Population Health Management in Diabetes Care: Combining Clinical Audit, Risk Stratification, and Multidisciplinary Virtual Clinics in a Community Setting to Improve Diabetes Care in a Geographically Defined Population. An Integrated Diabetes Care Pilot in the North East Locality, Oxfordshire, UK.

BACKGROUND: Disparities in diabetes care are prevalent, with significant inequalities observed in access to, and outcomes of, healthcare. A population health approach offers a solution to improve the quality of care for all with systematic ways of assessing whole population requirements and treating and monitoring sub-groups in need of additional attention. DESCRIPTION OF THE CARE PRACTICE: Collaborative working between primary, secondary and community care was introduced in seven primary care practices in one locality in England, UK, caring for 3560 patients with diabetes and sharing the same community and secondary specialist diabetes care providers. Three elements of the intervention included 1) clinical audit, 2) risk stratification, and 3) the multi-disciplinary virtual clinics in the community. METHODS: This paper evaluates the acceptability, feasibility and short-term impact on primary care of implementing a population approach intervention using direct observations of the clinics and surveys of participating clinicians. RESULTS AND DISCUSSION: Eighteen virtual clinics across seven teams took place over six months between March and July 2017 with organisation, resources, policies, education and approximately 150 individuals discussed. The feedback from primary care was positive with growing knowledge and confidence managing people with complex diabetes in primary care. CONCLUSION: Taking a population health approach helped to identify groups of people in need of additional diabetes care and deliver a collaborative health intervention across traditional organisational boundaries.

People with Type Diabetes Mellitus (T1DM) self-reported views on their own condition management reveal links to potentially improved outcomes and potential areas for service improvement.

BACKGROUND: The self-management of type 1 diabetes (T1DM) has moved forward in many areas over the last 40 years. Our study asked people with T1DM what is their experience of blood glucose (BG) monitoring day to day and how this influences decisions about insulin dosing. METHODS: An on-line self-reported questionnaire containing 44 questions prepared after consultation with clinicians and patients was circulated to people with T1DM 116 responders provided completed responses. Fixed responses were allocated specific values (e.g. not confident = 0 fairly confident = 1). Multivariate regression analysis was carried out. Only those 5 factors with p-value <0.05 were retained. RESULTS: 59% of respondents were >50 years old and 66% had diabetes for >20 years, with 63% of patients reporting HbA1c results ≤8% or 64 mmol/mol. Findings included; 75% used only 1 m; 56% had used the same meter for ≥3 years; 10% had tried flash monitors; 47% were concerned about current BG level; 85% were concerned about long-term impact of higher BG. 72% of respondents keep BG level high to avoid hypoglycaemia; 25% used ≥7 mmol/L as pre-meal BG target to calculate dose; 65% were concerned they might be over/under-dosing; 83% did not discuss accuracy when choosing meter. However 85% were confident in their meter's performance. The factors that linked to LOWER HbA1c included LESS units of basal insulin (p < 0.001), HIGHER number of daily BG tests (p = 0.008), LOWER bedtime blood glucose (p = 0.009), HIGHER patient's concern over long-term impact of high BG (BG) (p < 0.009 but LOWER patient's concern over current BG values (p = 0.009). The final statistical model could explain 41% of the observed variation in HbA1c. CONCLUSION: Many people still run their BG high to avoid hypoglycaemia. Concern about the longer-term consequences of suboptimal glycaemic control was associated with a lower HbA1c and is an area to explore in the future when considering how to help people with T1DM.

Importance of inpatient hypoglycaemia: impact, prediction and prevention.

Hypoglycaemia is a key barrier to achieving euglycaemic control in people who are hospitalized. Inpatient hypoglycaemia has been linked to adverse clinical outcomes, including mortality and longer stay in hospital. A number of studies have applied mathematical tools and statistical models to predict inpatient hypoglycaemia and identify factors that may result in hypoglycaemic events. Several different approaches have been tested to prevent inpatient hypoglycaemia. These can be categorized as human intervention, computerized methods or application of medical devices. In this review we provide an overview of the epidemiology of inpatient hypoglycaemia and its impact on patients and hospitals. We also discuss the existing methodology used to predict inpatient hypoglycaemia and the limited number of trials performed to prevent inpatient hypoglycaemia. The review highlights the urgent need for evidence-based methods to reduce inpatient hypoglycaemia.

Effect of glycaemic control on complications following cardiac surgery: literature review.

INTRODUCTION: No uniform consensus in the UK or Europe exists, for glycaemic management of patients with Diabetes or pre-diabetes undergoing cardiac surgery. OBJECTIVE: [i] Determine the relationship between glycaemic control and cardiac surgical outcomes; [ii] Compare current vs gold standard management of patients with Diabetes or pre-diabetes undergoing cardiac surgery. METHODS: Searches of MEDLINE, NHS Evidence and Web of Science databases were completed. Articles were limited to those in English, German and French. No date limit was enforced.13,232 articles were identified on initial literature review, and 50 relevant papers included in this review. RESULTS: No national standards for glycaemic control prior to cardiac surgery were identified. Upto 30% of cardiac surgical patients have undiagnosed Diabetes. Cardiac surgical patients without Diabetes with pre-operative hyperglycaemia have a 1 year mortality double that of patients with normoglyacemia, and equivalent to patients already diagnosed with Diabetes. Pre- and peri-operative hyperglycaemia is associated with worse outcomes. Evidence regarding tight glycaemic control vs moderate glycaemic control is conflicting. Tight control may be more effective in patients without Diabetes with pre-/peri-operative hyperglycaemia, and moderate control appears more effective in patients with pre-existing Diabetes. Patients with well controlled Diabetes may achieve comparable outcomes to patients without Diabetes with similar glycaemic control. CONCLUSIONS: Pre / peri-operative hyperglycaemia is associated with worse outcomes in both patients with, and without Diabetes undergoing CABG. This review supports the pre-operative screening, and optimisation of glycaemic control in patients undergoing cardiac surgery. Optimal glycaemic management remains unclear and clear guidelines are needed.

Leptin (rs7799039) and solute carrier family 30 zinc transporter (rs13266634) polymorphisms in Euro-Brazilian pregnant women with gestational diabetes.

Leptin (LEP), a protein that plays a fundamental role in the metabolism of energy reserves, and the solute carrier family 30 A8 zinc transporter (SLC30A8) have been consistently associated with diabetes. Women with gestational diabetes are at moderate risk of developing diabetes type 1 and 2 after pregnancy, in addition to complications to the fetus. We investigated the association of the polymorphisms rs7799039 (LEP) and rs13266634 (SLC30A8) in a case-control study in Euro-Brazilians with gestational diabetes (GDM, N = 134) and healthy pregnant women (control, N = 180). Real-time PCR with fluorescent probes (TaqMan system) was applied to genotyping. All polymorphisms were in Hardy-Weinberg equilibrium. The minor allele frequencies, for healthy and GDM, respectively, for the A-allele (LEP gene rs7799039) were 40.3% (95%CI = 35-45%) vs 36.6% (95%CI = 31-42%), P = 0.345; and for the T-allele (SLC30A8 gene rs13266634) were 27.8% (95%CI = 23-32%) vs 23.5% (95%CI = 18-29%), P = 0.227. Genotype comparisons for both polymorphisms showed no significant difference (P > 0.05). The polymorphisms rs7799039 and rs13266634 were not associated with GDM in the population studied (P > 0.05). The minor allele frequencies for both polymorphisms were similar to those of other Caucasian populations.

Six-year longitudinal study of Fasciola hepatica bulk milk antibody ELISA in the dairy dense region of the Republic Ireland.

Completion of the F. hepatica lifecycle is dependent on suitable climatic conditions for development of immature stages of the parasite, and its snail intermediate host. Few investigations have been conducted regarding temporal variations in F. hepatica status in Irish dairy herds. The current study aimed to conduct a longitudinal study examining annual and seasonal trends in bulk milk seropositivity over six years, while also investigating associations with soil temperature, rainfall and flukicide treatment. Monthly bulk milk samples (BTM) were submitted by 28 herds between March 2009 and December 2014. In all, 1337 samples were analysed using a Cathepsin L1 ELISA. Soil temperature, rainfall and management data were obtained for general estimating equation and regression analyses. A general decrease in milk seropositivity was observed over the six year study period and was associated with an increased likelihood of treating for liver fluke (OR range=2.73-6.96). Annual and seasonal analyses of rainfall and F. hepatica BTM status yielded conflicting results. Higher annual rainfall (>1150mm) yielded a lower likelihood of being BTM positive than annual rainfall of <1000mm (OR=0.47; P=0.036). This was most likely due to farmers being more proactive in treating for F. hepatica in wetter years, although a 'wash effect' by high rainfall of the free living stages and snails cannot be ruled out. Higher seasonal rainfall (>120mm), however, was associated with increased ELISA S/P% values (Coefficient=9.63S/P%; P=0.001). Soil temperature was not found to influence F. hepatica to the same extent as rainfall and may reflect the lack of severe temperature fluctuations in Ireland. Flukicides active against both immature and mature F. hepatica were approximately half as likely to record a positive F. hepatica herd BTM status than a flukicide active against only the mature stage of the parasite (OR≅0.45; P<0.01). This study highlights the importance of examining both annual and seasonal F. hepatica data, which can vary significantly. Additionally, it highlights the progress that can be achieved in fluke control by application of a continuous BTM monitoring program.

Relationships between host and symbiont cell cycles in sea anemones and their symbiotic dinoflagellates.

The processes by which cnidarians and their algal endosymbionts achieve balanced growth and biomass could include coordination of host and symbiont cell cycles. We evaluated this theory with natural populations of sea anemones hosting symbiotic dinoflagellates, focusing on the temperate sea anemone Anthopleura elegantissima symbiotic with Symbiodinium muscatinei in Washington State, USA, and the tropical anemone Stichodactyla helianthus associating with unknown Symbiodinium spp. in Belize. By extruding symbiont-containing gastrodermal cells from the relatively large tentacles of these species and using nuclear staining and flow cytometry, we selectively analyzed cell cycle distributions of the symbionts and the host gastrodermal cells that house them. We found no indications of diel synchrony in host and symbiont G2/M phases, and we observed evidence of diel periodicity only in Symbiodinium spp. associated with S. helianthus but not in the anemone itself. Seasonally, S. muscatinei showed considerable G2/M phase variability among samples collected quarterly over an annual period, while the G2/M phase of its host varied much less. Within samples taken at different times of the year, correlations between host and symbiont G2/M phases ranged from very weakly to very strongly positive, with significant correlations in only half of the samples (two of four A. elegantissima samples and one of two S. helianthus samples). Overall, the G2/M phase relationships across species and sampling periods were positive. Thus, while we found no evidence of close cell cycle coupling, our results suggest a loose, positive relationship between cell cycle processes of the symbiotic partners.

Low prevalence of glucokinase gene mutations in gestational diabetic patients with good glycemic control.

Glucokinase (GCK) plays a key role in glucose homeostasis. Gestational diabetes mellitus increases the risk of gestational complications in pregnant women and fetuses. We screened for mutations in coding and flanking regions of the GCK gene in pregnant women with or without gestational diabetes in a Brazilian population. A sample of 200 pregnant women classified as healthy (control, N = 100) or with gestational diabetes (N = 100) was analyzed for mutations in the GCK gene. All gestational diabetes mellitus patients had good glycemic control maintained by diet alone and no complications during pregnancy. Mutations were detected by single-strand conformation polymorphism and DNA sequencing. Thirteen of the 200 subjects had GCK gene mutations. The mutations detected were in intron 3 (c.43331A>G, new), intron 6 (c.47702T>C, rs2268574), intron 9 (c.48935C>T, rs2908274), and exon 10 (c.49620G>A, rs13306388). None of these GCK mutations were found to be significantly associated with gestational diabetes mellitus. In summary, we report a low frequency of GCK mutations in a pregnant Brazilian population and describe a new intronic variation (c.43331A>G, intron 3). We conclude that mutations in GCK introns and in non-translatable regions of the GCK gene do not affect glycemic control and are not correlated with gestational diabetes mellitus.

Theoretical assessment of principal factors influencing laser interstitial thermotherapy outcomes on pancreas.

The influence of some therapy-relevant parameters on Laser Induced Interstitial Thermotherapy (LITT) outcomes on pancreas is assessed. The aim is to execute a sensitivity analysis for an optimal treatment strategy on in vivo pancreas. A numerical model based on Bioheat Equation has been implemented to assess the influence of laser settings (power P and energy E), applicator radius (r(f)) and optical properties (effective attenuation coefficient, µ(eff)) on temperature (T) distribution. Effects on pancreas undergoing LITT have been evaluated with a twofold approach: 1) T rise and maximum T (T(max)) in tissue; 2) injured volumes (vaporized and coagulated ones). We consider parameters range in typical LITT values (P from 1.5 W to 6 W, E from 500 J to 1500 J, r(f) from 150 µm to 600 µm) and optical values reported in literature. Our analysis shows that, among others, P and µ(eff) are the principal influencing factors of thermal effects on pancreas undergoing LITT: P should be carefully chosen by operator to obtain the desired injured volumes, while the accurate measurement of tissue optical properties is crucial to carry out a safe and controlled thermal therapy on pancreas.

Laser Interstitial Thermotherapy for pancreatic tumor ablation: theoretical model and experimental validation.

This study aims to develop and verify a theoretical model to reproduce the thermal response of pancreatic tissue undergone Laser Induced Interstitial Thermotherapy (LITT). The model provides the evaluation of: a) ablated volumes induced by thermal ablation; b) tissue response time to irradiation; and c) heat extinction time. Theoretical volume values were compared with ex vivo healthy tissue and in vivo healthy and neoplastic tissue volume values. The theoretical model takes into account the differences between healthy and neoplastic tissue due to blood perfusion. Mathematical model shows that ablated volume of ex vivo healthy tissue is greater than in vivo one after the same treatment. Moreover, ablated neoplastic in vivo tissue volume is greater than healthy in vivo one, because of tumour angiogenesis. Ablated volume values were compared with experimental data obtained by laser treatment of 30 ex vivo porcine pancreases. Experimental ablated volume values show a good agreement with theoretical values, with an estimated increase of 61% when power increases from 3 W to 6 W, versus 46% of experimental data, and an estimated increase of 14% from 6 W to 10 W, versus 21% of experimental values. LITT could be an alternative or a neo-adjuvant treatment to surgical resection for pancreas cancer removal, and the proposed model could be the basis to supervising the evolution of ablated volumes during tumor treatment.

The functional polymorphisms -429T>C and -374T>A of the RAGE gene promoter are not associated with gestational diabetes in Euro-Brazilians.

The receptor for advanced glycation end products (RAGE or AGER) is a multiligand member of the immunoglobulin superfamily. RAGE is expressed in several tissues, including human myometrium, chorionic villi and placenta. Advanced glycation end products are the best studied ligands of RAGE; they have pro-inflammatory actions in human gestational tissues, increasing oxidative stress and the release of cytokines and prostaglandins. We investigated the association of RAGE gene promoter polymorphisms -429T>C (rs1800625) and -374T>A (rs1800624) with gestational diabetes. A sample of 750 unrelated European origin pregnant Brazilian women were classified as nondiabetic (control group, N = 600) or having gestational diabetes (N = 150) according to American Diabetes Association 2009 criteria. Genotyping was performed by PCR-RFLP. The frequencies of the rare alleles -429C (6.3 versus 9.1%) and -374A (26 versus 30%) were not significantly different between the gestational diabetes patients and healthy pregnant women. Also, the -429T>C and -374T>A polymorphisms were not associated with body mass index, lipid profile, fasting glycemia, HbA1C, or insulin requirement. We found that functional promoter polymorphisms of the RAGE gene were not associated with gestational diabetes or its complications in these Euro-Brazilian patients.

Suboptimal asthma control: prevalence, detection and consequences in general practice.

Telephone surveys describing suboptimal asthma control may be biased by low response rates. In order to obtain an unbiased assessment of asthma control and assess its impact in primary care, primary care physicians used a 1-page control questionnaire in 50 consecutive asthma patients. Of the 10,428 patients assessed by 354 physicians, 59% were uncontrolled, 19% well-controlled and 23% totally controlled. Physicians overestimated control, regarding only 42% of patients as uncontrolled. Physicians were more likely to report plans to alter the regimens of uncontrolled patients than controlled patients (1.29 versus 0.20 medication changes per patient) doing so in a fashion consistent with guideline recommendations. Of the uncontrolled patients, 59% required one or more urgent care or specialist visits versus 26 and 15% of well-controlled or totally controlled patients, respectively. Patients were more likely to report short-term symptom control when they had not required urgent or specialist care (odds ratio 5.68; 95% confidence interval 4.91-6.58). The majority of asthma patients treated in general practice are uncontrolled. Lack of control can be recognised by physicians who are likely to consider appropriate changes to therapy. A lack of short-term symptom control of asthma is associated with excess healthcare utilisation.

Effect of cardiac resynchronisation therapy on occurrence of ventricular arrhythmia in patients with implantable cardioverter defibrillators undergoing upgrade to cardiac resynchronisation therapy devices.

BACKGROUND: Cardiac resynchronisation therapy (CRT) improves outcomes in selected patients with heart failure and left ventricular dysfunction. One mechanism of benefit is believed to be favourable ventricular remodelling. Whether CRT also decreases the frequency of ventricular arrhythmias and risk of sudden death is unknown. OBJECTIVE: To determine the effect of CRT on frequency of ventricular arrhythmias and appropriate ICD therapies. DESIGN: Retrospective cohort study. SETTING: Single-centre, tertiary care facility (Mayo Clinic). PATIENTS: 52 patients (46 male), aged 70 (SD 10) years, who underwent upgrade from an implantable cardioverter defibrillator (ICD) to a CRT-defibrillator were included. INTERVENTIONS: Upgrade of ICD to CRT-defibrillator. MAIN OUTCOME MEASURES: Frequency of ventricular arrhythmias prior to and following upgrade to CRT device. RESULTS: Ejection fraction increased from 22% (SD 8%) to 27% (SD 11%) following CRT. However, the frequency of non-sustained ventricular arrhythmias, sustained ventricular arrhythmias, and ventricular fibrillation was not significantly changed prior to and following CRT (2.38 (SD 9.78) vs 58.51 (SD 412.73) per patient per month, p = 0.66; 0.07 (SD 0.17) vs 0.16 (SD 0.52), p = 0.70; 0.05 (SD 0.12) vs 0.25 (SD 1.40), p = 0.12). CONCLUSIONS: CRT is not associated with a decrease in the frequency of ventricular arrhythmia or appropriate device therapy. Thus, use of CRT alone is not beneficial in decreasing the frequency of ventricular arrhythmias or the risk of appropriate ICD therapies.

Effects of metformin and oleic acid on adipocyte expression of resistin.

AIM: The adipocyte-secreted hormone resistin has been implicated in obesity-induced insulin resistance and type 2 diabetes, but pharmacological and dietary factors that regulate resistin gene expression and the effects of resistin on cellular glucose uptake in muscle have not been clearly defined. METHODS: Expression of resistin mRNA was studied in differentiated 3T3-L1 adipocytes by using real-time semiquantitative reverse transcription-polymerase chain reaction. The effects of resistin on insulin-stimulated and insulin-independent 2-deoxyglucose uptake were evaluated in L6 muscle cells. RESULTS: Insulin 1 microm and rosiglitazone 10 microm markedly reduced resistin mRNA expression (relative to the control gene TF2D) by 4.7-fold (p < 0.05) and 5.3-fold (p < 0.02), respectively. Similar reductions in resistin mRNA were demonstrated with metformin 100 microm (6.2-fold reduction, p < 0.02) and oleic acid 100 microm (3.9-fold reduction, p < 0.03). Resistin 1 microm significantly reduced maximum insulin-stimulated 2-deoxyglucose uptake in L6 cells from 634 to 383% (relative to 100% for control, p < 0.001), and co-administration of rosiglitazone had no effect on resistin-induced insulin resistance. In the absence of insulin, however, resistin increased glucose uptake dose-dependently (e.g., 1.75-fold at 5 microm, p < 0.001) via a mitogen-activated protein kinase-dependent pathway. CONCLUSIONS: These results demonstrate that various glucose-lowering therapies and oleic acid reduce resistin gene expression in isolated adipocytes, and that resistin impairs insulin-stimulated glucose uptake in skeletal muscle-derived cells.

Butyrylcholinesterase and obesity in individuals with the CHE2 C5+ and CHE2 C5- phenotypes.

OBJECTIVE: To investigate the association between butyrylcholinesterase (BChE) activities (total and band specific) and body mass index (BMI) in obese and nonobese individuals, considering other variables (anthropometric, biochemical and hormonal) and the leanness process. SUBJECTS: Obese (BMI> or =30 kg/m(2); N=181) and nonobese individuals (N=265), classified according to the CHE2 locus phenotypes, with the obese patients being followed-up when submitted to a weight-loss program. MEASUREMENTS: Anthropometric (weight, height, BMI, waist, waist/hip ratio-WHR, triceps and subscapular skinfolds, percentage of body fat and arterial pressures), hormonal (insulin, estradiol-E(2), triiodothyronine-T(3) and thyroxine-T(4)) and biochemical (glucose, total cholesterol, HDL-C, triglycerides, uric acid, urea, creatinine, sodium, potassium and BChE activities) variables. RESULTS: Although obese CHE2 C5- individuals presented higher mean BChE activities than their CHE2 C5- controls and diminished mean activities with leanness, similar comparisons did not show any difference in the CHE2 C5+ group. Furthermore, the mean serum potassium values of obese individuals were significantly higher in the CHE2 C5+ than in the CHE2 C5- phenotype. The BChE activities were less related to BMI in obese CHE2 C5- individuals than in their controls. In the CHE2 C5- obese group, significant regression coefficients were found between BChE activity variables and BMI (+), ethnic origin (higher in Euro-Brazilians), sex (higher in males), diastolic pressure (-), triceps skinfold (+), total cholesterol (+), T(3) (+) and E(2) (-). The main findings in the CHE2 C5+ obese group: mean insulin levels decreased with leanness and a significant correlation was detected between the C(5) complex activity and creatinine (+), insulin (-) and WHR (-); a significantly higher frequency of weight loss occurred compared to the CHE2 C5- group. CONCLUSION: In the present study, different relations between obesity and some of the studied variables were found when CHE2 C5+ and CHE2 C5- individuals were compared.

The inherited episodic ataxias: how well do we understand the disease mechanisms?

The past few years have seen the elucidation of several neurological diseases caused by inherited mutations of ion channels. In contrast to many other types of genetic disorders, the "channelopathies" can be studied with high precision by applying electrophysiological methods. This review evaluates the success of this approach in explaining the mechanisms of two forms of episodic ataxia that are known to be caused by mutations of ion channels: episodic ataxia type 1 (EA1, caused by K+ channel mutations) and episodic ataxia type 2 (EA2, caused by Ca2+ channel mutations). Although both of these disorders are rare, they raise many important questions about the roles of identified channels in brain function. Indeed, a resolution of the mechanisms by which both diseases occur will represent a major milestone in understanding diseases of the CNS, in addition to opening the way to novel possible treatments.