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Evidence on therapeutic interventions and factors driving treatment intensification (TI) in people with incident depression in UK are scarce.To explore antidepressant prescribing patterns and factors influencing TI.and setting: Retrospective cohort study of adults with incident depression diagnosed between 2006 and 2017 using UK primary care database.Patterns of antidepressant prescriptions, and factors influencing TI were evaluated by sex.In 931,302 people with depression (90% initiating antidepressants), mean age was 39 years, 41% were male, 14% had cardiometabolic multimorbidity (CMM), and 54% were diagnosed at lt; 40 years. Being the most prescribed first-line antidepressant (62%), SSRI prescribing rate increased from 66 per 1000 person-years to 170 per 1000 person-years; 24% (2% dose escalation, 4% adding, 18% switching) of first-line antidepressant initiators intensified with 13 months median time to TI. Compared to 60-70 years, younger adults had significantly higher TI risk (range of hazards ratio, HR: 1.08-1.42). CMM and anxiety were associated with 15-24% and 39-49% significantly higher TI risks respectively. First-line antidepressant and deprivation status influenced TI differently by gender.Men and women with depression in UK have different antidepressant prescription patterns in real-world. Age at diagnosis, deprivation status and cardiometabolic multimorbidity are the major sociodemographic and non-psychiatric risk factors for therapeutic changes.

OBJECTIVE To explore risks and associated mediation effects of developing chronic kidney disease (CKD) and heart failure (HF) in young- and usual-onset type 2 diabetes (T2D) between White Americans (WAs) and African Americans (AAs). RESEARCH DESIGN AND METHODS From U.S. medical records, 1,491,672 WAs and 31,133 AAs were identified and stratified by T2D age of onset (18–39, 40–49, 50–59, 60–70 years). Risks, mediation effects, and time to CKD and HF were evaluated, adjusting for time-varying confounders. RESULTS In the 18–39, 40–49, 50–59, 60–70 age-groups, the hazard ratios (of developing CKD and HF in AAs versus WAs were 1.21 (95% CI 1.17–1.26) and 2.21 (1.98–2.45), 1.25 (1.22–1.28) and 1.86 (1.75–1.97), 1.21 (1.19–1.24) and 1.54 (1.48–1.60), and 1.10 (1.08–1.12) and 1.11 (1.07–1.15), respectively. In AAs and WAs aged 18–39 years, time in years to CKD (8.7 [95% CI 8.2–9.1] and 9.7 [9.2–10.2]) and HF (10.3 [9.3–11.2] and 12.1 [10.6–13.5]) were, on average, 3.6 and 4.0 and 3.1 and 4.1 years longer compared with those diagnosed at age 60–70 years. Compared with females, AA males aged CONCLUSIONS Developing cardiorenal complications within an average of 10 years of young-onset T2DM and high mediation effects of CKD on HF call for revisiting guidelines on early diagnosis and proactive treatment strategies for effective management of cardiometabolic risk.

Purpose Albumin and C-reactive protein (CRP) are non-specific markers of inflammation, which could affect muscle tissue during acute hospitalization. We investigated the association between albumin and CRP during acute hospitalization with functional and body composition parameters in patients admitted to geriatric rehabilitation. Methods The REStORing Health of Acutely Unwell AdulTs (RESORT) cohort includes geriatric rehabilitation patients assessed for change in activities of daily living (ADL, using the Katz index) during acute hospitalization, and subsequently for Katz ADL, gait speed (GS), handgrip strength (HGS) and skeletal muscle mass index (SMI) at geriatric rehabilitation admission. Albumin and CRP average (median), variation (interquartile range), and maximum or minimum were collected from serum samples, and were examined for their association with functional and body composition parameters using multivariable linear regression analysis adjusted for age, sex and length of acute hospital stay. Results 1769 Inpatients were included for analyses (mean age 82.6 years ± 8.1, 56% female). Median length of acute hospitalization was 7 [IQR 4, 13] days and median number of albumin and CRP measurements was 5 [IQR 3, 12] times. ADL declined in 89% of patients (median − 3 points, IQR − 4, − 2). Lower average albumin, higher albumin variation and lower minimum albumin were associated with larger declines in ADL and with lower ADL, GS, HGS and SMI at geriatric rehabilitation admission. Higher average and maximum CRP were associated with lower GS. Conclusion Inflammation, especially lower albumin concentrations, during acute hospitalization is associated with lower physical function at geriatric rehabilitation admission.

The aim of this study is to evaluate the temporal trends in systolic blood pressure control over 18 months after blood pressure‒lowering drug initiation in the U.S.From U.S. nationally representative electronic health records, 1,036,775 adults initiating and continuing blood pressure‒lowering drugs for ≥18 months during 2006-2018 were identified (January 2021). Prevalence trends of cardiovascular disease, diabetes, and depression at blood pressure‒lowering drug initiation, blood pressure‒lowering drug therapy intensification over 18 months, and the adjusted probability of achieving systolic blood pressure control 6 months after baseline and sustaining the control for over 18 months were evaluated.At blood pressure‒lowering drug initiation, the prevalence of diabetes and depression consistently increased during the study period across all age groups, particularly in those aged 18-49 years, whereas the prevalence of cardiovascular disease was stable. Adjusted probabilities of achieving sustainable systolic blood pressure control by age group were 0.62 (95% CI=0.61, 0.63) for ages 18-39 years, 0.55 (95% CI=0.55, 0.56) for ages 40-49 years, 0.50 (95% CI=0.49, 0.50) for ages 50-59 years, 0.43 (95% CI=0.42, 0.43) for ages 60-69 years, and 0.37 (95% CI=0.37, 0.38) for ages 70-80 years. Those with cardiovascular disease or cardiovascular disease and diabetes had approximately 20% lower adjusted probability of achieving systolic blood pressure control (31%/29%) than those without these conditions (52%, p0.01). Those with depression had a 4% higher probability of systolic blood pressure control than those without the condition (49% vs 45%, p0.01).In the U.S., only 30%-50% of the population are achieving sustainable blood pressure control over 18 months after blood pressure‒lowering drug initiation, with no indication of improvement in control over the last decade.

Summary Background Diabetes prevalence is increasing in most places in the world, but prevalence is affected by both risk of developing diabetes and survival of those with diabetes. Diabetes incidence is a better metric to understand the trends in population risk of diabetes. Using a multicountry analysis, we aimed to ascertain whether the incidence of clinically diagnosed diabetes has changed over time. Methods In this multicountry data analysis, we assembled aggregated data describing trends in diagnosed total or type 2 diabetes incidence from 24 population-based data sources in 21 countries or jurisdictions. Data were from administrative sources, health insurance records, registries, and a health survey. We modelled incidence rates with Poisson regression, using age and calendar time (1995–2018) as variables, describing the effects with restricted cubic splines with six knots for age and calendar time. Findings Our data included about 22 million diabetes diagnoses from 5 billion person-years of follow-up. Data were from 19 high-income and two middle-income countries or jurisdictions. 23 data sources had data from 2010 onwards, among which 19 had a downward or stable trend, with an annual estimated change in incidence ranging from −1·1% to −10·8%. Among the four data sources with an increasing trend from 2010 onwards, the annual estimated change ranged from 0·9% to 5·6%. The findings were robust to sensitivity analyses excluding data sources in which the data quality was lower and were consistent in analyses stratified by different diabetes definitions. Interpretation The incidence of diagnosed diabetes is stabilising or declining in many high-income countries. The reasons for the declines in the incidence of diagnosed diabetes warrant further investigation with appropriate data sources. Funding US Centers for Disease Control and Prevention, Diabetes Australia Research Program, and Victoria State Government Operational Infrastructure Support Program.

OBJECTIVE To investigate trends in the prevalence of hypertension and dyslipidaemia in incident type 2 diabetes (T2DM), time to antihypertensive (AHT) and lipid-lowering therapy (LLT), and the association with systolic blood pressure (SBP) and lipid control. RESEARCH DESIGN AND METHODS Using The Health Improvement Network UK primary care database, 254 925 people with incident T2DM and existing dyslipidaemia or hypertension were identified. Among those without atherosclerotic cardiovascular disease (ASCVD) history and not on AHT or LLT at diagnosis, the adjusted median months to initiating an AHT or an LLT, and the probabilities of high SBP or lipid levels over 2 years in people initiating therapy within or after 1 year were evaluated according to high and low ASCVD risk status. RESULTS At diabetes diagnosis, 66% and 66% had dyslipidaemia and hypertension, respectively. During 2005 to 2016, dyslipidaemia prevalence increased by 10% in people aged

AIM: To evaluate temporal patterns in co-morbidities, cardiometabolic risk factors and a high atherosclerotic cardiovascular disease (ASCVD) risk population at type 2 diabetes (T2D) diagnosis by age groups and sex. MATERIALS AND METHODS: From the UK primary care database, 248,619 people with a new diagnosis of T2D during 2005-2016 were identified. Among people without ASCVD, high ASCVD risk was defined as two or more of current smoker, grade 2+ obesity, hypertension, dyslipidaemia or microvascular disease. Cardiometabolic multimorbidity (CMM) was defined as two or more of cardiovascular disease, microvascular disease, hypertension, dyslipidaemia, grade 2+ obesity or cancer. Temporal patterns in the distribution of cardiometabolic risk factors were evaluated. RESULTS: While the prevalence of ASCVD was stable over time (approximately 18%), 50% were identified to have a high ASCVD risk (26% and 38% in the 18-39 and 40-49 years age groups, respectively), with an increasing trend across all age groups. Overall, 51% had CMM at diagnosis, increasing during 2005-2016 for the 18-39 years age group by 14%-17%, for the 40-49 years age group by 27%-33%, for the 50-59 years age group by 41%-50%, for the 60-69 years age group by 56%-65%, and for the 70-79 years age group by 65%-80%. People with young-onset T2D had significantly higher HbA1c, body mass index and lipids at diagnosis (all p

Aims To explore cardiometabolic risk profiles, the probability of sustainable control, and the effectiveness of treatment with sodium-glucose co-transporter-2 (SGLT2) inhibitors in black and white adults in the United States with type 2 diabetes. Materials and methods Using nationally representative US electronic medical records, 72 690 white and 10 004 black adults diagnosed with type 2 diabetes initiating SGLT2 inhibitors during the period 2013 to 2018, continuing it for ≥6 months, and with follow-up of ≥12 months, were identified. Glycated haemoglobin (HbA1c), body weight, systolic blood pressure (SBP) and lipid changes at 6 months, and sustainability of control over 18 months post SGLT2 inhibitor initiation were explored, separately in those with and without atherosclerotic cardiovascular disease (ASCVD). Results The white group was older (58 years) with lower mean HbA1c (8.5%), compared to the black group (age 54 years, HbA1c 9.0%). Body mass index distribution was similar. The proportions of people with uncontrolled SBP, LDL cholesterol, non-HDL cholesterol and triglyceride levels were 24%, 42%, 51% and 62%, respectively, in white patients, and 31%, 51%, 49% and 32%, respectively, in black patients. At 6-month follow-up white and black patients had similar adjusted reductions in HbA1c (1.1%), SBP (8-10 mmHg), LDL cholesterol (0.26 - 0.34 mmol / L) and body weight (1.1-1.4 kg). However, over 18 months' follow-up, compared to white patients, black patients were significantly less likely to achieve sustainable control in HbA1c (odds ratio [OR] 0.67, 95% confidence interval [CI] 0.63-0.72), body weight (OR 0.81, 95% CI 0.72-0.91), SBP (OR 0.67, 95% CI 0.61-0.74) and LDL cholesterol (OR 0.77, 95% CI 0.67-0.89). Triglyceride control was significantly better among black patients. Black patients had a significantly higher risk factor burden, irrespective of ASCVD status. Conclusions While the effectiveness of SGLT2 inhibitors was similar among black and white patients, irrespective of ASCVD status, black patients continued to have worse cardiometabolic risk factor burden after SGLT2 inhibitor initiation.

OBJECTIVE To evaluate temporal prevalence trend, cardiometabolic risk factors, and the risk of atherosclerotic cardiovascular disease (ASCVD) and all-cause mortality (ACM) in incident young- and usual-onset type 2 diabetes. RESEARCH DESIGN AND METHODS From the U.K. primary care database, 370,854 people with a new diagnosis of type 2 diabetes from 2000 to 2017 were identified. Analyses were conducted by age- group (18–39, 40–49, 50–59, 60–69, 70–79 years) and high-/low-risk status without history of ASCVD at diagnosis, with subjects with two or more of current smoking, high systolic blood pressure, high LDL cholesterol (LDL-C), or chronic kidney disease classified as high risk. RESULTS The proportion of people aged CONCLUSIONS Unlike usual-onset, young-onset type 2 diabetes has similar cardiovascular and mortality risk irrespective of cardiometabolic risk factor status at diagnosis. The guidelines on the management of young-onset type 2 diabetes for intensive risk factor management and cardioprotective therapies need to be urgently reevaluated through prospective studies.

Objective: To explore risks and associated mediation effects of developing chronic kidney disease (CKD) and heart failure (HF) in young- and usual-onset T2DM among White Caucasian (WC) and African American (AA). Research Design and Methods: From US medical records, 1,491,672 WC and 31,133 AA were identified and stratified by T2DM-onset age (18-39 /40-49 /50-59 /60-70 years). Risks, mediation effects and time to CKD and HF were evaluated adjusting for time-varying confounders. Results: In 18-39, 40-49, 50-59, 60-70 year-groups, HR (95% CI) of developing CKD /HF in AA compared to WC were 1.21 (1.17-1.26) /2.21 (1.98-2.45), 1.25 (1.22-1.28) /1.86 (1.75-1.97), 1.21 (1.19-1.24) /1.54 (1.48-1.60), 1.10 (1.08-1.12) /1.11 (1.07-1.15) respectively. In AA /WC aged 18-39 years, time (CI) in years to CKD [8.7 (8.2-9.1) /9.7 (9.2-10.2)] and HF [10.3 (9.3-11.2) /12.1 (10.6-13.5)] were on average 3.6 /4.0 and 3.1 /4.1 years longer compared to those diagnosed at 60-70 years. Compared to females, AA males aged The mediation effects (%) of CKD on the HF risk difference between ethnicities across age-groups (range: 54-91%) were higher compared to those of HF on CKD risk difference between ethnicities across age-groups (range: 13-39%). Conclusions: Developing cardio-renal complications on average within 10 years of young-onset T2DM, and high mediation effect of CKD on HF call for revisiting guidelines on early diagnosis and pro-active treatment strategies for effective management of cardio-metabolic risk.

BACKGROUND: Diabetes is a major public health issue. Because lifetime risk, life expectancy, and years of life lost are meaningful metrics for clinical decision making, we aimed to estimate these measures for type 2 diabetes in the high-income setting.; METHODS: For this multinational, population-based study, we sourced data from 24 databases for 23 jurisdictions (either whole countries or regions of a country): Australia; Austria; Canada; Denmark; Finland; France; Germany; Hong Kong; Hungary; Israel; Italy; Japan; Latvia; Lithuania; the Netherlands; Norway; Scotland; Singapore; South Korea; Spain; Taiwan; the UK; and the USA. Our main outcomes were lifetime risk of type 2 diabetes, life expectancy in people with and without type 2 diabetes, and years of life lost to type 2 diabetes. We modelled the incidence and mortality of type 2 diabetes in people with and without type 2 diabetes in sex-stratified, age-adjusted, and calendar year-adjusted Poisson models for each jurisdiction. Using incidence and mortality, we constructed life tables for people of both sexes aged 20-100 years for each jurisdiction and at two timepoints 5 years apart in the period 2005-19 where possible. Life expectancy from a given age was computed as the area under the survival curves and lifetime lost was calculated as the difference between the expected lifetime of people with versus without type 2 diabetes at a given age. Lifetime risk was calculated as the proportion of each cohort who developed type 2 diabetes between the ages of 20 years and 100 years. We estimated 95% CIs using parametric bootstrapping.; FINDINGS: Across all study cohorts from the 23 jurisdictions (total person-years 1577234194), there were 5119585 incident cases of type 2 diabetes, 4007064 deaths in those with type 2 diabetes, and 11854043 deaths in those without type 2 diabetes. The lifetime risk of type 2 diabetes ranged from 16·3% (95% CI 15·6-17·0) for Scottish women to 59·6% (58·5-60·8) for Singaporean men. Lifetime risk declined with time in 11 of the 15 jurisdictions for which two timepoints were studied. Among people with type 2 diabetes, the highest life expectancies were found for both sexes in Japan in 2017-18, where life expectancy at age 20 years was 59·2 years (95% CI 59·2-59·3) for men and 64·1 years (64·0-64·2) for women. The lowest life expectancy at age 20 years with type 2 diabetes was observed in 2013-14 in Lithuania (43·7 years [42·7-44·6]) for men and in 2010-11 in Latvia (54·2 years [53·4-54·9]) for women. Life expectancy in people with type 2 diabetes increased with time for both sexes in all jurisdictions, except for Spain and Scotland. The life expectancy gap between those with and without type 2 diabetes declined substantially in Latvia from 2010-11 to 2015-16 and in the USA from 2009-10 to 2014-15. Years of life lost to type 2 diabetes ranged from 2·5 years (Latvia; 2015-16) to 12·9 years (Israel Clalit Health Services; 2015-16) for 20-year-old men and from 3·1 years (Finland; 2011-12) to 11·2 years (Israel Clalit Health Services; 2010-11 and 2015-16) for 20-year-old women. With time, the expected number of years of life lost to type 2 diabetes decreased in some jurisdictions and increased in others. The greatest decrease in years of life lost to type 2 diabetes occurred in the USA between 2009-10 and 2014-15 for 20-year-old men (a decrease of 2·7 years).; INTERPRETATION: Despite declining lifetime risk and improvements in life expectancy for those with type 2 diabetes in many high-income jurisdictions, the burden of type 2 diabetes remains substantial. Public health strategies might benefit from tailored approaches to continue to improve health outcomes for people with diabetes.; FUNDING: US Centers for Disease Control and Prevention and Diabetes Australia. Copyright © 2022 Elsevier Ltd. All rights reserved.

Aims/hypothesis We aimed to investigate the prevalence and incidence of depression, and the interplay of cardiometabolic comorbidities, in the differentiation of depression risk between young-onset diabetes (diagnosis at age Methods Using electronic medical records from the UK and USA, retrospective cohorts of adults with incident type 2 diabetes diagnosed between 2006 and 2017 were examined. Trends in the prevalence and incidence of depression, and risk of developing depression, in participants with young-onset type 2 diabetes compared with usual-onset type 2 diabetes were assessed separately by sex and comorbidity status. Results In total 230,932/1,143,122 people with type 2 diabetes from the UK/USA (mean age 58/60 years, proportion of men 57%/46%) were examined. The prevalence of depression in the UK/USA increased from 29% (95% CI 28, 30)/22% (95% CI 21, 23) in 2006 to 43% (95% CI 42, 44)/29% (95% CI 28, 29) in 2017, with the prevalence being similar across all age groups. A similar increasing trend was observed for incidence rates. In the UK, compared with people aged ≥50 years with or without comorbidity, 18–39-year-old men and women had 23–57% and 20–55% significantly higher risks of depression, respectively. In the USA, compared with those aged ≥60 years with or without comorbidity, 18–39-year-old men and women had 5–17% and 8–37% significantly higher risks of depression, respectively. Conclusions/interpretation Depression risk has been increasing in people with incident type 2 diabetes in the UK and USA, particularly among those with young-onset type 2 diabetes, irrespective of other comorbidities. This suggests that proactive mental health assessment from the time of type 2 diabetes diagnosis in primary care is essential for effective clinical management of people with type 2 diabetes. Graphical abstract

Third-line antidiabetic drug (ADD) intensification patterns and glycemic control post intensification in type 2 diabetes mellitus (T2DM) have not been thoroughly explored in a real-world setting. This study explored the patterns and risks of third-line ADD intensification post second-line ADDs and the probability of desirable glucose control over 12 months by third-line ADD classes at the population level. We used the electronic medical records of 255,236 patients with T2DM in the USA initiating a second-line ADD post metformin from January 2013 to evaluate the rates and risks of third-line intensification and the probability of desirable glycemic control with different ADDs after addressing inherent heterogeneity using appropriate methodologies. Patients had a mean age of 60 years and glycated hemoglobin (HbA1c) of 8.5% at second-line ADD. Over 209,136 person-years (PY) of follow-up, 40% had initiated a third-line ADD at HbA1c of 8.8%. Patients receiving dipeptidyl peptidase-4 inhibitors (DPP-4i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) as the second-line ADD had a 7% (95% hazard ratio [HR] confidence interval [CI] 1.05–1.10) and 28% (95% HR CI 1.24–1.33) higher adjusted risk of intensifying with a third-line ADD than did those receiving sulfonylureas as the second-line ADD. Those receiving sodium-glucose cotransporter-2 inhibitors (SGLT-2i) as second-line ADD had a 17% (95% HR CI 0.80–0.87) lower risk. The adjusted probability of reducing HbA1c by ≥ 1% was similar in those receiving third-line sulfonylureas, thiazolidinediones, GLP-1 RAs, SGLT-2i, and insulin (minimum, maximum 95% CI of probability 0.61, 0.68), whereas those receiving DPP-4i had a significantly lower probability (0.58; 95% CI 0.56–0.59). Similarly, the probability of reducing HbA1c

Background Many people with advanced dementia live in residential aged care homes. Care home staff need the knowledge and skills to provide high-quality end-of-life (EOL) dementia care. However, several studies have found EOL dementia care to be suboptimal, and care staff have reported they would benefit from training in palliative care and dementia. Simulation offers an immersive learning environment and has been shown to improve learners’ knowledge and skills. However, there is little research on simulation training for residential care staff. This article presents the development and evaluation protocol of IMproving Palliative care Education and Training Using Simulation in Dementia (IMPETUS-D) - a screen-based simulation training program on palliative dementia care, targeted at residential care staff. IMPETUS-D aims to improve the quality of palliative care provided to people living with dementia in residential care homes, including avoiding unnecessary transfers to hospital. Methods A cluster RCT will assess the effect of IMPETUS-D. Twenty-four care homes (clusters) in three Australian cities will be randomised to receive either the IMPETUS-D intervention or usual training opportunities (control). The primary outcome is to reduce transfers to hospital and deaths in hospital by 20% over 6-months in the intervention compared to the control group. Secondary outcomes include uptake of goals of care plans over 6 and 12 months, change in staff knowledge and attitudes towards palliative dementia care over 6 months, change in transfers to hospital and deaths in hospital over 12 months. For the primary analysis logistic regression models will be used with standard errors weighted by the cluster effects. A mixed methods process evaluation will be conducted alongside the cluster RCT to assess the mechanisms of impact, the implementation processes and contextual factors that may influence the delivery and effects of the intervention. Discussion In Australia, the need for high-quality advanced dementia care delivered in residential aged care is growing. This study will assess the effect of IMPETUS-D a new simulation-based training program on dementia palliative and EOL care. This large multisite trial will provide robust evidence about the impact of the intervention. If successful, it will be distributed to the broader residential care sector. Trial registration ANZCTR, ACTRN12618002012257. Registered 14 December 2018.

Aim: Complex associations between T2DM, CKD and HF challenge treatment strategies and results in significant life years loss. Risk of CKD and HF in young- and usual-onset T2DM among White Caucasian (WC) and African American (AA) were explored. Methods: From nationally representative EMRs of USA, 1491672 WC and 31133 AA diagnosed with T2DM from 2000-2018 within age 18-39 /40-49/50-59/ 60-69 yrs were identified. The restricted mean time (RMT) to CKD and HF in AA and WC were compared, adjusting for anthropometric and time-varying disease confounders. Results: At T2DM Dx, 10 /12% and 2 /4% of WC /AA had existing CKD and HF; 48 /57% and 39 /32% had hypertension and dyslipidaemia. With mean 5 yrs follow-up, 95% CIs of CKD+HF incidence rates/1000PY were: (23-24) /(37-38) /(53-54) /(82-83) in 18-39 /40-49 /50-59/ 60-69 yrs grps for WC and (30-31) /(47-49) /(66-68) /(93-95) for AA. Compared to WC, AA had significantly higher risk of CKD and HF across all age groups (HR CI range: 1.1-2.4). In AA/WC aged 18-39 yrs, RMT (CI) in yrs to CKD [8.3 (7.8-8.7) /8.9 (8.5-9.2)] and HF [9.4 (8.6-10.3) /11.4 (9.8-12.9)] was on average only 3.2 /3.2 yrs and 2.7 /3.3 longer compared to those aged 60-69 yrs at Dx (Fig). Conclusion: Developing cardio-renal complications within 10 yrs of young-onset T2DM and significant higher risk among AA compared to WC call for more intense prevention strategies in young-onset population, particularly in AA. Disclosure S. K. Paul: Advisory Panel; Self; Sanofi, Consultant; Self; Roche Pharma. O. Montvida: None.

We determined the efficacy of tocilizumab (TCZ) in preventing grade 2-4 acute graft-versus-host disease (aGVHD) in patients with acute leukemia or myelodysplasia undergoing matched sibling donor (MSD) or volunteer unrelated donor (VUD) allogeneic stem cell transplantation after myeloablative or reduced-intensity conditioning across 5 Australian centers. A total of 145 patients (50 MSD, 95 VUD) were randomly assigned to placebo or TCZ on day −1. All patients received T-cell–replete peripheral blood stem cell grafts and graft-versus-host disease (GVHD) prophylaxis with cyclosporin/methotrexate. A planned substudy analyzed the VUD cohort. With a median follow-up of 746 days, the incidence of grade 2-4 aGVHD at day 100 for the entire cohort was 36% for placebo vs 27% for TCZ (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.38-1.26; P = .23) and 45% vs 32% (HR, 0.61; 95% CI, 0.31-1.22; P = .16) for the VUD subgroup. The incidence of grade 2-4 aGVHD at day 180 for the entire cohort was 40% for placebo vs 29% for TCZ (HR, 0.68; 95% CI, 0.38-1.22; P = .19) and 48% vs 32% (HR, 0.59; 95% CI, 0.30-1.16; P = .13) for the VUD subgroup. Reductions in aGVHD were predominantly in grade 2 disease. For the entire cohort, transplant-related mortality occurred in 8% vs 11% of placebo-treated vs TCZ-treated patients, respectively (P = .56), and overall survival was 79% vs 71% (P = .27). Median day to neutrophil and platelet engraftment was delayed by 2 to 3 days in TCZ-treated patients, whereas liver toxicity and infectious complications were similar between groups. In this phase 3 randomized double-blind trial, TCZ showed nonsignificant trends toward reduced incidence of grade 2-4 aGVHD in recipients from HLA-matched VUDs but no improvements in long term-survival.

OBJECTIVE To evaluate the temporal patterns of cardiometabolic multimorbidity (CM) and depression in White Caucasians (WCs) and African Americans (AAs) with early-onset type 2 diabetes and their impact on long-term atherosclerotic cardiovascular disease (ASCVD). RESEARCH DESIGN AND METHODS From U.S. electronic medical records, 101,104 AA and 505,336 WC subjects with type 2 diabetes diagnosed between 2000 and 2017 were identified (mean follow-up 5.3 years). Among those without ASCVD at diagnosis, risk of ASCVD and three-point major adverse cardiovascular events (MACE-3) (heart failure, myocardial infarction, or stroke) was evaluated between ethnicities by age-groups. RESULTS The proportion of patients diagnosed at CONCLUSIONS AAs have higher cardiovascular risk compared with WCs, particularly in early-onset type 2 diabetes. CM and depression at diabetes diagnosis have been increasing over the past two decades in both ethnic groups. Strategies for screening and optimal management of CM and depression, particularly in early-onset type 2 diabetes, may result in a lower cardiovascular risk.

Aims The aim of this study was to evaluate the temporal pattern of amputations in patients with type 2 diabetes mellitus (T2DM), the risk of amputations by new and older anti-diabetic drugs (ADDs), and the interplay of peripheral artery disease (PAD) with therapy and amputation risk. Methods and results Using Centricity Electronic Medical Records from USA, 3 293 983 patients with T2DM were identified: 169 739 received sodium-glucose cotransporter type-2 inhibitors (SGLT-2i; no exposure to incretins); 149 826 received glucagon-like peptide 1 receptor agonists [GLP-1RA, no SGLT-2i or dipeptidyl peptidase-4 inhibitor (DPP-4i) exposure]; 448 225 received DPP-4i (no exposure to GLP-1RA or SGLT-2i); and 1 954 353 received other ADDs. The proportion of incident amputations per 10 000 adults ranged between 4.7 and 6.8 during 2000–08 and significantly increased to 12.3 in 2017. Over 17 211 719 person-years follow-up post T2DM diagnosis, the rates per 1000 person-years of any and lower limb amputations (LLAs) were similar between SGLT-2i and incretins [95% confidence interval (CI) range: 1.06–1.67], and significantly higher in other groups (95% CI range: 1.96–2.29). In propensity score-adjusted pairwise analyses, the risk of LLA was not higher in SGLT-2i vs. GLP1-RA [hazard ratio (HR) (95% CI): 0.88 (0.73, 1.05)], and lower in SGLT-2i vs. DPP-4i/other ADD [HR (95% CI): 0.65 (0.56, 0.75)/0.43 (0.37, 0.49)]. The rate of LLA was similar in patients treated with canagliflozin, empagliflozin, or dapagliflozin. Patients with PAD had more than four-fold higher LLA risk (range of 95% CI of HR: 3.6–6.0). Conclusion The risk of amputation in patients treated with SGLT-2i and incretins was not higher compared with other ADDs. Pre-existing PAD was the greatest driver of amputation risk.

OBJECTIVE Individualized treatment of patients with diabetes requires detailed evaluation of risk factor dynamics at the population level. This study evaluated the persistent glycemic and cardiovascular (CV) risk factor burden over 2 years after treatment intensification (TI). RESEARCH DESIGN AND METHODS From U.S. Centricity Electronic Medical Records, 276,884 patients with incident type 2 diabetes who intensified metformin were selected. Systolic blood pressure (SBP) ≥130/140 mmHg and LDL ≥70/100 mg/dL were defined as uncontrolled for those with/without a history of CV disease at TI. Triglycerides ≥150 mg/dL and HbA1c ≥7.5% (58 mmol/mol) were defined as uncontrolled. Longitudinal measures over 2 years after TI were used to define risk factor burden. RESULTS With 3.7 years’ mean follow-up, patients were 59 years; 70% were obese; 22% had a history of CV disease; 60, 30, 50, and 48% had uncontrolled HbA1c, SBP, LDL, and triglycerides, respectively, at TI; and 81% and 69% were receiving antihypertensive and lipid-modifying therapies, respectively. The proportion of patients with consistently uncontrolled HbA1c increased from 31% in 2005 to 41% in 2014. Among those on lipid-modifying drugs, 41% and 37% had consistently high LDL and triglycerides over 2 years, respectively. Being on antihypertensive therapies, 29% had consistently uncontrolled SBP. Among patients receiving cardioprotective therapies, 63% failed to achieve control in HbA1c + LDL, 57% in HbA1c + SBP, 55% in LDL + SBP, and 63% in HbA1c + triglycerides over 2 years after TI. CONCLUSIONS Among patients on multiple therapies for risk factor control, more than one-third had uncontrolled HbA1c, lipid, and SBP levels, and more than one-half had two CV risk factors that were simultaneously uncontrolled after TI.

Background: Diabetic peripheral neuropathy (DPN) is a common complication in patients (pts) with diabetes. However, multinational data do not support any convincing efficacy of the current therapies for treating DPN. This necessitated the evaluation of safety and efficacy of alternative medicine to tackle DPN. Methods: A double-blinded RCT was conducted in 8 Chinese medicine hospitals in China, evaluating the safety and efficacy of 190 g Tangbi Waixi decoction (TW, intervention (Int)) compared with 19 g TW (control (Cont)). Change in Toronto Clinical Scoring System - Total Score (TCSS-TS) at 12 and 24 weeks follow-up was the primary outcome, with treatment ceasing at 12 weeks. Secondary outcomes included change in bilateral motor velocity (BMV) and sensory nerve conduction velocity (SNCV) of the common peroneal nerve (CPN). All pts received standard care for glycaemic management. The pts in the Int (n=317) and Cont (n=315) groups were analysed on ITT principle. All adverse events (AEs) were recorded. Results: The pts were mean 60 years old with median 10 yrs and 2 yrs of diabetes and DPN duration respectively at randomisation. With median TCSS-TS of 10 at randomisation in both groups, the median (95% CI) reduction in Int and Cont: at 12 weeks 2 (1.7, 2.3) and 3 (2.7, 3.3) respectively (median between group difference (MBGD): 1.0, p=0.011); at 24 weeks 3 (2.6, 3.4) in both groups. At 12 weeks, median (95% CI) CPN velocity increased in both Int and Cont - BMV Int vs. Cont: 2.7 (1.9, 4.9) m/s vs. 4.9 (2.7, 5.5) m/s, MBGD - 2.5 m/s (p=0.044); SNCV Int vs. Cont: 1.4 (0, 2) m/s vs. 2.7 (1.9, 4.9) m/s, MBGD - 0.7 m/s (p=0.26). Similar increase in CPN velocity was observed at 24 weeks in both groups. Overall 12% pts experienced at least one AE, with no difference between groups. Conclusion: Treatment of DPN with TW decoction significantly benefitted the pts and is safe, while lower dose of TW appears to be more effective than the higher does. Disclosure F. Guanjie: None. Y. Lin: None. S.K. Paul: Advisory Panel; Self; Sanofi. Research Support; Self; AstraZeneca, Genentech, Inc. H. Huang: None. T. Xianyu: None. Z. Yuehong: None. F. Zhaohui: None. Q. Xiaotang: None. D. Fang: None. S. Wang: None. M. Wang: None. H. Wei: None. Z. Ling: None. L. Zhenjie: None. Y. Fu: None. M. Wu: None. L. Anxiang: None. H. Jinzhu: None. Q. Li: None. Funding National Science and Technology Support Program (2015BAI04B09)

Current approaches to antibiotic dose determination in critically ill patients requiring renal replacement therapy are primarily based on the assessment of highly heterogeneous data from small number of patients. The standard modelling approaches limit the scope of constructing robust confidence boundaries of the distribution of pharmacokinetics (PK) parameters, especially when the evaluation of possible association of demographic and clinical factors at different levels of the distribution of drug clearance is of interest. Commonly used compartmental models generally construct the inferences through a linear or non-linear mean regression, which is inadequate when the distribution is skewed, multi-modal or effected by atypical observation. In this study, we discuss the statistical challenges in robust estimation of the confidence boundaries of the PK parameters in the presence of highly heterogenous patient characteristics. A novel stepwise approach to evaluate the confidence boundaries of PK parameters is proposed by combining PK modelling with mixed-effects quantile regression (MEQR) methods. This method allows the assessment demographic and clinical factors’ effects at any arbitrary quantiles of the outcome of interest, without restricting assumptions on the distributions. The MEQR approach allows us to investigate if the levels of association of the covariates are different at low, medium or high concentration. This methodological assessment is deemed as a background initial approach to support the development of a class of statistical algorithm in constructing robust confidence intervals of PK parameters which can be used for developing an optimised antibiotic dosing guideline for critically ill patients requiring renal replacement therapy.

Aims To estimate the risk of developing long-term major cardiovascular and renal complications in relation to levels of body mass index (BMI) in a population of White European (WE), African-Caribbean (AC), and South Asian (SA) patients with type 2 diabetes mellitus (T2DM). Materials and methods Patients with new diagnosis of T2DM, aged ≥ 18 years from January 2000 (n = 69,436) and their age-sex-ethnicity matched non-diabetic controls (n = 272,190) were identified from UK primary care database. Incidence rates ratios (IRRs) for non-fatal major cardiovascular events (MACE) and chronic kidney disease (CKD) in patients with T2DM compared to controls were estimated using multivariate Mantel-Cox model. Results Among normal weight patients with T2DM, WEs had significantly higher prevalence of cardiovascular multi-morbidity (95% CI 9.5, 11.3), compared to SAs (95% CI 4.8, 9.5). AC and SA overweight and obese patients had similar prevalence, while obese WEs had significantly higher prevalence. During a median 7 years of follow-up, risk of MACE was significantly higher for overweight (95% CI of IRR 1.50, 2.46) and obese (95% CI of IRR 1.49, 2.43) SAs compared to their WE counterparts. However, similar risk levels were observed for normal weight WEs and SAs, respectively. Risk of CKD was higher and uniform for BMI ≥ 25 kg/m2 amongst WEs and ACs, whereas only overweight patients had significantly higher risk of CKD amongst SA [IRR 2.08 (95% CI 1.49, 2.93)]. Conclusion Risk of MACE/CKD varies over levels of BMI within each ethnic group, with overweight SAs having a disproportionate risk of CKD. Electronic supplementary material The online version of this article (10.1186/s12933-018-0712-1) contains supplementary material, which is available to authorized users.

AIMS To inform patients and their carers about both the probability of reducing glycated haemoglobin (HbA1c) to clinically desirable levels and the sustainability of such control over 2 years with major second-line antidiabetic therapies, in individual risk scenarios, with and without third-line intensification. MATERIALS AND METHODS From US Centricity Electronic Medical Records, 163 081 patients with type 2 diabetes aged 18 to 80 years, who had initiated metformin, intensified their treatment with dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs), sulphonylureas (SUs), insulin or thiazolidinediones (TZDs), and continued second-line treatment for ≥6 months, were selected. Treatment groups were balanced with regard to baseline characteristics, and glycaemic achievements were estimated using logistic regression analysis. RESULTS With HbA1c concentrations of 58-63.9 mmol/mol (7.5-7.9%) at second-line treatment initiation, the adjusted probabilities of achieving HbA1c

Background:Identification of diseased patients from primary care based electronic medical records (EMRs) has methodological challenges that may impact epidemiologic inferences.Objective:To compare deterministic clinically guided selection algorithms with probabilistic machine learning (ML) methodologies for their ability to identify patients with type 2 diabetes mellitus (T2DM) from large population based EMRs from nationally representative primary care database.Methods:Four cohorts of patients with T2DM were defined by deterministic approach based on disease codes. The database was mined for a set of best predictors of T2DM and the performance of six ML algorithms were compared based on cross-validated true positive rate, true negative rate, and area under receiver operating characteristic curve.Results:In the database of 11,018,025 research suitable individuals, 379 657 (3.4%) were coded to have T2DM. Logistic Regression classifier was selected as best ML algorithm and resulted in a cohort of 383,330 patients with potential T2DM. Eighty-three percent (83%) of this cohort had a T2DM code, and 16% of the patients with T2DM code were not included in this ML cohort. Of those in the ML cohort without disease code, 52% had at least one measure of elevated glucose level and 22% had received at least one prescription for antidiabetic medication.Conclusion:Deterministic cohort selection based on disease coding potentially introduces significant mis-classification problem. ML techniques allow testing for potential disease predictors, and under meaningful data input, are able to identify diseased cohorts in a holistic way.

OJBECTIVE To explore temporal trends in antidiabetes drug (ADD) prescribing and intensification patterns, along with glycemic levels and comorbidities, and possible benefits of novel ADDs in delaying the need for insulin initiation in patients diagnosed with type 2 diabetes. RESEARCH DESIGN AND METHODS Patients with type 2 diabetes aged 18–80 years, who initiated any ADD, were selected (n = 1,023,340) from the U.S. Centricity Electronic Medical Records. Those who initiated second-line ADD after first-line metformin were identified (subcohort 1, n = 357,482); the third-line therapy choices were further explored. RESULTS From 2005 to 2016, first-line use increased for metformin (60–77%) and decreased for sulfonylureas (20–8%). During a mean follow-up of 3.4 years post metformin, 48% initiated a second ADD at a mean HbA1c of 8.4%. In subcohort 1, although sulfonylurea usage as second-line treatment decreased (60–46%), it remained the most popular second ADD choice. Use increased for insulin (7–17%) and dipeptidyl peptidase-4 inhibitors (DPP-4i) (0.4–21%). The rates of intensification with insulin and sulfonylureas did not decline over the last 10 years. The restricted mean time to insulin initiation was marginally longer in second-line DPP-4i (7.1 years) and in the glucagon-like peptide 1 receptor agonist group (6.6 years) compared with sulfonylurea (6.3 years, P < 0.05). CONCLUSIONS Most patients initiate second-line therapy at elevated HbA1c levels, with highly heterogeneous clinical characteristics across ADD classes. Despite the introduction of newer therapies, sulfonylureas remained the most popular second-line agent, and the rates of intensification with sulfonylureas and insulin remained consistent over time. The incretin-based therapies were associated with a small delay in the need for therapy intensification compared with sulfonylureas.

Background: Electronic Medical Records (EMRs) from primary/ ambulatory care systems present a new and promising source of information for conducting clinical and translational research. Objectives: To address the methodological and computational challenges in order to extract reliable medication information from raw data which is often complex, incomplete and erroneous. To assess whether the use of specific chaining fields of medication information may additionally improve the data quality. Methods: Guided by a range of challenges associated with missing and internally inconsistent data, we introduce two methods for the robust extraction of patient-level medication data. First method relies on chaining fields to estimate duration of treatment (“chaining”), while second disregards chaining fields and relies on the chronology of records (“continuous”). Centricity EMR database was used to estimate treatment duration with both methods for two widely prescribed drugs among type 2 diabetes patients: insulin and glucagon-like peptide-1 receptor agonists. Results: At individual patient level the “chaining” approach could identify the treatment alterations longitudinally and produced more robust estimates of treatment duration for individual drugs, while the “continuous” method was unable to capture that dynamics. At population level, both methods produced similar estimates of average treatment duration, however, notable differences were observed at individual-patient level. Conclusion: The proposed algorithms explicitly identify and handle longitudinal erroneous or missing entries and estimate treatment duration with specific drug(s) of interest, which makes them a valuable tool for future EMR based clinical and pharmaco-epidemiological studies. To improve accuracy of real-world based studies, implementing chaining fields of medication information is recommended.

Augmented renal clearance (ARC) is known to influence β-lactam antibiotic pharmacokinetics. This substudy of the BLING-II trial aimed to explore the association between ARC and patient outcomes in a large randomised clinical trial. BLING-II enrolled 432 participants with severe sepsis randomised to receive β-lactam therapy by continuous or intermittent infusion. An 8-h creatinine clearance (CLCr) measured on Day 1 was used to identify ARC, defined as CLCr ≥ 130 mL/min. Patients receiving any form of renal replacement therapy were excluded. Primary outcome was alive ICU-free days at Day 28. Secondary outcomes included 90-day mortality and clinical cure at 14 days following antibiotic cessation. A total of 254 patients were included, among which 45 (17.7%) manifested ARC [median (IQR) CLCr 165 (144–198) mL/min]. ARC patients were younger (P

Aims: To compare glucose control and safety of different basal insulin therapies (BI, including Insulin NPH, glargine and detemir) in real-world clinical settings based on a large-scale registry study.Methods: In this multi-center 6-month prospective observational study, patients with type 2 diabetes (HbA1c >= 7%) who were uncontrolled by oral anti-diabetic drugs (OADs) and were willing to initiate BI therapy were enrolled from 209 hospitals within 8 regions of China. Type and dose of BI were at the physician's discretion and the patients' willingness. Interviews were conducted at 0 months (visit 1), 3 months (visit 2) and 6 months (visit 3). Outcomes included change in HbA1c, hypoglycemia rate and body weight from baseline at 6 months.Results: A total of 16 341 and 9002 subjects were involved in Intention-To-Treat (ITT) and per-protocol (PP) analysis, respectively. After PS regression adjustment, ITT analysis showed that reduction in HbA1c in glargine (2.2% +/- 2.1%) and detemir groups (2.2% +/- 2.1%) was higher than that in the NPH group (2.0% +/- 2.2%) (P < .01). The detemir group had the lowest weight gain (-0.1 +/- 2.9 kg) compared with the glargine (+0.1 +/- 3.0 kg) and NPH (+0.3 +/- 3.1 kg) groups (P < .05). The glargine group had the lowest rate of minor hypoglycaemia, while there was no difference in severe hypoglycaemia among the 3 groups. The results observed in PP analyses were consistent with those in ITT analysis.Conclusion: In a real-world clinical setting in China, treatment with long-acting insulin analogues was associated with better glycaemic control, as well as less hypoglycaemia and weight gain than treatment with NPH insulin in type 2 diabetes patients. However, the clinical relevance of these observations must be interpreted with caution.

There is increasing interest in gait training devices to improve walking ability in people following stroke. This randomised controlled trial aimed to compare the effectiveness of the Robowalk, a novel cable-driven gait trainer combined with conventional physiotherapy to conventional physiotherapy alone in improving walking speed, endurance, balance, functional outcomes, and quality of life in people following stroke. Rehabilitation inpatients within 3 months following stroke (n = 40) were randomised to standard care with conventional physiotherapy ('control,' n = 20) and cable-driven gait trainer combined with conventional physiotherapy ('intervention,' n = 20). All participants received 1 hour of physiotherapy a day, 5 days a week. The control group received conventional physiotherapy only; the intervention group received a combination of 30 minutes of conventional physiotherapy and 30 minutes of cable-driven gait trainer consecutively. Outcome measures were 10-metre walk test (primary outcome), 6-minute walk test, timed up and go, step test, Functional Independence Measure, and EuroQol five-dimension scale. Evaluation timepoints were on admission (T0), discharge (T1), and 4 weeks post discharge (T2). There were no differences between groups at T0, T1, and T2 in all outcome measures although there was a trend towards a larger and more sustained improvement in 10-metre walk test in favour of the intervention group and in Functional Independence Measure motor and self-care in favour of the control group, both at T2. The combination of cable-driven gait trainer with conventional physiotherapy appears as effective as conventional physiotherapy alone in improving gait outcomes in people following a recent stroke. Further studies are required to confirm these findings and determine optimal dosing regimens and long-term outcomes.

Aim: Temporal trend in the prevalence and incidence of depression (DP), any mental illness (AMI) and use of anti-depressants (ADM) in incident T2DM pts is not well known. We evaluate these trends and the risk of developing DP in young pts in real world settings from U.S. and UK. Method: Adults with diagnosis (Dx) of T2DM from 2000 from Centricity Electronic Medical Records of U.S. and The Health Improvement Network (THIN) database of UK were examined. Results: In U.S. (n= 1,395,572)/UK (n= 343,714) cohorts, the age at T2DM Dx was 59/58 years, 2/8% had Dx of DP but were not on ADM, 16/10% were on ADM without DP or AMI Dx, 9/15% were using ADM with Dx of DP. The prevalence of DP, AMI and ADM use increased exponentially in UK since 2000 (Figure B), while an increasing prevalence in AMI and ADM use was seen in U.S. (Figure A). Between 2000-2016, the use of ADM without Dx of DP or AMI increased from 16-26%/5-41% in U.S./UK cohort. Incidence rates of DP and ADM use were significantly higher in the U.S. cohort compared to UK (Figures C and D). Among pts without a co-morbid condition at T2DM Dx, younger U.S./UK pts (≤ 50 years) had 28%/18% significantly higher risks of developing DP compared to older pts (≥ 60 years); among pts with existing co-morbidity, the risks were higher by 46%/33%. Conclusion: In incident T2DM pts in UK and U.S., a striking rise in the prevalence of DP and the ADP use without Dx of AMI is seen, with younger pts having higher risk of developing DP. Disclosure J. Dibato: None. D. Koye: None. W. Polonsky: Consultant; Self; Abbott, Bigfoot Biomedical, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Johnson & Johnson Diabetes Institute, Merck & Co., Inc., Novo Nordisk Inc., Sanofi, Servier. O. Montvida: None. S.K. Paul: Consultant; Self; AstraZeneca, Roche Pharma. Research Support; Self; Roche Pharma.

Aim: Benefits of early initiation of SGLT2 and GLP-1RA for glucose and cardiovascular (CV) risk factor control at population level real-world setting is not known. Association of early (≤ 6 months) vs. late (>6 months) initiation of these drugs in the antidiabetic therapy management pathway on sustainable HbA1c, body weight, blood pressure and lipid control was evaluated. Method: U.S. Centricity Electronic Medical Records of 21,897/28,266 pts with T2DM receiving SGLT2/GLP-1RA post 2013 without therapy overlap with min of 1 year follow-up was used. Odds of reducing CV risk factors within 6 month and maintaining the control over 1 year was estimated by timeline of these antidiabetes drug (ADD) initiation (first prescription date of SGLT2 or GLP-1RA - first prescription date of any first line ADD): HbA1c < 7.5%, body weight reduction > 5%, SBP < 130/140 mmHg and LDL-C 70/100 mg/dL for patients with/without CVD history. Propensity score based balanced analyses were conducted. Results: At SGLT2/GLP-1RA initiation, patients were 57/58 years old, mean HbA1c 8.7/8.8%, 79/76% had HbA1c ≥ 7.5%, body weight 102/107 Kg, 26/28% and 45/45% had uncontrolled SBP and LDL-C respectively, 22/22% had existing CVD, 80/78% and 84/86% were on lipid lowering and anti-hypertensive drugs respectively. Compared to late initiators, the early initiation of SGLT2/GLP-1RA was significantly associated with 47% (CI of OR: 1.27, 1.71)/23% (CI of OR: 1.07, 1.42) higher odds for longer term HbA1c control, and 58% (CI of OR: 1.31, 1.91)/52% (CI of OR: 1.28, 1.83) higher odds for at least two of the CV risk factors control simultaneously. The odds for risk factor control was similar for the two drugs, and similar for those with and without history of CVD. Conclusion: This study based on large representative U.S. data suggests significant benefits of initiating SGLT2 or GLP-1RA early on the antidiabetes therapy management pathway for holistic glycaemic and cardiovascular risk factor control in patients with and without existing CVD. Disclosure S.K. Paul: Consultant; Self; AstraZeneca, Roche Pharma. Research Support; Self; Roche Pharma. D. Koye: None. K. Khunti: Advisory Panel; Self; Amgen Inc., AstraZeneca, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis, Servier, Takeda Pharmaceutical Company Limited. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis. Speaker's Bureau; Self; AstraZeneca, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Menarini Group, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi, Servier, Takeda Pharmaceutical Company Limited. O. Montvida: None.

Aims To investigate the probability of developing type 2 diabetes mellitus (T2DM) at different body mass index levels compared to matched non-diabetic controls in a multi-ethnic population. Materials and methods This was a case-control study of 90 367 patients with incident diabetes and 362 548 age-sex-ethnicity matched controls from UK primary care. The probability of developing T2DM was estimated. Results Case and control patients were 56 years old at index and 56% were male. Patients with T2DM had significantly higher mean BMI levels by about 5 kg/m2 at diagnosis (32.2 kg/m2) compared to the matched controls (27.4 kg/m2). White Europeans (n = 79 270), African-Caribbeans (n = 4115) and South Asians (n = 7252) were 58, 48 and 46 years old with a mean BMI of 32.5, 31.1 and 29.2 kg/m2, respectively, at diagnosis. More South Asians developed T2DM at BMI below 30 kg/m2 (38%) than White Europeans (26%) and African-Caribbeans (29%) (all P

BackgroundThe need for healthcare workers (HCWs) to have skills and knowledge in non-cancer palliative care has been recognised. Simulation is increasingly being used for palliative care training, offering participants the opportunity to learn in a realistic environment and fully interactive way.ObjectiveThe aim of this systematic review was to summarise and critically appraise controlled studies on simulation training in non-cancer palliative care for HCWs.SelectionMedline, CINAHL, PubMed and Cochrane Library databases were searched using palliative care and simulation terms. Randomised controlled trials (RCTs), non-randomised RCTs and controlled before-and-after (CBA) studies were included. Two reviewers independently screened titles and abstracts and undertook full article review using predefined selection criteria. Studies that met the inclusion criteria had data extracted and risk of bias assessed using the Cochrane Effective Practice and Organisation of Care risk of bias criteria.FindingsFive articles were included: three RCTs and two CBA studies. All studies assessed learners’ palliative care communication skills, most studies evaluated learners’ perception of change in skills and one study assessed impact on patient outcomes and learners’ change in behaviour when applied in practice. There was variation in intervention content, intensity and duration, outcome measures and study design, making it difficult to compare and synthesise results.ConclusionThere is a paucity of evidence to support simulation training to improve non-cancer palliative care. This review highlights the need for more robust research, including multicentre studies that use standardised outcome measures to assess clinician skills, changes in clinical practice and patient-related outcomes.

Background and aims The association of beta-blockers and their selectivity with mortality and cardiovascular events in patients with and without hypoglycaemia is unknown. Methods and results Insulin-treated patients with diabetes were identified within the UK CPRD database. All-cause deaths, cardiovascular events, and hypoglycaemic episodes were captured to assess the interaction between beta-blocker therapy and selectivity with hypoglycaemia. 13,682 patients, of which 2036 (14.9%) with at least one hypoglycaemic episode, were included; 3148 deaths and 1235 cardiovascular events were recorded during a median of 2.3 and 4.7 years in patients with and without incident hypoglycaemia, respectively. Treatment with any beta-blocker was not associated with risk of death in both patients with and without hypoglycaemia, without significant interaction. Compared to no therapy, non-selective beta-blockers were associated with higher risk of death in patients without hypoglycaemia (hazard ratio (HR) 2.93 [1.26–6.83] in the fully adjusted model) but not in those with hypoglycaemia; interactions was not significant. For beta1-selective beta-blockers, there was no association with mortality in both patients with and without hypoglycaemia, without significant interaction. After missing data imputation, results were consistent for non-selective beta-blockers (HR in patients without hypoglycaemia 1.59 [1.22–2.08]) while indicated a reduced risk of death for beta1-selective beta-blockers in patients with hypoglycaemia (HR 0.76 [0.61–0.94]). Due to few cardiovascular events, complete-case analysis compared only any vs no beta-blocker therapy and indicated no associations with therapy or interaction by hypoglycaemia. Conclusion In patients with hypoglycaemic episodes, treatment with beta1-selective beta-blockers may potentially reduce the risk of death. These explorative findings and the potential role of confounding by indication need to be evaluated in other studies.

Aims: In people with metformin-treated diabetes, to evaluate the risk of acute pancreatitis, pancreatic cancer and other diseases of the pancreas post second-line anti-hyperglycaemic agent initiation. Methods: People with Type 2 diabetes diagnosed after 2004 who received metformin plus a dipeptidyl peptidase-4 inhibitor (DPP-4i, n = 50 095), glucagon-like peptide-1 receptor agonist (GLP-1RA, n = 12 654), sulfonylurea (n = 110 747), thiazolidinedione (n = 17 597) or insulin (n = 34 805) for at least 3 months were identified in the US Centricity Electronic Medical Records. Time to developing acute pancreatitis, other diseases of the pancreas and pancreatic cancer was estimated, balancing and adjusting anti-hyperglycaemic drug groups for appropriate confounders. Results: In the DPP-4i group, the adjusted mean time to acute pancreatitis was 2.63 [95% confidence intervals (CI) 2.38, 2.88] years; time to pancreatic cancer was 2.70 (2.19, 3.21) years; and time to other diseases of the pancreas was 2.73 (2.33, 3.12) years. Compared with DPP-4i, the insulin group developed acute pancreatitis 0.48 years (P

AIM: To evaluate the risk of CVD and all-cause mortality at different BMI levels in conjunction with weight change prior to diagnosis of T2DM in a multi-ethnic population. METHODS: Longitudinal study of 51,455 patients with T2DM and without a history of comorbid diseases at diagnosis. Weight changes prior to diagnosis of T2DM were evaluated, and the risk of CVD and all-cause mortality at different BMI levels among three ethnic groups estimated using treatment effects model. RESULTS: White Europeans (WE), African-Caribbeans (AC), and South Asians (SA) were mean 52, 49, and 47 years with a mean BMI of 33.0, 32.0, and 30.0 kg/m2 at diagnosis, respectively. Among WE, normal weight patients developed CVD significantly earlier by 0.5 years (95% CI 0.1, 0.9 years; p = 0.018) compared to obese patients. Furthermore, those with normal body weight at diagnosis were significantly more likely to die earlier by 0.6 years (95% CI 0.03, 1.2 years; p = 0.037) among WE and by 2.5 years (95% CI 0.3, 4.6 years; p = 0.023) among SA compared to their respective obese patients. However, BMI at diagnosis was not associated with increased risk of CVD and death among AC. CONCLUSIONS: This study suggests a paradoxical association of BMI with cardiovascular and mortality risks in different ethnic groups, which may partially be driven by different cardiovascular and glycaemic risk profiles at diagnosis.

A large proportion of diabetes patients do not receive a basic minimum of standard care. Telemedicine holds the promise of improving access to health care. However, the validity of remote consultation for diabetes has not been well researched. This pilot randomized control trial was designed to evaluate the agreement on prescription decisions of endocrinologists between two consultation formats: videoconferencing and face-to-face (in-person) consultation.Seventy-three patients were randomized to telemedicine (n=36) and reference group (n=37). Each study patient in the telemedicine group received one face-to-face consultation and one video consultation. The reference group received two face-to-face consultations. The paired consultations for each patient were performed by two different endocrinologists. The level of agreement between endocrinologists was evaluated by comparing their recommendations on antidiabetes and cardioprotective medications.The level of agreement between two endocrinologists on changing antidiabetes drugs was 64% in the telemedicine group and 78% in the reference group. Although the level of agreement was lower when one of the consultations was provided via videoconference, the difference was not significant. The level of agreement on changing cardiovascular drugs was 78% in the telemedicine group and 76% in the reference group, again not significantly different.The results of this study demonstrate the preliminary evidence on the validity of recommendations made by endocrinologists via video consultation. Known limitations of videoconferencing for clinical purposes did not have remarkable impact on the outcome of consultation in terms of adjustment of patient's medications. Video teleconsultation can substitute for a considerable proportion of conventional outpatient specialty consultations for people with diabetes.