Temporal trends in the prevalence and incidence of depression and the interplay of comorbidities in patients with young- and usual-onset type 2 diabetes from the USA and the UK.

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 <40 years) and usual-onset diabetes (diagnosis at age ≥40 years). 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.

The association of amputations and peripheral artery disease in patients with type 2 diabetes mellitus receiving sodium-glucose cotransporter type-2 inhibitors: real-world study.

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.

Temporal trends in co-morbidities and cardiometabolic risk factors at the time of type 2 diabetes diagnosis in the UK.

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 < .01). The proportions with an HbA1c of 7.5% or higher in the 18-39 and 40-49 years age groups were 58% and 54%, respectively, significantly and consistently higher over the last decade compared with those aged 50 years or older, with males having higher proportions of 15-26 and 10-18 percentage points, respectively, compared with females. CONCLUSIONS: CMM and high ASCVD risk have been increasing consistently across all age groups and in both sex, in particular CMM in those aged younger than 50 years. Our findings indicate that the European Society of Cardiology-European Association for the Study of Diabetes recommendations need to change to consider people with young-onset T2D as a high-risk group, as recommended in the Primary Care Diabetes Europe position statement.

Therapeutic inertia in the management of dyslipidaemia and hypertension in incident type 2 diabetes and the resulting risk factor burden: Real-world evidence from primary care.

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 <60 years, while hypertension prevalence remained stable in all age groups. Among those with high ASCVD risk status in the age groups 18 to 39, 40 to 49, and 50 to 59 years, the median number of months to initiation of therapy were 20.4 (95% confidence interval [CI] 20.3-20.5), 10.9 (95% CI 10.8-11.0), and 9.5 (95% CI 9.4-9.6) in the dyslipidaemia subcohort, and 28.1 (95% CI 28.0-28.2), 19.2 (95% CI 19.1-19.3), and 19.9 (95% CI 19.8-20.0) in the hypertension subcohort. Among people with high and low ASCVD risk status, respectively, compared to early LLT initiators, those who initiated LLT after 1 year had a 65.3% to 85.3% and a 65.0% to 85.3% significantly higher probability of failing lipid control at 2 years of follow-up, while late AHT initiators had a 46.5% to 57.9% and a 40.0% to 58.7% significantly higher probability of failing SBP control. CONCLUSIONS: Significant delay in initiating cardioprotective therapies was observed, and time to first prescription was similar in the primary prevention setting, irrespective of ASCVD risk status across all T2DM diagnosis age groups, resulting in poor risk factor control at 2 years of follow-up.

Cardiometabolic risk factor control in black and white people in the United States initiating sodium-glucose co-transporter-2 inhibitors: A real-world study.

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.

Long-term sustainability of glycaemic achievements with second-line antidiabetic therapies in patients with type 2 diabetes: A real-world study.

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 <53 mmol/mol (<7%) at 6 months were 32%, 38%, 39%, 26% and 38% in the SU, DPP-4 inhibitor, GLP-1RA, insulin and TZD groups, respectively, while with baseline HbA1c concentrations of 64-75 mmol/mol (8-9%), the corresponding probabilities of reducing HbA1c to <58 mmol/mol (<7.5%) were 38%, 44%, 40%, 34% and 42%, respectively. In these baseline HbA1c categories, the adjusted probabilities of sustaining HbA1c achievements over 2 years were higher in the GLP-1RA and TZD groups, compared with the SU and insulin groups (P < .01). With baseline HbA1c concentrations of 75.1-108 mmol/mol (9.1-12%) 38% of patients achieved an HbA1c concentration <58 mmol/mol (<7.5%) at 6 months. The adjusted probability of sustaining this control over 2 years was higher in the incretin and TZD groups (range 62%-75%), while insulin and SUs offered lower chances of sustainable control (range 54%-56%). CONCLUSIONS: Patients treated with second-line incretins and TZDs had a significantly higher probability of achieving and sustaining glycaemic control over 2 years without further intensification, compared with those treated with SUs or insulin.

Addition of or switch to insulin therapy in people treated with glucagon-like peptide-1 receptor agonists: A real-world study in 66 583 patients.

BACKGROUND: Real world outcomes of addition or switch to insulin therapy in type 2 diabetes (T2DM) patients on glucagon-like paptide-1 receptor agonist (GLP-1RA) with inadequately controlled hyperglycaemia, are not known. MATERIALS AND METHODS: Patients with T2DM (n = 66 583) with a minimum of 6 months of GLP-1RA treatment and without previous insulin treatment were selected. Those who added insulin (n = 39 599) or switched to insulin after GLP-1RA cessation (n = 4706) were identified. Adjusted changes in glycated haemoglobin (HbA1c), weight, systolic blood pressure (SBP), and LDL cholesterol were estimated over 24 months follow-up. RESULTS: Among those who continued with GLP-1RA treatment without adding or switching to insulin, the highest adjusted mean HbA1c change was achieved within 6 months, with no further glycaemic benefits observed during 24 months of follow-up. Addition of insulin within 6 months of GLP-1RA initiation was associated with 18% higher odds of achieving HbA1c <7% at 24 months, compared with adding insulin later. At 24 months, those who added insulin reduced HbA1c significantly by 0.55%, while no glycaemic benefit was observed in those who switched to insulin. Irrespective of intensification with insulin, weight, SBP and LDL cholesterol were significantly reduced by 3 kg, 3 mm Hg, and 0.2 mmol/L, respectively, over 24 months. CONCLUSIONS: Significant delay in intensification of treatment by addition of insulin is observed in patients with T2DM inadequately controlled with GLP-1RA. Earlier addition of insulin is associated with better glycaemic control, while switching to insulin is not clinically beneficial during 2 years of treatment. Non-responding patients on GLP-1RA would benefit from adding insulin therapy, rather than switching to insulin.

Racial disparity in the co-occurrence of depression and type 2 diabetes mellitus. An electronic medical record study involving African American and White Caucasian adults from the US.

INTRODUCTION: Depression and diabetes commonly co-exist, however the temporal trends in the bidirectional association of both diseases in different sociodemographic setting has not been explored. We investigated the trends in prevalence and likelihood of having either depression or type 2 diabetes (T2DM) in African American (AA, or black) and White Caucasians (WC, or white). METHODS: In this nationwide population-based study, the US Centricity Electronic Medical Records was used to establish cohorts of >2.5 million adults diagnosed with either T2DM or depression between 2006 and 2017. Logistic regression models were used to investigate ethnic differences in: (a) subsequent probability of depression in individuals with T2DM; and (b) subsequent probability of T2DM in individuals with depression; stratified by age and sex. RESULTS: A total of 920,771 (15 % black) adults were identified with T2DM and 1,801,679 (10 % black) with depression. AA diagnosed with T2DM were much younger (56 vs. 60 years) and had significantly lower prevalence of depression (17 vs. 28 %). AA diagnosed with depression were slightly younger (46 vs. 48 years) and had significantly higher prevalence of T2DM (21 % vs. 14 %). The prevalence of depression in T2DM increased from 12 % (11, 14) to 23 % (20, 23) in black and 26 (25, 26) to 32 (32, 33) in white. Depressive AA above 50 years recorded the highest adjusted probability of T2DM (men: 6.3 % (5.8, 7.0), women: 6.3 % (5.9, 6.7)), while diabetic white women below 50 years had the highest probability of depression (20.2 % (18.6, 22.0)). No significant ethnic difference in diabetes was observed for younger adults diagnosed with depression: black 3.1 % (2.7, 3.7); white 2.5 % (2.2, 2.7). CONCLUSIONS: We have observed significant difference in depression between AA and WC recently diagnosed with diabetes consistent across different demographics. Depression in people with diabetes is increasing with significantly higher values among white women younger than 50 years.

Robustness of Multiple Imputation Methods for Missing Risk Factor Data from Electronic Medical Records for Observational Studies.

Evaluating appropriate methodologies for imputation of missing outcome data from electronic medical records (EMRs) is crucial but lacking for observational studies. Using US EMR in people with type 2 diabetes treated over 12 and 24 months with dipeptidyl peptidase 4 inhibitors (DPP-4i, n = 38,483) and glucagon-like peptide 1 receptor agonists (GLP-1RA, n = 8,977), predictors of missingness of disease biomarker (HbA1c) were explored. Robustness of multiple imputation (MI) by chained equations, two-fold MI (MI-2F) and MI with Monte Carlo Markov Chain were compared to complete case analyses for drawing inferences. Compared to younger people (age quartile Q1), those in age quartile Q3 and Q4 were less likely to have missing HbA1c by 25-32% (range of OR CI: 0.55-0.88) at 6-month follow-up and by 26-39% (range of OR CI: 0.50-0.80) at 12-month follow-up. People with HbA1c ≥ 7.5% at baseline were 12% (OR CI: 0.83, 0.93) and 14% (OR CI: 0.77, 0.97) less likely to have missing data at 6-month follow-up in the DPP-4i and GLP-1RA groups, respectively. All imputation methods provided similar HbA1c distributions during follow-up as observed with complete case analyses. The clinical inferences based on absolute change in HbA1c and by proportion of people reducing HbA1c to a clinically acceptable level (≤ 7%) were also similar between imputed data and complete case analyses. MI-2F method provided marginally smaller mean difference between observed and imputed data with relatively smaller standard error of difference, compared to other methods, while evaluating for consistency through artificial within-sample analyses. The established MI techniques can be reliably employed for missing outcome data imputations in large EMR-based relational databases, leading to efficiently designing and drawing robust clinical inferences in pharmaco-epidemiological studies. Supplementary Information: The online version contains supplementary material available at 10.1007/s41666-022-00119-w.

Trend in Blood Pressure Control Post Antihypertensive Drug Initiation in the U.S.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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%, p<0.01). Those with depression had a 4% higher probability of systolic blood pressure control than those without the condition (49% vs 45%, p<0.01). CONCLUSIONS: 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.

Cardiorenal Complications in Young-Onset Type 2 Diabetes Compared Between White Americans and African Americans.

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 <60 years had an 11-49% higher CKD risk, while WA males aged <40 years had a 23% higher and those aged ≥50 years a 7-14% lower CKD risk, respectively. The mediation effects of CKD on the HF risk difference between ethnicities across age-groups (range 54-91%) were higher compared with those of HF on CKD risk difference between ethnicities across age-groups (13-39%). 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.

Antidepressant prescriptions and therapy intensification in men and women newly diagnosed with depression in the UK.

BACKGROUND: Evidence on therapeutic interventions and factors driving treatment intensification (TI) in people with incident depression in UK are scarce. AIMS: To explore antidepressant prescribing patterns and factors influencing TI. DESIGN: and setting: Retrospective cohort study of adults with incident depression diagnosed between 2006 and 2017 using UK primary care database. METHODS: Patterns of antidepressant prescriptions, and factors influencing TI were evaluated by sex. RESULTS: 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 < 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. CONCLUSIONS: 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.

Young Adult Depression, Antidepressant Prescriptions, and Therapy Intensification in People With Incident Depression in the United States.

Objective: To evaluate the temporal trend in young adult depression, prescription patterns of first- and second-line antidepressants, and factors influencing therapy intensification for depression stratified by sex.Methods: A retrospective cohort of people aged ≥ 18 years with incident depression between 2006 and 2017 was extracted from the Centricity Electronic Medical Records.Results: Among 2,201,086 people with depression (82% on antidepressants), the mean age was 47 years, 29% were male, 40% had cardiometabolic multimorbidity, and 32% were diagnosed at age < 40 years (young adult depression). Prevalence of young adult depression increased significantly from 26% to 36% with a higher proportion in females compared to males (34% vs 26%) between 2006 and 2017. Selective serotonin reuptake inhibitors (SSRIs) were the most prescribed first-line antidepressant (56%), with a prescribing rate increase from 47 per 1,000 person-years to 81 per 1,000 person-years. Among first-line antidepressant recipients, 23% had treatment intensification after a median of 17 months. Compared to those aged 60-70 years, younger males and females had a similar significantly higher treatment intensification risk (range of hazard ratio [HR], 1.09-1.46). Cardiometabolic multimorbidity was associated with a 2% (HR CI, 1.01-1.05) and 7% (HR CI, 1.05-1.09) higher treatment intensification risk in males and females, respectively, while anxiety increased the treatment intensification risk by 63% (HR CI, 1.57-1.68) in males and 57% (HR CI, 1.52-1.62) in females. Non-Whites and SSRI initiators had lower risks of treatment intensification (all HR CI < 1).Conclusions: More than one-third of US adults with depression are aged < 40 years with an increasing trend among females. The temporal antidepressant prescribing rates were similar between sex, while significant ethnic disparity in therapy intensification was observed between sex.

Association of biological antirheumatic therapy with risk for type 2 diabetes: a retrospective cohort study in incident rheumatoid arthritis.

OBJECTIVE: To explore possible associations of treatment with biological disease-modifying antirheumatic drugs (bDMARDs), including T-cell-based and interleukin-6 inhibition (IL-6i)-based therapies, and the risk for type 2 diabetes mellitus (T2DM) in patients with rheumatoid arthritis (RA). STUDY DESIGN, SETTING AND PARTICIPANTS: Five treatment groups were selected from a United States Electronic Medical Records database of 283 756 patients with RA (mean follow-up, 5 years): never received bDMARD (No bDMARD, n=125 337), tumour necrosis factor inhibitors (TNFi, n=34 873), IL-6i (n=1884), T-cell inhibitors (n=5935) and IL-6i+T cell inhibitor abatacept (n=1213). Probability and risk for T2DM were estimated with adjustment for relevant confounders. RESULTS: In the cohort of 169 242 patients with a mean 4.5 years of follow-up and a mean 641 200 person years of follow-up, the adjusted probability of developing T2DM was significantly lower in the IL-6i (probability, 1%; 95% CI 0.6 to 2.0), T-cell inhibitor (probability, 3%; 95% CI 2.3 to 3.3) and IL-6i+T cell inhibitor (probability, 2%; 95% CI 0.1 to 2.9) groups than in the No bDMARD (probability, 5%; 95% CI 4.6 to 4.9) and TNFi (probability, 4%; 95% CI 3.7 to 4.7) groups. Compared with No bDMARD, the IL-6i and IL-6i+T cell inhibitor groups had 37% (95% CI of HR 0.42 to 0.96) and 34% (95% CI of HR 0.46 to 0.93) significantly lower risk for T2DM, respectively; there was no significant difference in risk in the TNFi (HR 0.99; 95% CI 0.93 to 1.06) and T-cell inhibitor (HR 0.96; 95% CI 0.82 to 1.12) groups. CONCLUSIONS: Treatment with IL-6i, with or without T-cell inhibitors, was associated with reduced risk for T2DM compared with TNFi or No bDMARDs; a less pronounced association was observed for the T-cell inhibitor abatacept.

Retrospective cohort study evaluating the efficacy and safety of an orthopaedic consultant-led virtual fracture clinic in an Australian level 1 trauma centre.

BACKGROUND: In Australian health care, the consistent rise in demand for orthopaedic outpatient clinic services is creating marked challenges in the provision of quality care. This study investigates the efficacy and safety of a virtual fracture clinic (VFC) as an alternative model of care for the management of acute injuries and musculoskeletal conditions in the Australian public hospital setting. METHODS: A retrospective cohort study of consecutive emergency department (ED) referrals to the Department of Orthopaedic Surgery was conducted comparing outcomes prior to (November 2015-February 2017) and after (March 2017-June 2018) implementation of a VFC. The primary outcome measures assessed were the proportion of referrals virtually discharged and unplanned 30-day ED re-attendance rates. RESULTS: A total of 737 (36.4%) referrals managed by the VFC were discharged without requiring orthopaedic outpatient clinic attendance. The rate of unplanned ED re-attendances was 5.2% post-VFC implementation compared to 6.5% at baseline (P = 0.01). VFC implementation was also associated with reductions in the average number of orthopaedic outpatient clinic attendances per referral (1.1 versus 1.7, P < 0.01) and the number of referrals lost to follow-up (7.2% versus 14.7%, P < 0.01). In addition, patient wait times for first contact by the orthopaedic team were significantly reduced from a median of 7 (IQR 5, 9) days to 2 (IQR 1, 3) days post-intervention (P < 0.01). No complications or adverse events were reported. CONCLUSION: This study demonstrates that a VFC is applicable to the Australian healthcare system, and can lead to effective and safe provision of orthopaedic outpatient care.

Association of Cardiometabolic Multimorbidity and Depression With Cardiovascular Events in Early-Onset Adult Type 2 Diabetes: A Multiethnic Study in the U.S.

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 <50 years of age increased during 2012-2017 (AA 34-38%, WC 26-29%). Depression prevalence increased during 2000-2017 (AA 15-23%, WC 20-34%), with an increasing trend for CM at diagnosis in both groups. Compared with WC, the adjusted MACE-3 risk was significantly higher in AA across all age-groups, more pronounced in the 18-39-year age-group (hazard ratio 95% CI 1.42, 1.88), and in patients with and without depression. AAs had a 17% (1.05, 1.31) significantly higher adjusted ASCVD risk in the 18-39-year age-group only. Depression was independently associated with ASCVD and MACE-3 risk in both ethnic groups across all age-groups. Other comorbidities were independently associated with ASCVD and MACE-3 risk only among WCs. 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.

Third-Line Antidiabetic Therapy Intensification Patterns and Glycaemic Control in Patients with Type 2 Diabetes in the USA: A Real-World Study.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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 < 7.5% was similar in the sulfonylurea, GLP-1 RA, and SGLT-2i groups (minimum, maximum of 95% CI of probability 0.41, 0.49), whereas those receiving DPP-4i had a significantly lower probability of achieving an HbA1c < 7.5% (0.37; 95% CI 0.36-0.38). CONCLUSION: This study, based on a large representative cohort of patients with T2DM from the USA, suggests the need for revisiting real-world practices in choosing therapeutic intensification pathways and a more proactive strategy to tackle the persistent risk factor burden in patients with T2DM.

Evaluating the Representativeness of US Centricity Electronic Medical Records With Reports From the Centers for Disease Control and Prevention: Comparative Study on Office Visits and Cardiometabolic Conditions.

BACKGROUND: Electronic medical record (EMR)-based clinical and epidemiological research has dramatically increased over the last decade, although establishing the generalizability of such big databases for conducting epidemiological studies has been an ongoing challenge. To draw meaningful inferences from such studies, it is essential to fully understand the characteristics of the underlying population and potential biases in EMRs. OBJECTIVE: This study aimed to assess the generalizability and representativity of the widely used US Centricity Electronic Medical Record (CEMR), a primary and ambulatory care EMR for population health research, using data from the National Ambulatory Medical Care Surveys (NAMCS) and the National Health and Nutrition Examination Surveys (NHANES). METHODS: The number of office visits reported in the NAMCS, designed to meet the need for objective and reliable information about the provision and the use of ambulatory medical care services, was compared with similar data from the CEMR. The distribution of major cardiometabolic diseases in the NHANES, designed to assess the health and nutritional status of adults and children in the United States, was compared with similar data from the CEMR. RESULTS: Gender and ethnicity distributions were similar between the NAMCS and the CEMR. Younger patients (aged <15 years) were underrepresented in the CEMR compared with the NAMCS. The number of office visits per 100 persons per year was similar: 277.9 (95% CI 259.3-296.5) in the NAMCS and 284.6 (95% CI 284.4-284.7) in the CEMR. However, the number of visits for males was significantly higher in the CEMR (CEMR: 270.8 and NAMCS: 239.0). West and South regions were underrepresented and overrepresented, respectively, in the CEMR. The overall prevalence of diabetes along with age and gender distribution was similar in the CEMR and the NHANES: overall prevalence, 10.1% and 9.7%; male, 11.5% and 10.8%; female, 9.1% and 8.8%; age 20 to 40 years, 2.5% and 1.8%; and age 40 to 60 years, 9.4% and 11.1%, respectively. The prevalence of obesity was similar: 42.1% and 39.6%, with similar age and female distribution (41.5% and 41.1%) but different male distribution (42.7% and 37.9%). The overall prevalence of high cholesterol along with age and female distribution was similar in the CEMR and the NHANES: overall prevalence, 12.4% and 12.4%; and female, 14.8% and 13.2%, respectively. The overall prevalence of hypertension was significantly higher in the CEMR (33.5%) than in the NHANES (95% CI: 27.0%-31.0%). CONCLUSIONS: The distribution of major cardiometabolic diseases in the CEMR is comparable with the national survey results. The CEMR represents the general US population well in terms of office visits and major chronic conditions, whereas the potential subgroup differences in terms of age and gender distribution and prevalence may differ and, therefore, should be carefully taken care of in future studies.

Temporal Trend in Young-Onset Type 2 Diabetes-Macrovascular and Mortality Risk: Study of U.K. Primary Care Electronic Medical Records.

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 <50 years at diagnosis increased during 2000-2010 and then stabilized. The incidence rates of ASCVD and ACM declined in people aged ≥50 years but did not decrease in people <50 years. Compared with people aged ≥50 years, those aged 18-39 years at diagnosis had a higher proportion of obesity (71% obese) and higher HbA1c (8.6%), and 71% had high LDL-C, while only 18% were on cardioprotective therapy. Although 2% in this age-group had ASCVD at diagnosis, 23% were identified as high risk. In the 18-39-year age-group, the adjusted average years to ASCVD/ACM in high-risk individuals (9.1 years [95% CI 8.2-10.0]/9.3 years [8.1-10.4]) were similar to the years in those with low risk (10.0 years [9.5-10.5]/10.5 years [9.7-11.2]). However, individuals aged ≥50 years with high risk were likely to experience an ASCVD event 1.5-2 years earlier and death 1.1-1.5 years earlier compared with low-risk groups (P < 0.01). 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.

Cardiovascular Risk Factor Burden in People With Incident Type 2 Diabetes in the U.S. Receiving Antidiabetic and Cardioprotective Therapies.

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.