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1. Efficacy of <scp>iGlarLixi</scp> in adults with type 2 diabetes inadequately controlled ( <scp>glycated haemoglobin ≥8%,</scp> ≥64 mmol/mol) on two oral antidiabetes drugs: Post hoc analysis of the <scp>LixiLan‐O</scp> randomized trial

Author: Karen Palmer, Elisabeth Souhami, Julio Rosenstock, Elisabeth Niemoeller, Chen Ji, David Russell-Jones, Melanie J. Davies, Neil Skolnik, and Amar Ali
Subjects: medicine.medical_specialty, endocrine system diseases, Insulin glargine, business.industry, Endocrinology, Diabetes and Metabolism, nutritional and metabolic diseases, Type 2 diabetes, medicine.disease, Gastroenterology, law.invention, Metformin, Lixisenatide, chemistry.chemical_compound, Endocrinology, Postprandial, chemistry, Randomized controlled trial, law, Internal medicine, Mole, Post-hoc analysis, Internal Medicine, medicine, business, medicine.drug
Abstract: AIMS To assess the efficacy and safety of iGlarLixi (the titratable fixed-ratio combination of insulin glargine 100 U/mL [iGlar] plus lixisenatide [Lixi]), in adults with type 2 diabetes (T2D) with glycated haemoglobin (HbA1c) levels ≥8% (≥64 mmol/mol). MATERIALS AND METHODS The LixiLan-O study (NCT02058147) compared iGlarLixi with iGlar or Lixi in adults with T2D inadequately controlled on metformin ± a second oral antidiabetes drug (OAD). This exploratory analysis evaluated the LixiLan-O subgroup of participants with baseline HbA1c levels of ≥8% (≥64 mmol/mol) who were receiving metformin plus a second OAD at screening. RESULTS The mean diabetes duration was 10.0 years, and the mean duration of second OAD use was 4.5 years. iGlarLixi demonstrated greater mean reductions from baseline in HbA1c and 2-hour postprandial glucose (PPG) compared with iGlar or Lixi (HbA1c -1.9% vs. -1.6% or -1.0% [-20 vs. -17 or -10 mmol/mol; 2-hour PPG -7.2 vs. -4.6 or -5.5 mmol/L). Greater proportions of participants achieved HbA1c
Published: 2021
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2. HbA1c and hypoglycaemia outcomes for people with type 1 diabetes due to the introduction of a single-day structured education programme and flash glucose monitoring

Author: Helen Griffith, David W Hunt, Karen Mackie, Roselle Herring, Gillian Garden, Beverly Tuthill, and David Russell-Jones
Subjects: medicine.medical_specialty, Type 1 diabetes, Health professionals, business.industry, Diabetes mellitus, Internal medicine, medicine, Subgroup analysis, Distress screening, General Medicine, medicine.disease, business, Structured education
Abstract: People with type 1 diabetes who met NHS England funding criteria attended an accredited, intensive one-day structured education programme and completed the online FreeStyle Libre Academy training module followed by a 30-minute healthcare professional face-to-face practical training session. HbA1c, Gold hypoglycaemia score and Diabetes Distress Screening score were documented before commencement of the intervention and at 6 months. 213 people with type 1 diabetes (52% men; average age 48 years (range 18–87)) completed the 6-month intervention. Overall mean HbA1c reduced by 6 mmol/mol (0.5%) from 62±14 mmol/mol (7.8%) to 56±12 mmol/mol (7.3%) (p
Published: 2021
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3. Characteristics and outcomes of patients with COVID-19 at a district general hospital in Surrey, UK

Author: Matthew Cox, Nikhil Mayor, Aleksandra Kotwica, Harry Knights, Sanju Mathew, Morgan Hughes, Jack Baker, David Russell-Jones, Evgeniya Bunova, and Kristina Millar
Subjects: Male, medicine.medical_specialty, Palliative care, medicine.medical_treatment, Pneumonia, Viral, Comorbidity, 030204 cardiovascular system & hematology, Hospitals, General, Risk Assessment, Vulnerable Populations, Disease Outbreaks, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Oxygen therapy, Outcome Assessment, Health Care, Health care, medicine, Humans, Hospital Mortality, 030212 general & internal medicine, Pandemics, Aged, Retrospective Studies, Cross Infection, Frailty, business.industry, COVID-19 rapid report, Medical record, COVID-19, Retrospective cohort study, General Medicine, Middle Aged, Hospitals, District, medicine.disease, Combined Modality Therapy, United Kingdom, Hospitalization, Emergency medicine, Female, Coronavirus Infections, business, Risk assessment, Cohort study
Abstract: BACKGROUND: This retrospective cohort study aims to define the clinical findings and outcomes of every patient admitted to a district general hospital in Surrey with COVID-19 in March 2020, providing a snapshot of the first wave of infection in the UK. This study is the first detailed insight into the impact of frailty markers on patient outcomes and provides the infection rate among healthcare workers. METHODS: Data were obtained from medical records. Outcome measures were level of oxygen therapy, discharge and death. Patients were followed up until 21 April 2020. RESULTS: 108 patients were included. 34 (31%) died in hospital or were discharged for palliative care. 43% of patients aged over 65 died. The commonest comorbidities were hypertension (49; 45%) and diabetes (25; 23%). Patients who died were older (mean difference ±SEM, 13.76±3.12 years; p
Published: 2020
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4. An Evaluation of the Safety of Pilots With Insulin-Treated Diabetes in Europe Flying Commercial and Noncommercial Aircraft

Author: Graham A Roberts, Veronika Hofmann, Kenneth M. Shaw, Thomas P. Gaffney, Brian M. Frier, Julia L. Hine, David Russell-Jones, Gillian L. Garden, Simon Heller, Gerd Koehler, Stuart J Mitchell, and Ewan J Hutchison
Subjects: Adult, Blood Glucose, Male, Diabetes duration, Aircraft, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Hypoglycemia, Toxicology, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, Diabetes Mellitus, Internal Medicine, Extensive data, Humans, Insulin, Medicine, 030212 general & internal medicine, Glycemic, Advanced and Specialized Nursing, business.industry, Middle Aged, medicine.disease, Large cohort, Europe, Pilots, Female, business, Insulin treated diabetes
Abstract: OBJECTIVE The risk of hypoglycemia in people with insulin-treated diabetes has debarred them from certain “safety-critical” occupations, including flying commercial aircraft. This report evaluates the effectiveness of a protocol enabling a large cohort of insulin-treated pilots to fly commercially. RESEARCH DESIGN AND METHODS This was an observational study of pilots with insulin-treated diabetes who were granted medical certification to fly commercial and noncommercial aircraft. Clinical details, pre- and in-flight (hourly and 30 min before landing) blood glucose values were correlated against the protocol-specified ranges: green (5–15 mmol/L), amber (low, 4–4.9 mmol/L; high, 15.1–20 mmol/L), and red (low, 20 mmol/L). RESULTS A total of 49 pilots with type 1 (84%) or type 2 (16%) diabetes who had been issued class 1 or class 2 certificates were studied. Median diabetes duration was 10.9 years. Mean HbA1c was 7.2% (55.0 mmol/mol) before certification and 7.2% (55.1 mmol/mol) after certification (P = 0.97). Blood glucose values (n = 38,621) were recorded during 22,078 flying hours. Overall, 97.69% of measurements were within the green range, 1.42% within the low amber range, and 0.75% within the high amber range. Only 0.12% of readings were within the low red range and 0.02% within the high red range. Out-of-range readings declined from 5.7% in 2013 to 1.2% in 2019. No episodes of pilot incapacitation occurred, and glycemic control did not deteriorate. CONCLUSIONS The protocol is practical to implement, and no events compromising safety were reported. This study represents what is, to our knowledge, the most extensive data set from people with insulin-treated diabetes working in a “safety-critical” occupation, which may be relevant when estimating risk in other safety-critical occupations.
Published: 2020
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5. A potential diagnostic problem on the ICU: Euglycaemic diabetic Ketoacidosis associated with SGLT2 inhibition

Author: Idrisu Sanusi, Lui G. Forni, David Russell-Jones, and Alexander Sarnowski
Subjects: Blood Glucose, Male, medicine.medical_specialty, Diabetic ketoacidosis, MEDLINE, Critical Care and Intensive Care Medicine, Diabetic Ketoacidosis, law.invention, Type ii diabetes, 03 medical and health sciences, Patient Admission, 0302 clinical medicine, Sodium-Glucose Transporter 2, law, medicine, Humans, Hypoglycemic Agents, Intensive care medicine, Sodium-Glucose Transporter 2 Inhibitors, Aged, business.industry, 030208 emergency & critical care medicine, medicine.disease, Intensive care unit, Pathophysiology, Ketoacidosis, Intensive Care Units, Diabetes Mellitus, Type 2, 030228 respiratory system, Sodium/Glucose Cotransporter 2, Hypertension, Blood Gas Analysis, business, Oral hypoglycaemic
Abstract: Sodium glucose cotransporter 2 (SGLT2) inhibitors are the latest class of oral hypoglycaemic agents approved to treat type II diabetes. Their use is increasing and as such more patients will present to critical care whilst on this treatment. However, there have been several case reports of euglycaemic diabetic ketoacidosis associated with the use of these agents. Under such circumstances the blood glucose is often normal or only moderately elevated and hence the diagnosis may be delayed resulting in inappropriate therapy. In this review we describe a case of SGLT2 mediated ketoacidosis who presented to our intensive care unit, discuss the proposed pathophysiology behind this development of ketoacidosis as well as its potential prevention, management and treatment.
Published: 2020
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6. Changing inpatient diabetes care in a district general hospital

Author: Marie Wallner, David Russell-Jones, Roselle Herring, and Basharat Andrabi
Subjects: Service (business), business.industry, General Medicine, Bed days, medicine.disease, Patient flow, Harm, Multidisciplinary approach, Diabetes mellitus, medicine, In patient, Medical emergency, General hospital, business, health care economics and organizations
Abstract: Introduction: People with diabetes in hospital have longer lengths of stay and are at higher risk of experiencing avoidable harm. This has a significant impact on patient flow and capacity in any hospital Trust.Aims and Methods: A Trust-wide peripatetic inpatient diabetes service redesign was performed to deliver reduced medication errors, improved patient flow, reduced length of stay and reduced inpatient risk. The service redesign was delivered without new recurring expenditure on senior staff. The model of care was multidisciplinary and introduced consensus and evidence-based care with clear governance processes.Results: Following introduction of the new service on 7 December 2017 to 1 June 2018, a reduction in length of stay in both medicine and surgical divisions was seen with 2,168 ‘saved’ inpatient bed days compared with the same time period in the preceding year, which represented a significant cost saving for the Trust and improvement in patient flow. This was associated with a reduction in the number of diabetes-related Datix reports and serious untoward incidents.Conclusions: This is the first major diabetes service redesign in a small district general hospital. The introduction of a dedicated inpatient diabetes service has led to Trust-wide improvements in patient care and patient flow without additional cost to the Trust.
Published: 2019
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7. Take Control: A randomized trial evaluating the efficacy and safety of self‐ versus physician‐managed titration of insulin glargine 300 U/mL in patients with uncontrolled type 2 diabetes

Author: Elías Delgado, Aude Roborel de Climens, Luiza Popescu, Krzysztof Strojek, Hans A. Frandsen, George Dimitriadis, Bernd Schultes, Melanie J. Davies, Mireille Bonnemaire, Arnaud Dauchy, and David Russell-Jones
Subjects: Blood Glucose, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Insulin Glargine, 030209 endocrinology & metabolism, Type 2 diabetes, 030204 cardiovascular system & hematology, law.invention, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Randomized controlled trial, law, Internal medicine, Diabetes mellitus, randomized trial, Internal Medicine, Humans, Hypoglycemic Agents, Medicine, Adverse effect, Disease burden, Aged, Glycated Hemoglobin, business.industry, Insulin glargine, Self-Management, Incidence (epidemiology), Original Articles, Middle Aged, medicine.disease, Hypoglycemia, Confidence interval, glycaemic control, Diabetes Mellitus, Type 2, Original Article, Female, type 2 diabetes, business, hypoglycaemia, medicine.drug
Abstract: Aim To compare the efficacy and safety of self‐ versus physician‐managed titration of insulin glargine 300 U/mL (Gla‐300) in people with inadequately controlled type 2 diabetes. Methods Take Control (EudraCT number: 2015‐001626‐42) was a 24‐week, multi‐national, open‐label, controlled, two‐arm, parallel‐group study in insulin‐naïve and pre‐treated participants, randomized 1:1 to a self‐ or physician‐managed titration of Gla‐300. The fasting self‐monitored plasma glucose (SMPG) target was 4.4 to 7.2 mmol/L. The primary outcome was non‐inferiority of glycated haemoglobin (HbA1c) change from baseline to week 24. Secondary outcomes included SMPG target achievement without hypoglycaemia, hypoglycaemia incidence, adverse events and participant‐reported outcomes (PROs). Results At week 24, the least squares (LS) mean HbA1c reduction was 0.97% (10.6 mmol/mol) and 0.84% (9.2 mmol/mol) in the self‐ and physician‐managed groups, respectively, with an LS mean difference of −0.13% [95% confidence interval −0.2619 to −0.0004] (–1.4 mmol/mol [–2.863 to –0.004]), demonstrating non‐inferiority (P
Published: 2019
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8. Blood glucose monitoring by insulin-treated pilots of commercial and private aircraft: An analysis of out-of-range values

Author: Ewan J Hutchison, Graham A Roberts, Stuart J Mitchell, Declan Maher, Thomas P. Gaffney, Kenneth M. Shaw, Julia L. Hine, Veronika Hofmann, Gerd Koehler, David Russell-Jones, Gillian L. Garden, Simon Heller, and Brian M. Frier
Subjects: Blood glucose monitoring, Blood Glucose, medicine.diagnostic_test, Aircraft, business.industry, Endocrinology, Diabetes and Metabolism, Insulin, medicine.medical_treatment, Blood Glucose Self-Monitoring, medicine.disease, Hypoglycemia, Traffic signal, Endocrinology, Animal science, Diabetes mellitus, Range (aeronautics), Time course, Internal Medicine, medicine, Humans, Hypoglycemic Agents, Blood Glucose Measurement, business, Glycated haemoglobin
Abstract: AIM To examine blood glucose measurements recorded as part of the diabetes protocol operated by the UK, Ireland and Austria, which allows commercial airline pilots with insulin-treated diabetes to fly. METHODS An observational study was conducted in pilots with insulin-treated diabetes, granted medical certification to fly commercial or noncommercial aircraft, who recorded pre-flight and hourly in-flight blood glucose measurements. These values were correlated to a traffic light system (green 5.0 to 15.0 mmol/L; amber 4.0 to 4.9 mmol/L and 15.1 to 20.0 mmol/L; and red 20.0 mmol/L) and studied for trends in glucose concentrations, time course within flight and any consequences. Pilot demographics were also analysed. RESULTS Forty-four pilots (90%) recorded one or more blood glucose value outside the green range during the 7 years of the study. Pilot age, diabetes type and duration, and follow-up period were comparable among subgroups, and mean glycated haemoglobin did not differ before and after certification in a way which would indicate poorer glycaemic control in any subgroup. A total of 892 blood glucose values (2.31%) were outside the green range, with half reported in-flight at various time intervals. There were 48 (0.12%) low red range values recorded, 14 (0.04%) of which occurred in-flight; all but four were restored to within the green range by the time of the next measurement. Appropriate corrective action was taken for all out-of-range values, with no reports of pilot incapacitation from any cause. CONCLUSIONS The traffic light system appears effective in identifying and reducing the frequency and severity of out-of-range values.
Published: 2021

9. Pilots flying with insulin-treated diabetes

Author: Graham A Roberts, Ewan J Hutchison, and David Russell-Jones
Subjects: medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Diabetes mellitus, Diabetes Mellitus, Internal Medicine, medicine, Humans, Insulin, Intensive care medicine, business.industry, Diabetes, medicine.disease, Hypoglycemia, Clinical Physiology, Pilots, Blood sugar regulation, Aviation, Insulin treated diabetes, business, Hypoglycaemia
Abstract: People with diabetes treated with insulin have often faced blanket bans from safety-critical occupations, largely because of fear of incapacitation due to hypoglycaemia. Recent advances in insulin therapies, modes of administration, monitoring, and noninvasive monitoring techniques have allowed stereotypical views to be challenged. The aviation sector has led the way, in allowing pilots to fly while on insulin. Recently, countries that have traditionally been opposed to this have changed their minds, largely due to the increasing evidence of safety. The purpose of this review was to gather all available information to update clinicans. The physiology and pathophysiology underpinning glucose regulation and the management of diabetes in the air allowing certain insulin-treated pilots to fly are discussed.
Published: 2021

10. Leveraging advances in diabetes technologies in primary care: a narrative review

Author: Aaron King, Liana K. Billings, Bruce W. Bode, and David Russell-Jones
Subjects: Blood Glucose, Technology, health care facilities, manpower, and services, education, diabetes technologies, Type 2 diabetes, Primary care, Review Article, Medical care, Endocrinology, Nursing, health services administration, Diabetes mellitus, insulin delivery systems, Medicine, Humans, Hypoglycemic Agents, Insulin, Continuous glucose monitoring, self-measured blood glucose, health care economics and organizations, Primary Health Care, business.industry, Blood Glucose Self-Monitoring, food and beverages, General Medicine, medicine.disease, Hypoglycemia, Diabetes Mellitus, Type 2, time in range, Quality of Life, Community Resources, Narrative review, business
Abstract: Primary care providers (PCPs) play an important role in providing medical care for patients with type 2 diabetes. Advancements in diabetes technologies can assist PCPs in providing personalised care that addresses each patient’s individual needs. Diabetes technologies fall into two major categories: devices for glycaemic self-monitoring and insulin delivery systems. Monitoring technologies encompass self-measured blood glucose (SMBG), where blood glucose is intermittently measured by a finger prick blood sample, and continuous glucose monitoring (CGM) devices, which use an interstitial sensor and are capable of giving real-time information. Studies show people using real-time CGM have better glucose control compared to SMBG. CGM allows for new parameters including time in range (the time spent within the desired target glucose range), which is an increasingly relevant real-time metric of glycaemic control. Insulin pens have increased the ease of administration of insulin and connected pens that can calculate and capture data on dosing are becoming available. There are a number of websites, software programs, and applications that can help PCPs and patients to integrate diabetes technology into their diabetes management schedules. In this article, we summarise these technologies and provide practical information to inform PCPs about utility in their clinical practice. The guiding principle is that use of technology should be individualised based on a patient’s needs, desires, and availability of devices. Diabetes technology can help patients improve their clinical outcomes and achieve the quality of life they desire by decreasing disease burden.KEY MESSAGESIt is important to understand the role that diabetes technologies can play in primary care to help deliver high-quality care, taking into account patient and community resources. Diabetes technologies fall into two major categories: devices for glycaemic self-monitoring and insulin delivery systems. Modern self-measured blood glucose devices are simple to use and can help guide decision making for self-management plans to improve clinical outcomes, but cannot provide “live” data and may under- or overestimate blood glucose; patients’ monitoring technique and compliance should be reviewed regularly. Importantly, before a patient is provided with monitoring technology, they must receive suitably structured education in its use and interpretation.Continuous glucose monitoring (CGM) is now standard of care for people with type 1 diabetes and people with type 2 diabetes on meal-time (prandial) insulin. Real-time CGM can tell both the patient and the healthcare provider when glucose is in the normal range, and when they are experiencing hyper- or hypoglycaemia. Using CGM data, changes in lifestyle, eating habits, and medications, including insulin, can help the patient to stay in a normal glycaemic range (70–180 mg/dL). Real-time CGM allows for creation of an ambulatory glucose profile and monitoring of time in range (the time spent within target blood glucose of 70–180 mg/dL), which ideally should be at least 70%; avoiding time above range (>180 mg/dL) is associated with reduced diabetes complications and avoiding time below range (180 mg/dL) is associated with reduced diabetes complications and avoiding time below range (
Published: 2021
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11. Comparison of oxygen-haemoglobin dissociation curves(ODC) and 99mTc-macroaggregated-albumin lung scans(MAA) in the diagnosis of Hepatopulmonary Syndrome(HPS) in children

Author: Emma Russell-Jones, Tassos Grammatikopoulos, and Theodore Dassios
Subjects: medicine.medical_specialty, business.industry, medicine.medical_treatment, Oxygenation, Liver transplantation, medicine.disease, Chronic liver disease, Gastroenterology, 03 medical and health sciences, Liver disease, 0302 clinical medicine, 030228 respiratory system, Biliary atresia, Internal medicine, Alagille syndrome, medicine, 030212 general & internal medicine, Hepatopulmonary syndrome, business, Perfusion
Abstract: Introduction: HPS is chronic liver disease with impaired oxygenation caused by intrapulmonary shunting(IPS), pulmonary vessel dilation and angiogenesis. Currently only definitive treatment is liver transplantation(LT). Aim: To compare non-invasively derived ventilation/perfusion(VA/Q) and MAA scans to quantify respiratory impairment pre&post LT. Methods: Retrospective study of children meeting diagnostic criteria for HPS between 03/1998-05/2016. Clinical data, MAA and paired SpO2 and FiO2 pre & post LT were collected and ODC constructed to determine VA/Q ratio and R to L IPS. Results: 16 children with HPS with diagnoses of biliary atresia(11), cryptogenic liver disease(2), progressive intrahepatic cholestasis(2) and Alagille syndrome(1). All had SpO2s of ≤94% in air, other lung pathology excluded. HPS diagnosis at median 8.5(IQR 6-12) yrs. Symptoms: exertional dyspnoea(13), dyspnoea at rest(8), cyanosis(10) and oxygen dependency(7). MAA show median (IQR) shunting 18(13-31)% with ODC showing 20(17-25)%. 15 received a LT(1 died on LT list), median age 8.8(7-12) yrs. and waiting time 201(90-382)days. All pulmonary symptoms resolved in median(IQR) 43(14-90)days post LT. Median shunting on ODC pre LT 10(0-24)% & post LT (median 43(17-121)days) was 0(0-0)% p=0.009. Correlation coefficient is 0.91 using mild( Conclusion: Non-invasive ODC and MAA yield comparable results hence are useful in HPS grading in children. R to L IPS reverses with LT with residual pulmonary dysfunction as VA/Q abnormalities persist in same time.
Published: 2020
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12. A UK survey of the management of infants with bronchopulmonary dysplasia (BPD)

Author: Anne Greenough, Emma Russell-Jones, Eleanor Jeffreys, Emma Williams, and Sarah Sturrock
Subjects: Pediatrics, medicine.medical_specialty, business.industry, medicine.medical_treatment, Furosemide, Poor weight gain, medicine.disease, chemistry.chemical_compound, chemistry, Bronchopulmonary dysplasia, Premature birth, Spironolactone, Breathing, Medicine, Weaning, Diuretic, business, medicine.drug
Abstract: Introduction: BPD is the commonest adverse outcome of premature birth, hence appropriate management is essential. Methods: We undertook a survey of UK neonatal units to determine their management of infants with BPD. Results: Fifty-two neonatal units responded: 37% were level 3 NICUs, 49% level 2 and 14% level 1 units. Sixty percent of units had a BPD management guideline. Thirty-six units used patient triggered ventilation and 14 high frequency oscillatory ventilation. The majority (69%) used volume targeting. Nitric oxide was used by 29.9% of units with no consensus over dosage, range 5-20ppm. Diuretics were used by the majority (64.7%) for fluid overload. They were used routinely by 9.8% of units, reasons included poor weight gain (3.9%) or to facilitate weaning from invasive ventilation (2%). Chlorthiazide, spironolactone and furosemide were the most commonly used diuretics, but in varying combinations. Only 24% of units undertook regular renal ultrasound examinations for infants receiving chronic diuretic therapy. Nineteen units used a course of systemic corticosteroids >9 days, whereas 11 units a course Conclusion: Our survey demonstrates there is no consensus for the management of infants with BPD and emphasizes the need for appropriately designed trials to establish evidence based management.
Published: 2020
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13. Metabolic effects of an SGLT2 inhibitor (dapagliflozin) during a period of acute insulin withdrawal and development of ketoacidosis in people with type 1 diabetes

Author: Robert Garesse, Fariba Shojaee-Moradie, David Russell-Jones, Melanie J. Davies, Mary Stevenage, Sigurd Johnsen, Roselle Herring, Nicola Jackson, A. Margot Umpleby, Agampodi Mendis, and Barbara A. Fielding
Subjects: Advanced and Specialized Nursing, Insulin pump, medicine.medical_specialty, Type 1 diabetes, business.industry, Endocrinology, Diabetes and Metabolism, Insulin, medicine.medical_treatment, 030209 endocrinology & metabolism, medicine.disease, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Basal (medicine), chemistry, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Ketone bodies, Lipolysis, 030212 general & internal medicine, Dapagliflozin, business
Abstract: OBJECTIVE To determine the effect of the sodium–glucose cotransporter 2 inhibitor dapagliflozin on glucose flux, lipolysis, and ketone body concentrations during insulin withdrawal in people with type 1 diabetes. RESEARCH DESIGN AND METHODS A double-blind, placebo-controlled crossover study with a 4-week washout period was performed in 12 people with type 1 diabetes using insulin pump therapy. Participants received dapagliflozin or placebo in random order for 7 days. Stable isotopes were infused to measure the glucose Ra, Rd, and lipolysis. At isotopic steady state, insulin was withdrawn, and the study was terminated after 600 min or earlier if blood glucose reached 18 mmol/L, bicarbonate 5.0 mmol/L. RESULTS At baseline, glucose Ra was significantly higher for the dapagliflozin group than the placebo group. Following insulin withdrawal, plasma glucose concentrations at the end point were significantly lower with dapagliflozin than placebo and glucose Rd area under the curve (AUC)0–180 min and β-hydroxybutyrate (BOHB) AUC0–180 min were significantly higher. There was a small but significantly higher glycerol Ra (measure of lipolysis) AUC0–180 min with dapagliflozin. Nonesterified fatty acid concentrations were not different between treatments. When divided by BMI >27 and CONCLUSIONS During insulin withdrawal, the increase in BOHB with dapagliflozin may be partially due to increased lipolysis. However, reduced renal excretion, reduced BOHB uptake by peripheral tissues, or a metabolic switch to increased ketogenesis within the liver may also play a role.
Published: 2020
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14. Serious Injuries in the Mining Industry: Preparing the Emergency Response

Author: Martyn Cross, Alan Holmes, Marcus Cattani, Russell Jones, Jessica Boylan, Colin Boothroyd, and Joan Mattingley
Subjects: 050210 logistics & transportation, Emergency Medical Services, Referral, business.industry, 05 social sciences, Primary health care, Emergency Nursing, medicine.disease, Chemical effects, 03 medical and health sciences, Mining industry, 0302 clinical medicine, Emergency response, Health promotion, 0502 economics and business, Sprains and strains, Injury prevention, Emergency Medicine, medicine, 030212 general & internal medicine, Medical emergency, business
Abstract: Introduction Paramedics are employed by Australian and international mining and petroleum organisations to provide emergency medical response, injury prevention, health promotion, chronic disease management, medical referral, primary healthcare and repatriation co-ordination for miners in exploration, construction and production. These are challenging roles given the often isolated, potentially hazardous and clinically unpredictable nature of the sites where these paramedics work. The purpose of this article is to review injuries that occurred in the mining industry with a view to sharing this information with paramedics who work within the mining sector. Methods Data was collected under legislative authority by the Western Australian Department of Mines, Industry Regulation and Safety (DMIRS). Data efficacy was optimised via strong legislative support whereby all organisations involved in mining activities are legally compelled to report to the DMIRS all accidents involving injury. Results A total of 837 injuries were reported during the 6-month period between 1 July and 31 December 2013. These comprised 658 serious injuries, including three fatalities, and 179 minor injuries. Sprains and strains were the most common injury comprising 69% of injuries followed by fractures 10%, lacerations 6%, crushing injuries 5%, bruises and contusions 4%, and dislocations and displacements 2%. Foreign bodies, punctures, bites, amputations, chemical effects, thermal burns, flash and arc burns and loss of consciousness each recorded less than 1% of the injuries. Conclusion Findings presented in this article can be used by paramedics working in the mining sector across Australia and worldwide. Paramedic awareness of the nature and cause of injury is useful for optimally preparing paramedics to perform appropriate diagnosis and treatment and to minimise patient mortality and morbidity.
Published: 2019
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15. Cardioembolic Stroke in a Patient with Coronavirus Disease of 2019 (COVID-19) Myocarditis: A Case Report

Author: James S. Ford, Russell Jones, and James F. Holmes
Subjects: medicine.medical_specialty, Myocarditis, Coronavirus disease 2019 (COVID-19), Disease, 030204 cardiovascular system & hematology, Emergency Nursing, medicine.disease_cause, Intracardiac injection, 03 medical and health sciences, thromboembolic stroke, 0302 clinical medicine, Cardiac magnetic resonance imaging, Internal medicine, medicine, 030212 general & internal medicine, Coronavirus, Cardioembolic stroke, COVID-19 Case Report, medicine.diagnostic_test, SARS-CoV-2, business.industry, lcsh:Medical emergencies. Critical care. Intensive care. First aid, COVID-19, lcsh:RC86-88.9, medicine.disease, Thrombosis, Emergency Medicine, Cardiology, myocarditis, business
Abstract: Author(s): Ford, James S.; Holmes, James F.; Jones, Russell F. | Abstract: Introduction: There is a growing body of literature detailing coronavirus 2019 (COVID-19) cardiovascular complications and hypercoagulability, although little has been published on venous or arterial thrombosis risk.Case Report: In this report, we present a single case of cardioembolic stroke in the setting of COVID-19 related myocarditis, diagnosed via cardiac magnetic resonance imaging and echocardiography. COVID-19 infection was confirmed via a ribonucleic acid polymerase chain reaction assay.Conclusion: Further research is needed to evaluate the hypercoagulable state of patients with COVID-19 to determine whether prophylactic anticoagulation may be warranted to prevent intracardiac thrombi and cardioembolic disease in patients with COVID-19 related myocarditis.
Published: 2020

16. Investigating the Association Between Baseline Characteristics (HbA1c and Body Mass Index) and Clinical Outcomes of Fast-Acting Insulin Aspart in People with Diabetes: A Post Hoc Analysis

Author: Keith Bowering, David Russell-Jones, Simon Heller, Stewart B. Harris, Bruce W. Bode, Vincent Woo, Milivoj Piletič, Claus Dethlefsen, Chantal Mathieu, Helena W. Rodbard, and Vinay Babu
Subjects: medicine.medical_specialty, endocrine system diseases, Haemoglobin A, glycosylated, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, 030209 endocrinology & metabolism, Type 2 diabetes, 030204 cardiovascular system & hematology, Outcome, treatment, Insulin aspart, 03 medical and health sciences, 0302 clinical medicine, Index, body mass, Diabetes mellitus, Internal medicine, Post-hoc analysis, Internal Medicine, medicine, Original Research, Type 1 diabetes, business.industry, Insulin, Diabetes mellitus, type 1, nutritional and metabolic diseases, Diabetes mellitus, type 2, medicine.disease, Obesity, business, Body mass index, medicine.drug
Abstract: Introduction The aim of this study was to investigate the association between baseline characteristics [HbA1c and body mass index (BMI)] and the effect of mealtime fast-acting insulin aspart (faster aspart) relative to insulin aspart (IAsp) or basal-only insulin therapy on several efficacy and safety outcomes in people with diabetes. Methods Post hoc analysis of three randomised phase 3a trials in people with type 1 diabetes (T1D; onset 1) and type 2 diabetes (T2D; onset 2 and 3). Participants (N = 1686) were stratified according to baseline BMI ( 58– 7.5– 30 kg/m2 subgroup. Conclusions In participants with T1D and T2D, treatment differences (for change in HbA1c and overall hypoglycaemia) between mealtime faster aspart and insulin comparators were similar to the corresponding overall analysis across baseline HbA1c and BMI subgroups. The finding of a lower total daily insulin dose in participants with obesity (BMI > 30 kg/m2) and T1D treated with faster aspart, versus those treated with IAsp, may warrant further investigation. Trial Registration ClinicalTrials.gov NCT01831765 (onset 1); NCT01819129 (onset 2); NCT01850615 (onset 3). Funding Novo Nordisk A/S, Søborg, Denmark. Electronic supplementary material The online version of this article (10.1007/s13300-018-0553-7) contains supplementary material, which is available to authorized users.
Published: 2018
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17. Lessons for modern insulin development

Author: David Russell-Jones and R. Herring
Subjects: Dosage Forms, medicine.medical_specialty, business.industry, Endocrinology, Diabetes and Metabolism, Insulin, medicine.medical_treatment, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, medicine.disease, 03 medical and health sciences, Diabetes Mellitus, Type 1, 0302 clinical medicine, Endocrinology, Diabetes Mellitus, Type 2, Drug Development, Drug Design, Diabetes mellitus, Metabolic control analysis, Internal Medicine, medicine, Humans, Hypoglycemic Agents, business, Intensive care medicine
Abstract: There have been many advances in insulin with a realistic possibility of mimicking nature to improve insulin replacement, with a view to achieving improved metabolic control. Lessons can be learnt from the evolution of insulin, insulin development, and new advances in technology. This may lead to fewer side effects of therapy resulting in a lower risk of hypoglycaemia and less weight gain, which could in turn could reduce long-term complications for people with diabetes.
Published: 2018
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18. Efficacy and safety of fast‐acting insulin aspart in comparison with insulin aspart in type 1 diabetes (onset 1): A 52‐week, randomized, treat‐to‐target, phase III trial

Author: David Russell-Jones, Ludger Rose, Tina Graungaard, Bruce W. Bode, Edward Franek, Chantal Mathieu, Anne Birk Østerskov, and Athena Philis-Tsimikas
Subjects: Blood Glucose, Male, endocrine system diseases, type 1 diabetes, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, 030204 cardiovascular system & hematology, Gastroenterology, 0302 clinical medicine, Endocrinology, Insulin Detemir, Clinical endpoint, Meals, Insulin detemir, Middle Aged, Postprandial, Original Article, Drug Therapy, Combination, Female, Drug Monitoring, hormones, hormone substitutes, and hormone antagonists, medicine.drug, Adult, medicine.medical_specialty, Drug Compounding, 030209 endocrinology & metabolism, Drug Administration Schedule, Insulin aspart, 03 medical and health sciences, Double-Blind Method, Internal medicine, Internal Medicine, medicine, Humans, Hypoglycemic Agents, Adverse effect, Insulin Aspart, Glycated Hemoglobin, Type 1 diabetes, Dose-Response Relationship, Drug, business.industry, Insulin, Blood Glucose Self-Monitoring, nutritional and metabolic diseases, Original Articles, medicine.disease, Confidence interval, Hypoglycemia, Diabetes Mellitus, Type 1, insulin therapy, Hyperglycemia, business, Follow-Up Studies
Abstract: AIMS: To compare the safety and efficacy of fast-acting insulin aspart (faster aspart) with conventional insulin aspart (IAsp) in adults with type 1 diabetes (T1D). MATERIALS AND METHODS: onset 1 was a randomized, multicentre, treat-to-target, phase III, 52-week (initial 26 weeks + additional 26 weeks) trial conducted at 165 sites across 9 countries. Adults with T1D were randomly allocated to double-blind mealtime faster aspart or IAsp, each with once- or twice-daily insulin detemir. The primary endpoint, change in glycated haemoglobin (HbA1c) from baseline after the initial 26 weeks, has been reported previously. In the present paper, we report data from the full 52-week study period. RESULTS: Between August 2013 and June 2015, 381 participants were assigned to double-blind faster aspart and 380 participants to IAsp. After 52 weeks, estimated mean changes from baseline in HbA1c levels were -0.08% (faster aspart) and +0.01% (IAsp); estimated treatment difference significantly favoured faster aspart (-0.10% [95% confidence interval {CI} -0.19;-0.00]; P = .0424). Changes from baseline in 1-hour postprandial plasma glucose (PPG) increment (meal test; faster aspart -1.05 mmol/L; IAsp -0.14 mmol/L) also significantly favoured faster aspart (estimated treatment difference -0.91 mmol/L [95% CI -1.40;-0.43]; -16.48 mg/dL [95% CI -25.17;-7.80]; P = .0002). There was no difference in overall severe or blood glucose-confirmed hypoglycaemic episodes or treatment-emergent adverse events between treatments. CONCLUSIONS: At 52 weeks, overall glycaemic control had significantly improved with faster aspart vs IAsp, consistent with the 26-week study findings. Achieving an insulin profile closer to physiological insulin secretion with faster aspart translates into lower PPG and HbA1c levels compared with those achieved with IAsp in people with T1D. ispartof: Diabetes, Obesity & Metabolism vol:20 issue:5 pages:1148-1155 ispartof: location:England status: published
Published: 2018

19. Identification of barriers to insulin therapy and approaches to overcoming them

Author: Kamlesh Khunti, Frans Pouwer, and David Russell-Jones
Subjects: medicine.medical_specialty, Diabetes Mellitus, Type 2/drug therapy, Endocrinology, Diabetes and Metabolism, Best practice, medicine.medical_treatment, Global problem, Hypoglycemic Agents/therapeutic use, 030209 endocrinology & metabolism, Review Article, Review, Type 2 diabetes, Patient Acceptance of Health Care/psychology, Time-to-Treatment, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Internal medicine, Diabetes mellitus, Journal Article, Internal Medicine, medicine, Hypoglycemic Agents, Insulin, Humans, 030212 general & internal medicine, Intensive care medicine, Review Articles, Dose-Response Relationship, Drug, Treatment regimen, business.industry, Patient Acceptance of Health Care, medicine.disease, Diabetes Mellitus, Type 2, insulin therapy, Insulin/therapeutic use, type 2 diabetes, Level of care, business, Healthcare providers
Abstract: Poor glycaemic control in type 2 diabetes (T2D) is a global problem despite the availability of numerous glucose-lowering therapies and clear guidelines for T2D management. Tackling clinical or therapeutic inertia, where the person with diabetes and/or their healthcare providers do not intensify treatment regimens despite this being appropriate, is key to improving patients’ long-term outcomes. This gap between best practice and current level of care is most pronounced when considering insulin regimens, with studies showing that insulin initiation/intensification is frequently and inappropriately delayed for several years. Patient- and physician-related factors both contribute to this resistance at the stages of insulin initiation, titration and intensification, impeding achievement of optimal glycaemic control. The present review evaluates the evidence and reasons for this delay, together with available methods for facilitation of insulin initiation or intensification.
Published: 2017
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20. Effectiveness of a Decision Aid in Potentially Vulnerable Patients: A Secondary Analysis of the Chest Pain Choice Multicenter Randomized Trial

Author: Kelly P. Owen, Erik P. Hess, Deborah B. Diercks, Judd E. Hollander, Russell Jones, Zachary F. Meisel, Victor M. Montori, Annie LeBlanc, Jonathan Inselman, Nilay Shah, Michel Demers, Kristin L. Rising, Jason T. Schaffer, Jeffrey A. Kline, Jeph Herrin, and Carlos A. A. Torres
Subjects: Adult, Male, Chest Pain, Health Knowledge, Attitudes, Practice, Acute coronary syndrome, medicine.medical_specialty, Higher education, media_common.quotation_subject, Decision Making, Health literacy, 030204 cardiovascular system & hematology, Trust, Chest pain, Choice Behavior, Literacy, Decision Support Techniques, law.invention, 03 medical and health sciences, Sex Factors, 0302 clinical medicine, Randomized controlled trial, law, Numeracy, medicine, Humans, 030212 general & internal medicine, Aged, media_common, business.industry, Health Policy, Racial Groups, Age Factors, Middle Aged, Patient Acceptance of Health Care, medicine.disease, Health Literacy, Test (assessment), Socioeconomic Factors, Physical therapy, Female, Patient Participation, medicine.symptom, business
Abstract: Background. We test the hypotheses that use of the Chest Pain Choice (CPC) decision aid (DA) would be similarly effective in potentially vulnerable subgroups but increase knowledge more in patients with higher education and trust in physicians more in patients from racial minority groups. Methods. This was a secondary analysis of a multicenter randomized trial in adults with chest pain potentially due to acute coronary syndrome. The trial compared an intervention group engaged in shared decision making (SDM) using CPC to a control group receiving usual care (UC). We assessed for subgroup effects based on age, sex, race, income, insurance, education, literacy, and numeracy. We dichotomized each characteristic and tested for interactions using regression models with indicators for arm assignment and study site. Results. Of 898 patients (451 DA, 447 UC), over 50% were female, over one-third were black, nearly one-third had a high school education or less, and over 60% had “low” health literacy. The DA did not increase knowledge more in patients with higher education ( P for interaction = 0.06) but did increase knowledge more in the “typical” than in the “low” numeracy subgroup (10.6% v. 4.7%, absolute difference [AD] = 5.9%, P for interaction = 0.025). The DA did not significantly increase patient trust in physicians in racial minorities ( P for interaction = 0.06) but did increase trust more in patients with “low” literacy compared with those with “typical” literacy (3.7% v. –1.4%, AD = 5.1, P for interaction = 0.011). Conclusions. CPC benefited all sociodemographic groups to a similar extent, with greater knowledge transfer in patients with higher numeracy and greater physician trust in patients with “low” health literacy. Tailoring SDM interventions to patient characteristics may be necessary for optimal effectiveness.
Published: 2017
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21. A review of the NG17 recommendations for the use of basal insulin in type 1 diabetes

Author: H Schou, Miles Fisher, K. C. S. Lee, Emma G. Wilmot, Michael D. Feher, Mike Baxter, David Russell-Jones, Nick Hex, J Mahon, and Stephen C. Bain
Subjects: Pediatrics, medicine.medical_specialty, Systematic Review or Meta‐Analysis, Endocrinology, Diabetes and Metabolism, Network Meta-Analysis, Insulin, Isophane, Nice, Insulin Glargine, 030209 endocrinology & metabolism, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Insulin Detemir, Diabetes mellitus, Statistical significance, Post-hoc analysis, Internal Medicine, medicine, Humans, Hypoglycemic Agents, Insulin, 030212 general & internal medicine, Insulin detemir, computer.programming_language, Glycated Hemoglobin, Type 1 diabetes, business.industry, medicine.disease, Hypoglycemia, Insulin, Long-Acting, Diabetes Mellitus, Type 1, Basal (medicine), Meta-analysis, Practice Guidelines as Topic, business, Systematic Reviews or Meta‐analyses, computer, medicine.drug
Abstract: Aims To revisit the data analysis used to inform National Institute of Health and Care Excellence (NICE) NG17 guidance for initiating basal insulin in adults with type 1 diabetes mellitus (diabetes). Methods We replicated the data, methodology and analysis used by NICE diabetes in the NG17 network meta‐analysis (NMA). We expanded this data cohort to a more contemporary data set (extended 2017 NMA) and restricted the studies included to improve the robustness of the data set (restricted 2017 NMA) and in a post hoc analysis, changed the index comparator from neutral protamine Hagedorn (NPH) insulin twice daily to insulin detemir twice daily. Results The absolute changes in HbA1c were similar to those reported in the NG17. However, all 95% credible intervals for change in HbA1c point estimates crossed the line of null effect, except for detemir twice daily (in the NICE and extended 2017 NMAs) and NPH four times daily. In the detemir twice‐daily centred post hoc analysis, the 95% credible intervals for change in HbA1c crossed the line of null effect for all basal therapies, except NPH. Conclusions In NG17, comparisons of basal insulins were based solely on efficacy of glycaemic control. Many of the trials used in this analysis were treat‐to‐target, which minimize differences in HbA1c. In the NMAs, statistical significance was severely undermined by the wide credible intervals. Despite these limitations, point estimates of HbA1c were used to rank the insulins and formed the basis of NG17 guidance. This study queries whether such analyses should be used to make specific clinical recommendations., What's new? This study found no significant differences in HbA1c reduction between twice‐daily detemir and modern basal insulin comparators in efficacy trials; the apparent wide variation in HbA1c undermines the statistical robustness and the clinical relevance of the recommendation in the current National Institute of Health and Care Excellence (NICE) guidelines for type 1 diabetes in adults (NG17).The analyses highlight the importance of the quantity and quality of data used in network meta‐analyses to allow clinically meaningful recommendations.With the lack of differentiating evidence to support twice‐daily detemir as the basal insulin of choice for type 1 diabetes, selection of basal insulin should be personalized to individual needs.
Published: 2019

22. Glycaemic benefit of iGlarLixi in insulin-naive type 2 diabetes patients with high HbA1c or those with inadequate glycaemic control on two oral antihyperglycaemic drugs in the LixiLan-O randomized trial

Author: Dhalong Zhu, Cecile Dessapt-Baradez, Thomas M. Barber, David Russell-Jones, Fernando J. Lavalle-González, Rory J. McCrimmon, Melanie J. Davies, Gagik Radikovich Galstyan, and Mike Baxter
Subjects: Blood Glucose, Male, endocrine system diseases, type 2 diabetes mellitus, Endocrinology, Diabetes and Metabolism, Insulin Glargine, Type 2 diabetes, 030204 cardiovascular system & hematology, Weight Gain, iGlarLixi, law.invention, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Randomized controlled trial, law, Brief Report, Middle Aged, Metformin, Treatment Outcome, glycaemic control, insulin glargine 100 U, Drug Therapy, Combination, Female, medicine.symptom, lixisenatide, medicine.drug, Adult, medicine.medical_specialty, 030209 endocrinology & metabolism, 03 medical and health sciences, Lixisenatide, Internal medicine, Post-hoc analysis, Internal Medicine, medicine, Humans, Hypoglycemic Agents, Least-Squares Analysis, Glycated Hemoglobin, business.industry, Insulin glargine, Type 2 Diabetes Mellitus, nutritional and metabolic diseases, medicine.disease, Hypoglycemia, chemistry, Diabetes Mellitus, Type 2, Brief Reports, business, Peptides, Weight gain
Abstract: In this post hoc analysis of the randomized controlled LixiLan‐O trial in insulin‐naive patients with type 2 diabetes mellitus (T2DM) not controlled with metformin, with or without a second oral antihyperglycaemic drug (OAD), the efficacy and safety of the fixed‐ratio combination, iGlarLixi (insulin glargine 100 U [iGlar] and lixisenatide [Lixi]), compared to its individual components was assessed in two patient subgroups: group 1) baseline HbA1c ≥9% (n = 134); group 2) inadequate control (HbA1c ≥7.0% and ≤9.0%) despite administration of two OADs at screening (n = 725). Treatment with iGlarLixi resulted in significantly greater reduction in least squares mean HbA1c compared to treatment with iGlar or Lixi alone in both subgroups (group 1: 2.9%, 2.5%, 1.7% and group 2: 1.5%, 1.2%, 0.7%, respectively). Target HbA1c less than 7% was achieved in more than 70% of patients using iGlarLixi in both subgroups, while mitigating the weight gain observed with use of iGlar alone. Rates of hypoglycaemic events were low overall. These results suggest that treatment with iGlarLixi achieves superior glycaemic control compared to treatment with iGlar or Lixi alone in T2DM patients with HbA1c ≥9% or in those inadequately controlled with two OADs.
Published: 2019

23. Non-invasive assessment of intrapulmonary shunt and ventilation to perfusion ratio in children with hepatopulmonary syndrome before and after liver transplantation

Author: Theodore Dassios, Emma Russell-Jones, Tassos Grammatikopoulos, Anne Greenough, and Anil Dhawan
Subjects: Male, Pulmonary and Respiratory Medicine, Ventilation-Perfusion Scan, medicine.medical_specialty, Adolescent, medicine.medical_treatment, Population, Liver transplantation, Ventilation/perfusion ratio, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Albumins, Internal medicine, Ventilation-Perfusion Ratio, medicine, Humans, 030212 general & internal medicine, Child, education, Hepatopulmonary syndrome, Retrospective Studies, education.field_of_study, business.industry, Infant, Retrospective cohort study, medicine.disease, Liver Transplantation, 030228 respiratory system, Child, Preschool, Breathing, Cardiology, Female, business, Perfusion, Shunt (electrical), Hepatopulmonary Syndrome
Abstract: Objectives To use the oxyhaemoglobin dissociation curve (ODC) to non-invasively measure the ventilation perfusion ratio (VA/Q) and right-to-left intrapulmonary vascular shunt before and after liver transplantation (LT) in children with hepatopulmonary syndrome (HPS). To investigate whether the right-to-left shunt derived by ODC correlated with the shunt derived by technetium-99 labelled macroaggregated albumin lung perfusion scan (MAA). Methods A retrospective cohort study at King's College Hospital NHS Foundation Trust, London, UK was performed between 1998 and 2016. The VA/Q and right-to-left shunt were non-invasively measured pre and post LT. The pre-LT right-to-left intrapulmonary shunt was also measured by MAA. The non-invasively derived pre-LT shunt was correlated with the shunt derived by MAA. Results Fifteen children with HPS were studied with a median (IQR) age at LT of 8.8 (6.6–12.9) years. The median (IQR) pre-LT VA/Q [0.49 (0.42–0.65)] was lower compared to the post-LT VA/Q [0.61 (IQR 0.54–0.72), p = 0.012]. The median (IQR) pre-LT shunt was 19 (3–24) % which decreased to zero in all but one children post-LT, (p = 0.001). The MAA-derived shunt was significantly positively correlated with the ODC-derived shunt (r = 0.783, p = 0.001). The mean (SD) difference between shunt derived by ODC and shunt derived by MAA was 0.5 (7.2) %. Conclusions Ventilation/perfusion impairment reverses but not completely resolves after liver transplantation in children with hepatopulmonary syndrome. The non-invasive method for estimating intrapulmonary shunting could be used as an alternative to the macroaggregated albumin scan in this population.
Published: 2021
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24. Fast-Acting Insulin Aspart Improves Glycemic Control in Basal-Bolus Treatment for Type 1 Diabetes: Results of a 26-Week Multicenter, Active-Controlled, Treat-to-Target, Randomized, Parallel-Group Trial (onset 1)

Author: Vincent Woo, Bruce W. Bode, Richard M. Bergenstal, Edward Franek, Anne Birk Østerskov, Tina Graungaard, Simon Heller, Ludger Rose, Chantal Mathieu, Christophe De Block, Athena Philis-Tsimikas, and David Russell-Jones
Subjects: medicine.medical_specialty, endocrine system diseases, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, law.invention, Insulin aspart, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Diabetes mellitus, Internal medicine, Internal Medicine, Clinical endpoint, medicine, 030212 general & internal medicine, Glycemic, Insulin detemir, Advanced and Specialized Nursing, Type 1 diabetes, business.industry, nutritional and metabolic diseases, medicine.disease, Postprandial, Endocrinology, Anesthesia, Human medicine, business, hormones, hormone substitutes, and hormone antagonists, medicine.drug
Abstract: OBJECTIVE This multicenter, treat-to-target, phase 3 trial evaluated the efficacy and safety of fast-acting insulin aspart (faster aspart) versus conventional insulin aspart (IAsp) in adults with type 1 diabetes. RESEARCH DESIGN AND METHODS The primary end point was change from baseline in HbA1c after 26 weeks. After an 8-week run-in, subjects were randomized (1:1:1) to double-blind mealtime faster aspart (n = 381), IAsp (n = 380), or open-label postmeal faster aspart (n = 382)—each with insulin detemir. RESULTS HbA1c was reduced in both treatment groups, and noninferiority to IAsp was confirmed for both mealtime and postmeal faster aspart (estimated treatment difference [ETD] faster aspart–IAsp, mealtime, –0.15% [95% CI –0.23; –0.07], and postmeal, 0.04% [–0.04; 0.12]); mealtime faster aspart statistically significantly reduced HbA1c versus IAsp (P = 0.0003). Postprandial plasma glucose (PPG) increments were statistically significantly lower with mealtime faster aspart at 1 h (ETD –1.18 mmol/L [95% CI –1.65; –0.71], –21.21 mg/dL [–29.65; –12.77]; P < 0.0001) and 2 h (–0.67 mmol/L [–1.29; –0.04], –12.01 mg/dL [–23.33; –0.70]; P = 0.0375) after the meal test; superiority to IAsp for the 2-h PPG increment was confirmed. The overall rate of severe or blood glucose–confirmed (plasma glucose CONCLUSIONS Faster aspart effectively improved HbA1c, and noninferiority to IAsp was confirmed, with superior PPG control for mealtime faster aspart versus IAsp. Subjects randomized to postmeal faster aspart for all meals maintained HbA1c noninferior to that obtained with mealtime IAsp.
Published: 2017
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25. Basal insulin peglispro versus insulin glargine in insulin‐naïve type 2 diabetes: <scp>IMAGINE</scp> 2 randomized trial

Author: Jennie G. Jacobson, Junxiang Luo, Tibor Ivanyi, Mark L. Hartman, Z. Kerényi, David Russell-Jones, Scott J. Jacober, Juliana M. Bue-Valleskey, J.‐L. Selam, T. S. Bailey, and Melanie J. Davies
Subjects: Blood Glucose, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Administration, Oral, Insulin Glargine, 030209 endocrinology & metabolism, Insulin naive, Type 2 diabetes, 030204 cardiovascular system & hematology, Polyethylene Glycols, law.invention, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Double-Blind Method, Randomized controlled trial, law, Internal medicine, Internal Medicine, BIL, Humans, Hypoglycemic Agents, Medicine, Insulin lispro, insulin‐naïve, Circadian rhythm, Aged, Insulin Lispro, business.industry, Insulin glargine, Basal insulin, basal insulin peglispro, Fasting, Middle Aged, medicine.disease, Themed Section‐bil, Circadian Rhythm, Diabetes Mellitus, Type 2, insulin therapy, Original Article, Drug Therapy, Combination, Female, type 2 diabetes, business, medicine.drug
Abstract: Aims To compare, in a double‐blind, randomized, multi‐national study, 52‐ or 78‐week treatment with basal insulin peglispro or insulin glargine, added to pre‐study oral antihyperglycaemic medications, in insulin‐naïve adults with type 2 diabetes. Material and methods The primary outcome was non‐inferiority of peglispro to glargine with regard to glycated haemoglobin (HbA1c) reduction (margin = 0.4%). Six gated secondary objectives with statistical multiplicity adjustments focused on other measures of glycaemic control and safety. Liver fat content was measured using MRI, in a subset of patients. Results Peglispro was non‐inferior to glargine in HbA1c reduction [least‐squares (LS) mean difference: −0.29%, 95% confidence interval (CI) −0.40, −0.19], and had a lower nocturnal hypoglycaemia rate [relative rate 0.74 (95% CI 0.60, 0.91); p = .005), more patients achieving HbA1c
Published: 2016
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26. Exenatide, a GLP-1 agonist in the treatment of Type 2 diabetes

Author: David Russell-Jones, Devesh Sennik, and Fahad Ahmed
Subjects: medicine.medical_specialty, business.industry, Endocrinology, Diabetes and Metabolism, Glp 1 agonist, Incretin, Type 2 diabetes, Hypoglycemia, medicine.disease, Bioinformatics, Endocrinology, Weight loss, Diabetes mellitus, Internal medicine, medicine, medicine.symptom, business, Exenatide, medicine.drug, Hormone
Abstract: Incretin-based therapies represent a new and innovative treatment modality in the management of Type 2 diabetes. Their therapeutic actions address many of the key metabolic defects in the pathophysiology of diabetes. Incretin hormones augment insulin secretion in a glucose-dependent manner. They have a low risk of inducing hypoglycemia, unlike many other antidiabetic medications. They also have the beneficial effect of being associated with early satiety, decreased caloric intake and weight loss. Exenatide was the first incretin-based therapy to be licensed for use and has now been developed in a once-weekly preparation. We review the evidence base for the use of exenatide and discuss the implications for the management of diabetes.
Published: 2019

27. Safety Attitudes among Doctors and Nurses in an Emergency Department of an Australian Hospital

Author: Naif Alzahrani, Mohamed E Abdel-Latif, and Russell Jones
Subjects: team-work, business.industry, lcsh:R, Clinical Biochemistry, lcsh:Medicine, patient safety climate, General Medicine, Emergency department, medicine.disease, quality improvement, patient safety, Medicine, Medical emergency, business
Abstract: Introduction: Safety attitudes have been investigated in a number of countries across different hospital departments, however there are few studies including Emergency Departments. Aim: To investigate doctors’ and nurses’ attitudes towards patient safety in Emergency Department in an Australian hospital. Materials and Methods: A cross-sectional research design was used. The participants included 51 doctors and nurses who completed a Safety Attitudes Questionnaire (SAQ) and reported the number of errors they had witnessed over the last year. Multivariate and univariate analysis was used to compare mean subscale scores of safety attitudes between doctors vs. nurses. Results: The findings showed doctors had comparatively positive safety attitudes compared to nurses, who rated teamwork climate, safety climate, unit management and work conditions particularly low. Both doctors and nurses had low opinions of hospital management and working conditions. Doctors and nurses with longer tenures and those who reported a higher number of medical errors had good safety attitudes. Conclusion: This study provides an insight into the safety attitudes of doctors and nurses employed in an Emergency Department in an Australian hospital. Further investigation into the relationship between safety attitudes, error rates and reporting should be performed in future studies.
Published: 2019
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28. Lixisenatide reduces chylomicron triacylglycerol due to increased clearance

Author: Nicola Jackson, Fariba Shojaee-Moradie, Sharaf E Sharaf, Martin Whyte, Jeewaka Mendis, David Russell-Jones, A. Margot Umpleby, Barbara A. Fielding, Roman Hovorka, Hovorka, Roman [0000-0003-2901-461X], and Apollo - University of Cambridge Repository
Subjects: Blood Glucose, Male, medicine.medical_specialty, Very low-density lipoprotein, Metabolic Clearance Rate, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Clinical Biochemistry, 030209 endocrinology & metabolism, Type 2 diabetes, 030204 cardiovascular system & hematology, Biochemistry, Glucagon-Like Peptide-1 Receptor, 03 medical and health sciences, Lixisenatide, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Double-Blind Method, Diabetes mellitus, Internal medicine, Chylomicrons, Medicine, Humans, Hypoglycemic Agents, Clinical Research Articles, Triglycerides, Cross-Over Studies, Gastric emptying, business.industry, Insulin, Lipids and Cardiovascular, Biochemistry (medical), Middle Aged, medicine.disease, Postprandial Period, Crossover study, Postprandial, Treatment Outcome, chemistry, Diabetes Mellitus, Type 2, Gastric Emptying, business, Peptides
Abstract: Context Glucagon-like peptide-1 (GLP-1) agonists control postprandial glucose and lipid excursion in type 2 diabetes; however, the mechanisms are unclear. Objective To determine the mechanisms of postprandial lipid and glucose control with lixisenatide (GLP-1 analog) in type 2 diabetes. Design Randomized, double-blind, cross-over study. Setting Centre for Diabetes, Endocrinology, and Research, Royal Surrey County Hospital, Guildford, United Kingdom. Patients Eight obese men with type 2 diabetes [age, 57.3 ± 1.9 years; body mass index, 30.3 ± 1.0 kg/m2; glycosylated hemoglobin, 66.5 ± 2.6 mmol/mol (8.2% ± 0.3%)]. Interventions Two metabolic studies, 4 weeks after lixisenatide or placebo, with cross-over and repetition of studies. Main Outcome Measures Study one: very-low-density lipoprotein (VLDL) and chylomicron (CM) triacylglycerol (TAG) kinetics were measured with an IV bolus of [2H5]glycerol in a 12-hour study, with hourly feeding. Oral [13C]triolein, in a single meal, labeled enterally derived TAG. Study two: glucose kinetics were measured with [U-13C]glucose in a mixed-meal (plus acetaminophen to measure gastric emptying) and variable IV [6,6-2H2]glucose infusion. Results Study one: CM-TAG (but not VLDL-TAG) pool-size was lower with lixisenatide (P = 0.046). Lixisenatide reduced CM [13C]oleate area under the curve (AUC)60–480min concentration (P = 0.048) and increased CM-TAG clearance, with no effect on CM-TAG production rate. Study two: postprandial glucose and insulin AUC0–240min were reduced with lixisenatide (P = 0.0051; P < 0.05). Total glucose production (P = 0.015), rate of glucose appearance from the meal (P = 0.0098), and acetaminophen AUC0–360min (P = 0.006) were lower with lixisenatide than with placebo. Conclusions Lixisenatide reduced [13C]oleate concentrations, derived from a single meal in CM-TAG and glucose rate of appearance from the meal through delayed gastric emptying. However, day-long CM production, measured with repeated meal feeding, was not reduced by lixisenatide and decreased CM-TAG concentration resulted from increased CM-TAG clearance., Using stable isotopes, lixisenatide acutely slowed gastric emptying, lowering postprandial TAG levels. A more prolonged effect of reduced chylomicron TAG was from increased clearance.
Published: 2018

29. Novel diabetes subgroups

Author: Michael D. Feher, Neil Munro, Simon de Lusignan, David Russell-Jones, and Kamlesh Khunti
Subjects: medicine.medical_specialty, business.industry, Endocrinology, Diabetes and Metabolism, MEDLINE, 030209 endocrinology & metabolism, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, 030212 general & internal medicine, business
Published: 2018

30. Liraglutide and Renal Outcomes in Type 2 Diabetes

Author: Mann JFE, Ørsted DD, Brown-Frandsen K, Marso SP, Poulter NR, Rasmussen S, Tornøe K, Zinman B, Buse JB, LEADER Steering Committee and Investigators. Bergenstal R, Daniels G, Moses AC, Nauck M, Nissen S, Pocock S, Steinberg W, Stockner M, Kristensen P, Ravn LS, Zychma M, Flyvbjerg A, Ford I, Kloos RT, Schactman MJ, Sleight P, Swedberg K, Tenner SM, Akalın S, Arechavaleta R, Bain S, Babkowski MC, Benroubi M, Berard L, Comlekci A, Czupryniak L, Eliasson B, Eriksson M, Fonseca V, Franek E, Gross J, Hafidh K, Haluzik M, Hayes F, Huang YY, Jacob S, Kaddaha G, Khalil A, Kilhovd B, Laakso M, Leiter L, Lalic N, Ji L, Luedemann J, Mannucci E, Marre M, Masmiquel L, Mota M, Omar M, O’Shea D, Pan C, Petrie J, Pieber T, Pratley R, Raz I, Rea R, Rutten G, Satman I, Shestakova M, Simpson R, Smith D, Tack C, Tarnow L, Thomas N, Van Gaal L, Travert F, Vidal J, Warren M, Yoon KH, Tuttle RM, Sheerman SI, Hegedüs L, Baerwald H, Bergenstal M, Celik S, Dias C, Eder M, Fitzgibbons S, Irvhage L, Kloluckova J, Kriulianski R, McDuffie R, Moen S, Paster A, Saalfeld RM, Sankar K, Shehaj E, Swierzewska P, Tiktin M, Tovey S, Gibson CM, Chakrabarti AK, Dashe JF, Hinchey J, Leary MC, Pride Y, Wiviott S, Allen S, Mehr AP, Mutter WP, Parikh S, Ray S, Cheifetz A, Leffler D, Sheth S, Alexander E, Gaglia JL, Goessling W, Mitzner LD, Rosenberg C, Snow KJ, Wagner A, Piazza G, Abell S, Davis T, D'Emden M, Ding SA, Gilfillan C, Greenaway T, Gunawan F, Ho J, Jackson R, Kalra B, Lau SL, Lin J, MacIsaac R, Makepeace A, Malabu U, Marjason J, McCallum R, McLean M, Moin N, Petersons C, Price S, Roberts A, Roberts D, Sangla K, Stranks S, Tan Y, Thynne T, Walters J, Ward G, Wen W, Zhang J, Brix J, Feder A, Höbaus C, Höllerl F, Höller V, Kotter T, Kratz E, Krzizek EC, Leb-Stoeger U, Mader J, Mras N, Novak E, Obendorf F, Peric S, Pesau G, Prager R, Ribitsch A, Schnack C, Schernthaner G, Wascher T, Batens AH, Benhalima K, De Block C, Ernest P, Fouckova A, Jandrain B, Lapauw B, Letiexhe M, Mathieu C, Neven S, Peiffer F, Ruige J, Scheen A, Taes Y, Van Boxelaer I, Vandistel G, Van Durme Y, Verhaegen A, Alencar E, Alencar R, Almeida AC, Alves B, Alves E, Alves G, Alves J, Araujo L, Arruda V, Augusto GA, Baggentoss R, Balestrassi L, Barbosa M, Barcelos I, Belem L, de Bem A, Betti RT, Bona R, Bosco A, Branda J, Bronstein M, Bueno T, Bulcão T, Caiado F, Camazzola F, Cambréa MF, Campos S, Canani L, Carra MK, Caruso S, Carvalho N, Casillo A, Castro D, Cavalcanti T, Cavichioli V, Cercato C, Chacra A, Challela W, Charchar HS, Chaves C, Chrisman C, Correia-Deur J, da Costa A Jr, Costa M, Costi B, Coutinho P, Coutinho W, Cunha MR, Daher J Jr, Davini E, Democh D Jr, Eliaschewitz F, Esmanhoto Facin G, Farias F, Felício J, Fernandes V, Filho CS, Filho FF, Filho M, Fontan D, Fontenele AP, Forti A, Franco D, Freire K, Fusaro A, Genestreti P, Gerchman F, Godi A, Gomes KF, Gonçalves P, Gonçalves R, Griz L, Grossman M, Gurgel MH, Vasconcellos Haddad AW, Halpern A, Hissa M, Inuy A, Jaime J, Jonasson T, Jorge JC, Malucelli FJ, Kohara S, Kramer C, Lacerda C, Ladeira S, Lana J, Lastebasse F, Leitão A, Leite S, Lerário AC, Lima D, Lima M, Lippi V, Lunardi M, Machado E, Maia F, Maia J, Maia KP, Mañas N, Marchisotti F, Marinho C, Martins C, Figueiredo de Medeiros F, Melo A, Melo F, Mendonca E, Mendonça P, Filho RM, Miguel M, Miléo K, Miyahara M, Montenegro AP, Moraes A, Moreira A, Ítalo Mota J, Mothe FS, Murro A, Nakatani V, Napoli TF, Neto BG, Neto OQ, Niclewicz E, Ohe LN, Oliveira F, Oliveira M, Panarotto D, Parente E, Parolin S, Pechmann L, Costa da Penha P, Perlamagna L, Perotta B, Pimentel L, Pinto M, Poço C, Ponte C, Prazeres P, Quintao E, Raduan R, Rassi DT, Rassi N, Reck L, Montenegro R Jr, Ribeiro R, Rodovalho S, Silveira Rodrigues G, Rollin G, Rossi S, Sabino C, Sales AP, Salles J, Sampaio CR, Santana L, Sato V, da Silva Santos M, Santos NL, Santos R, Saraiva J, Sartori C, Sena R, Sevilha M, Sgarbi J, Silva D, D'albuquerque Silva L, Silva ME, Siqueira K, Soares S, Sobreira W, Sousa B, Souza AC, Souza B, Tambascia M, Tarantino R, Tenor F, Tomarchio M, Triches C, Tristão LJ, Valenti A, Vasques E, Vencio S, Vianna A, Munhoz Vidotto T, Vieira S, Villar H, Visconti G, Volaco A, Wajchenberg B, Zanatta L, Zimmerman L, Abbott EC, Abu-Bakare A, Advani A, Allison R, Bishara P, Bowering CK, Cheng A, Chouinard S, Clayton D, Conway J, D'Amours M, de Tugwell B, DeYoung P, D'Ignazio G, Dube F, Ekoe JM, Fagan S, Garceau C, Gottesman I, Hanna A, Harris S, Hramiak IM, Hurd C, Imran S, Josse R, Joyce C, Kaiser S, Khan F, Kirouac I, Kovacs C, Labonte I, Langlois WJ, Levac MF, Liutkus J, McDonald C, Milosevic V, Nyomba BL, Paul T, Raby K, Ransom T, Reichert SM, Retnakaran R, Rabasa-Lhoret R, Raff E, Shaikholeslami R, Sigalas J, Yip CE, Weisnagel SJ, Woo V, Bao Y, Cai X, Chen J, Chen K, Chen M, Chen X, Chen Y, Ji Y, Lei J, Li H, Liu P, Mu Y, Ren M, Ren Y, Shi Y, Wang D, Wang F, Wang J, Wang Y, Yan L, Yang G, Yang J, Yu X, Yuan G, Xu M, Zhao X, Zheng J, Zhou L, Anderlová K, Brožová J, Haluzík M, Hanušová V, Kosák M, Křížová J, Mráz M, Owen K, Rušavý Z, Tomešová J, Trachta P, Žourek M, Andersen PH, Boesgaard T, Christensen S, Gram J, Gregersen S, Henriksen JE, Hermansen K, Jakobsen PE, Jensen J, Krogsaa A, Larsen M, Lervang HH, Madsbad S, Mortensen L, Olesen T, Pietraszek A, Ridderstråle M, Safai N, Schioldan AG, Schmidt C, Snorgaard O, Stidsen J, Cederberg H, Haapamäki H, Hukkanen J, Jauhiainen R, Kujari ML, Lahtela J, Laine M, Mäkelä J, Miilunpohja M, Savolainen M, Taurio J, Vänttinen M, Creton C, Cosma NV, Dillinger J, Jacques JL, Guedj AM, Moulla M, Petit C, Ratsianoharana V, Richter D, Rodier M, Roussel R, Hinz A, Politz E, Esser M, Deuse U, Mittag D, Hagenow A, Jacob F, Jordan R, Gantke D, Venschott-Jordan U, Löhr C, Klausmann G, Eschenbrücher K, Karakas M, Jahrsdörfer B, Kunze MR, Wöhrle J, König W, Spielhagen H, Kilimnik A, Lüdemann HP, Lüdemann J, Mölle A, Mölle M, Müller J, Appelt S, Sauter A, Sauter J, Hartmann U, Löw A, Krötz F, Sohn HY, von Schacky C, Klauss V, Braun D, Segner A, Degtyareva E, Kreutzmann K, Paschmionka R, Hauck N, Sihal O, Busch AK, Maus O, Stübler P, Füllgraf-Horst S, Vietzke A, Müller C, Tosch-Sisting R, Lengsfeld B, Thaler J, Schaum T, Steindorf J, Steindorf S, König A, Reitschuster S, Schlott D, Clever HU, Witzel P, Kempe HP, Stemler L, Benis A, Diakoumopoulou E, Kazakos K, Kypraios N, Liatis S, Pagkalos E, Siami E, Tentolouris N, Alur VC, Agrawal M, Ali M, Asirvatham A, Asirvatham E, Bandgar TR, Balaji M, Bardoloi N, Baruah M, Bekur R, Bhansali A, Bhatia S, Bhonsley S, Bhuyan S, Borah B, Bright N, Ambrish C, Chaudhury T, Choudhury S, Chellan G, Das M, Dharmalingam M, Dutta P, Erugu A, Vinutha FP, Gunasekaran P, Das Gupta R, Iqbal A, Jagadish P, Jain S, Jebasingh H, John A, John M, Kalra S, Kasaragod P, Kesavadev J, Kumar H, Kumar P, Lakshmanan V, Lila AR, Mathew T, Miyen H, Mohan T, Motha A, Murthy C, Shivashankara N, Nanaiah A, Ommen T, Pani K, Pandey K, Paramesh S, Paramesh V, Pillai B, Prabhu M, Kalki RC, Ramachandran S, Ramu M, Rao Y, Reddy S, Saikia P, Saravu K, Selvam K, Sethi B, Shankar A, Sharma A, Shah N, Shankar P, Shetty R, Shivane V, Srivalli S, Thaseen S, Sarada S, Shirisha A, Subramani M, Balaji V, Mohan V, Padmanaban V, Verma M, Vidyasagar S, Walinjkar V, Walia R, Davenport C, Forde H, Gadintshware G, Gan KJ, Khattak A, O'Connell J, O'Shea D, Beilin V, Cahn A, Cohen O, Cukierman-Yaffe T, Daoud D, Darawsha M, Dicker D, Gavish A, Hochberg I, Ilany J, Inbal U, Itzhak B, Karasik A, Karnieli E, Khader N, Khamaisi M, Lender D, Lieberman GS, Mahamid R, Marcoviciu D, Michael L, Minuchin O, Mosenzon O, Narevichius F, Percik R, Potekhin M, Sabbah M, Sawaed S, Schurr D, Segal E, Slezak L, Vollach I, Zaina A, Zloczower M, Zolotov S, Antenore A, Arnone M, Arturi F, Barbaro V, Barone M, Di Biagio R, Buscemi C, Buscemi S, Buzzetti R, Di Carlo A, Carlone A, Caruso V, Casadidio I, Cerrelli F, Ciavarella A, Cipolloni L, Colella A, Colotto M, Consoli A, Crippa VG, Cuccuru I, Cufone S, Desideri C, Fallarino M, Febo F, Filetti S, Foffi C, Formoso G, Frosio L, Di Fulvio P, Gambineri A, Ginestra F, Grimaldi MS, Lamanna C, Leto G, Lucotti P, Lugarà M, Lumera G, Magistro A, Maranghi M, Martelli D, Mattina A, Monti LD, Parise M, Pedace E, Perticone F, Piatti P, Pompea Antonia Baldassarre M, Ragghianti B, Repaci A, Ribichini D, Da Ros S, Rossi M, Santilli M, Sesti G, Setola E, Succurro E, Sussolano E, Tarquini G, Verga S, Vitale V, Alanis RR, del Rosario Arechavaleta-Granell M, de Jesús Beltran Jaramillo T, de Jesús Rodríguez Berrones DA, Rodríguez Briones I, Rodríguez Briones R, Acevedo Castañeda ES, Chapa Grimaldo JB, Flores-Moreno CA, Garza Felix S, Nieto Flores J, Morales Franco G, Garza Morán RA, Hernández González SO, González-Gálvez G, González González JG, Hernández Salazar E, García Hernández PA, Campos Hurtado S, López-Velázco ML, Cardona Muñóz EG, Nuñez Márquez R, Campos Moreno OV, Cavazos Oliveros FJ, Haro Ortiz JA, Pelayo-Orozco ES, Sida Perez P, Vazquez Ramírez R, Uribe Rios MA, López Rodríguez JC, Rodríguez Rosales M, Robledo Durón I, Alvarado Ruíz R, González Saldivar G, Reyes Sánchez R, Sánchez-Michel BL, Contreras Sandoval AY, Velasco Gutiérrez A, Perez Verdín AE, Ramos Zavala MG, Abbink-Zandbergen E, Ahdi M, Bugter A, van Dijk M, Eisma G, Erdtsieck R, Gerards M, Gerdes V, Haak H, Harbers V, Hoogenberg K, Huvers F, Janssen W, Kars M, Kooy A, Lafeber M, Landewé-Cleuren S, Lieverse A, Meesters E, Moerman S, van Moorsel D, Nijhuis J, Smit CJ, Thevissen K, Timmerman Thijssen DM, Willemsen A, Birkeland K, Cooper J, Gulseth H, Hjelmesæth J, Jørgensen P, Kilhovd BK, Kulseng B, Nicolaisen B, Skadberg Ø, Wium C, Antkowiak-Piatyszek K, Arciszewska M, Bajkowska-Fiedziukiewicz A, Bogdanski P, Czubek U, Cypryk K, Dabrowski J, Dabrowska M, Dziedzic S, Dziewit T, Faligowska M, Fedor-Plenkowska G, Gajos G, Galicka-Latala D, Galuszka-Bilinska A, Gladysz I, Grycewicz J, Hachula G, Janas I, Jazwinska-Tarnawska E, Jedynasty K, Jozefowska M, Kaminska A, Katra B, Kitowska-Koterla J, Klupa T, Koblik T, Konduracka E, Konieczny J, Konieczny M, Kosinski M, Kulkowski G, Kunecki M, Kurmaniak M, Lesniewski R, Lominska T, Losa B, Majkowska D, Malecki M, Mirocka J, Misztal M, Mruk K, Musialik K, Olejniczak H, Opadczuk P, Peczynska J, Plinta M, Polaszewska-Muszynska M, Przech E, Pupek-Musialik D, Ruzga Z, Scibor Z, Sidorowicz-Bialynicka A, Siegel A, Stankiewicz A, Strzelecka-Sosik A, Swierszcz T, Szulinska M, Szymkowiak K, Trybul I, Witek P, Wozniak I, Zambrzycki J, Zarzycka-Lindner G, Zuradzka-Wajda D, Zurawska-Klis M, Ahn HY, Chin SO, Choi SH, Chon S, Han KA, Jang HC, Jeong KC, Kang SM, Kim JW, Kim HS, Kim SJ, Kim SW, Kim YS, Lee EY, Lim S, Min KW, Nam JY, Oh SJ, Park SY, Rhee SY, Shin JA, Son JI, Song YD, Woo JT, Yang HK, Yoo JS, Yoon JW, Avram R, Braicu MD, Carlan L, Catrinoiu D, Ciomos D, Ciorba A, Ghise G, Girgavu S, Guja C, Mihai D, Nicodim S, Nistor L, Pintilei DR, Pintilei E, Pletea N, Pop A, Rosu M, Savu O, Serban V, Sima A, Sitterli-Natea C, Suciu G, Szabo M, Szilagyi I, Timar B, Vlad A, Vladu IM, Alfaraj A, Dubova V, Dvoryashina I, Gaysina L, Gromova S, Gudkova K, Ivanova S, Ivashkina I, Kalashnikova M, Kazankova T, Khaykina E, Khaykina O, Kiseleva T, Komissarova E, Kononenko I, Koreneva V, Koshcheeva O, Koshel L, Kozachuk D, Kufelkina T, Kunitsyna M, Likhodey N, Lysenko T, Makarova O, Malceva A, Mikhailova S, Ogorodnikova E, Pavlikova I, Pekareva E, Postoeva A, Reshedko D, Reshedko G, Reshedko L, Rogaleva A, Rogova L, Rozanov D, Runov G, Samylina I, Semikina T, Sergeeva-Kondrachenko M, Shatskaya O, Shimokhina O, Smetanina S, Startseva M, Strelkova A, Suplotova L, Suvorova L, Sych Y, Valeeva A, Valeeva F, Venjkova T, Vinokurova V, Voychik E, Yanovskaya E, Yanovskaya M, Yarkova N, Yarygina E, Yuzhakova N, Zakharova T, Zanozina O, Zenovko A, Zhuk S, Zhukova E, Aleksic S, Bulatovic A, Buric B, Cvijovic G, Jelic MA, Jojic B, Jotic A, Kendereski A, Lalic K, Lukic L, Macesic M, Petkovic MM, Micic D, Milicic T, Popovic L, Prostran M, Rajkovic N, Seferovic J, Singh S, Stojanovic R, Stosic L, Vuksanovic M, Zamaklar M, Zivkovic TB, Zoric S, Aboo N, Albertse HW, Badat A, Basson M, Bawa E, Bester F, Blignaut S, Booysen S, Bosch FJ, Burgess L, Cassimjee S, Coetzee K, Du Bois J, Engelbrecht J, Finegan K, Gibson GJ, Hansa S, Hemus A, Immink IP, Jacovides A, Joshi P, Joshi S, Kapp C, KhoeleMachobane S, Uys Knox HJ, Kok J, Komati S, Lai E, Lakha D, Lehloenyane K, Mahomed AG, Meeding R, Moodley R, Moosa N, Nel J, Nell H, Van Niekerk FJ, Pillay N, Pretorius M, Prozesky H, Ramduth S, Roos J, Sarvan M, Seeber M, Siebert M, Somasundram P, Stavrides A, Venter N, Wadvalla S, Alcolea JO, Álvarez de Arcaya Vicente A, Pérez Arroyo MB, Romero Bobillo E, Buño MM, Carreira Arias JN, Cepero García D, Masmiquel Comas L, Coves Figueras MJ, de la Cuesta Mayor C, Feria-Carot MD, Frade Fernández AM, Ferreiro Gómez M, García García C, García Delgado E, Durán García S, Gómez Gómez LA, Soto González A, Hernán García C, Ángeles Tapia Herrero M, Jodar Gimeno E, Quevedo Juanals J, López Jiménez M, Masanes F, Marco Mur ÁL, Navarro López M, Ramis JN, Palmer AG, Calle Pascual A, Romero Pérez 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E, Martinez G, Martinez-Miss S, Marx P, Massara L, Mastoor M, Matfin G, Maturu A, Maurides P, May M, Mayfield R, Maynard B, Mazza A, McCann K, McCoy J, McCoy T, McCullen MK, McDaniel C, McDaniel AM, McDermott M, McDonald A, McMasters B, McMurray C, Medlin T, Meinel M, Mendez I, Menefee J, Meredith M, Merriweather M, Mersey J, Messino C, Meyer S, Meyers L, Michael D, Midyett C, Miklius A, Milford E, Miller B, Miller H, Milligan M, Minor A, Miranda-Palma B, Mirarchi N, Mittadodla S, Mittle J, Moffat A, Mohaupt S, Mohiuddin K, Mokshagundam S, Monaco S, Monsaert R, Montano-Pereira C, Montgomery A, Moody K, Moon M, Moore D, Moore L, Morawski E, Moreau C, Morin D, Moscoa C, Motzkin C, Mueller R, Munoz C, Munoz M, Myneni A, Naderi B, Nagireddy P, Naidu J, Naidu R, Naik S, Naimark R, Nardicchi M, Ndukwu I, Neller C, Netten-Foster L, Neumiller J, New T, Newman S, Newton T, Nguyen B, Nicol B, Nicol P, Ninivaggi L, Niswender K, Norman L, Noworatzky G, Nyenwe E, O'Brien H, O'Connell T, Oden W, Odugbesan A, Oliver M, Oliver T, Olmeda C, O'Neil C, Oremus R, Ortega T, Ortiz-Santos S, Osborn T, Padmanabhan S, Papacostea O, Park I, Parker A, Parker K, Parker R, Patel C, Patel M, Patel R, Patino M, Patterson S, Paulson K, Paz A, Pemba R, Pepe C, Perez J, Perez T, Perry D, Phillips B, Phillips J, Pickett A, Pinson M, Pitzer R, Poduri M, Poehls J, Poteat T, Powell L, Prasad S, Prevost J, Price E, Priest D, Prieto L, Purewal T, Purighalla R, Purighalla U, Quadrel M, Qureshi A, Radhamma R, Rafla E, Rajab H, Ramalingam R, Ramirez A, Ramirez J, Ramirez K, Ramirez M, Randall M, Rangaraj U, Rao V, Rasmussen P, Rasouli N, Ray A, Reed J, Rems L, Renaud K, Reno M, Resnick M, Reusch J, Reynolds L, Rhoton K, Rhudy J, Ricci C, Rice L, Richardson A, Richardson L, Rickard H, Rickels M, Riff D, Rightenour N, Risser J, Rizvi A, Robertson J, Robinson A, Robinson R, Rockwell M, Rodriguez JP, Rodriguez M, Rojas M, Rojas W, Rooker-Morris L, Root C, Rose M, Rosenberg R, Rosenstock J, Roth M, Ruby R, Sachson R, Sack P, Sadler RK, Sahai S, Salazar J, Salgam M, Samal A, Samson A, Sanagorski R, Sanchez A, Sandberg J, Sanderson M, Sandoval J, Santiago E, Sapp T, Saunders J, Schill J, Schott C, Schreiman R, Schu D, Schuh K, Schutta M, Schwartz J, Schweppe L, Scofield H, Scribner A, Seal J, Sealock J, Seaton B, Sedlak-Hanslik T, Seekins K, Segal M, Seggelke S, Semenza S, Sentman P, Serra M, Seshadri P, Sevilla E, Shah S, Shaheen K, Shanik M, Shaw J, Sheets M, Shellabarger C, Sher J, Shippey J, Shivaswamy V, Shomali M, Shore D, Shroff P, Siddiqui T, Siegwald A, Silver R, Simmons D, Simons R, Sinan A, Singh M, Sirinvaravong S, Skero J, Slover-Zipf J, Small S, Smith B, Smith K, Smith M, Sohl J, Solarz SH, Soler D, Sood A, Sora N, Souchet A, Soule J, Sparks J, Spector L, Speicher R, Spillers L, Spivey T, Springer N, Sprouse H, St John J, Stacey A, Stacey H, Stafford M, Stagner E, Staples K, Steadman E, Steed R, Steeves G, Steinberg H, Stell C, Stirman E, Straub K, Strock E, Sue M, Suris O, Sutton T, Tabbah I, Talsania M, Tang R, Tapia J, Taylor K, Taylor-Hancher R, Teator R, Tekateka M, Temple B, Temple K, Teodori M, Tharp P, Thethi T, Theuma P, Thomas S, Thottan A, Thrasher J, Thrasher L, Tiemeyer M, Tinney I, Tobin T, Toma S, Tovar M, Townsend J, Trantow C, Traylor H, Trevino M, Troy M, Trumper D, Tryggestad J, Tucker C, Turner J, Turney R, Tuten C, Tyzack J, Ullo L, Underkofler C, Unger J, Urdanetta R, Valdivia V, Valenti S, Vanderheiden A, Vanderlinde-Wood M, Varma C, Vasquez E, Vazquez M, Vickery D, Villafuerte B, Villegas C, Vivar J, Vivekananthan K, Vo G, Vukojicic K, Wachter A, Wahl D, Waitmann J, Walker D, Walsh J, Walsh K, Walton A, Wang A, Wardell K, Watkins S, Watkinson J, Watts M, Watwe V, Weaver N, Weber R, Wedick C, Weeks D, Weeks L, Weindorff K, Weinstein R, Weiss S, Wenger K, Wentworth M, Werner A, West M, Whelan S, White B, White J, Whitmire M, Whittington R, Wical J, Wigley C, Wilkins F, Will K, Williams A, Wilson LE, Wince M, Wine S, Winkle P, Winner C, Wise J, Witte M, Wittenmyer J, Wood C, Wood R, Woodruff C, Worthington B, Wynn D, Wysham C, Xavier P, Yela S, Yenoby L, Young L, Younus N, Yourell V, Zaid M, Zubair I., Mann, Jfe, Ørsted, Dd, Brown-Frandsen, K, Marso, Sp, Poulter, Nr, Rasmussen, S, Tornøe, K, Zinman, B, Buse, Jb, Bergenstal R, LEADER Steering Committee and Investigators., Daniels, G, Moses, Ac, Nauck, M, Nissen, S, Pocock, S, Steinberg, W, Stockner, M, Kristensen, P, Ravn, L, Zychma, M, Flyvbjerg, A, Ford, I, Kloos, Rt, Schactman, Mj, Sleight, P, Swedberg, K, Tenner, Sm, Akalın, S, Arechavaleta, R, Bain, S, Babkowski, Mc, Benroubi, M, Berard, L, Comlekci, A, Czupryniak, L, Eliasson, B, Eriksson, M, Fonseca, V, Franek, E, Gross, J, Hafidh, K, Haluzik, M, Hayes, F, Huang, Yy, Jacob, S, Kaddaha, G, Khalil, A, Kilhovd, B, Laakso, M, Leiter, L, Lalic, N, Ji, L, Luedemann, J, Mannucci, E, Marre, M, Masmiquel, L, Mota, M, Omar, M, O’Shea, D, Pan, C, Petrie, J, Pieber, T, Pratley, R, Raz, I, Rea, R, Rutten, G, Satman, I, 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Naidu, J, Naidu, R, Naik, S, Naimark, R, Nardicchi, M, Ndukwu, I, Neller, C, Netten-Foster, L, Neumiller, J, New, T, Newman, S, Newton, T, Nguyen, B, Nicol, B, Nicol, P, Ninivaggi, L, Niswender, K, Norman, L, Noworatzky, G, Nyenwe, E, O'Brien, H, O'Connell, T, Oden, W, Odugbesan, A, Oliver, M, Oliver, T, Olmeda, C, O'Neil, C, Oremus, R, Ortega, T, Ortiz-Santos, S, Osborn, T, Padmanabhan, S, Papacostea, O, Park, I, Parker, A, Parker, K, Parker, R, Patel, C, Patel, M, Patel, R, Patino, M, Patterson, S, Paulson, K, Paz, A, Pemba, R, Pepe, C, Perez, J, Perez, T, Perry, D, Phillips, B, Phillips, J, Pickett, A, Pinson, M, Pitzer, R, Poduri, M, Poehls, J, Poteat, T, Powell, L, Prasad, S, Prevost, J, Price, E, Priest, D, Prieto, L, Purewal, T, Purighalla, R, Purighalla, U, Quadrel, M, Qureshi, A, Radhamma, R, Rafla, E, Rajab, H, Ramalingam, R, Ramirez, A, J, Ramirez, Ramirez, K, Ramirez, M, Randall, M, Rangaraj, U, Rao, V, Rasmussen, P, Rasouli, N, Ray, A, Reed, J, Rems, L, Renaud, K, Reno, M, Resnick, M, Reusch, J, Reynolds, L, Rhoton, K, Rhudy, J, Ricci, C, Rice, L, Richardson, A, Richardson, L, Rickard, H, Rickels, M, Riff, D, Rightenour, N, Risser, J, Rizvi, A, Robertson, J, Robinson, A, Robinson, R, Rockwell, M, Rodriguez, Jp, Rodriguez, M, Rojas, M, Rojas, W, Rooker-Morris, L, Root, C, Rose, M, Rosenberg, R, Rosenstock, J, Roth, M, Ruby, R, Sachson, R, Sack, P, Sadler, Rk, Sahai, S, J, Salazar, Salgam, M, Samal, A, Samson, A, Sanagorski, R, Sanchez, A, Sandberg, J, Sanderson, M, Sandoval, J, Santiago, E, Sapp, T, Saunders, J, Schill, J, Schott, C, Schreiman, R, Schu, D, Schuh, K, Schutta, M, Schwartz, J, Schweppe, L, Scofield, H, Scribner, A, Seal, J, Sealock, J, Seaton, B, Sedlak-Hanslik, T, Seekins, K, Segal, M, Seggelke, S, Semenza, S, Sentman, P, Serra, M, Seshadri, P, Sevilla, E, Shah, S, Shaheen, K, Shanik, M, Shaw, J, Sheets, M, Shellabarger, C, Sher, J, Shippey, J, Shivaswamy, V, Shomali, M, Shore, D, Shroff, P, Siddiqui, T, Siegwald, A, Silver, R, Simmons, D, Simons, R, Sinan, A, Singh, M, Sirinvaravong, S, Skero, J, Slover-Zipf, J, Small, S, Smith, B, Smith, K, Smith, M, Sohl, J, Solarz, Sh, Soler, D, Sood, A, Sora, N, Souchet, A, Soule, J, Sparks, J, Spector, L, Speicher, R, Spillers, L, Spivey, T, Springer, N, Sprouse, H, St John, J, Stacey, A, Stacey, H, Stafford, M, Stagner, E, Staples, K, Steadman, E, Steed, R, Steeves, G, Steinberg, H, Stell, C, Stirman, E, Straub, K, Strock, E, Sue, M, Suris, O, Sutton, T, Tabbah, I, Talsania, M, Tang, R, Tapia, J, Taylor, K, Taylor-Hancher, R, Teator, R, Tekateka, M, Temple, B, Temple, K, Teodori, M, Tharp, P, Thethi, T, Theuma, P, Thomas, S, Thottan, A, Thrasher, J, Thrasher, L, Tiemeyer, M, Tinney, I, Tobin, T, Toma, S, Tovar, M, Townsend, J, Trantow, C, Traylor, H, Trevino, M, Troy, M, Trumper, D, Tryggestad, J, Tucker, C, Turner, J, Turney, R, Tuten, C, Tyzack, J, Ullo, L, Underkofler, C, Unger, J, Urdanetta, R, Valdivia, V, Valenti, S, Vanderheiden, A, Vanderlinde-Wood, M, Varma, C, Vasquez, E, Vazquez, M, Vickery, D, Villafuerte, B, Villegas, C, Vivar, J, Vivekananthan, K, Vo, G, Vukojicic, K, Wachter, A, Wahl, D, Waitmann, J, Walker, D, Walsh, J, Walsh, K, Walton, A, Wang, A, Wardell, K, Watkins, S, Watkinson, J, Watts, M, Watwe, V, Weaver, N, Weber, R, Wedick, C, Weeks, D, Weeks, L, Weindorff, K, Weinstein, R, Weiss, S, Wenger, K, Wentworth, M, Werner, A, West, M, Whelan, S, White, B, White, J, Whitmire, M, Whittington, R, Wical, J, Wigley, C, Wilkins, F, Will, K, Williams, A, Wilson, Le, Wince, M, Wine, S, Winkle, P, Winner, C, Wise, J, Witte, M, Wittenmyer, J, Wood, C, Wood, R, Woodruff, C, Worthington, B, Wynn, D, Wysham, C, Xavier, P, Yela, S, Yenoby, L, Young, L, Younus, N, Yourell, V, Zaid, M, Zubair, I., Mann J.F.E., Orsted D.D., Brown-Frandsen K., Marso S.P., Poulter N.R., Rasmussen S., Tornoe K., Zinman B., Buse J.B., and Buscemi S.
Subjects: Male, Settore MED/09 - Medicina Interna, Acute Kidney Injury, Aged, Albuminuria, Creatinine, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Double-Blind Method, Female, Follow-Up Studies, Glomerular Filtration Rate, Glucagon-Like Peptide 1, Humans, Hypoglycemic Agents, Intention to Treat Analysis, Kidney Failure, Chronic, Liraglutide, Middle Aged, Type 2 diabetes, 030204 cardiovascular system & hematology, urologic and male genital diseases, GLOMERULAR-FILTRATION-RATE, KIDNEY-FUNCTION, DISEASE, law.invention, Kidney Failure, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, law, Medicine, Settore MED/49 - Scienze Tecniche Dietetiche Applicate, Chronic, RISK, Kidney, Acute kidney injury, 11 Medical And Health Sciences, General Medicine, medicine.anatomical_structure, TRIAL, liraglutide, randomized controlled trial, type 2 diabetes, renal outcomes, Life Sciences & Biomedicine, Type 2, medicine.drug, medicine.medical_specialty, Renal function, 030209 endocrinology & metabolism, CARDIOVASCULAR OUTCOMES, Follow-Up Studie, 03 medical and health sciences, Medicine, General & Internal, General & Internal Medicine, Diabetes mellitus, Internal medicine, Diabetes Mellitus, Intensive care medicine, Science & Technology, business.industry, MORTALITY, medicine.disease, INTENSIVE GLUCOSE CONTROL, INDIVIDUALS, chemistry, Diabetic Nephropathie, LEADER Steering Committee and Investigators, business
Abstract: BACKGROUND: In a randomized, controlled trial that compared liraglutide, a glucagon-like peptide 1 analogue, with placebo in patients with type 2 diabetes and high cardiovascular risk who were receiving usual care, we found that liraglutide resulted in lower risks of the primary end point (nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes) and death. However, the long-term effects of liraglutide on renal outcomes in patients with type 2 diabetes are unknown. METHODS: We report the prespecified secondary renal outcomes of that randomized, controlled trial in which patients were assigned to receive liraglutide or placebo. The secondary renal outcome was a composite of new-onset persistent macroalbuminuria, persistent doubling of the serum creatinine level, end-stage renal disease, or death due to renal disease. The risk of renal outcomes was determined with the use of time-to-event analyses with an intention-to-treat approach. Changes in the estimated glomerular filtration rate and albuminuria were also analyzed. RESULTS: A total of 9340 patients underwent randomization, and the median follow-up of the patients was 3.84 years. The renal outcome occurred in fewer participants in the liraglutide group than in the placebo group (268 of 4668 patients vs. 337 of 4672; hazard ratio, 0.78; 95% confidence interval [CI], 0.67 to 0.92; P=0.003). This result was driven primarily by the new onset of persistent macroalbuminuria, which occurred in fewer participants in the liraglutide group than in the placebo group (161 vs. 215 patients; hazard ratio, 0.74; 95% CI, 0.60 to 0.91; P=0.004). The rates of renal adverse events were similar in the liraglutide group and the placebo group (15.1 events and 16.5 events per 1000 patient-years), including the rate of acute kidney injury (7.1 and 6.2 events per 1000 patient-years, respectively). CONCLUSIONS: This prespecified secondary analysis shows that, when added to usual care, liraglutide resulted in lower rates of the development and progression of diabetic kidney disease than placebo. (Funded by Novo Nordisk and the National Institutes of Health; LEADER ClinicalTrials.gov number, NCT01179048 .).
Published: 2017

31. G133(P) Improving parental communication in a busy district general neonatal unit

Author: EC Russell-Jones, J Sanpera-Iglesias, G Marais, N Monks, and H Fensom
Subjects: medicine.medical_specialty, Maternal risk factors, business.industry, media_common.quotation_subject, medicine.disease, Maternal pyrexia, Unit (housing), Nonverbal communication, Feeling, Temperature instability, Family medicine, Medicine, business, Premature rupture of membranes, Home leaving, media_common
Abstract: Introduction Communication is a vital part of Neonatal medicine. Effective communication enables parents to be fully-informed and up-to-date with their baby’s care. A significant proportion of newborns are screened and treated with antibiotics for suspected sepsis if there are positive maternal risk factors and/or baby is born in a poor condition or has abnormal observations such as tachypnoea, tachycardia and temperature instability. Maternal risk factors include Group-B Streptococcal infection, premature rupture of membranes, and maternal pyrexia. The decision to screen and treat frequently occurs on labour ward or theatre, where the mother herself may be unwell, therefore unable to acknowledge and process the verbal communication that takes place. Aim To improve parental communication by providing written information and evaluate if this would improve understanding, confidence going home, and overall care satisfaction. Method We surveyed 22 parents of newborns who were screened and treated with antibiotics. We produced a questionnaire to assess the need for written information, current understanding and confidence going home. We identified key information parents wished to know and from this produced a leaflet. The leaflet was trialled then implemented. Effectiveness was assessed through a further questionnaire. Results We found that with the pre-leaflet questionnaire 74% of parents thought written information would be useful. 72% of parents understood why their baby was on antibiotics and only 29% had knowledge of antibiotic duration. Worryingly only 75% of parents felt confident going home leaving 25% not confident. Post-implementation, 94% of parents understood why their baby was on antibiotics and 88% had knowledge of antibiotic duration. 95% of parents found the leaflet useful with an increase of 20% of parents feeling confident about going home (95%) see table 1. Conclusion Following introduction of our leaflet there has been an improvement in parental understanding and confidence going home. This in turn has led to an overall increase in parental satisfaction of their baby’s care.
Published: 2018
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32. Response to Comment on Russell-Jones et al. Diabetes Care 2017;40:943-950. Comment on Bowering et al. Diabetes Care 2017;40:951-957

Author: Keith Bowering, Bruce W. Bode, and David Russell-Jones
Subjects: Advanced and Specialized Nursing, Pediatrics, medicine.medical_specialty, Gastric emptying, business.industry, Endocrinology, Diabetes and Metabolism, Insulin, medicine.medical_treatment, 030209 endocrinology & metabolism, Hypoglycemia, medicine.disease, Insulin aspart, 03 medical and health sciences, 0302 clinical medicine, Postprandial, Diabetes Mellitus, Type 2, Diabetes mellitus, Internal Medicine, medicine, Humans, 030212 general & internal medicine, Dosing, business, Glycemic, medicine.drug
Abstract: We appreciate the relevant comments raised by Wu et al. (1) regarding the challenges faced by clinicians in safely achieving postprandial, and overall, glycemic control for patients with diabetes in the face of individual needs and physiological variation (including varying rates of gastric emptying/gastroparesis). Increasing awareness and understanding of factors affecting the complex physiology of postprandial glucose regulation, together with an understanding of the clinical pharmacological profile, are key in guiding appropriate dosing and timing of any mealtime insulin therapy. In the onset 1 and 2 trials, both mealtime (0–2 min before the meal) and postmeal dosing (20 min after the start of a meal investigated in onset 1) of fast-acting insulin aspart (faster aspart) demonstrated noninferior overall glycemic control compared with mealtime conventional insulin aspart. Importantly, no statistically significant differences in the overall rates of hypoglycemia were found in these trials …
Published: 2018

33. Effect of subcutaneous insulin detemir on glucose flux and lipolysis during hyperglycaemia in people with type 1 diabetes

Author: R. A. Herring, Fariba Shojaee-Moradie, R. H. Jones, A. M. Umpleby, David Russell-Jones, and Nicola Jackson
Subjects: Adult, Blood Glucose, Glycerol, Male, medicine.medical_specialty, Injections, Subcutaneous, Lipolysis, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Glucose uptake, Insulin, Isophane, NPH insulin, Body Mass Index, Endocrinology, Insulin Detemir, Internal medicine, Internal Medicine, medicine, Humans, Hypoglycemic Agents, Insulin detemir, Glycated Hemoglobin, Type 1 diabetes, business.industry, Insulin, Lipid metabolism, medicine.disease, Diabetes Mellitus, Type 1, Hyperglycemia, business, Body mass index, medicine.drug
Abstract: Aims To investigate, using a novel non-steady-state protocol, the differential effects of subcutaneous (s.c.) detemir and NPH insulin on glucose flux and lipid metabolism after insulin withdrawal. Methods After a period of insulin withdrawal resulting in whole-blood glucose concentration of 7 mmol/l, 11 participants (five men, mean age 41.0 years, mean body mass index 25 kg/m2) with type 1 diabetes (mean glycated haemoglobin concentration 57 mmol/mol, mean diabetes duration 14 years) received 0.5 units per kg body weight s.c. insulin detemir or NPH insulin in random order. Stable isotopes of glucose and glycerol were infused intravenously throughout the study protocol. Results Glucose concentration decreased after insulin treatment as a result of suppression of endogenous glucose production, which occurred to a similar extent with both detemir and NPH insulin. The rate of glucose disappearance (Rd) was not increased significantly with either type of insulin. When the effect of detemir and NPH insulin on glucose flux at glucose concentrations between 9 and 6 mmol/l was examined, glucose rate of appearance (Ra) was similar with the two insulins; however, glucose Rd was greater with NPH insulin than with detemir at glucose concentrations of 8.0, 8.5, 7.0 and 6.0 mmol/l (p
Published: 2015
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34. Impact of a Shared Decision Making Intervention on Health Care Utilization: A Secondary Analysis of the Chest Pain Choice Multicenter Randomized Trial

Author: Carlos A. A. Torres, Deborah B. Diercks, Victor M. Montori, Russell Jones, Jeph Herrin, Nilay Shah, Michel Demers, Jonathan Inselman, Jeffrey A. Kline, Jason T. Schaffer, Erik P. Hess, Judd E. Hollander, Zachary F. Meisel, Annie Leblanc, and Kelly P. Owen
Subjects: Adult, Male, Acute coronary syndrome, medicine.medical_specialty, Chest Pain, Decision Making, MEDLINE, 030204 cardiovascular system & hematology, Chest pain, Risk Assessment, law.invention, Decision Support Techniques, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Health care, Medicine, Humans, 030212 general & internal medicine, Aged, business.industry, General Medicine, Emergency department, Length of Stay, Middle Aged, Patient Acceptance of Health Care, medicine.disease, Confidence interval, Emergency medicine, Emergency Medicine, Female, medicine.symptom, business, Risk assessment, Emergency Service, Hospital
Abstract: Background Patients at low risk for acute coronary syndrome are frequently admitted for observation and cardiac testing, resulting in substantial burden and cost to the patient and the health care system. Objectives The purpose of this investigation was to measure the effect of the Chest Pain Choice (CPC) decision aid on overall health care utilization as well as utilization of specific services both during the index emergency department (ED) visit and in the subsequent 45 days. Methods This was a planned secondary analysis of data from a pragmatic multicenter randomized trial of shared decision making in adults presenting to the ED with chest pain who were being considered for observation unit admission for cardiac stress testing or coronary computed tomography angiography. The trial compared an intervention group engaged in shared decision making facilitated by the CPC decision aid to a control group receiving usual care. Hospital-level billing data were used to measure utilization for the index ED visit and during the following 45 days. Patients in both groups also were asked to keep a diary recording health care utilization over the same 45-day period. Outcomes assessed included length of time in the ED and observation, ED visits, office visits, hospitalizations, testing, imaging, and procedures. Results Of the 898 patients included in the original trial, we were able to contact 834 (92.9%) patients for 45-day health care diary review. There was no difference in patient-reported health care utilization between the study arms. Hospital-level billing data were obtained for all 898 (100%) patients. During the initial ED visit the length of stay (LOS) was similar, and there was no difference in the frequency of observation unit admission between study arms. However, the mean observation unit LOS was 95 minutes (95% confidence interval [CI] = 40.8-149.8) shorter in the CPC arm and the mean number of tests was lower in the CPC arm (decrease in 19.4 imaging studies per 100 patients, 95% CI = 15.5-23.3). When evaluating the entire encounter and follow-up period, the intervention arm underwent fewer tests (decrease in 125.6 tests per 100 patients, 95% CI = 29.3-221.6). More specifically, there were fewer advanced cardiac imaging tests completed (25.8 fewer per 100 patients, 95% CI = 3.74-47.9) in the intervention arm. Conclusions Shared decision making in low-risk chest pain can lead to decreased diagnostic testing without worsening outcomes measured over 45 days.
Published: 2017

35. Efficacy and Safety of Degludec versus Glargine in Type 2 Diabetes

Author: Marso, Steven P., McGuire, Darren K., Zinman, Bernard, Poulter, Neil R., Emerson, Scott S., Pieber, Thomas R., Pratley, Richard E., Haahr, Poul-Martin, Lange, Martin, Brown-Frandsen, Kirstine, Moses, Alan, Skibsted, Simon, Kvist, Kajsa, Buse, John B., Hansen, Liliana, Rabol, Rasmus, Bethel, Angelyn, de Lemos, James A., Senn, Stephen, Schwamm, Lee, Timmis, Adam, Alshekhlee, Amer, Bach, Richard G., Bertram, Therese M., Chaitman, Bernard R., Cruz-Flores, Salvador, Eckstein, Jane F., Feen, Eliahu S., Fisher, Simon J., Gosselin, Gilbert, Lim, Michael J., Rosenzweig, James L., Sherwin, Robert S., Tobin, Garry S., Vetrovec, George, Ziemer, David C., Daugaard, Gedske, Ozlem, Er, Pollak, Michael, Sengelov, Lisa, Ahn, Yu-Bae, Amod, Aslam, Benroubi, Mariana, Boonyavarakul, Apussanee, Canecki-Varzic, Silvija, Consoli, Agostino, Eliaschewitz, Freddy G., Franek, Edward, Jinnouchi, Hideaki, Khokhlov, Alexander L., Mithal, Ambrish, Philis-Tsimikas, Athena, Ong, Tiong Kiam, Pop, Lavinia, Reyna, Leobardo Sauque, Rodbard, Helena W., Roula, Daoud, Saravanan, Ponnusamy, Sesti, Giorgio, Sorli, Christopher, Sposetti, Georgina, Tinahones-Madueno, Francisco-Jose, Woo, Vincent, Berard, Lori, Caballero Mateos, Irene, Cooper, Alison, DeLuca, Clarisa, Fillary, Julie, Gan, Diyana Gan Abdul Rahman, Goondiwala, Amina, Tapia, Jessica, Busch, Robert, Chaykin, Louis, Hollander, Priscilla, Karounos, Dennis, Lane, Wendy, Lingvay, Ildiko, Odugbesan, A. Ola, Ohlson-Elliott, Theresa, Ovalle, Fernando, Pantalone, Kevin M., Phelps, Spencer, Pop-Busui, Rodica, Robertson, David, Shlesinger, Yshay, Silver, Robert, Warren, Mark, Arrar, Mohammed, Belkheir, Hassani, Benabbas, Youcef, Benferhat, Schahrazed, Benoun, Fatima, Bensalem, Samia, Bourezane, Samia, Elaoufi, Selmane Rafik, Gourine, Mouna, Hadjhabib, Mohamed, Hadjhamou, Fouzia, Hakem, Jamila, Kaouache, Nadjib, Khensal, Sabrina, Kitouni, Yacine, Lakhal, Lamine, Lezzar, Al-Kassem, Meftah, Imane Aicha, Mehenni, Lahouaria, Nouri, Nassim, Oumerzouk, Fatma, Sakouhi, Mounia, Talha, Kheira, Zemri, Zouaouia, Caeiro, Gabriela, Calveyra, Martha, Cluigt, Natalia, Geronazzo, Veronica, Lema, Silvina, Monferran, Pablo Martinez, Oviedo, Alejandra, Pozzi, Jose, Sala, Jorgelina, Schindler, Ana, Sernia, Virginia, Sicer, Maximiliano, Solis, Silvana, Varela, Patricia, Waitman, Jorge, Augusto, Gustavo Akerman, Alves, Breno, Alves, Erica, Barbosa, Luciana, Bona, Renata, Borges, Joao, Bosco, Adriana, Canani, Luis, Castro, Denise, Cavalcante, Lilian, Cechin, Laura, Cercato, Cintia, Chrisman, Carlos, Chrisman, Carolina, Cintra, Rebecca, Costa, Giselle, Fontenele, Ana Paula, Forti, Adriana, Francisco, Beatriz, Franco, Denise, Genestreti, Paulo, Gross, Jorge, Haddad, Ludmila, Halpern, Alfredo, Hissa, Miguel, Leanca, Camila, Leao, Beatriz, Marinho, Ana Elisabeth, Miranda, Isabela, Nunes, Adriano, Palhares, Fabiana, Poco, Christiani, Salles, Joao, Sampaio, Celia, Santomauro Jr., Augusto, Sartori, Carla, Sena, Rita, da Silva, Marina, da Silva, Paula, Siqueira, Katia, Turatti, Luiz, Valenti, Adriana, Vasques, Enio, Vencio, Sergio, Visconti, Guilherme, Belanger, Andre, Chilvers, Martyn, Dumas, Richard, Hurd, Carmen, Lafleche, Francois, Lam, Paul, Martinho, Valdemar, Palardy, Jean, Peterson, Sean, Raff, Errol, Sinnaeve, Linda, Sullivan, David, Baraban, Vedrana, Blaslov, Kristina, Bulum, Tomislav, Varzic, Silvija Canecki, Berkovic, Maja Cigrovski, Balen, Marica Jandric, Kruljac, Ivan, Lesnjakovic, Silvija, Lucijanic, Tomo, Majic, Ana, Rahelic, Dario, Smircic-Duvnjak, Lea, Vrkljan, Milan, Zibar, Karin, Zukanovic, Sidbela, Athanasopoulou, Elpida, Benis, Apostolos, Benroubi, Marian, Diakoumopoulou, Evanthia, Doupis, John, Griva, Theodora, Kazakos, Kyriakos, Kypraios, Nikolaos, Liatis, Stavros, Makrilakis, Konstantinos, Markou, Athina, Pagkalos, Emmanouil, Papanastasiou, Labrini, Piaditis, George, Sampanis, Christos, Siami, Evangelia, Tentolouris, Nikolaos, Tsiama, Vasiliki, Zografou, Ioanna, Adling, Pravishal, Ali, Mazher, Anjana, R. M., Arora, Arpita, Ayyar, Vageesh, Banerjee, Suvro, Bantwal, Ganapathi, Bhagwat, Nikhil, Bhattacharyya, Arpandev, Bhawarlal, Anandakumar, Chakraborty, Rabin, Chatterjee, Sanjay, Chaudhury, Tirthankar, Chowdhury, Subhankar, Damelia, Priyal, Das, Mrinal, Das, Sambit, Desai, Ankush, Devru, Nandani, Farooqui, Khalid, Ganie, Mohd Ashraf, George, Belinda, Ghosh, Debasis, Girithara, Gopalakrishnan, Haribhai, Zinzuwadia, Jain, Nupur, Jassar, Amandeep, Joshi, Ameya, Kale, Dilip, Kale, Shailaja, Kelwade, Jayant, Khatri, Ashok, Kulshreshtha, Bindu, Majumder, Bikas, Manikath, Neeraj, Margekar, Shubhalaxmi, Marwah, Tiven, Mathew, Vivek, Moulick, N. D., Mutha, Abhay, Muthu, Ramuu, Nalawade, Asmitha, Narvencar, Kedareshwar, Pandit, Kaushik, Pangtey, Ghanshyam, Parthasarathy, B., Phatak, Sanjeev, Prakash, Anupam, Prusty, Pitambar, Radhakrishnan, Chandni, Raja, Indu, Ravikumar, Ranjani, Saboo, Banshi, Sachdeva, Isha, Sangeetha, S., Selvam, Kasthuri, Sethi, Bipin, Shah, Asha, Shah, Harshal K., Shah, Priyanshu, Shah, Rushit, Shaikh, Sajid, Shaikh, Shehla, Singh, K. P., Sivagnanam, Nallaperumal, Tandon, Nikhil, Thonangi, Rajesh, Thulaseedharan, N., Toraskar, Kedar, Varthakavi, Premalatha, Yadav, Sameer, Andreozz, Francesco, Arturi, Franco, Baldassarre, Maria Pompea Antonia, Barone, Milena, Bonura, Alice, Bucciarelli, Loredana, Buscemi, Chiara, Buscemi, Silvio, Carnovale, Anna, Caselli, Chiara, Ceci, Gloria, Cimino, Elena, Colella, Alessandra, Crippa, Valentina, Cufone, Sabrina, D'Erasmo, Laura, De Remigis, Alessandra, Di Bartolo, Paolo, Dionisio, Rosa, Disoteo, Olga, Fabietti, Marcella, Febo, Fabrizio, Filetti, Sebastiano, Genovese, Stefano, Ginestra, Federica, Grancini, Valeria, Grieco, Elvira, Magistro, Andrea, Maranghi, Marianna, Monti, Lucilla, Orsi, Emanuela, Pellicano, Francesca, Pergolini, Daniela, Perticone, Francesca, Piatti, PierMarco, Pizzi, Gianluigi, Rondinelli, Maurizio, Rossi, Margherita, Rubino, Mariangela, Setola, Emanuela, Succurro, Elena, Tarquini, Giovanna, Tiseo, Giusy, Tonolo, Giancarlo, Villa, Valentina, Hong, Stefania Vo, Amano, Kazushi, Hachiya, Remi, Hieshima, Kunio, Hirao, Koichi, Hisatake, Tomoko, Honda, Ritsuko, Ihana, Noriko, Inoue, Kaori, Iwamoto, Yasuhiko, Jinnouchi, Tomio, Kajiwara, Keizou, Kawazu, Shoji, Kikuchi, Masatoshi, Kikuchi, Takako, Koike, Yoko, Komatsu, Mitsuhisa, Kumakura, Atsushi, Kurinami, Noboru, Kushiyama, Akifumi, Maeda, Hajime, Matsuda, Toshihisa, Nakamura, Shuji, Nakayama, Koujin, Nishio, Shin-ichi, Onishi, Yukiko, Sato, Nobuyuki, Sato, Yoshihiko, Shirabe, Shinichiro, Sugiyama, Seigo, Suzuki, Tomoko, Tahara, Tazu, Takao, Toshiko, Takei, Masahiro, Takemoto, Ikutaka, Takeshige, Keiko, Tanaka, Kentaro, Taniguchi, Shotaro, Tsujimoto, Tetsuro, Tsukuda, Katsunori, Wakabayashi, Sayaka, Yamazaki, Masanori, Yoshida, Yoko, Yoshimoto, Ayako, Abidin, Imran Zainal, Abdullah, Shahrin Tarmizi Che, Adam, Noor Lita, Ahmad, Madihah, Ahmad, Nik Nur Fatnoon Nik, Amin, Nor Hanim Mohd, Aw, Cheng Yew, Cham, Yee Ling, Chong, Hui Min, Chua, Seng Keong, Fauzi, Sharifah Aisyah Shahabudin Syed Ahmad, Fong, Alan Yean Yip, Ghapar, Abd Kahar Abd, Hanafi, Norliza, Abu Hassan, Muhammad Radzi, Iberahim, Rahimah, Khiew, Ning Zan, Lee, Gary Chin Keong, Lingam, Rakesh, Long, Richard Chay Shien, Mahendran, Kauthaman A., Oon, Yen Yee, Said, Asri, Sothiratnam, Radhakrishna, Sridhar, Ganiga Srinivasiah, Suan, Mohd Azri Mohd, Tan, Sian Kong, Tey, Julian Hock Chuan, Undok, Abdul Wahab, Waid, Anuar, Vijayasingham, Shalini, Voon, Chi Yen, Yew, Kuan Leong, Yong, Lit Sin, Aguilar-Parra, Lilia, Aguirre, Karen, Alvarez-Carrillo, Rebeca, Arechavaleta-Granell, Maria, Baez-Campos, Aurelia, Bayram Llamas, Edmundo Alfredo, Calvo-Vargas, Cesar, Cedano-Limon, Marielena, Beltran Jaramillo, Teresita de Jesus, de Jesus Marin-Lopez, Jose, Ruiz Cornejo, Maria de Jesus, Juarez Cervantes, Maria del Carmen, Estevez de Alba, Isabel, Estrada Garcia, Raul, Estrada, Suellen, Garza-Vergara, Marisol, Gonzalez-Perez, Rosa, Gonzalez-Valencia, Carlos, Guerrero-Reyes, Rosalinda, Haro Ortiz, Jose Alfredo, Hernandez Salazar, Eduardo, Illescas Diaz, Iris, Illescas Diaz, Jesus, Loredo, Imelda, Jimenez-Ramos, Silvia, Larios-Mora, Diana, Lopez Garcia, Maria Elena, Lopez-Serrano, Julieta, Martinez-Nolasco, Bertha, Nunez Marquez, Ricardo, Pacheco Aranda, Elizabeth, Peralta-Cantu, Irving, Perez Chagollan, Ana, Ramirez, Maria, Robledo Duron, Israel, Rodriguez Briones, Ignacio, Rodriguez, Maria, Sauque Reyna, Leobardo, Vazquez-Ceja, Adriana, Vera-Bocanegra, Alejandro, Vidrio Velazquez, Maricela, Contreras Sandoval, Aleida Yael, Bartelik, Karol, Bilska, Aleksandra, Biniszkiewicz, Tomasz, Bogdanski, Pawel, Chamienia, Agnieszka, Cieslak-Puchalska, Anna, Czochra, Wojciech, Gajewski, Bogdan, Gromniak, Elwira, Holda, Ewa, Jaskulska-Gorzelewska, Barbara, Jedynasty, Krystyna, Kloda, Elzbieta, Kmak-Balawender, Beata, Kobielusz-Gembala, Iwona, Konieczny, Marek, Kramarczuk, Elzbieta, Kuleta, Jerzy, Lesniewski, Robert, Lominska, Teresa, Lukaszewicz, Monika, Majewska, Izabella, Mlynarski, Tomasz, Mostowy, Aleksandra, Rybak, Anna, Skrypnik, Damian, Wolny, Malgorzata, Zmuda, Witold, Buduru, Alina Nicoleta, Cif, Adriana, Cozma, Mihaela, Crisan, Carmen, Barbonta, Cristian Gelu, Barbonta, Diana, Mihalcea, Madalina, Mociran, Mihaela, Muresan, Sorina, Popescu, Alexandrina, Pruna, Luchiana, Sandu, Nadia Ramona, Suleac, Oana Andreea, Vincze, Eva Cornelia, Andreeva, Elena, Berns, Svetlana, Barykina, Irina, Bernitcyna, Angela, Bezdenezhnykh, Natalia, Chumachek, Elena, Demarina, Svetlana, Didenko, Anna, Dubinina, Nadezhda, Dzherieva, Irina, Elsukova, Olga, Esenyan, Lev, Filippova, Ekaterina, Gabova, Nadezhda, Garina, Irina, Glikman, Yulia, Glova, Svetlana, Goncharova, Ekaterina, Gorbatova, Elena, Gordeev, Ivan, Grigorian, Inessa, Gromova, Svetlana, Ipatko, Irina, Karaban, Elena, Katushkina, Yulia, Kaygorodtseva, Olga, Kerova, Irina, Khaisheva, Larisa, Khmelnitskiy, Oleg, Khokhlov, Alexander, Khokhlov, Mikhail, Khorolets, Ekaterina, Klyuenkova, Elena, Konovalova, Olga, Korneva, Ksenia, Kosmacheva, Elena, Kunitsyna, Marina, Kupriyanova, Tatiana, Kuznetsova, Natalia, Lantseva, Olga, Ledyaeva, Alla, Lileeva, Elena, Markovich, Alexander, Martirosian, Narine, Maslova, Alisa, Milyukova, Galina, Mokhova, Irina, Nagirniak, Olga, Nastina, Elena, Nedogoda, Sergei, Orlova, Valeriia, Svetlana, Otarova, Ostapenko, Marina, Papaskiri, Nino, Pavlikova, Elena, Peskov, Andrey, Petrik, Galina, Petrov, Alexander, Petunina, Nina, Platonov, Dmitry, Poliakova, Yulia, Potapova, Zhanna, Pribylova, Svetlana, Razumovsky, Igor, Redkin, Alexander, Rodionova, Tatyana, Rudenko, Evgenia, Rykalina, Natalia, Salasyuk, Alla, Semikina, Tatiana, Serebryakova, Inna, Shanina, Larisa, Shmidt, Evgenia, Sinitsina, Olga, Smetanina, Svetlana, Smirnova, Marya, Smirnova, Victoria, Smolentseva, Nadezhda, Sobolev, Alexander, Soldatenkova, Anna, Soldatova, Yulia, Speshilova, Svetlana, Startseva, Olga, Strezhova, Larisa, Strongin, Leonid, Suplotova, Lyudmila, Suvorova, Daria, Tepaeva, Alisa, Trukhina, Liubov, Tyugaeva, Alisa, Vasyutkova, Olga, Vinokurova, Valentina, Yukhno, Elena, Yuzhakova, Natalia, Zagrebelnaya, Olga, Zalevskaya, Alsu, Zhukova, Elena, Aomar Millan, Ismael, Beltran Romero, Luis M., Ignacio Fernandez Navarro, Jose, Carlos Ferrer Garcia, Juan, Garcia Blasco, Lourdes, Garcia Garcia, Clara, Garcia Puig, Juan, Girbes Borras, Juan, Inigo Zaera, Pilar, Lopez de la Torre, Mart-n, Martinez Alfaro, Baldomera, Morales Portillo, Cristobal, Romero Sanchez, Paloma, Sebastian Ochoa, Nerea, Serrano Olmedo, Isabel, Tinahones Madueno, Francisco, Torres Jimenez, Rosa, Adeyemo, A. O., Bassa, Ayesha, Bhorat, A., Bhorat, Qasim, Blacking, Laura, Burgess, Lesley, Coetzee, Kathleen, Conradie, Hillet, Cyster, Henry, Distiller, Larry, Ellis, G. C., Gani, Mashra, Gordon, Debra, Govender, Parimala, Govender, Thirumani, Govender, Vimladhevi, Jivan, Daksha, Joffe, Barry, Jooma, Yaseer, Kaplan, Hilton, Komati, Stephanus, Kramer, Brian, Kruger, Sieglinde, Landau, Stanley, Latiff, Gulam, Maritz, L., Matthews, Peter, Middlemost, S. J., Ngcakani, Nomangesi, Nortje, Hennie, Osman, Yasmin, Padayachee, Trevenesan, Podgorski, Gracjan, Potts, Jenny, Pretorius, Catharina, Prozesky, Hans, Snyman, Hans, Tayob, Mohammed, Urbach, Dorothea, van der Merwe, Maryke, Vorajee, Haroon, Wilson, Nadine, Wing, J. R., Lee, Jie Eun, Ahn, Chang Ho, Kim, Nam Hoon, Kim, Sun Hwa, Hwangbo, Yul, Ko, Sun Hye, An, Jee Hyun, Ko, Seung Hyun, Lee, Ji Hyun, Noh, Jung Hyun, Ji, Myeong Jin, Kim, Kyeong Jin, Jung, Chan-Hyeon, Kim, DongJun, Kim, Kyongyoung, Kim, Lee-Kyung, Kim, SinGon, Kim, Eun Ky, Lee, Dong-Hwa, Cho, Young Min, Moon, Shin-Je, Oh, Chang-Myung, Hong, A. Ram, Park, Kyeong Seon, Yun, Jae Seung, Hong, Jae Won, Kim, Hee Young, Buranapin, Supawan, Deerochanawong, Chaicharn, Hengjeerajarus, Natavuth, Kosachunhanun, Natapong, Kuanprasert, Srun, Kunavisarut, Tada, Laortanakul, Rungnapa, Mangklabruks, Ampica, Phornphutkul, Mattabhorn, Prasitdamrong, Hutsaya, Snabboon, Thiti, Sriwijitkamol, Apiradee, Suwanwalaikorn, Sompongse, Tantiwong, Puntip, Tejavanija, Sirakarn, Vorasettakarnkit, Yongkasem, Alasabbagh, Samer, Bagais, Christos, Bingley, Polly, Borthwick, Les, Brett, Barbara, Davidson, Sue, Ewing, Jane, Garesse, Robert, Gillani, Syed, Gkastaris, Konstantinos, Herring, Roselle, Illsley, Graham, Johnson, Andrew, Kaplan, Felicity, Lonnen, Kathryn, Malcolm, Ellen, McCrimmon, Rory, Mcknight, John, Nair, Rajiv, Patel, Vinod, Pearson, Ewan, Raghavan, Rajeev, Raj, Suchitra, Russell-Jones, David, Sampson, Mike, Singh, Baldev, Sukamer, Nithya, Turner, Jeremy, Venkataraman, Hema, Viljoen, Adie, Wake, Deborah, Barnes, Cassandra, Boyd, Gary, Childress, Gwen, Coleman, Debora, Combs, Judy, Davis, Leon, Davison, Kentress, DeAtkine, David, Dunaway, Linda, Duncan, Janet, Hibbard, Nina, Martin, Melissa, Nichols, Melissa, Painter, Karolynn, Perkins, Tammy, Quinney, Rosylen, Raymond, Katrina, Roney, Christopher, Sanchez, Gilberto, Sosnowchik, James, Sultan, Farah, Talley, Shellie, Trippe, Bruce, Tuck, Pamela, Vaughan, T., Warriner, Amy, Watts, Tamara, Williams, Hayes, Abidov, Aiden, Abidov, Yulia, Anderson, Corey, Avila, Vanessa, Baraniak, James, Berry, Barbara, Bessette, Lynn, Blackwell, Gina, Burrows, Jennifer, Caldron, Meghan, Chang, Chui-An, Collins, Elizabeth, Crawford, Meli'sa, Delfin, Katherine, De'Loera, Jessie, Dokken, Betsy, Feld, Lawrence, Gill, Ryan, Gordon, James, Gordon, Rachel, Gullick, Nicole, Gutierrez, Diane, Harrison, Larissa, Haught, Annamarie, Hemmila, Karin, Hendrickson, Darell, Horsley, Craig, Hsu, Connie, Jerrell, Maggie, Kertesz, Briana, Khananisho, Paulina, Lenzmeier, Sonia, Lenzmeier, Thomas, Lipschitz, Barbara, Lonquist, Mark, Mather, Dana, (Shelley) Miceli, Michelene, Norris, Gwenth, Padilla, Ann Marie, Petersen, Dena, Riffer, Ernie, Scott, Susan, Sheridan, Kathryn, Smith, Misty, Stump, Craig, Thomson, Stephen, Torok, Ernese, Vesely, Kelly, Vincent, Tom, Wilson, Christy, Wilson, Sandra, Agarwal, Monica, Appleberry, Kady, Barden, M. Gregg, Brickell, Lorrie, Bravo, Eric, Cassis, Cady, Covington, Becky, Devine, De'Andrea, Dishongh, Katherine, Dugger, Joseph, Evans, Lauren, Francis, Spencer, Johnson, David, Koneru, Kalyana, Kurck, Sheryl, Lingisetty, Chandra, Menke, Jennifer, Miller, Beatrice, Montgomery, Cristal, Nimmo, Teresa, Pace, Daniel, Pellegrino, Richard, Rose, Joseph, Straub, Karl, Stubbs, Amanda, Thomas, Leslie, Thrasher, James, Thrasher, Lesa, Wijewardane, Priyantha, Williamson, Kimberly, Acevedo, Lizeth, Ahmad, Aakif, Andresen, Teri, Anderson-Berman, Nancy, Ayele, Etsegenet, Baker, Janice, Banares, Arlene, Barsalou, Thea, Becker, Steven, Benavidez, JoAnn, Benitez, Guadalupe, Bernstein, Richard, Bhasker, Kala, Blain, Arthur, Blustin, Joy, Bughi, Stephanie, Carney, Kimberly, Castro, Gerardo, Catangay, Jennifer, Chambers, Joseph, Chan, Eve, Chang, Amy, Chang, Anna, Chavous Jr., Donald, Chen, Constance, Chiu, Ken, Chochinov, Ronald, Chu, James, Cleghorn, Monica, Cohen-Gadol, Shariar, Cokely, David, Collins, Michelle, Collins, Yolanda, Colomy, Carissa, Cruz-Corona, Yolanda, Cunnea, Virginia, Dailey, George, Dang, Andy, Dang, Trinh, De La Luz, Mabel, Delgadillo, Rico, Delgado, Michael, Desta, Taddese, Doriguzzi, David, Dulgeroff, Anthony, Einhorn, Daniel, Emery, Pamela, Figueroa, Martin, Fink, Raymond, Flowe, Chelsea, Flowers, Francesca, Fregosi, Julie, Garcia, Gabriel, Garcia, Maria, Gaudiani, Linda, Gawad, Michael, Ghattas, Sam, Gilroy, Christine, Gonzalez, Viviana, Gonzalez, Yadira, Guadron-Hernandez, Liliana, Ha, Thu, Haas, Terry, Harbison, Judy, Hernandez, Graciela, Hernandez, Robert, Herrera, Nancy, Ho, Vincent, Hsu, Kang, Humphries, Denise, Huynh, Vincent, Jacobs, Shahram, Jardula, Michael, Jarman, Cheryl, Kabongo, Martin, Kafri, Hassan, Kaplan, Roy, Kim, Grace, Kobayashi, Gary, Korff, Gary, Kowalick, Alexandra, Levin, Ellis, Lewis, Erin, Lisovskiy, Svetlana, Luu, Hieu, Malkhassian, Daniel, Maletz, Louis, Martinez, Geraldine, Martinez, Gilbert, Martinez-Miss, Salomon, McCallum, James, Melikian, George, Metcalf, Francine, Michlin, Bernard, Michlin, Shira, Mitchell, Anitha, Moattari, Ali Reza, Montano-Pereira, Cynthia, Moon, Mia, Naderi, Bahar, Nagata, Jenna, Nguyen, Christopher, Norwood, Paul, Garcia, Sagrario Olmos, Olsen, Sharon, Pardino, Aarika, Parkes, Kathleen, Pascal, Aileen, Patel, Mihir, Paulson, Carolyn, Pernia, Kay, Perez, Marisol, Pham, David, Presant, Larry, Preston, Krista, Reeves, Laurie, Richards, Jessica, Rios-Santiago, Jessica, Risser, Joseph, Rodriguez, Silvia, (Cherrie) Rosal, Rosario, Rosenblit, Paul, Rosero, Raquel, Sadler, Chris, Samoa, Raynald, Sanchez, Liliana, Schaeffer, Cynthia, Schwartz, Alan, Scott, Christopher, Scott, Courtney, Scott, Cranford, Shartel, Jo-Ann, Shaw, Sylvia, Sivalingam, Kanagaratnam, Sligh, Scott, Sligh, Teresa, Smith, Bradley, Soler, Daniel, Spencer, Torre, Stalters, Sophia, Stone, Jenine, Szlachcic, Yaga, Thorsell, Ashley, Tu, Zhongheng, Unger, Jeffrey, Vela, Teresa, Walton, Anita, Whittle, Jessica, Wilson, Lou Ellen, Wing, Zandra, Wright, Philippa, Wyman, Shannan, Yao, Ni, Zlock, Douglas, Baker, Chelsea, Bakkum, Robyn, Bird, C. David, Carangi, Gwen, Cohen, Kenneth, Daza-Taylor, Kristen, Diesburg-Stanwood, Amy, Douglass, Sara, Finck, Lani, Karaboitis, Krisoula, Kerstein, Howard, Lesh, Kurt, Loesch, Ryan, McClure, Lori, Nevarez, Max, Pavol, Bristol, Rasouli, Neda, Rockler, Briana, Sanagorski, Rebecca, Solano, Royce, Underkofler, Chantal, Van Winkle, Rebecca, Weiss, Sarah, White, Katherine, Wirtemburg, Patricia, Zarrabi, Lida, Zemel, Leonard, Barchini, George, Casagni, Kimberely, Cordisco, Marie Elena, Davis, Amanda, Duffy-Hidalgo, Bobbi, Huntley, Richard, McNicol, Donald, Miller, Neil, Mukwaya, Margaret, Northrup, Patricia, Platt, Jonathan, Rabideau, Diane, Randolph, Pamela, Rose, Suzanne, Samuel, James, Savino, Robert, Soufer, Joseph, Torello, Carole, Abinader, Azarel, Agosto, Milagos, Aguirre, Frank, Alexander, Lori, Almanza, Orlando, Alvarez, Dalia, Anees, Muhammad, Aqua, Keith, Arazo, Luz, Asberry, Claudia, Ashley, Alyssa, Balentine, Tracy, Barta, Melissa, Bertot, Ivan, Binns-Leon, Michelle, Borello, Nora, Bostick, Janette, Boucher, Loria, Braddy, Dalton, Breton, Cristian, Broxton, Bridgitte, Burke, Deborah, Cabielles, Tania, Calderon, Juan, Canaan, Yamil, Canelon, Gustavo, Cardona, Jose, Castillo-Gonzalez, Sheila, Castro, Kenia, Chacon, Jessica, Chehade, Joe, Church, Lara, Cohen, Lisa, Crews, Erin, Cromer, Carol, Cromer, Michael, Cuello, Jorge, Cusi, Kenneth, de Leon, Karel, Delgado, Edmund, Delima, Selma, Denson, Janneral, DeVries, Benjamin, Diaz, Maritza, Digon, Beningo, Dowell, Michelle, Dunn, Kelly, Ellington, Dickson, Emerick, George, Encarnacion, Frances, Ezell, Leslie, Fahmie, Ashley, Fernandez, Noel, Figueredo, Rommel, Flores, Patricia, Fonseca, Juan, Freeman, Alain, Freeman, Erica, Frias, Juan, Garcia, Lazaro, Geronilla, Giovanni, Hamilton, Maxine, Hanabergh, Rodolfo, Hanson, Lenita, Harris, Kim, Hasan, Syed, Hendrick, Mary, Hicks, Melissa, Hoffman, Lara, Holt, Antoniwa, Hutchinson, Rachel, Iparraguirre, Harold, Janicka, Ania, Janovitz, Richard, Jones, Dawn, Jones, Sarah, Kaplun, Polina, Kelijman, Mirtha, Kersey, Angela, Khan, Ashraf, Khan, Misal, Kirk, Gregory, Konwai, Ada, Kovar, Meghan, Kutner, Mark, Lafaille, Jimmy, Leach, Dana, Levenson, David, Lewy-Alterbaum, Lorena, Light, Timothy, Lo, Margaret, Loman, Lusiana, Long, Sarah, Love, Jeremy, Madera, Arelis, Magee, James, Mallitz, Michelle, Marquez, Farid, Marshall, Richard, Mary, James, Mateu, Janet, McKenzie, Leanna, McKenzie, Rona, McKenzie, Wilfred, Mendelson, Reina, Mendez, Janet, Merlos, Ledis, Mierau, Jennifer, Miller, Robert, Miranda-Palma, Bresta, Montoya, Carla, Navarro, Eduardo, Neller, Christian, Nossa, Janette, Osborn, Tracey, Patel, Bijal, Penabad, Jesus, Perez, Gilberto, Pineda, Daniel, Pinero-Pilona, Antonio, Platt, George, Prestwood, Elfrida, Quintero, Luis, Rengifo, Rodney, Reyes, Dannier, Rivas, Aolani, Rivero, Mileydis, Robinson, Sonya, Robison, Dawn, Rodriguez, Dalier, Rodriguez, Ivete, Rodriguez, Toni, Rosario, Cristobal, Rosenwasser, Rebecca, Roura, Miguel, Schramm, Erich, Schramm, Rashi, Schweppe, Laurie, Segel, Scott, Sepulveda, Maria, Sheets, Lori, Shields, Karen, Smith, Krystal, Smith, Meridith, Somerstein, Claudia, Solano, Maria, Suarez, Manuel, Suarez, Omar, Suarez, Rogelio, Suarez, Victor, Sultan, Senan, Sutton, David, Szilagyi, Istvan, Thorne, Margaret, Travaglini, Stefano, Trevino, Miguel, Uriarte, Oscar, Vizcaino, Luis, Wadud, Khurram, Wehmeier, Kent, Weinstein, Debra, Welch, Celeste, White, Alexander, White, Basil, Williams, Tammy, Williamson, Cathi, Zwick, Lisa, Adams, Cynthia, Arkin, David, Bode, Bruce, Bonner, Sheila, Bonner, Wes, Bowen, Danielle, Bradley, Brooke, Bradley, Paul, Brennan, Elizaebeth, Brown, Cynthia, Brown, De'Aira, Burgess, Elizabeth, Collett, Taryn, Cook, Jennifer, Corse, Steven, Dukes, Kaitlyn, Durrence, Jenna, Dutton, Robin, Estes, Susie, Falcone, Laura, Gaskin, Katherine, Goswami, Ketan, Hart, Mari, Jester, Donni, Kies, Staci, Leiker, Abigail, Lu, Peter, Mahakala, Aparna, Maher, Maxine, Miller, Alan, Miller, Todd, Munoz, Miguel, Musto, Michele, Odugbesan, Adeniyi, Olson, Darin, Osborn, Nicole, Pace, Kerri, Pajkovic, Gordana, Paulus, Carolyn, Phillips, Lawrence, Reddick, William, Reed, John, Rowe, Shasta, Sadler, Barney, Sapp, Tabby, Savoye, Louise, Shore, David, Shuman, Susan, Sittle, Jessica, Standard, Shana, Wardell, Karla, Workman, Amy, Carreira, Tabitha, Fitz-Patrick, David, Hean, Vutheary, Limcolioc, April, Nihei, Megan, Park, Youngmee, Pau, Cindy, Shannon, Lindsey, Trotter, Alanna, Williams, Sierra, Coughenour, Tiffany, Liljenquist, John, Vance, Carl, Williams, Jonathan, Agaiby, Eva, Agaiby, John, Argo, Kelly, Azad, Nasrin, Backus, Arnetta, Bartlett, Andrew, Bellucci-Jackson, Jennifer, Boncu, Otilia, Brodt, Pamela, Carlson, Hope, Collins, Kathleen, Delibasic, Maja, Dor, Isaac, Dukett, Mary, Emanuele, Nicholas, Gabel, Faith, Giardino, Alexandra, Hoelzer, David, Hsieh, Annming, Jayaramaiah, Poornima, Kearney, Tracy, Kelley, Kathleen, Kravarusic, Jelena, Lawless, Andrea, Maheshwari, Hiralal, Martin, Elonia, McCall, Linda, Mikell, Frank, Nallala, Deepika, Said, Sufyan, Sakla, Nadia, Schiferi, Joanna, Smith, Patricia, Stokes, John, Sugimoto, Danny, Sugimoto, Michael, Swan, Delores, Alfata, Sarab, Beavins, Jill, Bogardus, Christine, Bogardus, Donald, Calvert, Brittany, Calvin, Krystle, Carlton, Kristin, Condit, Jonathan, Cornett, George, Covert, Carissa, Dela Llana, Alexander, Dixon, Rosie, Felker, Dean, Fogle, Sara, Harris, Leslie, Hoebeke, Roberta E., Silva, Ricardo, Johnson, Tabitha, Johnston, Kelly, King, Jennifer, Lang, Amber, Maynard, Kenneth, McDaniel, Vickie, McGrath, Caitlin, Moretto, Thomas, Ndukwu, Ikeadi, O'Connor, Leo, O'Connor, Thomas, Oliver, Tonya, Overmars, Stephanie, Patel, Minesh, Patterson, Geraldine, Powell, Talessa, Raphael, Annmarie, Raphael, Rod, Reedy, Mark, Reyes, Hubert S., Ridge, Terry, Rutherford, Mary S., Sebastian, Mike, Shaeffer, Laura, Sheets, Michelle, Thomas, Karen, Trueblood, Nancy, Tucker, Tiffany, White, Adrian, Wooldridge, Evan, Wright, Alison, Zapinski, Dawn, Cieloha, Megan, Coker, Clarine, Fletcher, Cherisa, Kay, Jennifer, Larsen, Katelyn, Marar, Isam, Motz, Zachary, Paul, Jamie, Pokorski, Alan, Rabadi-Marar, Diana, Scheideler, Kylie, Sobczyk, Jill, Sweeney, Kolbie, Brink, Nathalie, Buth, Dennis, Grimes, Katlyn, Lakin, Gregory, Loewen, Barbara, Secrist, Neal, Simon, William, Steere, Diane, Talbot, Kimberly, Wheeler, Christina, Adams, Derick, Armour, Wilhelmina, Asher, Whitney, Bays, Harold, Behl, Noreen, Conn, Brittany, Dye, Lyndsey, Earl, Jennifer, Farris, Neil, Figueroa, Sergio, Fruit, Olivia, Hobbs, Coury, Howard, Kristen, Jackson, Tamara, Kain, Angela, Karounos, Chrisi, Keiran, Sarah, Kennedy, Ryan, King, Kara, Krishnasamy, Sathya, Lambdin, Winona, Micklewright, Gezina, Mokshagundam, Sri, Mooney, Stephen, Moore, Melanie, Morgan, Denise, Morley, Robert, Newsome, Stacy, Nichols, Jennifer, Nims, Diana, Nockerts, Nichole, Oremus, Ruth, Ritchey, Barbara Michelle, Shelton, Christina, Smith, Danielle, Walker, Debra, Weiter, Kathleen, Whitehead, Rebecca, Wood, Robert, Woodruff, Robin, Young, J. DeShay, Alper, Arnold, Berry, Martha, Gauthier, Nadine, Griffin, Catina, Haynes, Elvia, Lawrence, Jereta, McCormack, Teraina (Terry), Midyett, Catherine, Rangaraj, Uma, Smith, William, Stricker, Makenzie, Tandron, Ileana, Vargas, Ramon, Wagner, Michele, Albert, Marie, Baillargeon, Gail, Stephens, John, Aroda, Vanita, Dempsey, Michael, Junker, Herman, Lopez, Meyling, Shepard, Marc, Ciccarelli, Carol, Datu, Joycelyn, Gallagher-Dorval, Karen, Hartigan, Celia, Kowaloff, Edward, Lock, John-Paul, Rosano, Nina, Shaw, Bernadette, Thompson, Michael, Abbo, Camerin, Anton, Salwan, Baker, Lydia, Bhan, Arti, Blackmer, Karla, Boley, Bryon, Hyde, Desirae, Bonema, John, Carlin, Tamara, Curran, Nancy, Dandois, Bethani, Dermyer, Abigail, Dubeck, Janet, Elkins, Jennifer, Ferris, Pamela, Fraser, Neil, Kozma, Julia Gargan, Gasparovich, David, Grodman, Robert, Hampson, Jaison, Hewitt, Mitzie, Hiatt, Judy, Hopkins, Ashley, Howard, Jennifer, Joliat, John, Joliat, Jonathan, Kalt, Steven, Katzman, Steven, Kogelman, Jesse, Kruger, Davida, Kurkowski, April, Lambert, Jodi, Levcovici, Elisabeta, Lockwood, Karen, Lumberg, Michael, McMullen, Lindsay, Meyers, Peter, Minto, Carrie, Nelson, Tina, Neuner, Gregory, Nurmi, Kevin, Perkins, Judy, Plunkett, Cynthia, Ruoff, Gary, Samantray, Julie, Sawah, Ahmed, Secord, Samantha, Seyoum, Berhane, Sherman, Sarah, Simpson, Michael, Sinkoff, Mark, Skoney, Joseph, Small, Jami, Szerlong, Heidi, Tinetti, Timothy, Toomey, Adam, VanDerWerff, Holly, Whitehouse, Fred, Wilkins, Raechelle, Wolf, Stephanie, Yarows, Steven, Eldred, Edward, Hester, Kim, Huling, Randall, Moore, Kerry, Preslar, Kristina, Proge, Nakia, Smith, Lora, Young, Gerri, Bybee, Kevin, Carr, George, Case, Christopher, Forker, Alan, Goeke, Lindsay, Kocher, Darlene, Lin, Oscar, Littlefield, James, Mendoza, Robinson, Moore, Michelle, Oberhaus, Barbara, Reed, Larry, Rutherford, Cheryl, Windsor, Sheryl, Ackerman, Kim, Christensen, Reed, De Souza, Jose, Douglas, Kirsten, Hrncirik, Therese, Lefkowicz, Magen, McDonnell, Lindsey, Severa, Larry, Tjaden, Jeffrey, Ward, Laura, Addison, Shayla, Anderson, Robert, Baker, Claire, Baum, Robert, Belitz, Jenny, Boerner, Shannon, Desouza, Cyrus, Drincic, Andjela, Fitzgibbons, William, Francis, Jessica, Garvin, Maureen, Goldner, Whitney, Goodrich, Melissa, Grubbs, Lisa, Hatcher, Theresa, Hochstein, Renee, Hunter, Christine, Keuchel, Janet, Konigsberg, Sarah, Kuechenmeister, Lisa, Mack, Lynn, McKnight, Thomas, Mensik, Hanna, Mitchell, Jan, Moeller, Jennifer, Montanez, Edward, Montoya, Paul, Nemecek, Tiffany, Neumeister, Amy, Newcomb, Jefferey, Pracht, Shelby, Radke, Kaitlin, Rahman, Jennifer, Renter, Samantha, Reynolds, Jill, Grace Rodriguez, Maria, Satorie, Jessica, Schiermann, Lynnda, Severson, Megan, Shivaswamy, Vijay, Snyder, Janice, Tillson, Renee, Vasey, Andrew, Wahl, Timothy, Weeks, William, Wolf, Thomas, Springer, Brian, Mitchell, Janice, Woodruff, Mark, Alvarez, Isis, Bowers, Rachel, Cala-Anaya, Franklin, Castellanos-Rodriguez, Rudiber, Christopher, Janice, Concepcion, Gelvis, Fernandez, Dareana, Ghanem, Paula, Harmon, Nicolette, Kaiser, Heather, Kaplan, Westbrook, Klugh, Serena, Le, Nicholas, Lehrner, Stephanie, Lopez, Robert, Martin, Olga, Martinez, Tina, Martini, Nicole, Molin, Clifford, Nakhle, Samer, Newsome, Yvonne, Neylon, Ellen, Olsen, Jarvis, Palal, Betsy, Philander, Peter, Rosario, Adriana Ruiz, Sanchez, Mary, Sierra-Garcia, Miguel, Smith, Myesha, Trenche, Samuel, Trippi, Danna, Vernetti, Nicholas, Villegas, Laura, White, Briana, Wilcox, Simmon, Carmolli-Cornette, Lisa, Chuang, Ellie, Hoffman, Sheila, Laliberte, Alison, Marshall, Lisa, Meroski, Pamela, O'Neil, Christine, Shippey, Jeanette, Spector, Linda, Cam, Jenny, Chen, Tina, Damle, Jagadish, Holman, Rebecca, Liu, Jenny, Milazzo, Carmelo, Quach, Brenda, Yang, Bin, Ahmad, Basharat, Aro, Dominic, Azeem, Fouzal, Bonaccorso, Antoinette, Brancato, Lenore, Brautigam, Donald, Charatz, Seth, Chiarot, June, Cunningham, Linda, DiCerbo, Nancy, DiGiovanna, Michael, Dluge-Aungst, Dawn, Dolbeer, Traci, Donovan, Daniel, Duma, Carol, Ellwood, Rebecca, Freedman, Zachary, Gorman, Timothy, Gunther, David, Hogan, Eileen, Hoffman, Lisa, Kapoor, Anoop, Kelly, Michelle, Kitchen, Timothy, Lam, David, Levister, Camilla, Levy, Carol, Lopez, Carlos, Lyons-Patterson, Jane, Makam, Sashi, Mauceri, Diana, McClary, Carole, Murak, Daniel, Nolan, Kelly, Nunez, Carlos, Elliott, Theresa Ohlson, Ostrowski, Phillip, Pallai, Ajish, Porges, Andrew, Rodes, Alfredo, Rosenberg, Richard, Rubel, Lance, Serrano, Lelanie, Shannon, Daniel, Sinha, Rabi, Snyder, Brian, Sy, Claude, Tang, Rocky, Varavenkataraman, Raghupathy, Winterberger, Amy, Allen, Stacy, Anderson, Marshall, Asbill, Mark, Beasley, Amanda, Bennett, Chrisitian, Bergamo, Katherine, Bilbro, Scott, Brannock, Sarah, Brown, Laura, Bryant, Danielle, Buck, Genena, Burdette, Tara, Buse, John, Butler, Laura, Caldwell, Ronald, Cannon, Daniel, Cannon, Kevin, Carter, Casey, Cherry, Amanda, Comer, Zoe, Crittenden, Susan, Cuffee, Juanita, Culmer, Dawn, Daly-Barnes, Kristie, Evensen, Erick, Saavedra, Rubin, Dean, John, Dezube, Milana, Diner, Jaime, Dodis, Regina, Dostou, Jean, Duclos, Michelle, Elmore, Miles, Ferree, Kristin, Foster, Leslie, Fuller, Gail, Garner, Susan, Godwin, Sarah, Goley, April, Gore, Whitney, Green, Brenda, Harris, Elizabeth, Harris, Joy, Harris, Rebecca, Hatharasinghe, Roger, Herring, Charles, Hill, Chernessa, Holmes, Robert, Hutchens, Erin, Jennings, Stuart, Kaake, Ashley, Kaygun, Handan, Kirkman, Marian Sue, Kretzschmar, Heather, Lang, Jaqueline, Largay, Joseph, Lewis, Melissa, Long, Maria Ann, Lucas, Kathryn, McCall, Roshanda, McDaniel, Catrina, McGinnis, Lee Ann, Mogabgab, Edward, Montero, Manuel, Montgomery, Richard, Moran, Joseph, Morgan, Katie, Motley, Taylor, Narendran, Mahendra, Narron, Brooke, Newman, Walter, Nicholson, John, Norris, Stephanie, Norton, Jennifer, Nowell, Erin, O'Brien, Heather, Otero, Heydin, Perkins, Victoria, Quesada, Reyna, Raad, George, Raley, Rosalie, Raman, Sujatha, Rappaport, Jonathan, Ray, Robert, Ray, Shannon, Rice, Lucian, Roberts, Christine, Ross, Kaylee, Scanlon, Erica, Schroder, Derek, Schulte, Michelle, Schultzaberger, Richard, Shoffner, Sylvia, Skrzynski, Michael, Smith, Brian, Smith, Holly, Smith, Jennifer, Smith, Justin, Smith, Kendall, Smith, Leigh, Sparks, Jeffrey, Speece, Jessica, Spivey, Jessica, Stebich, Andrew, Temple, Karen, Tessena, Boryana, Thompson, Casey, Traylor, Henry, Turner, Juliana, Turner, Sh-Rhonda, Van Cleeff, Martin, Vukojicic, Katarina, Wanchick, Leslie, Weinrib, Stephen, Werner, Devorah, Wishon, Candace, Wilson, Jonathan, Wilson, Stephanie, Wright, Heather, Young, Laura, Brown, Jamie, Lillestol, Michael, Allen, Mary Jo, Barker, Bruce, Bedel, Gary, Beuerlein, Shawn, Bhati, Amar, Breslaw, Nicole, Brown, April, Burtch, Brian, Check, Ellen, Chiodi, Shawnie, Colosimo, Linda, Cope, Kathie, Coressel, Denise, Cramer, Bethany, Crowel, Amy, Daboul, Nizar, DeLong, Rebecca, Dirkes, William, Farooki, Zia, Fixler, Don, Friedhof, Linda, Griffen, Julie, Hagan, Anjani, Haney, Kevin, Harris, Kira, Hoffmann, Amanda, Hsieh, Ronald, Ismail-Beigi, Faramarz, Kelso, Kim, Khamousia, Nidaa, Kremer, Gerald, Krol, Adrienne, Kulow, Tanya, Kuttler, Mary, Lee, Andy, Leksan, Jane, McElroy-Marcus, Susan, McNeil, Donald, Mulligan, Guy, Pantalone, Kevin, Perrino, Frank, Peysha, Lori, Pickett, Alicia, Pritchard, James, Provanzana, Kathleen, Rancitelli, Philip, Raupp, Randa, Schnall, Adrian, Siddiqui, Jaweriah, Smith, Cynthia, Sood, Ajay, Sortor, Jennifer, Spinelli, Kristin, Taylor, Diana, Thornton, Aaron, Tiktin, Margaret, Twine, Melissa, Urbank, Ann, Voegele, Francis, Wang, Lawrence, Weiss, Daniel, Werner, Amanda, Williams, Daniel, Wilson, Charles, Aberle, Teresa, Arcon-Rios, Sirlys, Arodak, Bassam, Aziz, Ammara, Bixler, Lacey, Brisko, Carolann, Cannon, Melanie, Choe, James, Connery, Lisa, Elkosseifi, Myriam, George, Aja, Hummer, Kimberly, LaBryer, Lauren, Lane, James, Lim, Jonea, Mirza, Lubna, Mittadodla, Saritha, Priest, Diane, Rao, Veitla, Ricci, Cassie, Salazar, Jennifer, Shaw, Jessica, St John, Jennifer, Talsania, Mitali, Joarder, Farahnaz, Riddle, Matthew, Yuen, Kevin, Ahmed, Intekhab, Austin, Barry, Bagnata, Linda, Bartkowiak, Anthony, Batrus, Jennifer, Baumgarten, Thomas, Belejchak, Paula, Belucher, Christine, Benton, Julia, Berger, Peter, Biscoveanu, Mihaela, Blasick, Abbie, Blyler, Kay, Casey, Linda, Chandler, Bronell, Chapman, Kim, Chou, Brian, Cisar, Jennifer, Clatterbuck, Tabetha, Cook, Richard, Cook II, Richard, Dardi, Inderpreet, DeSalle, Dina, Edevane, Shari, Elliott, Kelsey, Everhart, Brian, Furlong, Kevin J., Geishauser, Jennifer, Goisse, Marcy, Goodman, Yvonne, Gordon, Murray, Gutowski, Catherine, Harris, Ronald, Hu, Ying, Hull, Jenny, Iachini, Kathleen, Iannamorelli, Anthony, Jabbour, Serge, Jackson, Timothy, Jameson, Brian, Janosov, Paula, Jordan, Terry, Kennedy, John, Kurtzer, Gayle, Labuda, Joseph, LaRochelle, Anne, Levinson, Lawrence, Madder, Robert, Marconnet, Kari, Mareda, Patricia, Michael, Donna, Michaels, Debra, Miller, Cathy, Miller, Jeffrey, Minnock, Ann, Mitchell, Michele, Moturi, Hemlata, Moyer, Heather, Nagelberg, Steven, Oliver, Michael, Pepe, Constance, Porter, Patricia, Posey, Dora, Purighalla, Raman, Redmond, Jessica, Reiling, Joseph, Reiling, Susan, Rine, Kathy, Rust, William, Sandutch, Jill, Shaffer, Anette, Shalongo, Annette, Shawley, Sarah, Shonk, Pamela, Singh, Vinay, Slucki, Andrea, Spiller, Kellie, Springer, Nina, Sprouse, Heidi, Sun, Albert, Taylor, Judith, Watine, Robert, Watkinson, Jean, Weaver, Nancy, Wenocur, Howard, Yeoman, Gary, Ackermann, Jeremy, Averill, Nathan, Ballard, Thomas, Byars, William, Carter, Caroline, Castay, Cathleen, Cheek, Shonda, Collins, Jessica, Collins-Jamison, Traci, Cooksey, Erin, Crockford, Nicole, Cutshall, Christopher, Dar, Moahad, Drake, Almond, Dugat, Kameron, Durham, John, Durham, Nancy, Eagerton, Donald, Edmonds, Nataish, Farmer III, Joseph, Fogarty, Charles, Gatlin, June, Geisberg, Harry, Grossman, Margaret, Harrell, Wendy, Harrison, John, Harrison, Kristina, Heincelman, Sarah, Holladay, Lauren, Huberty, Chad, Isakov, Ingrid, Jordan, Norma, Kunkel, Michael, Laserna, Susan, Lawrence, Amanda, Lawrence, Andrew, Livingston, Yolanda, Lloyd, Eric, Lopez, Lina, Manuel, Joyce, Mayfield, Ronald, McDonald, Margaret, Morgan, Caroleann, Munn, Joanie, Murphy, Lauren, Nicol, Brent, Nicol, Philip, Norris, Rebecca, Phillips, Bunny, Reeves, Angela, Roach, Jacqueline, Ross, Irene, Santi, Jeffrey, Saunders, Jacqueline, Shugart, Henry, Singleton, Monnieque, Slee, Erin, Smalley, Kathleen, Smith, Kristy, Sofley, Carl, Solheim, Vesna, Spell, Samantha, Tanenberg, Robert, Whitley, Chester, Widel, Michele, Wilhoit, Gordon, Wood, Ruth, Wright, Jaime, Wulf, Alissa, Zapkowski, Julie, Adams, Kristi, Adams, Roberta, Ananthula, Parvati, Bass, Caitlin, Bates, Chad, Baum, Howard, Bays, Anna, Beck, Teresa, Bilbrey, Brett, Brown, Ashley, Carlton, Anna, Carter, Jenny, Cheri, Laura, Childress, Richard, Cloud, Mark, Cohen, A. Jay, Coulter, Alice, Dotson, Kimberly, Green, Christopher, Helton, Ashley, Houstrup, Jody, Huffman, David, Hurst, Fred, Hurst, James, Jantzi, Curtis, Jerkins, Randy, Jerkins, Terri, Jones, Mandy, Kelley, Shane, Kroulek, Judy, Lawhun, Dennis, Lee, Marcus, Louthan, James, Manning, Rickey, May, Michael, Means, Katherine, Monroe, Jeanabe, Morawski, Emily, Morin, David, Morris, Barbara, Murray, John, Nichols, Robert, Olivi, Stacie, Pennington, Kristina, Poe, Jenny, Pour, Omid Rad, Reeves, Michael, Reeves, Pamela, Root, Connie, Rose, Karen, Rutledge, Lily, Ryan, Eugene, Schwartz, Patricia, Shafer, Jennifer, Singh, Chitra, Smith, Ashley, Snow, Rodney, Stamps, Henry, Staton, Peggy, Stevens, Jeffrey, Stovall, Cathy, Sturgeon, Rodney, Tapp, John, Tapp, Stacy, Warner, Carla, Weiss, Melissa, White, Judith, Wierum, Craig, Williams, Konya, Wright, Tiffanie, Abreu, Marconi, Agarwal, Vandana, Ahmad, Aftab, Ahmad, Asma, Ahmed, Faiz, Ahn, Lily, Alaoui, Rachid, Alarcon, Stephanie, Allison, Dale, Annamalai, Rajasekaran, Arain, Khadija, Arellano, Angelica, Arispe, Barbara, Aronoff, Stephen, Arroyo, Jesus, Bachand, Trista, Bailey, Becky, Bajaj, Chris, Banarer, Salomon, Barnella, Christine, Bartz, Mary, Bates, Jason, Becerra, Karen, Benavides, Melissa, Bhuchar, Subodh, Blevins, Thomas, Bonazzi, Amanda, Brinson, Cynthia, Brown, Timiki, Buckley, Brandee, Bunker, Christy, Burbano, Jose, Busch, Vickey, Bustamante, Rosibel, Calais, Natalee, Camacho, Allison, Camp, Shana, Canada, Nancy, Canchola, Daniel, Cano, Monica, Cardenas, Veronica, Carl, Leighton, Casaubon, Luis, Castaneda, Jessica, Castro, Cindy, Ceniceros, Diego, Chaicha-Brom, Tira, Chaudhuri, Sudipta, Chavez-Velazquez, Alberto, Chen, Jocelyn, Cheyne, Theresa, Chilka, Sapna, Chionh, Kristen, Chunawala, Imran, Cope, Pamela, Cotton, Sonja, Daudjee, Munib, Davidson, Tichina, De Loa, Geraldine, Deniega, Ann, Dillow, Naco, Dominguez, Michael, Dorfman, Steven, Doshi, Ankur, Dunnam, Theresa, Dutta, Papiya, Eiler-Prater, Megann, Eizensmits, Christina, Espinosa, Valerie, Evans, Charles, Frisinger, Cathy, Ganta, Shylesh, Galtney, Kirsten, Gammon, John, Garcia, Analisa Marie, Garcia, Ronald, Glaspie, Tina, Golici, Laura, Gonzalez, Julian, Grant, David, Green, Carrie, Groce, Lindsay, Guevara, Stephanie, Gutierrez, Mary, Hance, Cortney, Harden, Tiffany, Harrison, Lindsay, Herrera, Carlos, Hettler, Evelyn, Holcomb, Michelle, Hoste, Laura, Hudson, Tina, Huerta, Leticia, Jain, Mahendra, Jayaram, Preeth, Johnson, Monique, Johnson, Olivia, Jones, Laurie, Joseph, John, Juarez, Misty, Karimjee, Najmuddin, Kephart, Ashley, Khan, Armgan, Khan, Jalil, Killian, Michael, Kniffen, Wendy, Koops, Maureen, Kwan, Louise, La, John, Laabs, Jessica, Ledesma, Gilbert, Lee, Monica, Leuck, Kathryn, Livingston, Carrie, Llanas, Teresa, Longoria, Andy, Lorta, Jesse, Lothringer, Larry, MacAdams, Maria, MacAdams, Michael, MacGillivray, Brian, Mageno, Melissa, Malek, Megan, Manley, Meghan, Marler, Karen, Martinez, Cristina, Massie, Jodi, Mateos, Glenda, Mathew, Reena, Maya, Claudia, Mazour, Meg, Mbogua, Caroline, McClendon, Robert, McMullen, Deirdre, Meisner, Carl, Menchaca, Ethelina, Meyers, Linda, Miklius, Audrey, Milam, Alissa, Milam, Ronnie, Miller, Tracey, Mize, Lisa, Moczygemba, Roger, Nafegar, Alexandria, Naidu, Jayaram, Nair, Archana, Nguyen, Alison, Nielsen, Douglas, Nisnisan, Josier, Nisnisan, Maria, Oden, Wendy, Orsak, Jessica, Ozer, Kerem, Papacostea, Olivia, Panchal, Ravi, Parikh, Manish, Parthiban, Beneta, Perrin, Brittney, Perkins, Harvonya, Poduri, Madhuri, Pop, Laurentiu, Portales, Nancy, Porter-Tucci, Linda, Postell, Sharon, Pucillo, Ronald, Reddy, Madhavi, Reddy, Rajneesh, Almodovar, Ramon Gilberto Reyes, Richard, Timiki, Richardson, Michele, Riesch, Louie, Rivera-Flores, Samuel, Rizvi, Abid, Rizvi, Samana, Rodas, Kristen, Rodgers, Mark, Roe, Erin, Rogers, Rebecca, Romero, Reina, Rooker-Morris, Leslie, Rosenstock, Julio, Sachson, Richard, Salcedo, Alfredo, Schill, Joseph, Schuh, Kristy, Schuster, Randall, Scribner, Anita, Shah, Arunkumar, Shaw, Stephanie, Shirley, Jefferey, Shook, Mindy, Siddiqui, Muhammad, Sims, Jamie, Singh, Kamalpreet, Skero, Jennifer, Smejdir, Debra, Stacey, Amy, Strzinek, Robert, Tan, Anjanette, Tayabali, Khadija, Tercero, Almundena, Terry, Jessica, Tinney, Irene, Toe, Florence, Toler, Sara, Tripathy, Devjit, Tumyan, Anna, Ulrich, Michelle, Underwood, Krissandra, Valdez, Christina, Valdivieso, April, Vanderheiden, Anna, Vandre, Morgan, Vardeman, Megan, Vargas, Richard, Vilchis, Monica, Warne, Desiree, Wallace, Jeannine, Weindorff, Kathleen, Welch, Heather, Wellmon, Brandy, Werntz, Gary, White, Leta, Williams, Tearani, Wilson, Maria, Wilson, Robyn, Wilson, Ronald, Wood, John, Wright, David, Yeatts, Rhonda, Zahir, Rezwana, Crockett, Becky, Fawson, Ashlee, Graham, Timothy, Mitchell, Zachary, Quinn, Sally, Reddy, Deepika, Rhudy, Jackson, Rosen, Priscilla, Shakespear, Kaylynn, Simmons, Debra, Turner, Ashley, Vanderhoof, Erin, Wahl, Matthew, Zubair, Imran, Algus, Michael, Gilbert, Matthew, Gorson, David, Marney, Annis, Rodriguez, Juan Pablo Perdomo, Roth, Marilynn, Scofield, Sheilah, Thottan, Anna, Bittorf, Margaret, Botros, Emad, Carpenter, Jeanette, Dashiell, Carie, Dimascio-Johnson, Nancy, Fredrickson, Sonja, Gruenther, M., Hall, Lisa, Hartman, Aaron, Hiner, Janette, Kelley, Donna, Kimmel, Melissa, Larrick, Laura, Lawson, Marie, Levy, James, Lewis, Teneshia, Lovell, Charles, Newby, James, Nichols, Michelle, O'Donnell, Philip, Orengo, Sheyla, Pecsok, Thomas, Reiss, Lind, Tarkington, Phillip, Yeatts, Donald, Zieve, Franklin, Ahmed, Imtiaz, Ali, Sajid, Anwar, Sami, Cathcart, Harold, Dawson, Lucia, Floresca, Rolando, Galvan, Ashley, Gardner, Timothy, Halsey, Kami, Hashmi, Farrukh, Hegel, Jackie, Landon, Megan, Moulton, Katlynn, Nand, Cheta, Sakic, Amra, Sevey, Brandie, Wilson, Bruce, Ahl, Scott, Blank, Robert, Coly, Gerard, Hoenig, Jennifer, Jain, Rajeev, Joseph, Elizabeth, Kasprzak, Debra, Kisiel, Lalaine, Maaske, Maurene, Manadhar, Smriti, Patel, Shailendra, Sickler, Whitney, Grp, D.E.V.O.T.E. Study, Acibadem University Dspace, Marso S.P., Mcguire D.K., Zinman B., Poulter N.R., Emerson S.S., Pieber T.R., Pratley R.E., Haahr P.-M., Lange M., Brown-Frandsen K., Moses A., Skibsted S., Kvist K., Buse J.B., and Buscemi S
Subjects: Insulin degludec, Blood Glucose, Male, medicine.medical_treatment, DEVOTE Study Group, Insulin Glargine, Type 2 diabetes, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, law.invention, diabetes, insulin, 0302 clinical medicine, Randomized controlled trial, law, Cardiovascular Disease, GLUCOSE CONTROL, 11 Medical and Health Sciences, RISK, COMPLICATIONS, OUTCOMES, Incidence, General Medicine, Middle Aged, Insulin, Long-Acting, VARIABILITY, Cardiovascular Diseases, diabetes mellitus, Female, Life Sciences & Biomedicine, Human, medicine.drug, medicine.medical_specialty, 030209 endocrinology & metabolism, Aged, Diabetes Mellitus, Type 2, Double-Blind Method, Humans, Hypoglycemia, Hypoglycemic Agents, Medicine (all), Bedtime, Article, EVENTS, 03 medical and health sciences, HYPOGLYCEMIA, Medicine, General & Internal, Internal medicine, Diabetes mellitus, General & Internal Medicine, medicine, Intensive care medicine, METAANALYSIS, Science & Technology, Hypoglycemic Agent, Insulin glargine, business.industry, Insulin, medicine.disease, business, BASAL INSULIN
Abstract: BACKGROUND Degludec is an ultralong-Acting, once-daily basal insulin that is approved for use in adults, adolescents, and children with diabetes. Previous open-label studies have shown lower day-To-day variability in the glucose-lowering effect and lower rates of hypoglycemia among patients who received degludec than among those who received basal insulin glargine. However, data are lacking on the cardiovascular safety of degludec. METHODS We randomly assigned 7637 patients with type 2 diabetes to receive either insulin degludec (3818 patients) or insulin glargine U100 (3819 patients) once daily between dinner and bedtime in a double-blind, treat-To-Target, event-driven cardiovascular outcomes trial. The primary composite outcome in the time-To-event analysis was the first occurrence of an adjudicated major cardiovascular event (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) with a prespecified noninferiority margin of 1.3. Adjudicated severe hypoglycemia, as defined by the American Diabetes Association, was the prespecified, multiplicity-Adjusted secondary outcome. RESULTS Of the patients who underwent randomization, 6509 (85.2%) had established cardiovascular disease, chronic kidney disease, or both. At baseline, the mean age was 65.0 years, the mean duration of diabetes was 16.4 years, and the mean (±SD) glycated hemoglobin level was 8.4±1.7%; 83.9% of the patients were receiving insulin. The primary outcome occurred in 325 patients (8.5%) in the degludec group and in 356 (9.3%) in the glargine group (hazard ratio, 0.91; 95% confidence interval, 0.78 to 1.06; P
Published: 2017

36. Projected long-term outcomes in patients with type 1 diabetes treated with fast-acting insulin aspart vs conventional insulin aspart in the UK setting

Author: Simon Heller, Barnaby Hunt, William J. Valentine, Sarah Buchs, Anna Sandberg, and David Russell-Jones
Subjects: Pediatrics, endocrine system diseases, Cost effectiveness, type 1 diabetes, Endocrinology, Diabetes and Metabolism, Cost-Benefit Analysis, Cohort Studies, 0302 clinical medicine, Endocrinology, Cost of Illness, Long term outcomes, 030212 general & internal medicine, health care economics and organizations, Incidence, Insulin, Short-Acting, cost‐effectiveness, Middle Aged, Models, Economic, Cardiovascular Diseases, Baseline characteristics, Cohort, Original Article, hormones, hormone substitutes, and hormone antagonists, medicine.drug, Risk, medicine.medical_specialty, 030209 endocrinology & metabolism, Drug Costs, Direct Service Costs, Insulin aspart, 03 medical and health sciences, Double-Blind Method, Internal Medicine, medicine, Humans, Hypoglycemic Agents, In patient, Intensive care medicine, Insulin Aspart, Glycemic, Glycated Hemoglobin, Type 1 diabetes, business.industry, nutritional and metabolic diseases, Original Articles, medicine.disease, Hypoglycemia, United Kingdom, Diabetes Mellitus, Type 1, Hyperglycemia, insulin therapy, Quality of Life, business, Biomarkers
Abstract: Aims Many patients with type 1 diabetes mellitus (T1DM) fail to achieve optimal glycemic control and mealtime insulins that more closely match physiological insulin secretion can help improve treatment. In the onset 1 trial, fast-acting insulin aspart (faster aspart) was shown to improve glycemic control in patients with T1DM compared with conventional insulin aspart (insulin aspart). In the UK, faster aspart and insulin aspart are associated with the same acquisition cost, and therefore the present analysis assessed the impact of faster aspart versus insulin aspart on long-term clinical outcomes and costs for patients with T1DM in the UK setting. Methods The QuintilesIMS CORE Diabetes Model was used to project clinical outcomes and costs over patient lifetimes in a cohort with baseline characteristics from the onset 1 trial. Treatment effects were taken from the 26-week main phase of the onset 1 trial, with costs and utilities based on literature review. Future costs and clinical benefits were discounted at 3.5% annually. Results Projections indicated that faster aspart was associated with improved discounted quality-adjusted life expectancy (by 0.13 quality-adjusted life years) versus insulin aspart). Improved clinical outcomes resulted from fewer diabetes-related complications and a delayed time to their onset with faster aspart. Faster aspart was found to be associated with reduced costs versus insulin aspart (cost savings of GBP 1,715), resulting from diabetes-related complications avoided and reduced treatment costs. Conclusions Faster aspart was associated with improved clinical outcomes and cost savings versus insulin aspart for patients with T1DM in the UK setting.
Published: 2017

37. Efficacy and safety of empagliflozin added to existing antidiabetes treatment in patients with type 2 diabetes and chronic kidney disease: a randomised, double-blind, placebo-controlled trial

Author: Jenny Manassie, Ambrish Mithal, Hans-Juergen Woerle, Uli C. Broedl, Henning Rattunde, Anthony H. Barnett, and Russell Jones
Subjects: Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Population, Placebo-controlled study, Type 2 diabetes, Placebo, law.invention, Endocrinology, Double-Blind Method, Glucosides, Randomized controlled trial, law, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Empagliflozin, Humans, Hypoglycemic Agents, Benzhydryl Compounds, Renal Insufficiency, Chronic, education, education.field_of_study, business.industry, Middle Aged, medicine.disease, Surgery, Treatment Outcome, Diabetes Mellitus, Type 2, Drug Therapy, Combination, Female, business, Kidney disease
Abstract: Diabetes is a leading cause of chronic kidney disease (CKD) worldwide. Optimum glycaemic control in patients with type 2 diabetes is important to minimise the risk of microvascular and macrovascular complications and to slow the progression of CKD. We assessed the efficacy and safety of empagliflozin as an add-on treatment in patients with type 2 diabetes and CKD.We did a phase 3, randomised, double-blind, parallel-group, placebo-controlled trial at 127 centres in 15 countries. Patients with HbA1c of 7% or greater to 10% or less were eligible for inclusion. Patients with stage 2 CKD (estimated glomerular filtration rate [eGFR] ≥60 to90 mL/min per 1·73 m(2); n=290) were randomly assigned (1:1:1) to receive empagliflozin 10 mg or 25 mg or placebo once daily for 52 weeks. Patients with stage 3 CKD (eGFR ≥30 to60 mL/min per 1·73 m(2); n=374) were randomly assigned (1:1) to receive empagliflozin 25 mg or placebo for 52 weeks. Randomisation was done with a computer-generated random sequence and stratified by renal impairment, HbA1c, and background antidiabetes medication. Treatment assignment was masked from patients and investigators. The primary endpoint was change from baseline in HbA1c at week 24 by ANCOVA in the full analysis set. This study is registered with ClinicalTrials.gov, number NCT01164501.In patients with stage 2 CKD, adjusted mean treatment differences versus placebo in changes from baseline in HbA1c at week 24 were -0·52% (95% CI -0·72 to -0·32) for empagliflozin 10 mg and -0·68% (-0·88 to -0·49) for empagliflozin 25 mg (both p0·0001). In patients with stage 3 CKD, adjusted mean treatment difference versus placebo in change from baseline in HbA1c at week 24 was -0·42% (-0·56 to -0·28) for empagliflozin 25 mg (p0·0001). In patients with stage 2 CKD, adverse events were reported over 52 weeks by 83 patients (87%) on placebo (15 severe [16%] and 11 serious [12%]), 86 (88%) on empagliflozin 10 mg (six severe [6%] and six serious [6%]) and 78 (80%) on empagliflozin 25 mg (eight severe [8%] and seven serious [7%]). In patients with stage 3 CKD, adverse events were reported over 52 weeks by 156 patients (83%) on placebo (15 severe [8%] and 23 serious [12%]) and 156 (83%) on empagliflozin 25 mg (18 severe [10%] and 22 serious [12%]).In patients with type 2 diabetes and stage 2 or 3 CKD, empagliflozin reduced HbA1c and was well tolerated. However, our findings might not be applicable to the general population of patients with type 2 diabetes and renal impairment.Boehringer Ingelheim, Eli Lilly.
Published: 2014
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38. SGLT2 inhibitors in Type 1 diabetes: is this the future?

Author: R. Herring and David Russell-Jones
Subjects: Clinical Trials as Topic, Type 1 diabetes, business.industry, Endocrinology, Diabetes and Metabolism, MEDLINE, 030209 endocrinology & metabolism, medicine.disease, Bioinformatics, 03 medical and health sciences, Diabetes Mellitus, Type 1, 0302 clinical medicine, Endocrinology, Text mining, Diabetes mellitus, Internal Medicine, Humans, Hypoglycemic Agents, Medicine, 030212 general & internal medicine, business, Sodium-Glucose Transporter 2 Inhibitors
Published: 2018
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39. A brighter future for melanoma

Author: R. Russell‐Jones
Subjects: Oncology, medicine.medical_specialty, business.industry, Melanoma, MEDLINE, Dermatology, medicine.disease, Text mining, Internal medicine, medicine, Humans, Lymph Nodes, business
Published: 2019
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40. Linagliptin for patients aged 70 years or older with type 2 diabetes inadequately controlled with common antidiabetes treatments: a randomised, double-blind, placebo-controlled trial

Author: Holger Huisman, Hans-Juergen Woerle, Russell Jones, Maximilian von Eynatten, Sanjay Patel, and Anthony H. Barnett
Subjects: medicine.medical_specialty, education.field_of_study, business.industry, Population, Placebo-controlled study, General Medicine, Type 2 diabetes, Linagliptin, medicine.disease, Placebo, Surgery, Metformin, law.invention, Randomized controlled trial, law, Internal medicine, medicine, Clinical endpoint, business, education, medicine.drug
Abstract: Summary Background A substantial proportion of patients with type 2 diabetes are elderly (≥65 years) but this group has been largely excluded from clinical studies of glucose-lowering drugs. We aimed to assess the effectiveness of linagliptin, a dipeptidyl peptidase-4 inhibitor, in elderly patients with type 2 diabetes. Methods In this randomised, double-blind, parallel-group, multinational phase 3 study, patients aged 70 years or older with type 2 diabetes, glycated haemoglobin A 1c (HbA 1c ) of 7·0% or more, receiving metformin, sulfonylureas, or basal insulin, or combinations of these drugs, were randomised (by computer-generated randomisation sequence, concealed with a voice–response system, stratified by HbA 1c level [ vs ≥8·5%] and insulin use [yes vs no], block size four) in a 2:1 ratio to once-daily oral treatment with linagliptin 5 mg or matching placebo for 24 weeks. Investigators and participants were masked to assignment throughout the study. The primary endpoint was change in HbA 1c from baseline to week 24. This trial is registered with ClinicalTrials.gov, number NCT01084005. Findings 241 community-living outpatients were randomised (162 linagliptin, 79 placebo). Mean age was 74·9 years (SD 4·3). Mean HbA 1c was 7·8% (SD 0·8). At week 24, placebo-adjusted mean change in HbA 1c with linagliptin was −0·64% (95% CI −0·81 to −0·48, p Interpretation In elderly patients with type 2 diabetes linagliptin was efficacious in lowering glucose with a safety profile similar to placebo. These findings could inform treatment decisions for achieving individualised glycaemic goals with minimal risk in this important population of patients. Funding Boehringer Ingelheim.
Published: 2013
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41. Initial combination of linagliptin and metformin in patients with type 2 diabetes: efficacy and safety in a randomised, double-blind 1-year extension study

Author: Thomas Meinicke, Hans-Juergen Woerle, M. von Eynatten, S. Weber, Russell Jones, and Thomas Haak
Subjects: Male, medicine.medical_specialty, endocrine system diseases, Treatment outcome, Linagliptin, Type 2 diabetes, Double blind, Endocrinology, Double-Blind Method, Internal medicine, medicine, Humans, Hypoglycemic Agents, In patient, Glycated Hemoglobin, Dose-Response Relationship, Drug, business.industry, Extension study, nutritional and metabolic diseases, General Medicine, Middle Aged, medicine.disease, Metformin, Treatment Outcome, Diabetes Mellitus, Type 2, Purines, Quinazolines, Drug Therapy, Combination, Female, business, medicine.drug
Abstract: Objective To determine the efficacy and safety of linagliptin in initial combination with metformin in patients with type 2 diabetes. Methods This 1-year randomised, double-blind study was an extension of a 6-month randomised controlled trial, in which adults with type 2 diabetes received one of six treatment regimens (linagliptin 2.5 mg plus metformin 500 mg bid, linagliptin 2.5 mg plus metformin mg 1000 bid, metformin 1000 mg bid, metformin 500 mg bid, linagliptin 5 mg qd or placebo). In the extension, patients in the first three treatment groups continued their regimen (non-switched group, n = 333) while the metformin 500 mg bid, linagliptin 5 mg qd and placebo groups were re-randomised to one of the three continuing regimens (switched group, n = 233). Results All three non-switched groups maintained reductions in glycosylated haemoglobin (HbA1c; mean ± standard deviation reductions across the 1.5-year period: linagliptin 2.5 plus metformin 1000 bid, –1.63 ± 1.05%; linagliptin 2.5 plus metformin 500 bid, –1.32 ± 1.06%; metformin 1000 bid, –1.25 ± 0.91%) while the switched groups showed additional HbA1c reductions. During the extension, there were no clinically meaningful changes in body weight in any group. Adverse event rates were similar between groups, with most events being mild or moderate, and the incidence of investigator-defined hypoglycaemia was low, with no severe events. Discussion Initial combination of linagliptin and metformin was well tolerated over the 1-year extension period, with low risk of hypoglycaemia, and improved glycaemic control vs. metformin alone. Conclusion The initial combination of linagliptin and metformin appears to provide a useful treatment option in patients whose blood glucose levels are increased to an extent that metformin monotherapy may not achieve treatment targets.
Published: 2013

42. Efficacy and safety of insulin degludec three times a week versus insulin glargine once a day in insulin-naive patients with type 2 diabetes: results of two phase 3, 26 week, randomised, open-label, treat-to-target, non-inferiority trials

Author: Bernard Zinman, Robert E. Ratner, J. Hans DeVries, Alan C. Moses, Lawrence A. Leiter, David Russell-Jones, Thue Johansen, and Bruce W. Bode
Subjects: Adult, Blood Glucose, Male, Insulin degludec, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Insulin Glargine, Type 2 diabetes, Rate ratio, Drug Administration Schedule, law.invention, Endocrinology, Randomized controlled trial, law, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Humans, Aged, business.industry, Insulin glargine, Insulin, Middle Aged, medicine.disease, Hypoglycemia, Metformin, Insulin, Long-Acting, Treatment Outcome, Diabetes Mellitus, Type 2, Female, business, medicine.drug
Abstract: Results of an exploratory phase 2 study showed that insulin degludec, a basal insulin with an action profile of longer than 42 h, provided similar glycaemic control when injected three times a week (IDeg 3TW) to once-daily insulin glargine (IGlar OD). To provide further evidence, we did two phase 3 trials to compare the efficacy and safety of IDeg 3TW with IGlar OD in insulin-naive patients with type 2 diabetes.In two 26 week, randomised, open-label, parallel group, non-inferiority trials IDeg was injected Monday, Wednesday, and Friday before breakfast (IDeg 3TW(AM)) in the AM trial (94 sites in seven countries) or with the evening meal (IDeg 3TW(PM)) in the PM trial (89 sites in seven countries), and compared with IGlar OD. Adults with type 2 diabetes (HbA(1c) 7.0-10.0%; body-mass index ≤45 kg/m(2)) were randomly allocated (1:1) without stratification by a central interactive response system to IDeg 3TW or IGlar OD. Both groups continued taking metformin with or without dipeptidyl peptidase-4 inhibitors. Insulin was titrated to achieve a prebreakfast self-monitored blood glucose (SMBG) concentration of between 3.9 and less than 5.0 mmol/L. The primary outcome was non-inferiority of IDeg 3TW compared with IGlar OD, as assessed by change in HbA(1c) from baseline to 26 weeks (non-inferiority limit of 0.4%) by ANOVA in an intent-to-treat analysis (full analysis set). These trials are registered with ClinicalTrials.gov, numbers NCT01068678 and NCT01076647.We recruited 460 patients for the AM trial (IDeg 3TW(AM), n=230; IGlar OD, n=230) and 467 patients for the PM trial (IDeg 3TW(PM), n=233; IGlar OD, n=234). After 26 weeks, mean HbA decreased by 0.9% (IDeg 3TW(AM)) and 1.3% (IGlar OD) in the AM trial, and by 1.1% (IDeg 3TW(PM)) and 1.4% (IGlar OD) in the PM trial. Non-inferiority was not confirmed in either trial (estimated treatment difference [IDeg 3TW(AM)-IGlar OD] 0.34%, 95% CI 0.18-0.51; [IDeg 3TW(PM)-IGlar OD] 0.26%, 0.11-0.41). Across the two trials, rates of confirmed hypoglycaemia (SMBG3.1 mmol/L or severe [needing assistance]) ranged from 1.0 to 1.6 episodes per patient-year and were similar for IDeg 3TW(AM) and IGlar OD (estimated rate ratio [ERR] 1.04, 95% CI 0.69-1.55), but higher for IDeg 3TW(PM) than for IGlar OD (ERR 1.58, 1.03-2.43). The rate of nocturnal confirmed hypoglycaemia was higher for IDeg 3TW(AM) than for IGlar OD (ERR 2.12, 1.08-4.16); we noted no significant difference between IDeg 3TW(PM) and IGlar OD (ERR 0.60, 0.21-1.69).The inferior glycaemic control and increased risk of hypoglycaemia with IDeg 3TW compared with IGlar OD do not support a three-times-weekly dosing regimen.Novo Nordisk.
Published: 2013
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43. Insulin degludec improves glycaemic control with lower nocturnal hypoglycaemia risk than insulin glargine in basal–bolus treatment with mealtime insulin aspart in Type 1 diabetes (BEGIN ® Basal–Bolus Type 1): 2‐year results of a randomized clinical trial

Author: Simon Heller, L. Merker, Satish K. Garg, John B. Buse, David Russell-Jones, Michel Marre, Miles Fisher, Charlotte T. Hansen, Eric Renard, Bruce W. Bode, and A. Rana
Subjects: Insulin degludec, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, 030209 endocrinology & metabolism, Hypoglycemia, Insulin aspart, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, 030212 general & internal medicine, 2. Zero hunger, Type 1 diabetes, business.industry, Insulin glargine, Insulin, medicine.disease, 3. Good health, Basal (medicine), business, medicine.drug
Abstract: Aims The goal of this study was to compare the long-term safety and efficacy of the basal insulin analogue, insulin degludec with insulin glargine (both with insulin aspart) in Type 1 diabetes, over a 2-year time period. Methods This open-label trial comprised a 1-year main trial and a 1-year extension. Patients were randomized to once-daily insulin degludec or insulin glargine and titrated to pre-breakfast plasma glucose values of 3.9–4.9 mmol/l. Results The rate of nocturnal confirmed hypoglycaemia was 25% lower with insulin degludec than with insulin glargine (P = 0.02). Rates of confirmed hypoglycaemia, severe hypoglycaemia and adverse events, and reductions in glycated haemoglobin and fasting plasma glucose were similar between groups. Despite achieving similar glycaemic control, insulin degludec-treated patients used 12% less basal and 9% less total daily insulin than did insulin glargine-treated patients (P
Published: 2013
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44. Aggressive epidermotropic cutaneous CD8+ lymphoma: A cutaneous lymphoma with distinct clinical and pathological features. Report of an EORTC Cutaneous Lymphoma Task Force Workshop

Author: Alistair Robson, Christine Castillo, Maria Geerts, Sean Whittaker, Chalid Assaf, Nicola Pimpinelli, Rein Willemze, Tony Petrella, Joclim Roewert, Mattias Steinhoff, Marco Santucci, Frederic Franck, Emilio Berti, Robin Russell-Jones, Lorenzo Cerroni, Janine Wechsler, Robert Knobler, Pierre Dechelotte, Nicola Chimenti, Cesare Massone, Chris J.L.M. Meijer, John R. Goodlad, Werner Kempf, Sylke Gellrich, Eduardo Calonje, Wolfram Sterry, Martine Bagot, Pablo Ortiz, Günter Burg, Robson, A, Assaf, C, Bagot, M, Burg, G, Calonje, J, Castillo, C, Cerroni, L, Chimenti, N, Dechelotte, P, Franck, F, Geerts, M, Gellrich, S, Goodlad, J, Kempf, W, Knobler, R, Massone, C, Meijer, C, Ortiz, P, Petrella, T, Pimpelli, N, Roewert, J, Russell-Jones, R, Santucci, M, Steinhoff, M, Sterry, W, Wechsler, J, Whittaker, S, Willemze, R, Berti, E, Pathology, and CCA - Innovative therapy
Subjects: Adult, Male, mycosis fungoide, Pathology, medicine.medical_specialty, Histology, Lymphoma, diagnosis, Prognosi, CD8-Positive T-Lymphocytes, Cutaneous lymphoma, Pathology and Forensic Medicine, Immunophenotyping, hemic and lymphatic diseases, Medicine, Neoplasm, Humans, Lymphomatoid papulosis, Pathological, Aged, Aged, 80 and over, Mycosis fungoides, business.industry, mycosis fungoides, CD8 antigen, lymphoma, diagnosis, mycosis fungoides, prognosis, General Medicine, CD8 antigen, Middle Aged, medicine.disease, Lymphoma, T-Cell, Cutaneous, diagnosi, Pagetoid, Female, prognosis, business, CD8
Abstract: AIMS: Aggressive epidermotropic cutaneous CD8+ lymphoma is currently afforded provisional status in the WHO classification of lymphomas. An EORTC Workshop was convened to describe in detail the features of this putative neoplasm and evaluate its nosological status with respect to other cutaneous CD8+ lymphomas.METHODS & RESULTS: Sixty-one CD8+ cases were analysed at the workshop; clinical details, often with photographs, histological sections, immunohistochemical results, treatment and patient outcome were discussed & recorded. Eighteen cases had distinct features and conformed to the diagnosis of aggressive epidermotropic cutaneous CD8+ lymphoma. The patients typically present with widespread plaques and tumours, often ulcerated and haemorrhagic, and have striking pagetoid epidermotropism histologically. A CD8+ CD45RA+ CD45RO- CD2- CD5- CD56- phenotype, with 1 or more cytotoxic markers was found in 7/18 with a very similar phenotype in the remainder.. The tumours seldom involve lymph nodes but mucosae and central nervous system involvement are not uncommon. The prognosis is poor, with a median survival of 12 months. Examples of CD8+ mycosis fungoides, lymphomatoid papulosis and Woringer-Kolopp presented the typical features well documented in the CD4+ forms of those diseases.CONCLUSIONS: Aggressive Epidermotropic Cutaneous CD8+ Lymphoma is a distinct lymphoma that warrants inclusion as a distinct entity in future revisions of lymphoma classifications. This article is protected by copyright. All rights reserved.
Published: 2015
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45. Efficacy and Safety of Insulin Degludec in a Flexible Dosing Regimen vs Insulin Glargine in Patients With Type 1 Diabetes (BEGIN: Flex T1): A 26-Week Randomized, Treat-to-Target Trial With a 26-Week Extension

Author: Stephen C. Bain, John G. Cooper, Priscilla Hollander, Edward Franek, S. C Tamer, David Russell-Jones, B. Miranda-Palma, Chantal Mathieu, and Jens Larsen
Subjects: Insulin degludec, Adult, Blood Glucose, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Clinical Biochemistry, Insulin Glargine, Self Administration, Biochemistry, Drug Administration Schedule, law.invention, Endocrinology, Randomized controlled trial, law, Internal medicine, Diabetes mellitus, medicine, Humans, Hypoglycemic Agents, Dosing, Glycated Hemoglobin, Type 1 diabetes, Dose-Response Relationship, Drug, Insulin glargine, business.industry, Endocrine Care, Insulin, Biochemistry (medical), Middle Aged, medicine.disease, Insulin, Long-Acting, Regimen, Diabetes Mellitus, Type 1, Treatment Outcome, Female, business, medicine.drug
Abstract: Objective: This study investigated the efficacy and safety of insulin degludec (IDeg) once daily (OD), varying injection timing day to day in subjects with type 1 diabetes. Research Design and Methods: This 26-week, open-label, treat-to-target, noninferiority trial compared IDeg forced flexible (Forced-Flex) OD (given in a fixed schedule with a minimum 8 and maximum 40 hours between doses) with IDeg or insulin glargine (IGlar) given at the same time daily OD. In the 26-week extension, all IDeg subjects were transferred to a free-flexible (Free-Flex) regimen, which allowed any-time-of-day dosing, and compared with subjects continued on IGlar. Results: After 26 treatment weeks, mean glycosylated hemoglobin was reduced with IDeg Forced- Flex (−0.40%), IDeg (−0.41%), and IGlar (−0.58%). IDeg Forced-Flex noninferiority was achieved. Fasting plasma glucose reductions were similar with IDeg Forced-Flex and IGlar but greater with IDeg (−2.54 mmol/L) than IDeg Forced-Flex (−1.28 mmol/L) (P = .021). At week 52, IDeg Free-Flex subjects had similar glycosylated hemoglobin but greater fasting plasma glucose reductions than IGlar subjects (−1.07 mmol/L) (P = .005). Confirmed hypoglycemia rates (plasma glucose
Published: 2013

46. Shared decision making in patients with low risk chest pain: prospective randomized pragmatic trial

Author: Erik P. Hess, Russell Jones, Jeffrey A. Kline, Ana Castaneda-Guarderas, Michel Demers, Zachary F. Meisel, Jason T. Schaffer, Jonathan Inselman, Kelly P. Owen, Carlos A. A. Torres, Victor M. Montori, Judd E. Hollander, Annie LeBlanc, Deborah B. Diercks, Nilay Shah, and Jeph Herrin
Subjects: Adult, Male, Acute coronary syndrome, medicine.medical_specialty, Chest Pain, Health Knowledge, Attitudes, Practice, Referral, Attitude of Health Personnel, Decision Making, Psychological intervention, Myocardial Infarction, Aftercare, Observation, Chest pain, Trust, Choice Behavior, Risk Assessment, law.invention, Decision Support Techniques, Conflict, Psychological, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Complaint, Ambulatory Care, Medicine, Humans, In patient, 030212 general & internal medicine, Acute Coronary Syndrome, business.industry, 030208 emergency & critical care medicine, General Medicine, Middle Aged, Patient Acceptance of Health Care, medicine.disease, Confidence interval, Hospitalization, Patient Satisfaction, Emergency medicine, Physical therapy, Female, medicine.symptom, Patient Participation, business, Emergency Service, Hospital, Hospital Units
Abstract: Objective To compare the effectiveness of shared decision making with usual care in choice of admission for observation and further cardiac testing or for referral for outpatient evaluation in patients with possible acute coronary syndrome. Design Multicenter pragmatic parallel randomized controlled trial. Setting Six emergency departments in the United States. Participants 898 adults (aged >17 years) with a primary complaint of chest pain who were being considered for admission to an observation unit for cardiac testing (451 were allocated to the decision aid and 447 to usual care), and 361 emergency clinicians (emergency physicians, nurse practitioners, and physician assistants) caring for patients with chest pain. Interventions Patients were randomly assigned (1:1) by an electronic, web based system to shared decision making facilitated by a decision aid or to usual care. The primary outcome, selected by patient and caregiver advisers, was patient knowledge of their risk for acute coronary syndrome and options for care; secondary outcomes were involvement in the decision to be admitted, proportion of patients admitted for cardiac testing, and the 30 day rate of major adverse cardiac events. Results Compared with the usual care arm, patients in the decision aid arm had greater knowledge of their risk for acute coronary syndrome and options for care (questions correct: decision aid, 4.2 v usual care, 3.6; mean difference 0.66, 95% confidence interval 0.46 to 0.86), were more involved in the decision (observing patient involvement scores: decision aid, 18.3 v usual care, 7.9; 10.3, 9.1 to 11.5), and less frequently decided with their clinician to be admitted for cardiac testing (decision aid, 37% v usual care, 52%; absolute difference 15%; P Conclusions Use of a decision aid in patients at low risk for acute coronary syndrome increased patient knowledge about their risk, increased engagement, and safely decreased the rate of admission to an observation unit for cardiac testing. Trial registration ClinicalTrials.gov NCT01969240.
Published: 2016

47. The Discovery of a Potent, Selective, and Peripherally Restricted Pan-Trk Inhibitor (PF-06273340) for the Treatment of Pain

Author: Russell Jones, Inaki Morao, Colin Robinson, Stupple Paul Anthony, Susan Cole, David G. Brown, Karl Richard Gibson, Angus N. R. Nedderman, Gareth Waldron, Sarah Elizabeth Skerratt, James Bilsland, Andrews Mark David, Kiyoyuki Omoto, Peter J. Bungay, Kimberly Skinner, Sharan K. Bagal, and Thomas Ryckmans
Subjects: 0301 basic medicine, Models, Molecular, Druggability, Pain, Quantitative Structure-Activity Relationship, Neurotrophin-3, Pharmacology, 01 natural sciences, Receptor tyrosine kinase, 03 medical and health sciences, Drug Discovery, medicine, Humans, Pyrroles, Protein Kinase Inhibitors, Brain-derived neurotrophic factor, biology, Dose-Response Relationship, Drug, Molecular Structure, 010405 organic chemistry, Chronic pain, medicine.disease, 0104 chemical sciences, 030104 developmental biology, Nerve growth factor, Pyrimidines, nervous system, Trk receptor, QD431, biology.protein, Molecular Medicine, Protein Kinases, Neurotrophin
Abstract: The neurotrophin family of growth factors, comprised of nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), and neurotrophin 4 (NT4), is implicated in the physiology of chronic pain. Given the clinical efficacy of anti-NGF monoclonal antibody (mAb) therapies, there is significant interest in the development of small molecule modulators of neurotrophin activity. Neurotrophins signal through the tropomyosin related kinase (Trk) family of tyrosine kinase receptors, hence Trk kinase inhibition represents a potentially “druggable” point of intervention. To deliver the safety profile required for chronic, nonlife threatening pain indications, highly kinase-selective Trk inhibitors with minimal brain availability are sought. Herein we describe how the use of SBDD, 2D QSAR models, and matched molecular pair data in compound design enabled the delivery of the highly potent, kinase-selective, and peripherally restricted clinical candidate PF-06273340.
Published: 2016

48. Neuroblastoma in a 6-year-old boy

Author: EC Russell-Jones, C Wynne, and K Iliadis
Subjects: medicine.medical_specialty, Abdominal pain, medicine.diagnostic_test, Abdominal ultrasound, business.industry, General Medicine, medicine.disease, Pancytopenia, Abdominal mass, Surgery, chemistry.chemical_compound, chemistry, Lactate dehydrogenase, Neuroblastoma, medicine, medicine.symptom, business, Liver function tests, Normal range
Abstract: A previously healthy 6-year-old boy presented to the children's Accident and Emergency Department with right-sided abdominal pain. On examination, there was a palpable, non-tender abdominal mass, with no lymphadenopathy. Initial investigations revealed pancytopenia (haemoglobin was 5.7 g/dL, white cell count 3.7 × 109/L, platelets 134 × 109/L) and lactate dehydrogenase 1690 (normal range 240–480) with normal urea and electrolytes/liver function tests. Abdominal ultrasound showed a …
Published: 2016

49. Recent advances in incretin-based therapies

Author: David Russell-Jones and Stephen C. L. Gough
Subjects: endocrine system, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Incretin, Type 2 diabetes, Saxagliptin, Linagliptin, Incretins, Glucagon-Like Peptide-1 Receptor, chemistry.chemical_compound, Endocrinology, Glucagon-Like Peptide 1, Internal medicine, Receptors, Glucagon, medicine, Animals, Humans, Hypoglycemic Agents, Vildagliptin, Dipeptidyl-Peptidase IV Inhibitors, Venoms, business.industry, Liraglutide, digestive, oral, and skin physiology, medicine.disease, Diabetes Mellitus, Type 2, chemistry, Sitagliptin, Exenatide, Peptides, business, hormones, hormone substitutes, and hormone antagonists, medicine.drug
Abstract: The global burden of type 2 diabetes is growing. Traditional therapies are suboptimal and there is a clear unmet need for treatments that offer effective glucose control while addressing the comorbid factors associated with diabetes, such as obesity and risk of cardiovascular disease, without the fear of hypoglycaemia. Glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors offer a novel way of reducing hyperglycaemia by targeting the incretin system. This review provides an overview of the development of incretin-based therapies and explains their differing modes of action compared with traditional interventions. A comparison of the clinical profiles of current glucagon-like peptide-1 receptor agonists [liraglutide and exenatide (twice-daily and once-weekly)] and dipeptidyl peptidase-4 inhibitors (sitagliptin, saxagliptin, vildagliptin and linagliptin) is performed alongside a discussion of the placement of incretin-based therapies in treatment guidelines. Further improvements in this class are expected, and we will examine some of the novel glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors currently under development.
Published: 2016

50. A shift in the phenotype of melan-A-specific CTL identifies melanoma patients with an active tumor-specific immune response

Author: Martin Lipp, A L Harris, P R Dunbar, A Evans, Federica Sallusto, D Chao, Caroline L. Smith, Robin Russell-Jones, Mariolina Salio, Dale A. Shepherd, Antonio Lanzavecchia, Fareed Mirza, and Vincenzo Cerundolo
Subjects: Adult, Male, Immunology, Epitopes, T-Lymphocyte, chemical and pharmacologic phenomena, CD8-Positive T-Lymphocytes, Biology, Epitope, Immunophenotyping, Lymphocytes, Tumor-Infiltrating, MART-1 Antigen, Immune system, Antigens, Neoplasm, Cell Movement, Tumor Cells, Cultured, medicine, Humans, Immunology and Allergy, Melanoma, Aged, Cell Line, Transformed, Aged, 80 and over, Middle Aged, medicine.disease, Lymphocyte Subsets, In vitro, Neoplasm Proteins, CTL, Female, Lymph Nodes, Ex vivo, T-Lymphocytes, Cytotoxic
Abstract: In a significant proportion of melanoma patients, CTL specific for the melan-A26/7–35 epitope can be detected in peripheral blood using HLA-A2/peptide tetramers. However, the functional capacity of these CTL has been controversial, since although they prove to be effective killers after in vitro expansion, in some patients they have blunted activation responses ex vivo. We used phenotypic markers to characterize melan-A tetramer+ cells in both normal individuals and melanoma patients, and correlated these markers with ex vivo assays of CTL function. Melanoma patients with detectable melan-A tetramer+ cells in peripheral blood fell into two groups. Seven of thirteen patients had a CCR7+ CD45R0− CD45RA+ phenotype, the same as that found in some healthy controls, and this phenotype was associated with a lack of response to melan-A peptide ex vivo. In the remaining six patients, melan-A tetramer+ cells were shifted toward a CCR7− CD45R0+ CD45RA− phenotype, and responses to melan-A peptide could be readily demonstrated ex vivo. When lymph nodes infiltrated by melan-A-expressing melanoma cells were examined, a similar dichotomy emerged. These findings demonstrate that activation of melan-A-specific CTL occurs in only some patients with malignant melanoma, and that only patients with such active immune responses are capable of responding to Ag in ex vivo assays.
Published: 2016

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