80% were retained in the study at 6 months. Work package 5 – barriers to diagnosis and management of Lewy body dementia were complex. Managing Lewy body dementia often requires input from a range of specialties and, therefore, care pathways may be fragmented. Positive attitudes to diagnosing Lewy body dementia, working with a team with expertise in Lewy body dementia and opportunities for cross-specialty discussion of patients with complex needs facilitated diagnosis and management. The toolkits were generally well received, particularly the management toolkit. Implementation, however, varied, reflecting differences in attitudes, skills, time and local leadership. Work package 1 repeated – following introduction of the assessment toolkit, we found that 9.7% of dementia cases had dementia with Lewy bodies (a significant increase from baseline p = 0.0019), but Parkinson’s disease dementia rates were similar (8.2%) to baseline. We included only two geographical regions and evidence informing the management toolkit was limited. Work package 4 was a pilot study and, therefore, we did not set out to assess the extent to which use of the management toolkit altered outcomes at the in idual patient level. We noted implementation of the toolkits was variable. The increase in diagnostic rates in dementia with Lewy bodies following introduction of the assessment toolkits cannot be necessarily causally attributed to them. Dementia with Lewy bodies and Parkinson’s disease dementia were diagnosed in secondary care NHS services, with a lower frequency (around half) than that expected from known prevalence rates. The introduction of assessment toolkits for dementia with Lewy bodies and Parkinson’s disease dementia was associated with increased diagnostic rates of dementia with Lewy bodies, but not Parkinson’s disease dementia. Qualitative studies indicated inherent complexities of the disease itself, with treatment requiring input from different specialties and the potential for fragmented services, a workforce with variable training and confidence in Lewy body dementia, and negative attitudes towards diagnosis. The cluster randomised pilot trial demonstrated that patients could be successfully recruited, and provided preliminary evidence that the toolkits could be implemented in clinical services. The evidence base informing the management of Lewy body dementia is limited, especially for non-pharmacological interventions. More well-designed randomised controlled trials for both cognitive and non-cognitive symptoms are needed. Current Controlled Trials ISRCTN11083027. 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. 7. See the NIHR Journals Library website for further project information.
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: 23-05-2002
DOI: 10.1002/CNCR.10575
Abstract: African-American women are at increased risk for breast cancer mortality compared with white American women, and the extent to which socioeconomic factors account for this outcome disparity is unclear. A MEDLINE search was conducted to identify published studies that used a Cox proportional hazards regression model to evaluate the outcome of African-American women and white American women with breast carcinoma after adjusting for socioeconomic status. A meta-analysis was performed using specialized statistical software the random-effects method of statistical evaluation was used because of the a priori impression that the studies reviewed would be at least moderately heterogeneous in study design and patient populations. The initial literature search yielded 3962 studies. Fourteen studies met all criteria for inclusion in the meta-analysis, resulting in a s le size of 10,001 African-American patients and 42,473 white American patients with breast carcinoma. There was substantial variation in the method used for defining socioeconomic status. Summary statistics revealed a significant odds ratio of 1.22 (95% confidence interval, 1.13-1.30) for the adverse effect of African-American ethnicity on breast cancer mortality. Subset meta-analyses yielded similar results, supporting the robustness of this finding. This meta-analysis revealed that African-American ethnicity is an independent predictor of a worse breast cancer outcome. The pooled analysis has added strength because of the aggregate s le size and indicates that the true biologic and/or therapeutic determinants of disparities in breast cancer outcome for different ethnic groups and for different socioeconomic strata are incompletely understood.
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: Springer Science and Business Media LLC
Date: 06-07-2020
DOI: 10.1186/S40814-020-00635-9
Abstract: Patellar instability is a relatively common condition that leads to disability and restriction of activities. People with recurrent instability may be given the option of physiotherapy or surgery though this is largely driven by clinician preference rather than by a strong evidence base. We sought to determine the feasibility of conducting a definitive trial comparing physiotherapy with surgical treatment for people with recurrent patellar instability. This was a pragmatic, open-label, two-arm feasibility randomised control trial (RCT) with an embedded interview component recruiting across three NHS sites comparing surgical treatment to a package of best conservative care ‘Personalised Knee Therapy’ (PKT). The primary feasibility outcome was the recruitment rate per centre (expected rate 1 to 1.5 participants recruited each month). Secondary outcomes included the rate of follow-up (over 80% expected at 12 months) and a series of participant-reported outcomes taken at 3, 6 and 12 months following randomisation, including the Norwich Patellar Instability Score (NPIS), the Kujala Patellofemoral Disorder Score (KPDS), EuroQol-5D-5L, self-reported global assessment of change, satisfaction at each time point and resources use. We recruited 19 participants. Of these, 18 participants (95%) were followed-up at 12 months and 1 (5%) withdrew. One centre recruited at just over one case per month, one centre was unable to recruit, and one centre recruited at over one case per month after a change in participant screening approach. Ten participants were allocated into the PKT arm, with nine to the surgical arm. Mean Norwich Patellar Instability Score improved from 40.6 (standard deviation 22.1) to 28.2 (SD 25.4) from baseline to 12 months. This feasibility trial identified a number of challenges and required a series of changes to ensure adequate recruitment and follow-up. These changes helped achieve a sufficient recruitment and follow-up rate. The revised trial design is feasible to be conducted as a definitive trial to answer this important clinical question for people with chronic patellar instability. The trial was prospectively registered on the International Standard Randomised Controlled Trial Number registry on the 22/12/2016 (reference number: ISRCTN14950321). www.isrctn.com/ISRCTN14950321
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: 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: BMJ
Date: 05-2020
DOI: 10.1136/BMJOPEN-2020-036829
Abstract: Shoulder pain due to irreparable rotator cuff tears can cause substantial disability, but treatment options are limited. A balloon spacer is a relatively simple addition to a standard arthroscopic debridement procedure, but it is costly and there is no current randomised trial evidence to support its use. This trial will evaluate the clinical and cost-effectiveness of a subacromial balloon spacer for in iduals undergoing arthroscopic debridement for irreparable rotator cuff tears. New surgical procedures can provide substantial benefit to patients. Good quality randomised controlled trials (RCTs) are needed, but trials in surgery are typically long and expensive, exposing patients to risk and the healthcare system to substantial costs. One way to improve the efficiency of trials is with an adaptive s le size. Such methods are well established in drug trials but have rarely, if ever, been used in surgical trials. Subacromial spacer for Tears Affecting Rotator cuff Tendons: a Randomised, Efficient, Adaptive Clinical Trial in Surgery (START:REACTS) is a participant and assessor blinded, adaptive, multicentre RCT comparing arthroscopic debridement with the InSpace balloon (Stryker, USA) to arthroscopic debridement alone for people with a symptomatic irreparable rotator cuff tear. It uses a group sequential adaptive design where interim analyses are performed using all of the 3, 6 and 12-month data that are available at each time point. A maximum of 221 participants will be randomised (1:1 ratio), this will provide 90% power (at the 5% level) for a 6 point difference in the primary outcome the Oxford Shoulder Score at 12 months. A substudy will use deltoid-active MRI scans in 56 participants to assess the function of the balloon. Analysis will be on an intention-to-treat basis and reported according to principles established in the Consolidated Standards of Reporting Trials statement. NRES number 18/WM/0025. The results will be disseminated via peer-reviewed publications, presentations at conferences, lay summaries and social media. ISRCTN17825590
Publisher: Springer Science and Business Media LLC
Date: 05-02-2018
Publisher: Springer Science and Business Media LLC
Date: 31-03-2017
Publisher: Springer Science and Business Media LLC
Date: 12-2019
DOI: 10.1186/S13063-019-3708-6
Abstract: There is widespread concern across the clinical and research communities that clinical trials, powered for patient-reported outcomes, testing new surgical procedures are often expensive and time-consuming, particularly when the new intervention is shown to be no better than the standard. Conventional (non-adaptive) randomised controlled trials (RCTs) are perceived as being particularly inefficient in this setting. Therefore, we have developed an adaptive group sequential design that allows early endpoints to inform decision making and show, through simulations and a worked ex le, that these designs are feasible and often preferable to conventional non-adaptive designs. The methodology is motivated by an ongoing clinical trial investigating a saline-filled balloon, inserted above the main joint of the shoulder at the end of arthroscopic debridement, for treatment of tears of rotor cuff tendons. This research question and setting is typical of many studies undertaken to assess new surgical procedures. Test statistics are presented based on the setting of two early outcomes, and methods for estimation of sequential stopping boundaries are described. A framework for the implementation of simulations to evaluate design characteristics is also described. Simulations show that designs with one, two and three early looks are feasible and, with appropriately chosen futility stopping boundaries, have appealing design characteristics. A number of possible design options are described that have good power and a high probability of stopping for futility if there is no evidence of a treatment effect at early looks. A worked ex le, with code in R, provides a practical demonstration of how the design might work in a real study. In summary, we show that adaptive designs are feasible and could work in practice. We describe the operating characteristics of the designs and provide guidelines for appropriate values for the stopping boundaries for the START:REACTS (Sub-acromial spacer for Tears Affecting Rotator cuff Tendons: a Randomised, Efficient, Adaptive Clinical Trial in Surgery) study. ISRCTN Registry, ISRCTN17825590. Registered on 5 March 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: Springer Science and Business Media LLC
Date: 24-03-2017
Publisher: American Psychiatric Association Publishing
Date: 08-2015
DOI: 10.1176/APPI.AJP.2015.14121582
Abstract: The authors examined research on effects, costs, and patient and caregiver views of pharmacological management strategies for Lewy body dementia. Studies were identified through bibliographic databases, trials registers, gray literature, reference lists, and experts. The authors used the search terms "Lewy or parkinson" and "dementia" through March 2015 and used the following inclusion criteria: participants with diagnoses of Lewy body dementia, dementia with Lewy bodies, or Parkinson's disease dementia (or participants' caregivers) investigation of pharmacological management strategies outcome measures and test scores reported. Data extraction and quality assessment were conducted by at least two authors. Meta-analyses were conducted, and when studies could not be combined, summaries were provided. Forty-four studies examining 22 strategies were included in the review. Meta-analysis indicated beneficial effects of donepezil and rivastigmine for cognitive and psychiatric symptoms. Rivastigmine, but not donepezil, was associated with greater risk of adverse events. Meta-analysis of memantine suggested that it is well tolerated but with few benefits. Descriptive summaries provide some evidence of benefits for galantamine, modafinil, levodopa, rotigotine, clozapine, duloxetine, clonazepam, ramelteon, gabapentin, zonisamide, and yokukansan. Piracetam, amantadine, selegiline, olanzapine, quetiapine, risperidone, and citalopram do not appear to be effective. High-level evidence related to pharmacological strategies for managing Lewy body dementia is rare. Strategies for important areas of need in Lewy body dementia, such as autonomic symptoms and caregiver burden, have not been investigated, nor have the views of patients and caregivers about pharmacological strategies.
Publisher: National Institute for Health and Care Research
Date: 08-2023
DOI: 10.3310/TKJY2101
Publisher: American Medical Association (AMA)
Date: 03-02-1999
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for James Mason.