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A cluster randomised controlled trial, process and economic evaluation of quality improvement collaboratives aligned to a national audit to improve the care for people with diabetes (EQUIPD): study protocol.
Sykes, M, Copsey, B, Finch, T, Meads, D, Farrin, A, McSharry, J, Holman, N, Young, B, Berry, A, Ellis, K, et al
Implementation science : IS. 2023;(1):37
Abstract
BACKGROUND People with type 1 diabetes and raised glucose levels are at greater risk of retinopathy, nephropathy, neuropathy, cardiovascular disease, sexual health problems and foot disease. The UK National Institute for Health and Care Excellence (NICE) recommends continuous subcutaneous 'insulin pump' therapy for people with type 1 diabetes whose HbA1c is above 69 mmol/mol. Insulin pump use can improve quality of life, cut cardiovascular risk and increase treatment satisfaction. About 90,000 people in England and Wales meet NICE criteria for insulin pumps but do not use one. Insulin pump use also varies markedly by deprivation, ethnicity, sex and location. Increasing insulin pump use is a key improvement priority. Audit and feedback is a common but variably effective intervention. Limited capabilities of healthcare providers to mount effective responses to feedback from national audits, such as the National Diabetes Audit (NDA), undermines efforts to improve care. We have co-developed a theoretically and empirically informed quality improvement collaborative (QIC) to strengthen local responses to feedback with patients and carers, national audits and healthcare providers. We will evaluate whether the QIC improves the uptake of insulin pumps following NDA feedback. METHODS We will undertake an efficient cluster randomised trial using routine data. The QIC will be delivered alongside the NDA to specialist diabetes teams in England and Wales. Our primary outcome will be the proportion of people with type 1 diabetes and an HbA1c above 69 mmol/mol who start and continue insulin pump use during the 18-month intervention period. Secondary outcomes will assess change in glucose control and duration of pump use. Subgroup analyses will explore impacts upon inequalities by ethnicity, sex, age and deprivation. A theory-informed process evaluation will explore diabetes specialist teams' engagement, implementation, fidelity and tailoring through observations, interviews, surveys and documentary analysis. An economic evaluation will micro-cost the QIC, estimate cost-effectiveness of NDA feedback with QIC and estimate the budget impact of NHS-wide QIC roll out. DISCUSSION Our study responds to a need for more head-to-head trials of different ways of reinforcing feedback delivery. Our findings will have implications for other large-scale audit and feedback programmes. TRIAL REGISTRATION ISRCTN82176651 Registered 18 October 2022.
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Developing services to support the delivery of care to people with early-onset type 2 diabetes.
Misra, S, Gable, D, Khunti, K, Barron, E, Young, B, Kar, P, Valabhji, J
Diabetic medicine : a journal of the British Diabetic Association. 2022;(10):e14927
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Abstract
Early-onset type 2 diabetes occurring in childhood or early adulthood carries a significant excess burden of microvascular diabetes complications, cardiovascular disease and premature death, compared to later onset type 2 diabetes along with adverse pregnancy outcomes in women of child-bearing age. National audit data in England reveal that 122,780 individuals under the age of 40 years are currently living with type 2 diabetes, with an over-representation of people from minority ethnicities and those in the most socioeconomically deprived quintiles. A diagnosis of type 2 diabetes earlier in life poses some unique challenges to healthcare providers that are not routinely encountered when type 2 diabetes presents later. These include; (1) the need to ensure correct diabetes classification in an age group that carries a higher probability of other types of diabetes, (2) overcoming difficulties in engaging with individuals who are of working age or in full-time education, (3) appreciating and addressing the lower attainment of diabetes treatment targets and (4) proactively supporting women of child-bearing age to optimise their future pregnancy outcomes through better preparation for pregnancy, including achieving optimum glycaemic control at the time of conception. Meanwhile, approaches to prevent type 2 diabetes in younger age groups are challenged by difficulties in identifying those at highest risk, by poorer attendance at lifestyle interventions to prevent or delay the onset of type 2 diabetes and by attenuation of associated weight loss in those that do attend. In this article, we discuss the importance of recognising and addressing the distinct challenges in delivering healthcare to those with early-onset type 2 diabetes, the greater challenges in preventing type 2 diabetes at younger ages, and key components of strategies that might address these challenges to drive improvements in pregnancy outcomes, microvascular and cardiovascular outcomes.
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SAVER: sodium valproate for the epigenetic reprogramming of high-risk oral epithelial dysplasia-a phase II randomised control trial study protocol.
McCarthy, C, Sacco, J, Fedele, S, Ho, M, Porter, S, Liloglou, T, Greenhalf, B, Robinson, M, Young, B, Cicconi, S, et al
Trials. 2021;(1):428
Abstract
BACKGROUND Sodium valproate (VPA) has been associated with a reduced risk of head and neck cancer development. The potential protective mechanism of action is believed to be via inhibition of histone deacetylase and subsequent epigenetic reprogramming. SAVER is a phase IIb open-label, randomised control trial of VPA as a chemopreventive agent in patients with high-risk oral epithelial dysplasia (OED). The aim of the trial is to gather preliminary evidence of the clinical and biological effects of VPA upon OED and assess the feasibility and acceptability of such a trial, with a view to inform a future definitive phase III study. METHODS One hundred and ten patients with high-risk OED will be recruited from up to 10 secondary care sites in the UK and randomised into either VPA or observation only for 4 months. Women of childbearing potential will be excluded due to the teratogenic properties of VPA. Tissue and blood samples will be collected prior to randomisation and on the last day of the intervention/observation-only period (end of 4 months). Clinical measurement and additional safety bloods will be taken at multiple time points during the trial. The primary outcome will be a composite, surrogate endpoint of change in lesion size, change in grade of dysplasia and change in LOH profile at 8 key microsatellite regions. Feasibility outcomes will include recruitment targets, compliance with the study protocol and adverse effects. A qualitative sub-study will explore patient experience and perception of the trial. DISCUSSION The current management options for patients with high-risk OED are limited and mostly include surgical resection and clinical surveillance. However, there remains little evidence whether surgery can effectively lead to a notable reduction in the risk of oral cancer development. Similarly, surveillance is associated with concerns regarding delayed diagnosis of OED progressing to malignancy. The SAVER trial provides an opportunity to investigate the effects of a repurposed, inexpensive and well-tolerated medication as a potential chemopreventive strategy for patients with high-risk OED. The clinical and biological findings of SAVER will inform the appropriateness, design and feasibility of a definitive phase III trial. TRIAL REGISTRATION The trial is registered with the European Clinical Trials Database ( Eudra-CT 2018-000197-30 ). ( http://www.isrctn.com/ISRCTN12448611 ). The trial was prospectively registered on 24/04/2018.
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Risk factors for COVID-19-related mortality in people with type 1 and type 2 diabetes in England: a population-based cohort study.
Holman, N, Knighton, P, Kar, P, O'Keefe, J, Curley, M, Weaver, A, Barron, E, Bakhai, C, Khunti, K, Wareham, NJ, et al
The lancet. Diabetes & endocrinology. 2020;8(10):823-833
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Diabetes, cardiovascular disease, and hypertension are the most common chronic conditions predisposing people to severe COVID-19 disease. The aim of this population-based cohort study, using data from 98% of general practices in England, was to investigate the associations between various risk factors, including poor blood sugar control, and COVID-19-related deaths in people with type 1 and type 2 diabetes. Between Feb 16 and May 11, 2020, 1604 people with type 1 diabetes and 36 291 people with type 2 diabetes died from all causes, of which almost 30% had COVID-19 listed on the death certificate, either a primary underlying or secondary cause of death. Male gender, age and being of Black or Asian ethnicity were associated with an increased mortality from COVID-19. Poor blood sugar control, as determined by HbA1C, prior to infection was strongly associated with COVID-19-related death, independent of other risk factors. Obesity (BMI of 30 or over) as well as being underweight were also significantly associated with COVID-19 mortality. The authors discuss that people with diabetes are at increased risk of many serious infections and that high blood glucose levels are known to impair immunity and may amplify the hyperimmune response associated with severe COVID-19.
Abstract
BACKGROUND Diabetes has been associated with increased COVID-19-related mortality, but the association between modifiable risk factors, including hyperglycaemia and obesity, and COVID-19-related mortality among people with diabetes is unclear. We assessed associations between risk factors and COVID-19-related mortality in people with type 1 and type 2 diabetes. METHODS We did a population-based cohort study of people with diagnosed diabetes who were registered with a general practice in England. National population data on people with type 1 and type 2 diabetes collated by the National Diabetes Audit were linked to mortality records collated by the Office for National Statistics from Jan 2, 2017, to May 11, 2020. We identified the weekly number of deaths in people with type 1 and type 2 diabetes during the first 19 weeks of 2020 and calculated the percentage change from the mean number of deaths for the corresponding weeks in 2017, 2018, and 2019. The associations between risk factors (including sex, age, ethnicity, socioeconomic deprivation, HbA1c, renal impairment [from estimated glomerular filtration rate (eGFR)], BMI, tobacco smoking status, and cardiovascular comorbidities) and COVID-19-related mortality (defined as International Classification of Diseases, version 10, code U07.1 or U07.2 as a primary or secondary cause of death) between Feb 16 and May 11, 2020, were investigated by use of Cox proportional hazards models. FINDINGS Weekly death registrations in the first 19 weeks of 2020 exceeded the corresponding 3-year weekly averages for 2017-19 by 672 (50·9%) in people with type 1 diabetes and 16 071 (64·3%) in people with type 2 diabetes. Between Feb 16 and May 11, 2020, among 264 390 people with type 1 diabetes and 2 874 020 people with type 2 diabetes, 1604 people with type 1 diabetes and 36 291 people with type 2 diabetes died from all causes. Of these total deaths, 464 in people with type 1 diabetes and 10 525 in people with type 2 diabetes were defined as COVID-19 related, of which 289 (62·3%) and 5833 (55·4%), respectively, occurred in people with a history of cardiovascular disease or with renal impairment (eGFR <60 mL/min per 1·73 m2). Male sex, older age, renal impairment, non-white ethnicity, socioeconomic deprivation, and previous stroke and heart failure were associated with increased COVID-19-related mortality in both type 1 and type 2 diabetes. Compared with people with an HbA1c of 48-53 mmol/mol (6·5-7·0%), people with an HbA1c of 86 mmol/mol (10·0%) or higher had increased COVID-19-related mortality (hazard ratio [HR] 2·23 [95% CI 1·50-3·30, p<0·0001] in type 1 diabetes and 1·61 [1·47-1·77, p<0·0001] in type 2 diabetes). In addition, in people with type 2 diabetes, COVID-19-related mortality was significantly higher in those with an HbA1c of 59 mmol/mol (7·6%) or higher than in those with an HbA1c of 48-53 mmol/mol (HR 1·22 [95% CI 1·15-1·30, p<0·0001] for 59-74 mmol/mol [7·6-8·9%] and 1·36 [1·24-1·50, p<0·0001] for 75-85 mmol/mol [9·0-9·9%]). The association between BMI and COVID-19-related mortality was U-shaped: in type 1 diabetes, compared with a BMI of 25·0-29·9 kg/m2, a BMI of less than 20·0 kg/m2 had an HR of 2·45 (95% CI 1·60-3·75, p<0·0001) and a BMI of 40·0 kg/m2 or higher had an HR of 2·33 (1·53-3·56, p<0·0001); the corresponding HRs for type 2 diabetes were 2·33 (2·11-2·56, p<0·0001) and 1·60 (1·47-1·75, p<0·0001). INTERPRETATION Deaths in people with type 1 and type 2 diabetes rose sharply during the initial COVID-19 pandemic in England. Increased COVID-19-related mortality was associated not only with cardiovascular and renal complications of diabetes but, independently, also with glycaemic control and BMI. FUNDING None.
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Ketogenic diets as an adjuvant therapy for glioblastoma (KEATING): a randomized, mixed methods, feasibility study.
Martin-McGill, KJ, Marson, AG, Tudur Smith, C, Young, B, Mills, SJ, Cherry, MG, Jenkinson, MD
Journal of neuro-oncology. 2020;(1):213-227
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Abstract
PURPOSE We conducted a feasibility study to investigate the use of ketogenic diets (KDs) as an adjuvant therapy for patients with glioblastoma (GBM), investigating (i) trial feasibility; (ii) potential impacts of the trial on patients' quality of life and health; (iii) patients' perspectives of their decision-making when invited to participate in the trial and (iv) recommending improvements to optimize future phase III trials. METHODS A single-center, prospective, randomized, pilot study (KEATING), with an embedded qualitative design. Twelve newly diagnosed patients with GBM were randomized 1:1 to modified ketogenic diet (MKD) or medium chain triglyceride ketogenic diet (MCTKD). Primary outcome was retention at three months. Semi-structured interviews were conducted with a purposive sample of patients and caregivers (n = 15). Descriptive statistics were used for quantitative outcomes and qualitative data were analyzed thematically aided by NVivo. RESULTS KEATING achieved recruitment targets, but the recruitment rate was low (28.6%). Retention was poor; only four of 12 patients completed the three-month diet (MCTKD n = 3; MKD n = 1). Participants' decisions were intuitive and emotional; caregivers supported diet implementation and influenced the patients' decision to participate. Those who declined made a deliberative and considered decision factoring diet burden and quality of life. A three-month diet was undesirable to patients who declined and withdrew. CONCLUSION Recruitment to a KD trial for patients with GBM is possible. A six-week intervention period is proposed for a phase III trial. The role of caregivers should not be underestimated. Future trials should optimize and adequately support the decision-making of patients.
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Is anemia an independent risk factor for postpartum depression in women who have a cesarean section? - A prospective observational study.
Chandrasekaran, N, De Souza, LR, Urquia, ML, Young, B, Mcleod, A, Windrim, R, Berger, H
BMC pregnancy and childbirth. 2018;(1):400
Abstract
BACKGROUND The symptoms of anemia and depression are very similar suggesting that there may be an association between the two entities. The aim of this study is to assess whether postpartum anemia (PPA) is an independent risk factor for de novo postpartum depression (PPD)in women undergoing elective cesarean section. METHODS Women after an uncomplicated term cesarean section were recruited and their hemoglobin and iron status were measured on day 3-5 post section and again at 6 weeks. Postpartum depression was screened using the Edinburgh Postnatal Depression Scale (EPDS) and functional capacity was assessed with the RAND 12-item Health survey. RESULTS One hundred and three women completed the study. The incidence of probable postpartum depression (PPD) as defined by EPDS score ≥ 10 was 17% at 6 weeks. There was no difference in hemoglobin or iron status in women who had PPD compared to those without (OR-0.69; 95% CI-0.15-2.49). Similarly, there was no significant association between low hemoglobin and maternal functional status (OR -1.03; 95% CI-0.34 - 2.94). CONCLUSIONS Neither anemia or low iron stores were found to be an independent risk factors for postpartum depression or decreased postpartum functional capacity in women who undergo an elective cesarean section.
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The HIV care continuum in Latin America: challenges and opportunities.
Piñeirúa, A, Sierra-Madero, J, Cahn, P, Guevara Palmero, RN, Martínez Buitrago, E, Young, B, Del Rio, C
The Lancet. Infectious diseases. 2015;(7):833-9
Abstract
Combination antiretroviral therapy (ART), also known as highly active antiretroviral therapy, provides clinical and immunological benefits for people living with HIV and is an effective strategy to prevent HIV transmission at the individual level. Early initiation of ART as part of a test and treat approach might decrease HIV transmission at the population level, but to do so the HIV continuum of care, from diagnosis to viral suppression, should be optimised. Access to ART has improved greatly in Latin America, and about 600,000 people are on treatment. However, health-care systems are deficient in different stages of the HIV continuum of care, and in some cases only a small proportion of individuals achieve the desired outcome of virological suppression. At present, data for most Latin American countries are not sufficient to build reliable metrics. Available data and estimates show that many people living with HIV in Latin America are unaware of their status, are diagnosed late, and enter into care late. Stigma, administrative barriers, and economic limitations seem to be important determinants of late diagnosis and failure to be linked to and retained in care. Policy makers need reliable data to optimise the HIV care continuum and improve individual-based and population-based outcomes of ART in Latin America.
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Surgical manifestations of gastrointestinal cytomegalovirus infection in children: Clinical audit and literature review.
Arnold, M, Itzikowitz, R, Young, B, Machoki, SM, Hsiao, NY, Pillay, K, Alexander, A
Journal of pediatric surgery. 2015;(11):1874-9
Abstract
INTRODUCTION Gastrointestinal sequelae of cytomegalovirus are rare, usually associated with significant immune compromise, and carry a high morbidity and mortality. Gastrointestinal disease frequently requires surgical intervention for diagnosis and management. AIM: The aim of the study is to evaluate the incidence, presentation and management of gastrointestinal cytomegalovirus disease in a pediatric population. METHOD Between January 2003 and June 2011, a retrospective folder review was conducted of all symptomatic children with proven CMV disease, presenting to the surgical service. Eligible patients were identified using the surgical, histopathology and serology databases. RESULTS Thirty-eight patients (1.8/1000 surgical admissions) were identified with a median presenting age of 5months (range 3days-12years). Esophagitis (n=18) and small bowel disease (n=16) predominated, but CMV was seen throughout the gastrointestinal tract. Risk factors included HIV infection (n=21, 55%) and recent gastrointestinal surgery or infection (n=10, 26%). Characteristic multiple jejunoileal perforations were seen in six patients. Compared to upper GIT disease, intestinal involvement was associated with younger age and doubled mortality. In HIV-infected children, median CD4 (%) was lower in intestinal compared to upper gastrointestinal disease. Morbidities included anastomotic breakdowns (5), anastomotic strictures (3), relook laparotomies (10), resistant esophageal strictures (5) and prolonged parenteral nutrition (5). Anti-CMV drugs were given in 63%. Overall mortality was 32% (12/38) and was associated with lower GIT disease. CONCLUSION Invasive CMV gastrointestinal disease in our children was predominantly HIV-associated, or followed a major lower gastrointestinal inflammatory insult in infants younger than 6months. Successful therapy requires a high index of suspicion of active CMV disease to allow early implementation of CMV viral load control and aggressive treatment of the underlying immune impairment. Multiple surgical interventions are often required for both tissue diagnosis and management of acute and chronic complications. CMV-viral-load-tailored anti-CMV therapy is supported by recent literature.
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Does seasonal level of serum 25-OH vitamin D correlate with the activity of Crohn's disease?
Kini, GP, Young, B, Herbison, P, Schultz, M
The New Zealand medical journal. 2014;(1394):51-9
Abstract
BACKGROUND AND AIM Vitamin D has immune modulating effects and normal to high levels might be correlated with less severe Crohn's disease (CD). We aimed to review seasonal vitamin D levels in CD patients in correlation with disease activity. METHODS CD patients were identified from an inflammatory bowel disease (IBD) database and given two questionnaires enquiring about vitamin D supplementation, sun exposure, sunblock application and symptoms to complete the CDAI. Participants were examined and serum 25-OH vitamin D [25(OH)D] levels and haematocrit were determined in winter (06/2011-09/2011) and summer (12/2011-03/2012). Patients taking vitamin D supplements or with extensive small bowel resection were excluded. RESULTS 32 patients (19 women, mean age 39 plus or minus 16 years, range 18-73 years), from Dunedin, New Zealand (45 degrees 52' S, 170 degrees 30' E) consented to participate in the study. Of these, three took vitamin D supplements and were excluded. In winter 76% of the participants had serum 25(OH)D levels classified as deficient (<50 nmol/L) and all of them had insufficient 25(OH)D levels (<75 nmol/L). In summer, serum 25(OH)D levels were deficient only in 10% but insufficient in 55% of the participants. Mean serum 25(OH)D level was 35.9 nmol/L (norm 50-150nmol/L) in winter (range 5-67, SD 17.5) and 69.6 nmol/L in summer (range 13-119, SD 19.0) (p<0.0005). There was no significant difference in the seasonal levels of serum 25(OH)D between male and female participants (p=0.601). Mean CDAI score was 103.9 in winter (range -10-262, SD 76.9) and 90.2 in summer (range -13-331, SD 84.0) (p=0.365). A mixed-effects regression analysis showed no statistically significant correlation between seasonal levels of serum 25(OH)D and CDAI (p=0.612) among our study participants. CONCLUSION Suboptimal levels of serum 25(OH)D were found in the majority of our study participants particularly in winter and they would benefit from supplementation. Our study showed no statistically significant correlation between seasonal serum 25(OH)D levels and CD activity. Given the limitations of the study, the role of 25(OH)D as a predictor of disease activity could not be clearly concluded.
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Cost-effectiveness of a multicondition collaborative care intervention: a randomized controlled trial.
Katon, W, Russo, J, Lin, EH, Schmittdiel, J, Ciechanowski, P, Ludman, E, Peterson, D, Young, B, Von Korff, M
Archives of general psychiatry. 2012;(5):506-14
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CONTEXT Patients with depression and poorly controlled diabetes mellitus, coronary heart disease (CHD), or both have higher medical complication rates and higher health care costs, suggesting that more effective care management of psychiatric and medical disease control might also reduce medical service use and enhance quality of life. OBJECTIVE To evaluate the cost-effectiveness of a multicondition collaborative treatment program (TEAMcare) compared with usual primary care (UC) in outpatients with depression and poorly controlled diabetes or CHD. DESIGN Randomized controlled trial of a systematic care management program aimed at improving depression scores and hemoglobin A(1c) (HbA(1c)), systolic blood pressure (SBP), and low-density lipoprotein cholesterol (LDL-C) levels. SETTING Fourteen primary care clinics of an integrated health care system. PATIENTS Population-based screening identified 214 adults with depressive disorder and poorly controlled diabetes or CHD. INTERVENTION Physician-supervised nurses collaborated with primary care physicians to provide treatment of multiple disease risk factors. MAIN OUTCOME MEASURES Blinded assessments evaluated depressive symptoms, SBP, and HbA(1c) at baseline and at 6, 12, 18, and 24 months. Fasting LDL-C concentration was assessed at baseline and at 12 and 24 months. Health plan accounting records were used to assess medical service costs. Quality-adjusted life-years (QALYs) were assessed using a previously developed regression model based on intervention vs UC differences in HbA(1c), LDL-C, and SBP levels over 24 months. RESULTS Over 24 months, compared with UC controls, intervention patients had a mean of 114 (95% CI, 79 to 149) additional depression-free days and an estimated 0.335 (95% CI, -0.18 to 0.85) additional QALYs. Intervention patients also had lower mean outpatient health costs of $594 per patient (95% CI, -$3241 to $2053) relative to UC patients. CONCLUSIONS For adults with depression and poorly controlled diabetes, CHD, or both, a systematic intervention program aimed at improving depression scores and HbA(1c), SBP, and LDL-C levels seemed to be a high-value program that for no or modest additional cost markedly improved QALYs. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00468676