Dexter in Print
Dexter has been published in a wide variety of medical and healthcare related publications and papers. Copies of any of the following are available on request.
2019
Bhachu, Harjeet Kaur; Cockwell, Paul; Subramanian, Anuradhaa; Nirantharakumar, Krishnarajah; Kyte, Derek; Calvert, Melanie
In: BMJ Open, vol. 9, iss. 6, 2019, ISSN: 20446055.
@article{Bhachu2019,
title = {Cross-sectional observation study to investigate the impact of risk-based stratification on care pathways for patients with chronic kidney disease: Protocol paper},
author = {Harjeet Kaur Bhachu and Paul Cockwell and Anuradhaa Subramanian and Krishnarajah Nirantharakumar and Derek Kyte and Melanie Calvert},
doi = {10.1136/BMJOPEN-2018-027315},
issn = {20446055},
year = {2019},
date = {2019-01-01},
journal = {BMJ Open},
volume = {9},
issue = {6},
publisher = {BMJ Publishing Group},
abstract = {Introduction Chronic kidney disease (CKD) management in the UK is usually primary care based, with National Institute for Health and Care Excellence (NICE) guidelines defining criteria for referral to secondary care nephrology services. Estimated glomerular filtration rate (EGFR) is commonly used to guide timing of referrals and preparation of patients approaching renal replacement therapy. However, EGFR lacks sensitivity for progression to end-stage renal failure; as a consequence, the international guideline group, Kidney Disease: Improving Global Outcomes has recommended the use of a risk calculator. The validated Kidney Failure Risk Equation may enable increased precision for the management of patients with CKD; however, there is little evidence to date for the implication of its use in routine clinical practice. This study will aim to determine the impact of the Kidney Failure Risk Equation on the redesignation of patients with CKD in the UK for referral to secondary care, compared with NICE CKD guidance. Method and analysis This is a cross-sectional population-based observational study using The Health Improvement Network database to identify the impact of risk-based designation for referral into secondary care for patients with CKD in the UK. Adult patients registered in primary care and active in the database within the period 1 January 2016 to 31 March 2017 with confirmed CKD will be analysed. The proportion of patients who meet defined risk thresholds will be cross-referenced with the current NICE guideline recommendations for referral into secondary care along with an evaluation of urinary albumin-creatinine ratio monitoring. Ethics and dissemination Approval was granted by The Health Improvement Network Scientific Review Committee (Reference number: 18THIN061). Study outcomes will inform national and international guidelines including the next version of the NICE CKD guideline. Dissemination of findings will also be through publication in a peer-reviewed journal, presentation at conferences and inclusion in the core resources of the Think Kidneys programme.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Introduction Chronic kidney disease (CKD) management in the UK is usually primary care based, with National Institute for Health and Care Excellence (NICE) guidelines defining criteria for referral to secondary care nephrology services. Estimated glomerular filtration rate (EGFR) is commonly used to guide timing of referrals and preparation of patients approaching renal replacement therapy. However, EGFR lacks sensitivity for progression to end-stage renal failure; as a consequence, the international guideline group, Kidney Disease: Improving Global Outcomes has recommended the use of a risk calculator. The validated Kidney Failure Risk Equation may enable increased precision for the management of patients with CKD; however, there is little evidence to date for the implication of its use in routine clinical practice. This study will aim to determine the impact of the Kidney Failure Risk Equation on the redesignation of patients with CKD in the UK for referral to secondary care, compared with NICE CKD guidance. Method and analysis This is a cross-sectional population-based observational study using The Health Improvement Network database to identify the impact of risk-based designation for referral into secondary care for patients with CKD in the UK. Adult patients registered in primary care and active in the database within the period 1 January 2016 to 31 March 2017 with confirmed CKD will be analysed. The proportion of patients who meet defined risk thresholds will be cross-referenced with the current NICE guideline recommendations for referral into secondary care along with an evaluation of urinary albumin-creatinine ratio monitoring. Ethics and dissemination Approval was granted by The Health Improvement Network Scientific Review Committee (Reference number: 18THIN061). Study outcomes will inform national and international guidelines including the next version of the NICE CKD guideline. Dissemination of findings will also be through publication in a peer-reviewed journal, presentation at conferences and inclusion in the core resources of the Think Kidneys programme.
2018
Kumarendran, Balachandran; O’Reilly, Michael W.; Manolopoulos, Konstantinos N.; Toulis, Konstantinos A.; Gokhale, Krishna M.; Sitch, Alice J.; Wijeyaratne, Chandrika N.; Coomarasamy, Arri; Arlt, Wiebke; Nirantharakumar, Krishnarajah
In: PLoS Medicine, vol. 15, iss. 3, 2018, ISSN: 15491676.
@article{Kumarendran2018,
title = {Polycystic ovary syndrome, androgen excess, and the risk of nonalcoholic fatty liver disease in women: A longitudinal study based on a United Kingdom primary care database},
author = {Balachandran Kumarendran and Michael W. O’Reilly and Konstantinos N. Manolopoulos and Konstantinos A. Toulis and Krishna M. Gokhale and Alice J. Sitch and Chandrika N. Wijeyaratne and Arri Coomarasamy and Wiebke Arlt and Krishnarajah Nirantharakumar},
doi = {10.1371/JOURNAL.PMED.1002542},
issn = {15491676},
year = {2018},
date = {2018-01-01},
journal = {PLoS Medicine},
volume = {15},
issue = {3},
publisher = {Public Library of Science},
abstract = {Background: Androgen excess is a defining feature of polycystic ovary syndrome (PCOS), which affects 10% of women and represents a lifelong metabolic disorder, with increased risk of type 2 diabetes, hypertension, and cardiovascular events. Previous studies have suggested an increased risk of nonalcoholic fatty liver disease (NAFLD) in individuals with PCOS and implicated androgen excess as a potential driver. Methods and findings: We carried out a retrospective longitudinal cohort study utilizing a large primary care database in the United Kingdom, evaluating NAFLD rates in 63,120 women with PCOS and 121,064 age-, body mass index (BMI)-, and location-matched control women registered from January 2000 to May 2016. In 2 independent cohorts, we also determined the rate of NAFLD in women with a measurement of serum testosterone (n = 71,061) and sex hormone-binding globulin (SHBG; n = 49,625). We used multivariate Cox models to estimate the hazard ratio (HR) for NAFLD and found that women with PCOS had an increased rate of NAFLD (HR = 2.23, 95% CI 1.86–2.66, p < 0.001), also after adjusting for BMI or dysglycemia. Serum testosterone >3.0 nmol/L was associated with an increase in NAFLD (HR = 2.30, 95% CI 1.16–4.53},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background: Androgen excess is a defining feature of polycystic ovary syndrome (PCOS), which affects 10% of women and represents a lifelong metabolic disorder, with increased risk of type 2 diabetes, hypertension, and cardiovascular events. Previous studies have suggested an increased risk of nonalcoholic fatty liver disease (NAFLD) in individuals with PCOS and implicated androgen excess as a potential driver. Methods and findings: We carried out a retrospective longitudinal cohort study utilizing a large primary care database in the United Kingdom, evaluating NAFLD rates in 63,120 women with PCOS and 121,064 age-, body mass index (BMI)-, and location-matched control women registered from January 2000 to May 2016. In 2 independent cohorts, we also determined the rate of NAFLD in women with a measurement of serum testosterone (n = 71,061) and sex hormone-binding globulin (SHBG; n = 49,625). We used multivariate Cox models to estimate the hazard ratio (HR) for NAFLD and found that women with PCOS had an increased rate of NAFLD (HR = 2.23, 95% CI 1.86–2.66, p < 0.001), also after adjusting for BMI or dysglycemia. Serum testosterone >3.0 nmol/L was associated with an increase in NAFLD (HR = 2.30, 95% CI 1.16–4.53
Nirantharakumar, Krishnarajah; Mohammed, Nuredin; Toulis, Konstantinos A.; Thomas, G. Neil; Narendran, Parth
In: Diabetologia, vol. 61, iss. 5, pp. 1064-1070, 2018, ISSN: 14320428.
@article{Nirantharakumar2018,
title = {Clinically meaningful and lasting HbA1c improvement rarely occurs after 5 years of type 1 diabetes: an argument for early, targeted and aggressive intervention following diagnosis},
author = {Krishnarajah Nirantharakumar and Nuredin Mohammed and Konstantinos A. Toulis and G. Neil Thomas and Parth Narendran},
doi = {10.1007/S00125-018-4574-6},
issn = {14320428},
year = {2018},
date = {2018-01-01},
journal = {Diabetologia},
volume = {61},
issue = {5},
pages = {1064-1070},
publisher = {Springer Verlag},
abstract = {Aims/hypothesis: Our objectives were to explore whether the phenomenon of HbA1c ‘tracking’ occurs in individuals with type 1 diabetes, how long after diagnosis does tracking take to stabilise, and whether there is an effect of sex and age at diagnosis on tracking. Methods: A total of 4525 individuals diagnosed with type 1 diabetes between 1 January 1995 and 1 May 2015 were identified from The Health Improvement Network (THIN) database. Mixed models were applied to assess the variability of HbA1c levels over time with random effects on general practices (primary care units) and individuals within practices. Results: 4525 individuals diagnosed with type 1 diabetes were identified in THIN over the study period. The greatest difference in mean HbA1c measurement (−7.0 [95% CI −8.0, −6.1] mmol/mol [0.6%]) was seen when comparing measurements made immediately after diagnosis (0–1 year since diagnosis) with those at 10 or more years (the reference category). The mean difference in HbA1c for the successive periods compared with 10 or more years after diagnosis declined and was no longer statistically significant after 5 years. In the stratified analysis using sex and age group there was considerable heterogeneity with adult onset type 1 diabetes appearing to track earlier and at a lower mean HbA1c. Conclusions/interpretation: In individuals with type 1 diabetes, glycaemic control measured by HbA1c settles onto a long-term ‘track’ and this occurs on average by 5 years following diagnosis. Age at diagnosis modifies both the rate at which individuals settle into their track and the absolute HbA1c tracking level for the next 10 years.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Aims/hypothesis: Our objectives were to explore whether the phenomenon of HbA1c ‘tracking’ occurs in individuals with type 1 diabetes, how long after diagnosis does tracking take to stabilise, and whether there is an effect of sex and age at diagnosis on tracking. Methods: A total of 4525 individuals diagnosed with type 1 diabetes between 1 January 1995 and 1 May 2015 were identified from The Health Improvement Network (THIN) database. Mixed models were applied to assess the variability of HbA1c levels over time with random effects on general practices (primary care units) and individuals within practices. Results: 4525 individuals diagnosed with type 1 diabetes were identified in THIN over the study period. The greatest difference in mean HbA1c measurement (−7.0 [95% CI −8.0, −6.1] mmol/mol [0.6%]) was seen when comparing measurements made immediately after diagnosis (0–1 year since diagnosis) with those at 10 or more years (the reference category). The mean difference in HbA1c for the successive periods compared with 10 or more years after diagnosis declined and was no longer statistically significant after 5 years. In the stratified analysis using sex and age group there was considerable heterogeneity with adult onset type 1 diabetes appearing to track earlier and at a lower mean HbA1c. Conclusions/interpretation: In individuals with type 1 diabetes, glycaemic control measured by HbA1c settles onto a long-term ‘track’ and this occurs on average by 5 years following diagnosis. Age at diagnosis modifies both the rate at which individuals settle into their track and the absolute HbA1c tracking level for the next 10 years.
Chandan, J. S.; Thomas, T.; Lee, S.; Marshall, T.; Willis, B.; Nirantharakumar, K.; Gill, P.
The association between idiopathic thrombocytopenic purpura and cardiovascular disease: a retrospective cohort study Journal Article
In: Journal of Thrombosis and Haemostasis, vol. 16, iss. 3, pp. 474-480, 2018, ISSN: 15387836.
@article{Chandan2018,
title = {The association between idiopathic thrombocytopenic purpura and cardiovascular disease: a retrospective cohort study},
author = {J. S. Chandan and T. Thomas and S. Lee and T. Marshall and B. Willis and K. Nirantharakumar and P. Gill},
doi = {10.1111/JTH.13940},
issn = {15387836},
year = {2018},
date = {2018-01-01},
journal = {Journal of Thrombosis and Haemostasis},
volume = {16},
issue = {3},
pages = {474-480},
publisher = {Blackwell Publishing Ltd},
abstract = {Essentials We estimated the cardiovascular risk of patients with idiopathic thrombocytopenic purpura (ITP). The risk of cardiovascular disease was 38% higher in ITP patients compared with controls. Among the ITP patients, splenectomy was associated with higher cardiovascular disease. Clinicians should consider cardiovascular risk when managing ITP patients. Summary: Background Idiopathic thrombocytopenic purpura (ITP) is classically characterized by a transient or persistent decrease of platelet count. Mortality is higher in the ITP population than the general population, with a possible association with increased cardiovascular disease (CVD). Objectives The objective was to assess the strength of the association between ITP and CVD, with a secondary aim to assess the impact of splenectomy on CVD. Methods A population-based retrospective, open cohort study using clinical codes was performed using data from 6591 patients with ITP and 24 275 randomly matched controls (up to 1:4 ratio matched by age, sex, body mass index and smoking status). The main outcome was the risk of CVD, which included ischemic heart disease, stroke, trans-ischemic attack and heart failure. Adjusted incidence rate ratios were calculated using Poisson regression. Results During a median 6-year observation period there was a CVD diagnosis recorded in 392 (5.9%) ITP patients and 1114 (4.5%) control patients. There was an increased risk of developing CVD in the ITP cohort (incidence rate ratio [IRR], 1.38; 95% confidence interval [CI], 1.23–1.55), which remained robust even after a sensitivity analysis only including incident cases of ITP. Findings suggested that patients who had undergone splenectomy were at even further increased risk of developing CVD when compared with the ITP population who had not undergone splenectomy (adjusted IRR, 1.69; 95% CI, 1.22–2.34). Conclusion There is an increased risk of developing CVD in patients with ITP and even further increased risk for those patients with ITP who underwent splenectomy.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Essentials We estimated the cardiovascular risk of patients with idiopathic thrombocytopenic purpura (ITP). The risk of cardiovascular disease was 38% higher in ITP patients compared with controls. Among the ITP patients, splenectomy was associated with higher cardiovascular disease. Clinicians should consider cardiovascular risk when managing ITP patients. Summary: Background Idiopathic thrombocytopenic purpura (ITP) is classically characterized by a transient or persistent decrease of platelet count. Mortality is higher in the ITP population than the general population, with a possible association with increased cardiovascular disease (CVD). Objectives The objective was to assess the strength of the association between ITP and CVD, with a secondary aim to assess the impact of splenectomy on CVD. Methods A population-based retrospective, open cohort study using clinical codes was performed using data from 6591 patients with ITP and 24 275 randomly matched controls (up to 1:4 ratio matched by age, sex, body mass index and smoking status). The main outcome was the risk of CVD, which included ischemic heart disease, stroke, trans-ischemic attack and heart failure. Adjusted incidence rate ratios were calculated using Poisson regression. Results During a median 6-year observation period there was a CVD diagnosis recorded in 392 (5.9%) ITP patients and 1114 (4.5%) control patients. There was an increased risk of developing CVD in the ITP cohort (incidence rate ratio [IRR], 1.38; 95% confidence interval [CI], 1.23–1.55), which remained robust even after a sensitivity analysis only including incident cases of ITP. Findings suggested that patients who had undergone splenectomy were at even further increased risk of developing CVD when compared with the ITP population who had not undergone splenectomy (adjusted IRR, 1.69; 95% CI, 1.22–2.34). Conclusion There is an increased risk of developing CVD in patients with ITP and even further increased risk for those patients with ITP who underwent splenectomy.
Adderley, Nicola J.; Nirantharakumar, Krishnarajah; Marshall, Tom
Risk of stroke and transient ischaemic attack in patients with a diagnosis of resolved atrial fibrillation: Retrospective cohort studies Journal Article
In: BMJ (Online), vol. 361, 2018, ISSN: 17561833.
@article{Adderley2018,
title = {Risk of stroke and transient ischaemic attack in patients with a diagnosis of resolved atrial fibrillation: Retrospective cohort studies},
author = {Nicola J. Adderley and Krishnarajah Nirantharakumar and Tom Marshall},
doi = {10.1136/BMJ.K1717},
issn = {17561833},
year = {2018},
date = {2018-01-01},
journal = {BMJ (Online)},
volume = {361},
publisher = {BMJ Publishing Group},
abstract = {Objectives To determine rates of stroke or transient ischaemic attack (TIA) and all cause mortality in patients with a diagnosis of "resolved" atrial fibrillation compared to patients with unresolved atrial fibrillation and without atrial fibrillation. Design Two retrospective cohort studies. Setting General practices contributing to The Health Improvement Network, 1 January 2000 to 15 May 2016. Participants Adults aged 18 years or more with no previous stroke or TIA: 11 159 with resolved atrial fibrillation, 15 059 controls with atrial fibrillation, and 22 266 controls without atrial fibrillation. Main outcome measures Primary outcome was incidence of stroke or TIA. Secondary outcome was all cause mortality. Results Adjusted incidence rate ratios for stroke or TIA in patients with resolved atrial fibrillation were 0.76 (95% confidence interval 0.67 to 0.85, P<0.001) versus controls with atrial fibrillation and 1.63 (1.46 to 1.83, P<0.001) versus controls without atrial fibrillation. Adjusted incidence rate ratios for mortality in patients with resolved atrial fibrillation were 0.60 (0.56 to 0.65, P<0.001) versus controls with atrial fibrillation and 1.13 (1.06 to 1.21, P<0.001) versus controls without atrial fibrillation. When patients with resolved atrial fibrillation and documented recurrent atrial fibrillation were excluded the adjusted incidence rate ratio for stroke or TIA was 1.45 (1.26 to 1.67, P<0.001) versus controls without atrial fibrillation. Conclusion Patients with resolved atrial fibrillation remain at higher risk of stroke or TIA than patients without atrial fibrillation. The risk is increased even in those in whom recurrent atrial fibrillation is not documented. Guidelines should be updated to advocate continued use of anticoagulants in patients with resolved atrial fibrillation.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Objectives To determine rates of stroke or transient ischaemic attack (TIA) and all cause mortality in patients with a diagnosis of "resolved" atrial fibrillation compared to patients with unresolved atrial fibrillation and without atrial fibrillation. Design Two retrospective cohort studies. Setting General practices contributing to The Health Improvement Network, 1 January 2000 to 15 May 2016. Participants Adults aged 18 years or more with no previous stroke or TIA: 11 159 with resolved atrial fibrillation, 15 059 controls with atrial fibrillation, and 22 266 controls without atrial fibrillation. Main outcome measures Primary outcome was incidence of stroke or TIA. Secondary outcome was all cause mortality. Results Adjusted incidence rate ratios for stroke or TIA in patients with resolved atrial fibrillation were 0.76 (95% confidence interval 0.67 to 0.85, P<0.001) versus controls with atrial fibrillation and 1.63 (1.46 to 1.83, P<0.001) versus controls without atrial fibrillation. Adjusted incidence rate ratios for mortality in patients with resolved atrial fibrillation were 0.60 (0.56 to 0.65, P<0.001) versus controls with atrial fibrillation and 1.13 (1.06 to 1.21, P<0.001) versus controls without atrial fibrillation. When patients with resolved atrial fibrillation and documented recurrent atrial fibrillation were excluded the adjusted incidence rate ratio for stroke or TIA was 1.45 (1.26 to 1.67, P<0.001) versus controls without atrial fibrillation. Conclusion Patients with resolved atrial fibrillation remain at higher risk of stroke or TIA than patients without atrial fibrillation. The risk is increased even in those in whom recurrent atrial fibrillation is not documented. Guidelines should be updated to advocate continued use of anticoagulants in patients with resolved atrial fibrillation.
Toulis, Konstantinos A.; Robbins, Tim; Reddy, Narendra; Balachandran, Kumarendran; Gokhale, Krishna; Wijesinghe, Haren; Cheng, Kar Keung; Karavitaki, Niki; Wass, John; Nirantharakumar, Krishnarajah
Males with prolactinoma are at increased risk of incident cardiovascular disease Journal Article
In: Clinical Endocrinology, vol. 88, iss. 1, pp. 71-76, 2018, ISSN: 13652265.
@article{Toulis2018,
title = {Males with prolactinoma are at increased risk of incident cardiovascular disease},
author = {Konstantinos A. Toulis and Tim Robbins and Narendra Reddy and Kumarendran Balachandran and Krishna Gokhale and Haren Wijesinghe and Kar Keung Cheng and Niki Karavitaki and John Wass and Krishnarajah Nirantharakumar},
doi = {10.1111/CEN.13498},
issn = {13652265},
year = {2018},
date = {2018-01-01},
journal = {Clinical Endocrinology},
volume = {88},
issue = {1},
pages = {71-76},
publisher = {Blackwell Publishing Ltd},
abstract = {Objective: To investigate whether the risk of incident cardiovascular disease (CVD) is increased in patients with prolactinoma. Design: Population-based, retrospective, open-cohort study using The Health Improvement Network (THIN) database. Patients: A total of 2233 patients with prolactinoma and 10 355 matched controls (1:5 ratio) from UK General Practices contributing to THIN were included. Sex, age, body mass index and smoking status were used as matching parameters. The primary outcome was any incident CVD, defined by Read codes suggesting myocardial infarction, angina pectoris, stroke, transient ischaemic attack or heart failure. Sex-specific-adjusted incidence rate ratios (aIRRs) were calculated with Poisson regression, using clinically relevant parameters as model covariates. Sensitivity analyses were performed to check whether a change in the initial assumptions could have an impact on the findings. Results: During the 6-year observation period, the composite CVD outcome was recorded in 54 patients with prolactinoma and 180 “nonexposed” individuals. The incidence rate was 1.8 and 14.8 per 1000 person-years for the females and males with prolactinoma, respectively. The aIRRs for CVD were estimated at 0.99 [95% confidence interval (CI): 0.61-1.61},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Objective: To investigate whether the risk of incident cardiovascular disease (CVD) is increased in patients with prolactinoma. Design: Population-based, retrospective, open-cohort study using The Health Improvement Network (THIN) database. Patients: A total of 2233 patients with prolactinoma and 10 355 matched controls (1:5 ratio) from UK General Practices contributing to THIN were included. Sex, age, body mass index and smoking status were used as matching parameters. The primary outcome was any incident CVD, defined by Read codes suggesting myocardial infarction, angina pectoris, stroke, transient ischaemic attack or heart failure. Sex-specific-adjusted incidence rate ratios (aIRRs) were calculated with Poisson regression, using clinically relevant parameters as model covariates. Sensitivity analyses were performed to check whether a change in the initial assumptions could have an impact on the findings. Results: During the 6-year observation period, the composite CVD outcome was recorded in 54 patients with prolactinoma and 180 “nonexposed” individuals. The incidence rate was 1.8 and 14.8 per 1000 person-years for the females and males with prolactinoma, respectively. The aIRRs for CVD were estimated at 0.99 [95% confidence interval (CI): 0.61-1.61
Harvey, Philip R.; Thomas, Tom; Chandan, Joht S.; Mytton, Jemma; Coupland, Ben; Bhala, Neeraj; Evison, Felicity; Patel, Prashant; Nirantharakumar, Krishnarajah; Trudgill, Nigel J.
Incidence, morbidity and mortality of patients with achalasia in England: Findings from a study of nationwide hospital and primary care data Journal Article
In: Gut, 2018, ISSN: 14683288.
@article{Harvey2018,
title = {Incidence, morbidity and mortality of patients with achalasia in England: Findings from a study of nationwide hospital and primary care data},
author = {Philip R. Harvey and Tom Thomas and Joht S. Chandan and Jemma Mytton and Ben Coupland and Neeraj Bhala and Felicity Evison and Prashant Patel and Krishnarajah Nirantharakumar and Nigel J. Trudgill},
doi = {10.1136/GUTJNL-2018-316089},
issn = {14683288},
year = {2018},
date = {2018-01-01},
journal = {Gut},
publisher = {BMJ Publishing Group},
abstract = {Background: Achalasia is an uncommon condition characterised by failed lower oesophageal sphincter relaxation. Data regarding its incidence, prevalence, disease associations and long-term outcomes are very limited. Methods: Hospital Episode Statistics (HES) include demographic and diagnostic data for all English hospital attendances. The Health Improvement Network (THIN) includes the primary care records of 4.5 million UK subjects, representative of national demographics. Both were searched for incident cases between 2006 and 2016 and THIN for prevalent cases. Subjects with achalasia in THIN were compared with age, sex, deprivation tand smoking status matched controls for important comorbidities and mortality. Results: There were 10 509 and 711 new achalasia diagnoses identified in HES and THIN, respectively. The mean incidence per 100 000 people in HES was 1.99 (95% CI 1.87 to 2.11) and 1.53 (1.42 to 1.64) per 100 000 person-years in THIN. The prevalence in THIN was 27.1 (25.4 to 28.9) per 100 000 population. Incidence rate ratios (IRRs) were significantly higher in subjects with achalasia (n=2369) compared with controls (n=3865) for: oesophageal cancer (IRR 5.22 (95% CI: 1.88 to 14.45), p<0.001), aspiration pneumonia (13.38 (1.66 to 107.79)},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background: Achalasia is an uncommon condition characterised by failed lower oesophageal sphincter relaxation. Data regarding its incidence, prevalence, disease associations and long-term outcomes are very limited. Methods: Hospital Episode Statistics (HES) include demographic and diagnostic data for all English hospital attendances. The Health Improvement Network (THIN) includes the primary care records of 4.5 million UK subjects, representative of national demographics. Both were searched for incident cases between 2006 and 2016 and THIN for prevalent cases. Subjects with achalasia in THIN were compared with age, sex, deprivation tand smoking status matched controls for important comorbidities and mortality. Results: There were 10 509 and 711 new achalasia diagnoses identified in HES and THIN, respectively. The mean incidence per 100 000 people in HES was 1.99 (95% CI 1.87 to 2.11) and 1.53 (1.42 to 1.64) per 100 000 person-years in THIN. The prevalence in THIN was 27.1 (25.4 to 28.9) per 100 000 population. Incidence rate ratios (IRRs) were significantly higher in subjects with achalasia (n=2369) compared with controls (n=3865) for: oesophageal cancer (IRR 5.22 (95% CI: 1.88 to 14.45), p<0.001), aspiration pneumonia (13.38 (1.66 to 107.79)
2017
Toulis, Konstantinos A.; Willis, Brian H.; Marshall, Tom; Kumarendran, Balachadran; Gokhale, Krishna; Ghosh, Sandip; Thomas, G. Neil; Cheng, Kar Keung; Narendran, Parth; Hanif, Wasim; Nirantharakumar, Krishnarajah
In: Journal of Clinical Endocrinology and Metabolism, vol. 102, iss. 5, pp. 1719-1725, 2017, ISSN: 19457197.
@article{Toulis2017,
title = {All-cause mortality in patients with diabetes under treatment with dapagliflozin: A population-based, open-cohort study in the health improvement network database},
author = {Konstantinos A. Toulis and Brian H. Willis and Tom Marshall and Balachadran Kumarendran and Krishna Gokhale and Sandip Ghosh and G. Neil Thomas and Kar Keung Cheng and Parth Narendran and Wasim Hanif and Krishnarajah Nirantharakumar},
doi = {10.1210/JC.2016-3446},
issn = {19457197},
year = {2017},
date = {2017-01-01},
journal = {Journal of Clinical Endocrinology and Metabolism},
volume = {102},
issue = {5},
pages = {1719-1725},
publisher = {Endocrine Society},
abstract = {Context: Empagliflozin was found to decrease mortality in patients with type 2 diabetes mellitus (T2DM) and a prior cardiovascular disease (CVD) event. Objectives: To establish whether these benefits can be replicated in a real-world setting, should be expected with the use of dapagliflozin, and apply to T2DM patients at low risk of CVD. Design: General practice, population-based, retrospective cohort study (January 2013 to September 2015). Setting: The Health Improvement Network database. Participants: A total of 22,124 T2DM patients (4444 exposed to dapagliflozin; 17,680 unexposed T2DM patients) matched for age, sex, body mass index, T2DM duration, and smoking. Main Outcome Measures: The primary outcome was all-cause mortality (high and low risk for CVD) in the total study population, expressed as the adjusted incidence rate ratio (aIRR) with 95% confidence intervals (CIs). As a secondary analysis in the low-risk population, all-cause mortality and incident CVD were considered. Results: Patients with T2DM exposed to dapagliflozin were significantly less likely to die of any cause (aIRR: 0.50; 95% CI: 0.33 to 0.75; P = 0.001). Similarly, in low-risk patients, death from any cause was significantly lower in the cohort exposed to dapagliflozin (aIRR: 0.44; 95% CI: 0.25 to 0.78; P = 0.002). The difference in the risk of incident CVD did not reach statistical significance between groups in low-risk patients (aIRR: 0.89; 95% CI: 0.61 to 1.31; P = 0.546). Conclusions: Patients with T2DM who were exposed to dapagliflozin had a lower risk of death from any cause irrespective of baseline CVD status.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Context: Empagliflozin was found to decrease mortality in patients with type 2 diabetes mellitus (T2DM) and a prior cardiovascular disease (CVD) event. Objectives: To establish whether these benefits can be replicated in a real-world setting, should be expected with the use of dapagliflozin, and apply to T2DM patients at low risk of CVD. Design: General practice, population-based, retrospective cohort study (January 2013 to September 2015). Setting: The Health Improvement Network database. Participants: A total of 22,124 T2DM patients (4444 exposed to dapagliflozin; 17,680 unexposed T2DM patients) matched for age, sex, body mass index, T2DM duration, and smoking. Main Outcome Measures: The primary outcome was all-cause mortality (high and low risk for CVD) in the total study population, expressed as the adjusted incidence rate ratio (aIRR) with 95% confidence intervals (CIs). As a secondary analysis in the low-risk population, all-cause mortality and incident CVD were considered. Results: Patients with T2DM exposed to dapagliflozin were significantly less likely to die of any cause (aIRR: 0.50; 95% CI: 0.33 to 0.75; P = 0.001). Similarly, in low-risk patients, death from any cause was significantly lower in the cohort exposed to dapagliflozin (aIRR: 0.44; 95% CI: 0.25 to 0.78; P = 0.002). The difference in the risk of incident CVD did not reach statistical significance between groups in low-risk patients (aIRR: 0.89; 95% CI: 0.61 to 1.31; P = 0.546). Conclusions: Patients with T2DM who were exposed to dapagliflozin had a lower risk of death from any cause irrespective of baseline CVD status.
Dafoulas, George E.; Toulis, Konstantinos A.; Mccorry, Dougall; Kumarendran, Balachadran; Thomas, G. Neil; Willis, Brian H.; Gokhale, Krishna; Gkoutos, George; Narendran, Parth; Nirantharakumar, Krishnarajah
Type 1 diabetes mellitus and risk of incident epilepsy: a population-based, open-cohort study Journal Article
In: Diabetologia, vol. 60, iss. 2, pp. 258-261, 2017, ISSN: 14320428.
@article{Dafoulas2017,
title = {Type 1 diabetes mellitus and risk of incident epilepsy: a population-based, open-cohort study},
author = {George E. Dafoulas and Konstantinos A. Toulis and Dougall Mccorry and Balachadran Kumarendran and G. Neil Thomas and Brian H. Willis and Krishna Gokhale and George Gkoutos and Parth Narendran and Krishnarajah Nirantharakumar},
doi = {10.1007/S00125-016-4142-X},
issn = {14320428},
year = {2017},
date = {2017-01-01},
journal = {Diabetologia},
volume = {60},
issue = {2},
pages = {258-261},
publisher = {Springer Verlag},
abstract = {Aims/Hypothesis: The aim of this research was to explore the relationship between incident epilepsy and type 1 diabetes in British participants. Methods: Using The Health Improvement Network database, we conducted a retrospective, open-cohort study. Patients who were newly diagnosed with type 1 diabetes mellitus at the age of ≤40 years were identified and followed-up from 1 January 1990 to 15 September 2015. These patients, identified as not suffering from epilepsy at the time of diagnosis, were randomly matched with up to four individuals without type 1 diabetes mellitus, based on age, sex and participating general practice. A Cox regression analysis was subsequently performed using Townsend deprivation index, cerebral palsy, head injury and learning disabilities as model covariates. Results: The study population consisted of a total of 24,610 individuals (4922 with type 1 diabetes and 19,688 controls). These individuals were followed up for a mean of 5.4 years (approximately 132,000 person-years of follow up). Patients with type 1 diabetes were significantly more likely to be diagnosed with epilepsy during the observation period compared with controls (crude HR [95% CI]: 3.02 [1.95, 4.69]). The incidence rate was estimated to be 132 and 44 per 100,000 person-years in patients and controls, respectively. This finding persisted after adjusting for model covariates (adjusted HR [95% CI]: 3.01 [1.93, 4.68]) and was also robust to sensitivity analysis, excluding adult-onset type 1 diabetes mellitus. Conclusions/Interpretation: Patients with type 1 diabetes are at approximately three-times greater risk of developing epilepsy compared with matched controls without type 1 diabetes. This should be considered when investigating seizure-related disorders in patients with type 1 diabetes mellitus.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Aims/Hypothesis: The aim of this research was to explore the relationship between incident epilepsy and type 1 diabetes in British participants. Methods: Using The Health Improvement Network database, we conducted a retrospective, open-cohort study. Patients who were newly diagnosed with type 1 diabetes mellitus at the age of ≤40 years were identified and followed-up from 1 January 1990 to 15 September 2015. These patients, identified as not suffering from epilepsy at the time of diagnosis, were randomly matched with up to four individuals without type 1 diabetes mellitus, based on age, sex and participating general practice. A Cox regression analysis was subsequently performed using Townsend deprivation index, cerebral palsy, head injury and learning disabilities as model covariates. Results: The study population consisted of a total of 24,610 individuals (4922 with type 1 diabetes and 19,688 controls). These individuals were followed up for a mean of 5.4 years (approximately 132,000 person-years of follow up). Patients with type 1 diabetes were significantly more likely to be diagnosed with epilepsy during the observation period compared with controls (crude HR [95% CI]: 3.02 [1.95, 4.69]). The incidence rate was estimated to be 132 and 44 per 100,000 person-years in patients and controls, respectively. This finding persisted after adjusting for model covariates (adjusted HR [95% CI]: 3.01 [1.93, 4.68]) and was also robust to sensitivity analysis, excluding adult-onset type 1 diabetes mellitus. Conclusions/Interpretation: Patients with type 1 diabetes are at approximately three-times greater risk of developing epilepsy compared with matched controls without type 1 diabetes. This should be considered when investigating seizure-related disorders in patients with type 1 diabetes mellitus.
Toulis, K. A.; Hanif, W.; Saravanan, P.; Willis, B. H.; Marshall, T.; Kumarendran, B.; Gokhale, K.; Ghosh, S.; Cheng, K. K.; Narendran, P.; Thomas, G. N.; Nirantharakumar, K.
All-cause mortality in patients with diabetes under glucagon-like peptide-1 agonists: A population-based, open cohort study Journal Article
In: Diabetes and Metabolism, vol. 43, iss. 3, pp. 211-216, 2017, ISSN: 18781780.
@article{Toulis2017b,
title = {All-cause mortality in patients with diabetes under glucagon-like peptide-1 agonists: A population-based, open cohort study},
author = {K. A. Toulis and W. Hanif and P. Saravanan and B. H. Willis and T. Marshall and B. Kumarendran and K. Gokhale and S. Ghosh and K. K. Cheng and P. Narendran and G. N. Thomas and K. Nirantharakumar},
doi = {10.1016/J.DIABET.2017.02.003},
issn = {18781780},
year = {2017},
date = {2017-01-01},
journal = {Diabetes and Metabolism},
volume = {43},
issue = {3},
pages = {211-216},
publisher = {Elsevier Masson SAS},
abstract = {Aim The glucagon-like peptide-1 receptor agonist (GLP1a) liraglutide has been described to benefit patients with type 2 diabetes mellitus (T2DM) at high cardiovascular risk. However, there are still uncertainties relating to these cardiovascular benefits: whether they also apply to an unselected diabetic population that includes low-risk patients, represent a class-effect, and could be observed in a real-world setting. Methods We conducted a population-based, retrospective open cohort study using data derived from The Health Improvement Network database between Jan 2008 to Sept 2015. Patients with T2DM exposed to GLP1a (n = 8345) were compared to age, gender, body mass index, duration of T2DM and smoking status-matched patients with T2DM unexposed to GLP1a (n = 16,541). Results Patients with diabetes receiving GLP1a were significantly less likely to die from any cause compared to matched control patients with diabetes (adjusted incidence rate ratio [aIRR]: 0.64, 95% CI: 0.56–0.74, P-value < 0.0001). Similar findings were observed in low-risk patients (aIRR: 0.64, 95% CI: 0.53–0.76, P -value = 0.0001). No significant difference in the risk of incident CVD was detected in the low-risk patients (aIRR: 0.93, 95% CI: 0.83–1.12). Subgroup analyses suggested that effect is persistent in the elderly or across glycated haemoglobin categories. Conclusions GLP1a treatment in a real-world setting may confer additional mortality benefit in patients with T2DM irrespective of their baseline CVD risk, age or baseline glycated haemoglobin and was sustained over the observation period.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Aim The glucagon-like peptide-1 receptor agonist (GLP1a) liraglutide has been described to benefit patients with type 2 diabetes mellitus (T2DM) at high cardiovascular risk. However, there are still uncertainties relating to these cardiovascular benefits: whether they also apply to an unselected diabetic population that includes low-risk patients, represent a class-effect, and could be observed in a real-world setting. Methods We conducted a population-based, retrospective open cohort study using data derived from The Health Improvement Network database between Jan 2008 to Sept 2015. Patients with T2DM exposed to GLP1a (n = 8345) were compared to age, gender, body mass index, duration of T2DM and smoking status-matched patients with T2DM unexposed to GLP1a (n = 16,541). Results Patients with diabetes receiving GLP1a were significantly less likely to die from any cause compared to matched control patients with diabetes (adjusted incidence rate ratio [aIRR]: 0.64, 95% CI: 0.56–0.74, P-value < 0.0001). Similar findings were observed in low-risk patients (aIRR: 0.64, 95% CI: 0.53–0.76, P -value = 0.0001). No significant difference in the risk of incident CVD was detected in the low-risk patients (aIRR: 0.93, 95% CI: 0.83–1.12). Subgroup analyses suggested that effect is persistent in the elderly or across glycated haemoglobin categories. Conclusions GLP1a treatment in a real-world setting may confer additional mortality benefit in patients with T2DM irrespective of their baseline CVD risk, age or baseline glycated haemoglobin and was sustained over the observation period.