Jonathan Valabhji

Changes in health in England, with analysis by English regions and areas of deprivation, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

Summary Background In the Global Burden of Disease Study 2013 (GBD 2013), knowledge about health and its determinants has been integrated into a comparable framework to inform health policy. Outputs of this analysis are relevant to current policy questions in England and elsewhere, particularly on health inequalities. We use GBD 2013 data on mortality and causes of death, and disease and injury incidence and prevalence to analyse the burden of disease and injury in England as a whole, in English regions, and within each English region by deprivation quintile. We also assess disease and injury burden in England attributable to potentially preventable risk factors. England and the English regions are compared with the remaining constituent countries of the UK and with comparable countries in the European Union (EU) and beyond. Methods We extracted data from the GBD 2013 to compare mortality, causes of death, years of life lost (YLLs), years lived with a disability (YLDs), and disability-adjusted life-years (DALYs) in England, the UK, and 18 other countries (the first 15 EU members [apart from the UK] and Australia, Canada, Norway, and the USA [EU15+]). We extended elements of the analysis to English regions, and subregional areas defined by deprivation quintile (deprivation areas). We used data split by the nine English regions (corresponding to the European boundaries of the Nomenclature for Territorial Statistics level 1 [NUTS 1] regions), and by quintile groups within each English region according to deprivation, thereby making 45 regional deprivation areas. Deprivation quintiles were defined by area of residence ranked at national level by Index of Multiple Deprivation score, 2010. Burden due to various risk factors is described for England using new GBD methodology to estimate independent and overlapping attributable risk for five tiers of behavioural, metabolic, and environmental risk factors. We present results for 306 causes and 2337 sequelae, and 79 risks or risk clusters. Findings Between 1990 and 2013, life expectancy from birth in England increased by 5·4 years (95% uncertainty interval 5·0–5·8) from 75·9 years (75·9–76·0) to 81·3 years (80·9–81·7); gains were greater for men than for women. Rates of age-standardised YLLs reduced by 41·1% (38·3–43·6), whereas DALYs were reduced by 23·8% (20·9–27·1), and YLDs by 1·4% (0·1–2·8). For these measures, England ranked better than the UK and the EU15+ means. Between 1990 and 2013, the range in life expectancy among 45 regional deprivation areas remained 8·2 years for men and decreased from 7·2 years in 1990 to 6·9 years in 2013 for women. In 2013, the leading cause of YLLs was ischaemic heart disease, and the leading cause of DALYs was low back and neck pain. Known risk factors accounted for 39·6% (37·7–41·7) of DALYs; leading behavioural risk factors were suboptimal diet (10·8% [9·1–12·7]) and tobacco (10·7% [9·4–12·0]). Interpretation Health in England is improving although substantial opportunities exist for further reductions in the burden of preventable disease. The gap in mortality rates between men and women has reduced, but marked health inequalities between the least deprived and most deprived areas remain. Declines in mortality have not been matched by similar declines in morbidity, resulting in people living longer with diseases. Health policies must therefore address the causes of ill health as well as those of premature mortality. Systematic action locally and nationally is needed to reduce risk exposures, support healthy behaviours, alleviate the severity of chronic disabling disorders, and mitigate the effects of socioeconomic deprivation. Funding Bill & Melinda Gates Foundation and Public Health England.

Changes in the Incidence of Lower Extremity Amputations in Individuals With and Without Diabetes in England Between 2004 and 2008

OBJECTIVE To describe recent trends in the incidence of nontraumatic amputations among individuals with and without diabetes and estimate the relative risk of amputations among individuals with diabetes in England. RESEARCH DESIGN AND METHODS We identified all patients aged >16 years who underwent any nontraumatic amputation in England between 2004 and 2008 using national hospital activity data from all National Health Service hospitals. Age- and sex-specific incidence rates were calculated using the total diabetes population in England every year. To test for time trend, we fitted Poisson regression models. RESULTS The absolute number of diabetes-related amputations increased by 14.7%, and the incidence decreased by 9.1%, from 27.5 to 25.0 per 10,000 people with diabetes, during the study period (P > 0.2 for both). The incidence of minor and major amputations did not significantly change (15.7–14.9 and 11.8–10.2 per 10,000 people with diabetes; P = 0.66 and P = 0.29, respectively). Poisson regression analysis showed no statistically significant change in diabetes-related amputation incidence over time (0.98 decrease per year [95% CI 0.93–1.02]; P = 0.12). Nondiabetes-related amputation incidence decreased from 13.6 to 11.9 per 100,000 people without diabetes (0.97 decrease by year [0.93–1.00]; P = 0.059). The relative risk of an individual with diabetes undergoing a lower extremity amputation was 20.3 in 2004 and 21.2 in 2008, compared with that of individuals without diabetes. CONCLUSIONS This national study suggests that the overall population burden of amputations increased in people with diabetes at a time when the number and incidence of amputations decreased in the aging nondiabetic population.

Type 2 Diabetes Is Associated with Reduced ATP-Binding Cassette Transporter A1 Gene Expression, Protein and Function

Objective Increasing plasma glucose levels are associated with increasing risk of vascular disease. We tested the hypothesis that there is a glycaemia-mediated impairment of reverse cholesterol transport (RCT). We studied the influence of plasma glucose on expression and function of a key mediator in RCT, the ATP binding cassette transporter-A1 (ABCA1) and expression of its regulators, liver X receptor-α (LXRα) and peroxisome proliferator-activated receptor–γ (PPARγ). Methods and Results Leukocyte ABCA1, LXRα and PPARγ expression was measured by polymerase chain reaction in 63 men with varying degrees of glucose homeostasis. ABCA1 protein concentrations were measured in leukocytes. In a sub-group of 25 men, ABCA1 function was quantified as apolipoprotein-A1-mediated cholesterol efflux from 2–3 week cultured skin fibroblasts. Leukocyte ABCA1 expression correlated negatively with circulating HbA1c and glucose (rho = −0.41, p<0.001; rho = −0.34, p = 0.006 respectively) and was reduced in Type 2 diabetes (T2DM) (p = 0.03). Leukocyte ABCA1 protein was lower in T2DM (p = 0.03) and positively associated with plasma HDL cholesterol (HDL-C) (rho = 0.34, p = 0.02). Apolipoprotein-A1-mediated cholesterol efflux correlated negatively with fasting glucose (rho = −0.50, p = 0.01) and positively with HDL-C (rho = 0.41, p = 0.02). It was reduced in T2DM compared with controls (p = 0.04). These relationships were independent of LXRα and PPARγ expression. Conclusions ABCA1 expression and protein concentrations in leukocytes, as well as function in cultured skin fibroblasts, are reduced in T2DM. ABCA1 protein concentration and function are associated with HDL-C levels. These findings indicate a glycaemia- related, persistent disruption of a key component of RCT.

Conservative management of diabetic forefoot ulceration complicated by underlying osteomyelitis: the benefits of magnetic resonance imaging.

Aims  To assess efficacy of conservative management of neuropathic forefoot ulcers with underlying osteomyelitis in subjects with diabetes when magnetic resonance imaging (MRI) is used to confirm or establish diagnosis and to guide antibiotic duration.

Screening for Type 2 diabetes in the accident and emergency department

Aim  To assess the proportion of patients, aged 40 years and over, attending an inner city accident and emergency department that have Type 2 diabetes, and the proportion previously undiagnosed, and to assess whether the identification of undiagnosed Type 2 diabetes is feasible in this setting.

99mTc-Nanocolloid scintigraphy for assessing osteomyelitis in diabetic neuropathic feet

Distinguishing osteomyelitis from neuropathic osteoarthropathy in diabetic feet is a common and difficult clinical problem with no highly accurate discriminatory investigation. This study assesses the novel use of marrow scintigraphy and compares it with magnetic resonance imaging (MRI) for the diagnosis of osteomyelitis in neuropathic osteoarthropathic diabetic feet. Nine diabetic patients with chronic foot ulcers were prospectively assessed independently using 99mTc-nanocolloid scintigraphy and MRI. Those patients showing features of osteomyelitis underwent percutaneous bone biopsy or surgical ray excision for histological confirmation. Other patients were followed up clinically for a minimum of 6 months to exclude osteomyelitis. Marrow scintigraphy, in agreement with MRI, demonstrated all four cases of biopsy proven osteomyelitis and excluded three cases with neuropathic osteoarthropathy alone. One case of suspected osteomyelitis of the ankle on marrow scintigraphy, but not MRI, was not confirmed clinically. One case of suspected osteomyelitis on both imaging modalities was shown on biopsy to demonstrate changes of avascular necrosis but not osteomyelitis. In this study 99mTc-nanocolloid scintigraphy shows a sensitivity of 100% and specificity of 60%. An important false positive result is seen with avascular necrosis, both on marrow scintigraphy and on MRI. Although larger studies are needed to evaluate this technique, 99mTc-nanocolloid marrow scintigraphy may be an alternative to MRI for assessing diabetic feet for osteomyelitis.

Rates of cholesterol esterification and esterified cholesterol net mass transfer between high-density lipoproteins and apolipoprotein B-containing lipoproteins in Type 1 diabetes

Aims Type 1 diabetes is associated with a high incidence of coronary heart disease (CHD) despite paradoxically normal or high high‐density lipoprotein (HDL) cholesterol concentrations. Triglyceride (TG) concentrations have been shown to be important determinants of two aspects of HDL metabolism: cholesterol esterification rate and esterified cholesterol (EC) net mass transfer rate between HDL and the apolipoprotein B‐containing lipoproteins. In order to try to explain the paradox, we aimed to assess the relationships between plasma TG and these two processes in Type 1 diabetic compared with non‐diabetic subjects.

Midfoot and Hindfoot Bone Marrow Edema Identified By Magnetic Resonance Imaging in Feet of Subjects With Diabetes and Neuropathic Ulceration Is Common but of Unknown Clinical Significance

OBJECTIVE We conducted a retrospective cohort study assessing the prevalence and clinical and radiological outcome of remote areas of bone marrow edema on magnetic resonance imaging (MRI) in the feet of subjects with diabetes and neuropathic foot ulceration. RESEARCH DESIGN AND METHODS MRIs performed over 6 years looking for osteomyelitis associated with neuropathic lesions were assessed for remote areas of signal change. RESULTS Seventy MRI studies were assessed. Remote areas of signal change were present in 21 (30%) subjects, involved midfoot or hindfoot in 20 subjects, were associated with younger age and renal replacement therapy, and did not predict future Charcot neuroarthropathy or infection at that site. Repeat MRIs in 11 subjects with such areas found that none had progressed, six had improved, and two had resolved; in 29 subjects without such areas, five had developed new areas. CONCLUSIONS Bone marrow edema in the midfoot and hindfoot of subjects with diabetes and neuropathic lesions is common, often transient, and of unknown significance.

Changes in lipoprotein profile and urinary albumin excretion in familial LCAT deficiency with lipid lowering therapy.

Familial lecithin:cholesterol acyltransferase deficiency (FLD) is a monogenic autosomal recessive condition, affecting cholesterol esterification and leads to progressive renal impairment and end-stage renal failure, probably due to the abnormal lipoprotein (X) (Lp(X)). We report a case of FLD, whom we treated with a combination of nicotinic acid 1.5g nocte and fenofibrate M/R 160mg od and report changes in lipid profile and Lp(X), after six weeks and serum creatinine and urine albumin/creatinine ratio after 12 months. We assessed the cardiovascular risk using electron beam computed tomography. At baseline total cholesterol was 6.61mmol/L; HDL cholesterol 0.57mmol/L; Lp(X) cholesterol 3.24mmol/L; triglyceride 4.13mmol/L; apolipoprotein A1 46mg/dL; and apolipoprotein B 53mg/dL. After six weeks of treatment his total cholesterol was 4.16; HDL cholesterol 0.52; Lp(X) cholesterol 1.73mmol/L; triglyceride 1.80mmol/L; apolipoprotein A1 36mg/dL; and apolipoprotein B 50mg/dL. Baseline serum creatinine was 106micromol/L and urine albumin/creatinine ratio was 127.3mg/mmol and after 12 months was 101micromol/L and 31.5mg/mmol respectively. His coronary artery calcification score was zero. We have shown, we believe for the first time, that combination lipid modifying therapy in FLD leads to a reduction in Lp(X) concentration and an associated reduction in urine albumin excretion at 12 months.

Does higher quality of primary healthcare reduce hospital admissions for diabetes complications? A national observational study

To determine if hospital admission rates for diabetes complications (acute complications, chronic complications, no complications and hypoglycaemia) were associated with primary care diabetes management.