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Obesity is the most common chronic disease in the U.S. Patients with obesity have many cardiovascular risk factors, often modifiable. It is important to identify patients with obesity at high risk of atherosclerotic cardiovascular disease (ASCVD) to be able to appropriately direct treatment and resources. We conducted an observational study of EMR data of 399,360 adults with BMI ≥ 25 kg/m2 and without baseline ASCVD between 2000 and 2019. We first identified a literature-based pool of risk factors for ASCVD onset and conducted variable selection by applying least absolute shrinkage and selection operator (LASSO) penalized Cox regression with ten-fold cross-validation on an 80% training dataset. We estimated a regular Cox model on the training dataset with selected variables and evaluated model performance on the remaining 20% dataset. Over the mean of 7.4 years of follow-up, 37,424 (11.7%) of study patients developed ASCVD. The predictive model achieved a Harrell’s C-statistic of 0.81. The greatest risk of ASCVD onset was associated with older age (HR 2.16 per 1 SD = 15.4 years; 95% CI 2.13- 2.20), heart failure (HR 1.85; 95% CI 1.74-1.97), valvular heart disease (HR 1.61; 95% CI 1.53-1.68) and stimulant abuse (HR 1.60; 95% CI 1.41-1.81). Female sex was associated with a lower risk of ASCVD (HR 0.64; 95% CI 0.63-0.65). Patient characteristics found in >5% of patients that carried additional risk included history of smoking (39.9% of patients; HR 1.40; 95% CI 1.37-1.43), proteinuria (5.5%; HR 1.33; 95% CI 1.29-1.38) and hypertension (23.6%; HR 1.29; 95% CI 1.26-1.32). Each standard deviation increase in BMI (5.3 kg/m2) was associated with a 1.15-fold (95% CI 1.14-1.16) increase in the risk of ASCVD onset. It is feasible to use predictive modeling to identify patients with overweight and obesity at high ASCVD risk. This approach could be utilized to guide population management and clinical treatment decisions. Disclosure A. Turchin: Consultant; Self; Proteomics International, Research Support; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Pfizer Inc., Sanofi, Stock/Shareholder; Self; Brio Systems. F. J. Morrison: None. M. Shubina: None. S. Shinde: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. N. Ahmad: Employee; Self; Eli Lilly and Company. H. Kan: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Bristol-Myers Squibb Company, GlaxoSmithKline plc. Funding Eli Lilly and Company

Obesity is the most common chronic disease in the U.S. Patients with obesity are at high risk for type 2 diabetes mellitus (T2DM); however, many of their risk factors for T2DM are modifiable. It is important to identify patients with obesity at high risk for T2DM to appropriately direct treatment and resources. We conducted an observational study of EMR data of 399,711 adults with BMI ≥ 25 kg/m2 and without baseline T2DM between 2000 and 2019. We first identified a literature-based pool of risk factors for T2DM onset and conducted variable selection by applying LASSO penalized Cox regression with ten-fold cross-validation on an 80% training dataset. We estimated a regular Cox model on the training dataset with selected variables and evaluated model performance on the remaining 20% dataset. Over a mean of 7.4 years of follow-up, 38,898 (9.8%) study patients developed T2DM. The predictive model achieved a Harrell’s C-statistic of 0.81. The greatest risk of T2DM was associated with gestational diabetes (HR 2.53; 95% CI 2.12-3.01), Asian and Hispanic race/ethnicity (HRs 2.38 and 1.94; 95% CIs 2.24-2.53 and 1.86-2.02, respectively), family history of DM (HR 2.00; 95% CI 1.95-2.04) and PCOS (HR 1.84; 95% CI 1.63-2.07). Female sex (HR 0.77; 95% CI 0.75-0.79), having a partner (HR 0.90; 95% CI 0.88-0.92) or commercial insurance (HR 0.86; 95% CI 0.84-0.88) were associated with a lower risk of T2DM. Characteristics found in >5% of patients that carried additional risk included proteinuria (5.0% of patients; HR 1.53; 95% CI 1.47-1.59), hypertension (23.9%; HR 1.21; 95% CI 1.18-1.25), high cholesterol (11.9%; HR 1.19; 95% CI 1.15-1.23), and history of smoking (40.5%; HR 1.18; 95% CI 1.15-1.21). Each standard deviation increase in BMI (5.2 kg/m2) was associated with a 1.51-fold (95% CI 1.49-1.52) increase in T2DM onset. It is feasible to use predictive modeling to identify patients with overweight and obesity at high risk of T2DM. This approach could be utilized to guide population management and clinical treatment decisions. Disclosure A. Turchin: Consultant; Self; Proteomics International, Research Support; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Pfizer Inc., Sanofi, Stock/Shareholder; Self; Brio Systems. F. J. Morrison: None. M. Shubina: None. S. Shinde: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. N. Ahmad: Employee; Self; Eli Lilly and Company. H. Kan: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Bristol-Myers Squibb Company, GlaxoSmithKline plc. Funding Eli Lilly and Company

Background Evidence suggests that insulin therapy of patients with type 2 diabetes mellitus (T2DM) is frequently discontinued. However, the reasons for discontinuing insulin and factors associated with insulin discontinuation in this patient population are not well understood. Methods We conducted a retrospective cohort study of adults with T2DM prescribed insulin between 2010 and 2017 at Partners HealthCare. Reasons for discontinuing insulin and factors associated with insulin discontinuation were studied using electronic medical records (EMR) data. Natural language processing (NLP) was applied to identify reasons from unstructured clinical notes. Factors associated with insulin discontinuation were extracted from structured EMR data and evaluated using multivariable logistic regression. Results Among 7009 study patients, 2957 (42.2%) discontinued insulin within 12 months after study entry. Most patients who discontinued insulin (2121 / 71.7%) had reasons for discontinuation documented. The most common reasons were improving blood glucose control (33.2%), achieved weight loss (18.5%) and initiation of non-insulin diabetes medications (16.7%). In multivariable analysis adjusted for demographics and comorbidities, patients were more likely to discontinue either basal or bolus insulin if they were on a basal-bolus regimen (OR 1.6, 95% CI 1.3 to 1.8; p p Conclusions In this large real-world evidence study conducted in an area with a high penetration of health insurance, insulin discontinuation countenanced by healthcare providers was common. In most cases it was linked to achievement of glycemic control, achieved weight loss and initiation of other diabetes medications. Factors associated with and stated reasons for insulin discontinuation were different from those previously described for non-adherence to insulin therapy, identifying it as a distinct clinical phenomenon.

OBJECTIVE To investigate the association between ambulatory medication reconciliation and health care utilization in patients with diabetes. RESEARCH DESIGN AND METHODS In this retrospective cohort analysis, we studied adults taking at least one diabetes medication treated in primary care practices affiliated with two academic medical centers between 2000 and 2014. We assessed the relationship between the fraction of outpatient diabetes medications reconciled over a 6-month period and the composite primary outcome of combined frequency of emergency department (ED) visits and hospitalizations over the subsequent 6 months. RESULTS Among 261,765 reconciliation assessment periods contributed by 31,689 patients, 176,274 (67.3%), 27,775 (10.6%), and 57,716 (22.1%) had all, some, or none of the diabetes medications reconciled, respectively. Patients with all, some, or no diabetes medications reconciled had 0.354, 0.377, and 0.384 primary outcome events per 6 months, respectively (P < 0.0001). In a multivariable analysis adjusted for demographics and comorbidities, having some or all versus no diabetes medications reconciled was associated with a lower risk of the primary outcome (rate ratio 0.94 [95% CI 0.90–0.98; P = 0.0046] vs. 0.92 [0.89–0.95; P < 0.0001], respectively). Introduction of feedback to individual providers was associated with a significant increase in the odds of all diabetes medications being reconciled (2.634 [2.524–2.749]; P < 0.0001). CONCLUSIONS A higher fraction of reconciled outpatient diabetes medications was associated with a lower frequency of ED visits and hospitalizations. Individual performance feedback could help to achieve more comprehensive medication reconciliation.

AIM To determine the relationship between decline of insulin therapy by individuals with type 2 diabetes and subsequent blood glucose control. METHODS We retrospectively studied adults with type 2 diabetes and suboptimal (HbA1c ≥ 53 mmol/mol [7.0%]) glycaemic control followed at two academic hospitals between 2000 and 2014 who were recommended insulin therapy. Decline of insulin therapy recommendations was identified using natural language processing of provider notes. Time to HbA1c < 53 mmol/mol (7.0%) served as the primary outcome. RESULTS Of 5307 study participants, 2267 (42.7%) declined insulin therapy. Median time to HbA1c control in individuals who declined vs. started insulin therapy was 50 vs. 38 months, respectively (P < 0.001). In multivariable analysis, decline of insulin therapy was associated with hazard ratio for HbA1c control of 0.89 (95% CI 0.82 to 0.97; P = 0.008). Participants were more likely to accept insulin therapy recommendations if they had diabetes complications (OR 1.32; 95% CI 1.13 to 1.53; P < 0.001) or a higher HbA1c (OR 1.10; 95% CI 1.07 to 1.13; P < 0.001), and less likely if they were older (OR 0.81; 95% CI 0.76 to 0.86; P < 0.001) or were taking more non-insulin diabetes medications (OR 0.78; 95% CI 0.74 to 0.83; P < 0.001). CONCLUSIONS Individuals with uncontrolled type 2 diabetes who declined insulin therapy subsequently had worse glycaemic control. These findings highlight the need to improve our understanding of the relationship of this common but poorly explored clinical phenomenon to blood glucose control and ultimately diabetes complications.

Insulin is an important part of treatment of type 2 diabetes mellitus (T2DM). Nevertheless, reasons for discontinuation of insulin therapy are poorly understood. We conducted a real-world-evidence analysis of EMR data at Partners HealthCare to study adults with T2DM who were prescribed insulin between 2010 and 2016. Reasons for insulin discontinuation were identified from a combination of structured EMR data and natural language processing analysis of EMR notes using a validated tool (sensitivity 76.9% and positive predictive value 89.7%). The mean age of study patients was 60.2 years; 52.7% were male. Among 7,009 study patients, 2,957 (42.2%) discontinued insulin within 12 months after study start. In multivariable logistic regression analysis adjusted for demographics and comorbidities, patients were more likely to discontinue either basal or bolus insulin if they were on a basal-bolus regimen compared to basal only (OR 1.56, 95% CI 1.33 to 1.83; p < 0.001) or if they were being seen by an endocrinologist (OR 2.58; 95% CI 2.22 to 2.99; p < 0.001). Most patients (2,121/71.7%) had one or more reasons for discontinuation documented. The most common reasons were improving blood glucose (BG) control (33.2%), weight loss (likely ultimately also leading to lower BG) (18.5%) and initiation of non-insulin diabetes medications (16.7%). In multivariable analysis, patients were more likely to stop insulin due to achievement of good BG control if they were treated by an endocrinologist (OR 2.52; 95% CI 2.11 to 3.00; p < 0.001) or by a female physician (OR 1.43; 95% CI 1.26 to 1.63; p < 0.001). This study represents a successful attempt to use natural language processing to understand reasons for insulin discontinuation. Insulin discontinuation is common, and particularly so for patients on a basal-bolus regimen. Achievement of glycemic control, weight loss and initiation of other diabetes medications were the most common reasons for insulin discontinuation. Disclosure J. Wu: None. F.J. Morrison: None. Z. Zhao: Employee; Self; Lilly Diabetes. X. He: Employee; Self; Eli Lilly and Company. M. Shubina: None. S. Malmasi: None. W. Ge: None. X. Peng: None. A. Turchin: Advisory Panel; Self; Monarch Medical Technologies. Research Support; Self; Eli Lilly and Company. Stock/Shareholder; Self; Brio Systems. Funding Eli Lilly and Company

OBJECTIVE To investigate the relationship between lifestyle counseling in primary care settings and clinical outcomes in patients with diabetes. RESEARCH DESIGN AND METHODS We retrospectively studied hyperglycemic adults with diabetes treated at primary care practices between 2000 and 2014. We analyzed the relationship between frequency of lifestyle counseling (identified using natural language processing of electronic notes) and a composite outcome of death and cardiovascular events during subsequent follow-up. RESULTS Among patients with monthly counseling or more, 10-year cumulative incidence of the primary outcome was 33.0% compared with 38.1% for less than monthly counseling (P = 0.0005). In multivariable analysis, higher frequency of lifestyle counseling was associated with lower incidence of the primary outcome (hazard ratio 0.88 [95% CI 0.82–0.94]; P < 0.001). CONCLUSIONS More frequent lifestyle counseling was associated with a lower incidence of cardiovascular events and death among patients with diabetes.

Obesity is the most common chronic disease in the U.S. Patients with obesity have many risk factors for cancer, often modifiable. It is important to identify patients with obesity at high risk of cancer to be able to appropriately direct treatment and resources. Given that the risk pool is large, it is imperative to identify a clinically meaningful metric for risk stratification to help guide interventions. We conducted an observational study of electronic medical records data for 394,161 adults aged between 18 and 80, with BMI ≥ 25 kg/m2 and without baseline history of cancer between 2000 and 2019. We first identified a literature-based pool of risk factors for cancer onset and conducted variable selection by applying least absolute shrinkage and selection operator (LASSO) penalized Cox regression with ten-fold cross-validation on an 80% training dataset. Effects of the selected variables on risk of cancer (excluding non-melanoma skin cancer) onset were assessed using Cox regression on the 80% training dataset. The resulting model accuracy was evaluated using Cox regression on a withheld 20% validation dataset. Participants had a mean age of 46.7 (SD: 15.5) years and mean body mass index (BMI) of 30.5 (SD: 5.4) kg/m2; 51.9% were women. Over a mean of 7.5 years of follow-up, 34,679 (8.8%) of study patients developed cancer. The predictive model achieved a Harrell’s C-statistic of 0.73. The greatest risk of cancer incidence was associated with HIV infection (HR 2.22; 95% CI 1.88–2.63; 0.27% of patients), older age (HR 2.05 per 1 SD = 15.5 years; 95% CI 2.01- 2.09), hepatitis C infection (HR 1.48; 95% CI 1.34–1.63; 0.96% of patients), and family history of cancer (HR 1.44; 95% CI 1.41–1.48; 42.5% of patients). Additional patient characteristics found in >5% of patients that also carried risk included proteinuria (5.8% of patients; HR 1.23; 95% CI 1.18–1.29) and history of smoking (40.7% of patients; HR 1.20; 95% CI 1.17–1.23). Each standard deviation increase in BMI (5.4 kg/m2) was associated with a hazard ratio of 1.06 (95% CI 1.05–1.07) for incident cancer. It is feasible to use predictive modeling to identify patients with overweight and obesity at high cancer risk. This approach could be utilized to guide population management and clinical treatment decisions.

Objective To characterize the relationship between body mass index (BMI) and all-cause mortality among adults with hypertension. Methods We conducted a retrospective cohort study of adults with hypertension from The Health Improvement Network primary care research database in the United Kingdom. Mortality rates within each BMI category were compared after adjustment for age, sex, pre existing medical conditions, smoking, alcohol use, and socioeconomic status. Results During a median follow-up period of 8.0 years, 34,354 deaths occurred (8.8%) among the 388,724 study patients. In multivariable analysis that included interaction terms between smoking, heavy alcohol use, preexisting cardiovascular disease and chronic obstructive pulmonary disease (COPD), and BMI category to account for these conditions' association with increased mortality at lower BMI levels, a U-shaped relationship was observed between BMI and mortality, with no difference in mortality in overweight (25.0–29.9 kg/m2) versus normal (18.5–24.9 kg/m2) BMI (risk ratio 1.00, 95% confidence interval 0.95 to 1.04, P = 0.80). In multivariable analysis that used narrower BMI categories, lowest mortality was observed between BMI of 23.0 and 26.9 kg/m2. Conclusions Patients with hypertension who have no history of smoking, heavy alcohol use, cardiovascular disease, or COPD have lowest mortality between BMI of 23.0 and 26.9 kg/m2.

OBJECTIVE To establish quantitative characteristics of lifestyle counseling documentation associated with improved glycemic control in patients with diabetes. RESEARCH DESIGN AND METHODS We retrospectively studied 10,870 hyperglycemic (HbA1c ≥7.0% [53 mmol/mol]) adults with diabetes followed at primary care practices affiliated with two academic hospitals between 2000 and 2010. Documentation intensity was represented by the mean number of characters per note documenting lifestyle counseling. Heterogeneity was calculated as the normalized Levenshtein distance between lifestyle counseling sentences between consecutive notes. Cox proportional hazards model was constructed to assess association of heterogeneity and intensity of lifestyle counseling documentation to time to HbA1c RESULTS Comparing patients in the highest versus lowest tertile by documentation heterogeneity and documentation intensity, median time to HbA1c CONCLUSIONS Higher heterogeneity and intensity of lifestyle counseling documentation in provider notes were associated with better glycemic control. Further studies involving direct observation of patient care are needed to establish the nature of the relationship between documentation characteristics and patient outcomes.

Many patients can tolerate statin therapy after an adverse reaction. However, optimal patient selection criteria and methods of reattempting statin therapy after an adverse reaction are unknown.To identify patient and treatment characteristics associated with a successful statin reattempt after an adverse reaction.We retrospectively studied adults treated in primary care practices affiliated with 2 academic medical centers between 2000 and 2012 who reattempted statin therapy after an adverse reaction. Statin reattempts were considered successful if the patient had at least 2 statin prescriptions after discontinuation of the original statin, and had an active electronic medical record statin record at 2 years after the adverse reaction.Among 6196 patients included in the study, 4536 (73.2%) successfully reattempted statin therapy. In multivariable analysis, history of coronary artery disease, stroke, or diabetes (odds ratio [OR] 1.195; P = .008) and reattempted treatment with a different statin (OR 1.463; P .0001) were associated with greater odds of a successful reattempt. Adverse reaction during the first year after statin initiation (OR 0.721; P .0001) or myalgia or myopathy (OR 0.807; P = .001) as well as history of adverse reactions to nonstatin drugs (OR 0.908; P .0001) were associated with lower odds.Nature and timing of the adverse reaction, patient's medical history and the medication prescribed affected the likelihood of a successful reattempt of statin therapy after an adverse reaction. These findings suggest that a patient-centered approach to restarting statins should be considered for patients at high cardiovascular risk to improve the chances of success.

Background Many patients discontinue statin treatment, often after having a possible adverse reaction. The risks and benefits of continued statin therapy after an adverse reaction are not known. Objective To examine the relationship between continuation of statin therapy (any prescription within 12 months after an adverse reaction) and clinical outcomes. Design Retrospective cohort study. Setting Primary care practices affiliated with 2 academic medical centers. Participants Patients with a presumed adverse reaction to a statin between 2000 and 2011. Measurements Information on adverse reactions to statins was obtained from structured electronic medical record data or natural-language processing of narrative provider notes. The primary composite outcome was time to a cardiovascular event (myocardial infarction or stroke) or death. Results Most (81%) of the adverse reactions to statins were identified from the text of electronic provider notes. Among 28 266 study patients, 19 989 (70.7%) continued receiving statin prescriptions after the adverse reaction. Four years after the presumed adverse event, the cumulative incidence of the composite primary outcome was 12.2% for patients with continued statin prescriptions, compared with 13.9% for those without them (difference, 1.7% [95% CI, 0.8% to 2.7%]; P < 0.001). In a secondary analysis of 7604 patients for whom a different statin was prescribed after the adverse reaction, 2014 (26.5%) had a documented adverse reaction to the second statin, but 1696 (84.2%) of those patients continued receiving statin prescriptions. Limitations The risk for recurrent adverse reactions to statins could not be established for the entire sample. It was also not possible to determine whether patients actually took the statins. Conclusion Continued statin prescriptions after an adverse reaction were associated with a lower incidence of death and cardiovascular events. Primary Funding Source Chinese National Key Program of Clinical Science, National Natural Science Foundation of China, and Young Scientific Research Fund of Peking Union Medical College Hospital.

Background/Aims: Many patients with chronic kidney disease (CKD) do not receive lipid-lowering therapy despite their high cardiovascular risk. The reasons for this are unknown. Methods: We have conducted a retrospective cohort study of discontinuation of lipid-lowering drugs in patients with CKD stage 3 and higher treated in practices affiliated with two academic medical centers between 2000 and 2010. Information on medication discontinuation and its reasons was obtained from electronic medical records, including natural language processing of electronic notes using previously validated software. Results: Out of 14,034 patients in the study cohort, 10,072 (71.8%) stopped their lipid-lowering drugs at least once, and 2,444 (17.4%) stopped them for at least 1 month. Patients who had a comorbidity associated with higher cardiovascular risk were less likely to stop lipid-lowering drugs. Insurance request was the most common explicitly documented reason for discontinuation, and adverse reactions were the most common reason for long-term discontinuation. In a multivariable analysis, patients were more likely to stop a lipid-lowering drug because of an insurance request if they had government insurance and they were also more likely to stop a lipid-lowering drug because of adverse reactions if they had a history of multiple adverse reactions to other medications. There was no significant relationship between CKD stage and the reason for discontinuation of lipid-lowering drugs. Conclusions: Patients with CKD frequently stop lipid-lowering drugs. Insurance requests and adverse reactions are common reasons for the discontinuation. Further research is needed to ensure appropriate lipid-lowering therapy for these individuals at high cardiovascular risk. i 2014 S. Karger AG, Basel

OBJECTIVE Studies have shown that patients without a consistent primary care provider have inferior outcomes. However, little is known about the mechanisms for these effects. This study aims to determine whether primary care physicians (PCPs) provide more frequent medication intensification, lifestyle counseling, and patient encounters than other providers in the primary care setting. RESEARCH DESIGN AND METHODS This retrospective cohort study included 584,587 encounters for 27,225 patients with diabetes and elevated A1C, blood pressure, and/or LDL cholesterol monitored for at least 2 years. Encounters occurred at primary care practices affiliated with two teaching hospitals in eastern Massachusetts. RESULTS Of the encounters documented, 83% were with PCPs, 13% were with covering physicians, and 5% were with midlevel providers. In multivariable analysis, the odds of medication intensification were 49% (P < 0.0001) and 26% (P < 0.0001) higher for PCPs than for covering physicians and midlevel providers, respectively, whereas the odds of lifestyle counseling were 91% (P < 0.0001) and 21% (P = 0.0015) higher. During visits with acute complaints, covering physicians were even less likely, by a further 52% (P < 0.0001), to intensify medications, and midlevel providers were even less likely, by a further 41% (P < 0.0001), to provide lifestyle counseling. Compared with PCPs, the hazard ratios for time to the next encounter after a visit without acute complaints were 1.11 for covering physicians and 1.19 for midlevel providers (P < 0.0001 for both). CONCLUSIONS PCPs provide better care through higher rates of medication intensification and lifestyle counseling. Covering physicians and midlevel providers may enable more frequent encounters when PCP resources are constrained.

Historical literature reports risk of fetal demise after diabetic ketoacidosis (DKA) in pregnancy as high as 25–60% (1,2). However, estimates have generally been based on small sample sizes, with limited investigation of other fetal outcomes or risk factors associated with poor fetal outcomes. We aimed to provide an updated assessment of the incidence and risk factors for fetal demise and other adverse outcomes in women with DKA during pregnancy. This retrospective cohort study included pregnancies between 1996 and 2015 with at least one DKA event in women with type 1 diabetes at one of three teaching hospitals in Boston. Data were collected through medical record review. Pregnancies were excluded if information on birth status (live or demise) and gestational age at birth or demise were unknown. Among the 77 DKA events in 64 pregnancies in 62 women included in the study, fetal demise, preterm …

Patients with both diabetes and coronary artery disease (CAD) have exceedingly high cardiovascular risk. Nevertheless, little is known about prevalence of statin therapy in this population and reasons why some patients may not be receiving this potentially life-saving treatment.To investigate prevalence and predictors of statin therapy in patients with combined diabetes and CAD.We conducted a retrospective cohort study of primary care patients with diabetes and CAD followed at 2 academic medical centers between 2000 and 2011. We used multivariable logistic regression to identify patient and provider characteristics associated with (1) statin initiation (any history of statin therapy) and (2) statin persistence (active statin prescription at the study end).Of 8488 study patients, 7427 (87.5%) ever received statins and 6212 (73.2%) had persistent statin therapy. Younger age (odds ratio [OR], 1.26 per decade), smoking (OR, 1.49) and cardiologist evaluation (OR, 2.26) were associated with statin initiation (P .0001 for all). Younger age (OR, 1.17), family history of CAD (OR, 1.39), no adverse reactions to statins (OR, 1.40; P .0001 for all), female sex (OR, 1.22; P = .005), history of smoking (OR, 1.22; P = .003), cardiologist evaluation (OR, 1.23; P = .002), and lower HbA1c (OR, 1.04; P = 0.003) were associated with persistent statin therapy. Only 362 (29.8%) of the 1215 patients without persistent statin therapy had tried at least 2 statins, and 58 (4.8%) tried 3 statins.Many patients with combined CAD and diabetes are not treated with statins, although in this very high-risk group, even moderate-intensity statins result in meaningful reductions in cardiovascular events. Higher cardiovascular risk and cardiologist evaluation were associated with higher prevalence of statin therapy.

OBJECTIVE In clinical trials, diet, exercise, and weight counseling led to short-term improvements in blood glucose, blood pressure, and cholesterol levels in patients with diabetes. However, little is known about the long-term effects of lifestyle counseling on patients with diabetes in routine clinical settings. RESEARCH DESIGN AND METHODS This retrospective cohort study of 30,897 patients with diabetes aimed to determine whether lifestyle counseling is associated with time to A1C, blood pressure, and LDL cholesterol control in patients with diabetes. Patients were included if they had at least 2 years of follow-up with primary care practices affiliated with two teaching hospitals in eastern Massachusetts between 1 January 2000 and 1 January 2010. RESULTS Comparing patients with face-to-face counseling rates of once or more per month versus less than once per 6 months, median time to A1C CONCLUSIONS Lifestyle counseling in the primary care setting is strongly associated with faster achievement of A1C, blood pressure, and LDL cholesterol control. These results confirm that the findings of controlled clinical trials are applicable to the routine care setting and provide evidence to support current treatment guidelines.

OBJECTIVE Hypoglycemia is associated with adverse outcomes in mixed populations of patients in intensive care units. It is not known whether the same risks exist for diabetic patients who are less severely ill. In this study, we aimed to determine whether hypoglycemic episodes are associated with higher mortality in diabetic patients hospitalized in the general ward. RESEARCH DESIGN AND METHODS This retrospective cohort study analyzed 4,368 admissions of 2,582 patients with diabetes hospitalized in the general ward of a teaching hospital between January 2003 and August 2004. The associations between the number and severity of hypoglycemic (≤50 mg/dl) episodes and inpatient mortality, length of stay (LOS), and mortality within 1 year after discharge were evaluated. RESULTS Hypoglycemia was observed in 7.7% of admissions. In multivariable analysis, each additional day with hypoglycemia was associated with an increase of 85.3% in the odds of inpatient death (P = 0.009) and 65.8% (P = 0.0003) in the odds of death within 1 year from discharge. The odds of inpatient death also rose threefold for every 10 mg/dl decrease in the lowest blood glucose during hospitalization (P = 0.0058). LOS increased by 2.5 days for each day with hypoglycemia (P < 0.0001). CONCLUSIONS Hypoglycemia is common in diabetic patients hospitalized in the general ward. Patients with hypoglycemia have increased LOS and higher mortality both during and after admission. Measures should be undertaken to decrease the frequency of hypoglycemia in this high-risk patient population.

BACKGROUND:Women are less likely to be prescribed statins than men. Existing reports explain only a fraction of this difference. We conducted a study to identify factors that account for sex differences in statin therapy among patients with coronary artery disease (CAD). METHODS AND RESULTS:We retrospectively studied 24,338 patients with CAD who were followed for at least a year between 2000 and 2011 at two academic medical centers. Women (9,006 / 37% of study patients) were less likely to either have initiated statin therapy (81.9% women vs. 87.7% men) or to have persistent statin therapy at the end of follow-up (67.0% women vs. 71.4% men). Women were older (72.9 vs. 68.4 years), less likely to have ever smoked (49.8% vs. 65.6%), less likely to have been evaluated by a cardiologist (57.5% vs. 64.5%) and more likely to have reported an adverse reaction to a statin (27.1% vs. 21.7%) (p < 0.0001 for all). In multivariable analysis, patients with history of smoking (OR 1.094; p 0.017), younger age (OR 1.013 / year), cardiologist evaluation (OR 1.337) and no reported adverse reactions to statins (OR 1.410) were more likely (p < 0.0001 for all) to have persistent statin therapy. Together, these four factors accounted for 90.4% of the sex disparity in persistent statin therapy. CONCLUSIONS:Several specific factors appear to underlie divergent statin therapy in women vs. men. Identifying such drivers may facilitate programmatic interventions and stimulate further research to overcome sex differences in applying proven interventions for cardiovascular risk reduction.

Overexpression of the NEDD9/HEF1/Cas-L scaffolding protein is frequent, and drives invasion and metastasis in breast, head and neck, colorectal, melanoma, lung and other types of cancer. We have examined the consequences of genetic ablation of Nedd9 in the MMTV-HER2/ERBB2/neu mouse mammary tumor model. Unexpectedly, we found that only a limited effect on metastasis in MMTV-neu;Nedd9(-/-) mice compared with MMTV-neu;Nedd9(+/+) mice, but instead a dramatic reduction in tumor incidence (18 versus 80%), and a significantly increased latency until tumor appearance. Orthotopic reinjection and tail-vein injection of cells arising from tumors, coupled with in vivo analysis, indicated tumors arising in MMTV-neu;Nedd9(-/-) mice had undergone mutational selection that overcame the initial requirement for Nedd9. To better understand the defects in early tumor growth, we compared mammary progenitor cell pools from MMTV-neu;Nedd9(-/-) versus MMTV-neu;Nedd9(+/+) mice. The MMTV-neu;Nedd9(-/-) genotype selectively reduced both the number and colony-forming potential of mammary luminal epithelial progenitor cells, while not affecting basal epithelial progenitors. MMTV-neu;Nedd9(-/-) mammospheres had striking defects in morphology and cell polarity. All of these defects were seen predominantly in the context of the HER2/neu oncogene, and were not associated with randomization of the plane of mitotic division, but rather with depressed expression the cell attachment protein FAK, accompanied by increased sensitivity to small molecule inhibitors of FAK and SRC. Surprisingly, in spite of these significant differences, only minimal changes were observed in the gene expression profile of Nedd9(-/-) mice, indicating critical Nedd9-dependent differences in cell growth properties were mediated via post-transcriptional regulation of cell signaling. Coupled with emerging data indicating a role for NEDD9 in progenitor cell populations during the morphogenesis of other tissues, these results indicate a functional requirement for NEDD9 in the growth of mammary cancer progenitor cells.

Background Home blood pressure (BP) is closely linked to patient outcomes. However, the prevalence of its documentation has not been examined. The objective of this study was to analyze the prevalence and factors affecting documentation of home BP in routine clinical care. Methods A retrospective study of 142,973 encounters of 9,840 hypertensive patients with diabetes from 2000 to 2005 was performed. The prevalence of recorded home BP and the factors associated with its documentation were analyzed. We assessed validity of home BP information by comparing the difference between home and office BP to previously published prospective studies. Results Home BP was documented in narrative notes for 2.08% of encounters where any blood pressure was recorded and negligibly in structured data (EMR flowsheets). Systolic and diastolic home BP in narrative notes were lower than office BP readings by 9.6 and 2.5 mm Hg, respectively (p < 0.0001 for both), consistent with prospective data. Probability of home BP documentation increased by 23.0% for each 10 mm Hg of office systolic BP (p < 0.0001), by 6.2% for each $10,000 in median income of zip code (p = 0.0055), and by 17.7% for each decade in the patient's age (p < 0.0001). Conclusions Home BP readings provide a valid representation of the patient's condition, yet are seldom documented despite their potential utility in both patient care and research. Strong association between higher patient income and home BP documentation suggests that the cost of the monitors may be a limiting factor; reimbursement of home BP monitoring expenses should be pursued.

The relationship between encounter frequency (average number of provider-patient encounters over a period of time) and blood pressure for hypertensive patients is unknown. We tested the hypothesis that shorter encounter intervals are associated with faster blood pressure normalization. We performed a retrospective cohort study of 5042 hypertensive patients with diabetes mellitus treated at primary care practices affiliated with 2 academic hospitals between 2000 and 2005. Distinct periods of continuously elevated blood pressure (≥130/85 mm Hg) were studied. We evaluated the association of the average encounter interval with time to blood pressure normalization and rate of blood pressure decrease. Blood pressure of the patients with the average interval between encounters ≤1 month normalized after a median of 1.5 months at the rate of 28.7 mm Hg/month compared with 12.2 months at 2.6 mm Hg/month for the encounter interval >1 month ( P P P

Background—Regular recertification is mandatory to maintain board certification status in all specialties. However, the evidence that physicians’ performance decreases with time since initial certification is limited. We therefore carried out a study to determine whether the frequency of antihypertensive treatment intensification for diabetic patients changes with time since their physicians’ last board certification.Methods and Results—In this retrospective cohort study, we analyzed treatment of 8127 hypertensive patients with diabetes mellitus treated by 301 internists at primary care practices affiliated with 2 large academic hospitals. Patient visits with documented blood pressure ≥130/85 mm Hg between January 1, 2000, and August 31, 2005, were studied. The association between the number of years since the physician’s last board certification and the probability of pharmacological antihypertensive treatment intensification at a given visit was analyzed. Frequency of treatment intensification decreased from 26.7% for physicians who were board certified the previous year to 6.9% for physicians who were board certified 31 years before the visit. Treatment intensification rate was 22.5% for physicians certified ≤10 years ago versus 16.9% for physicians last certified >10 years ago (PP=0.0097).Conclusion—Physician intensification of pharmacological therapy for blood pressure levels above the recommended treatment goals decreases with time since the last board certification. This finding supports the current policy of mandatory recertification.

Hyperglycemia is common among diabetic inpatients, and has been linked to adverse outcomes. However, antihyperglycemic treatment is seldom intensified in noncritical care patients, and the relationship between intensification frequency and glucose control is poorly understood. We evaluated the relationship between treatment intensification and changes in blood glucose in hospitalized diabetic patients.We retrospectively analyzed 3,613 hospitalized diabetic patients who were admitted to the hospital between January 2003 and August 2004, were not hospitalized in an ICU, were not prescribed IV insulin or total parenteral nutrition (TPN), had a length of stay of at least 3 days, and had at least one point-of-care blood glucose measurement. A linear model was used to assess the relationship between intensification of antihyperglycemic medications and the average daily change in point-of-care glucose measurements.Hyperglycemia (180 mg/dL) was documented at least once for 82.5% of patient admissions. Antihyperglycemic treatment was intensified for 22.0% of days with hyperglycemia. Intensifications of scheduled and sliding scale insulin, but not oral medications, were associated with a 11.1 mg/dL (p0.0001) and 12.2 mg/dL (p0.0001) reduction in the average daily glucose, respectively. Hypoglycemia (50 mg/dL) was documented on 2.2% of days after antihyperglycemic treatment intensification.In this cohort, lack of treatment intensification in response to inpatient hyperglycemia was common. Antihyperglycemic treatment intensification was strongly associated with decrease in average daily glucose, while hypoglycemia was uncommon. This suggests that increasing the frequency of treatment intensifications could lead to improved glycemic control in inpatients with diabetes.

OBJECTIVE—The volume of patients cared for by an individual physician (physician volume) has been linked to improved outcomes for a number of conditions. It is not known whether a similar association exists for treatment of diabetes. In this study we aimed to determine whether physician volume is associated with improved process measures and outcomes in diabetes care. RESEARCH DESIGN AND METHODS—This retrospective cohort study analyzed electronic medical records data for 7,120 patients with diabetes treated by 368 primary care physicians at practices affiliated with two large academic hospitals. The associations between physician volume of diabetic patients (diabetes volume) and annual A1C and LDL testing, as well as blood pressure, A1C, and LDL levels, were evaluated. RESULTS—In multivariable analysis, absolute diabetes volume was linked to decreased odds of A1C testing (4% less for each additional patient seen; P = 0.05), and relative diabetes volume (fraction of the total patients seen who had diabetes) was associated with decreased odds of both A1C (25% less for every 10% increase in the number of diabetic patients seen annually; P = 0.03) and LDL testing (20% less for every 10% increase in the number of diabetic patients; P < 0.001). Physician volume was not significantly associated with the odds of blood pressure, A1C, or LDL control at the end of the study. CONCLUSIONS—Higher physician volume in care of diabetic patients is associated with decreased adherence to surveillance guidelines and no measurable difference in treatment outcomes.

To investigate the optimal systolic blood pressure goal above which new antihypertensive medications should be added or doses of existing medications increased ("systolic intensification threshold") and to determine the relation between delays in medication intensification and follow-up and the risk of cardiovascular events or death.Retrospective cohort study.Primary care practices in the United Kingdom, 1986-2010.88 756 adults with hypertension from The Health Improvement Network nationwide primary care research database.Rates of acute cardiovascular events or death from any cause for patients with different hypertension treatment strategies (defined by systolic intensification threshold, time to intensification, and time to follow-up over the course of a 10 year treatment strategy assessment period) after adjustment for age, sex, smoking status, socioeconomic deprivation, history of diabetes, cardiovascular disease or chronic kidney disease, Charlson comorbidity index, body mass index, medication possession ratio, and baseline blood pressure.During a median follow-up of 37.4 months after the treatment strategy assessment period, 9985 (11.3%) participants had an acute cardiovascular event or died. No difference in risk of the outcome was seen between systolic intensification thresholds of 130-150 mm Hg, whereas systolic intensification thresholds greater than 150 mm Hg were associated with progressively greater risk (hazard ratio 1.21, 95% confidence interval 1.13 to 1.30; P0.001 for intensification threshold of 160 mm Hg). Outcome risk increased progressively from the lowest (0-1.4 months) to the highest fifth of time to medication intensification (hazard ratio 1.12, 1.05 to 1.20; P=0.009 for intensification between 1.4 and 4.7 months after detection of elevated blood pressure). The highest fifth of time to follow-up (2.7 months) was also associated with increased outcome risk (hazard ratio 1.18, 1.11 to 1.25; P0.001).Systolic intensification thresholds higher than 150 mm Hg, delays of greater than 1.4 months before medication intensification after systolic blood pressure elevation, and delays of greater than 2.7 months before blood pressure follow-up after antihypertensive medication intensification were associated with increased risk of an acute cardiovascular event or death. These findings support the importance of timely medical management and follow-up in the treatment of patients with hypertension.

More frequent patient-provider encounters may lead to faster control of hemoglobin A1c level, blood pressure (BP), and low-density lipoprotein (LDL) cholesterol (LDL-C) level (hereafter referred to as hemoglobin A1c, BP, and LDL-C) and improve outcomes, but no guidelines exist for how frequently patients with diabetes mellitus (DM) should be seen.This retrospective cohort study analyzed 26,496 patients with diabetes and elevated hemoglobin A1c, BP, and/or LDL-C treated by primary care physicians at 2 teaching hospitals between January 1, 2000, and January 1, 2009. The relationship between provider encounter (defined as a note in the medical record) frequency and time to hemoglobin A1c, BP, and LDL-C control was assessed.Comparing patients who had encounters with their physicians between 1 to 2 weeks vs 3 to 6 months, median time to hemoglobin A1c less than 7.0% was 4.4 vs 24.9 months (not receiving insulin) and 10.1 vs 52.8 months (receiving insulin); median time to BP lower than 130/85 mm Hg was 1.3 vs 13.9 months; and median time to LDL-C less than 100 mg/dL was 5.1 vs 32.8 months, respectively (P.001 for all). In multivariable analysis, doubling the time between physician encounters led to an increase in median time to hemoglobin A1c (not receiving [35%] and receiving [17%] insulin), BP (87%), and LDL-C (27%) targets (P.001 for all). Time to control decreased progressively as encounter frequency increased up to once every 2 weeks for most targets, consistent with the pharmacodynamics of the respective medication classes.Primary care provider encounters every 2 weeks are associated with fastest achievement of hemoglobin A1c, BP, and LDL-C targets for patients with diabetes mellitus.

Study objective The potential of infectious disease spread in diseases such as tuberculosis, infectious disease epidemic such as avian flu and the threat of terrorism with agents capable of airborne transmission have focused attention on the need for increased surge capacity for patient isolation. Total negative pressure isolation using portable bioisolation tents may provide a solution. The study assesses the ability of health care workers to perform emergency procedures in this environment. Methods Physician performance in completing predetermined critical actions in 5 emergency care scenarios inside and outside of a bioisolation tent ("setting") was studied in an advanced medical simulation laboratory. By design, no pretraining of subjects about total negative pressure isolation use occurred. Impact of setting on time to completion of predetermined critical actions was the primary outcome measured. Secondary variables studied included impact of study groups, scenarios, and run order (inside or outside of the tent first). Subjective assessments were obtained through questionnaires. Results Four teams of 3 physicians completed 5 emergency patient care scenarios during 2 4-hour sessions. Mean time to completion of critical actions was for tent/no tent 298 seconds/284 seconds (P=.69, one way ANOVA), respectively. Mean time to completion for first versus second performance of a scenario in the crossover design was 338 versus 243 (P=.01). The mean score for self-assessed performance did not differ according to setting. Conclusion The ability of physicians naive to the total negative pressure isolation environment to perform emergency medical critical actions was not significantly degraded by a simulated bioisolation tent patient care environment.