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Introduction: Benign breast disease (BBD) and high mammographic breast density (MBD) are prevalent and independent risk factors for invasive breast cancer. It has been suggested that temporal changes in MBD may impact future invasive breast cancer risk, but this has not been studied among women with BBD. Methods: We undertook a nested case–control study within a cohort of 15,395 women with BBD in Kaiser Permanente Northwest (KPNW; 1970–2012, followed through mid-2015). Cases (n = 261) developed invasive breast cancer > 1 year after BBD diagnosis, whereas controls (n = 249) did not have breast cancer by the case diagnosis date. Cases and controls were individually matched on BBD diagnosis age and plan membership duration. Standardized %MBD change (per 2 years), categorized as stable/any increase (≥ 0%), minimal decrease of less than 5% or a decrease greater than or equal to 5%, was determined from baseline and follow-up mammograms. Associations between MBD change and breast cancer risk were examined using adjusted unconditional logistic regression. Results: Overall, 64.5% (n = 329) of BBD patients had non-proliferative and 35.5% (n = 181) had proliferative disease with/without atypia. Women with an MBD decrease (≤ − 5%) were less likely to develop breast cancer (Odds Ratio (OR) 0.64; 95% Confidence Interval (CI) 0.38, 1.07) compared with women with minimal decreases. Associations were stronger among women ≥ 50 years at BBD diagnosis (OR 0.48; 95% CI 0.25, 0.92) and with proliferative BBD (OR 0.32; 95% CI 0.11, 0.99). Discussion: Assessment of temporal MBD changes may inform risk monitoring among women with BBD, and strategies to actively reduce MBD may help decrease future breast cancer risk. [ABSTRACT FROM AUTHOR]

Unmet basic needs (eg, food insecurity, inadequate housing) are major barriers to diabetes self-management. The purpose of this study was to identify the prevalence of unmet basic needs and examine the association with diabetes control and care utilization among insured persons with diabetes. A total of 4043 adult patients with diabetes were screened for unmet basic needs using Your Current Life Situation, a screener for unmet basic needs, during a clinical encounter or as an online survey, during the study period (January 1, 2016–August 31, 2017). Hemoglobin A1c and care utilization (outpatient, emergency department [ED], hospitalization, diabetes-related prescription refills) were extracted from the electronic health record 12 months prior to screening. The authors compared patients with unmet basic needs to those with no needs on poor diabetes control (ie, A1c ≥8%) and care utilization using multivariable regression models. Of the 4043 patients screened, 25% endorsed ≥1 unmet basic need. In adjusted analyses, the presence of unmet basic needs was associated with an increased likelihood of having an A1c ≥8% (OR = 1.77; 95% CI 1.47, 2.13), more outpatient visits (incidence rate ratio [IRR] = 1.3; 1.2, 1.4), more ED visits (IRR = 2.3; 2.0, 2.6), more hospitalizations (IRR = 1.8; 1.5, 2.2), and more delays in refilling diabetes medication (IRR = 1.21; 1.13, 1.30). Findings indicate that unmet basic needs are highly prevalent, even among an insured patient population, and are associated with poor diabetes-related clinical outcomes and excess utilization. Future studies to determine best strategies to integrate this information into treatment planning are warranted. [ABSTRACT FROM AUTHOR]

Background Benign breast disease (BBD) is a strong breast cancer risk factor, but identifying patients that might develop invasive breast cancer remains a challenge. Methods By applying machine-learning to digitized hematoxylin and eosin–stained biopsies and computer-assisted thresholding to mammograms obtained circa BBD diagnosis, we generated quantitative tissue composition metrics and determined their association with future invasive breast cancer diagnosis. Archival breast biopsies and mammograms were obtained for women (18-86 years of age) in a case-control study, nested within a cohort of 15 395 BBD patients from Kaiser Permanente Northwest (1970-2012), followed through mid-2015. Patients who developed incident invasive breast cancer (ie, cases; n = 514) and those who did not (ie, controls; n = 514) were matched on BBD diagnosis age and plan membership duration. All statistical tests were 2-sided. Results Increasing epithelial area on the BBD biopsy was associated with increasing breast cancer risk (odds ratio [OR]Q4 vs Q1 = 1.85, 95% confidence interval [CI] = 1.13 to 3.04; P trend =.02). Conversely, increasing stroma was associated with decreased risk in nonproliferative, but not proliferative, BBD (P heterogeneity =.002). Increasing epithelium-to-stroma proportion (ORQ4 vs Q1 = 2.06, 95% CI =1.28 to 3.33; P trend =.002) and percent mammographic density (MBD) (ORQ4 vs Q1 = 2.20, 95% CI = 1.20 to 4.03; P trend =.01) were independently and strongly predictive of increased breast cancer risk. In combination, women with high epithelium-to-stroma proportion and high MBD had substantially higher risk than those with low epithelium-to-stroma proportion and low MBD (OR = 2.27, 95% CI = 1.27 to 4.06; P trend =.005), particularly among women with nonproliferative (P trend =.01) vs proliferative (P trend =.33) BBD. Conclusion Among BBD patients, increasing epithelium-to-stroma proportion on BBD biopsies and percent MBD at BBD diagnosis were independently and jointly associated with increasing breast cancer risk. These findings were particularly striking for women with nonproliferative disease (comprising approximately 70% of all BBD patients), for whom relevant predictive biomarkers are lacking. [ABSTRACT FROM AUTHOR]

Background: Among women diagnosed with invasive breast cancer, 30% have a prior diagnosis of benign breast disease (BBD). Thus, it is important to identify factors among BBD patients that elevate invasive cancer risk. In the general population, risk factors differ in their associations by clinical pathologic features; however, whether women with BBD show etiologic heterogeneity in the types of breast cancers they develop remains unknown.Methods: Using a nested case-control study of BBD and breast cancer risk conducted in a community healthcare plan (Kaiser Permanente Northwest), we assessed relationships of histologic features in BBD biopsies and patient characteristics with subsequent breast cancer risk and tested for heterogeneity of associations by estrogen receptor (ER) status, tumor grade, and size. The study included 514 invasive breast cancer cases (median follow-up of 9 years post-BBD diagnosis) and 514 matched controls, diagnosed with proliferative or non-proliferative BBD between 1971 and 2006, with follow-up through mid-2015. Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained using multivariable polytomous logistic regression models.Results: Breast cancers were predominantly ER-positive (86%), well or moderately differentiated (73%), small (74% < 20 mm), and stage I/II (91%). Compared to patients with non-proliferative BBD, proliferative BBD with atypia conferred increased risk for ER-positive cancer (OR = 5.48, 95% CI = 2.14-14.01) with only one ER-negative case, P-heterogeneity = 0.45. The presence of columnar cell lesions (CCLs) at BBD diagnosis was associated with a 1.5-fold increase in the risk of both ER-positive and ER-negative tumors, with a 2-fold increase (95% CI = 1.21-3.58) observed among postmenopausal women (56%), independent of proliferative BBD status with and without atypia. We did not identify statistically significant differences in risk factor associations by tumor grade or size.Conclusion: Most tumors that developed after a BBD diagnosis in this cohort were highly treatable low-stage ER-positive tumors. CCL in BBD biopsies may be associated with moderately increased risk, independent of BBD histology, and irrespective of ER status. [ABSTRACT FROM AUTHOR]

Background: Studies of progression of kidney dysfunction typically focus on renal replacement therapy or percentage decline in estimated glomerular filtration rate (eGFR) as outcomes. Our aim was to compare real-world patients with and without T2D to estimate progression from and to clinically defined categories of kidney disease and all-cause mortality.Methods: This was an observational cohort study of 31,931 patients with and 33,201 age/sex matched patients without type 2 diabetes (T2D) who had a serum creatinine and urine albumin-to-creatinine ratio (UACR) or dipstick proteinuria (DP) values. We used the first available serum creatinine value between 2006 and 2012 to calculate baseline eGFR and categorized them and the corresponding UACR/DP values using the Kidney Disease Improving Global Outcomes (KDIGO) categories. To assess our primary outcomes, we extracted probabilities of eGFR progression or mortality from life-table analyses and conducted multivariable Cox regression analyses of relative risk adjusted for age, sex, race/ethnicity, smoking, ischemic heart disease, heart failure, and use of renal-angiotensin-aldosterone system inhibitors.Results: Patterns of eGFR decline were comparable among patients with vs. without T2D with larger percentage declines at higher albuminuria levels across all eGFR categories. eGFR decline was generally larger among T2D patients, particularly in those with severely increased albuminuria. Across all CKD categories, risk of progression to the next higher category of eGFR was substantially increased with increasing albuminuria. For example, the risk was 23.5, 36.2, and 65.1% among T2D patients with eGFR 30-59 ml/min/1.73m2 and UACR < 30, 30-299, and > 300 mg/dL, respectively (p < 0.001). Other comparisons were similarly significant. Among patients with low eGFR and normal to mildly increased albuminuria, the relative risk was up to 8-fold greater for all-cause mortality compared with the non-CKD subgroup (eGFR> 60 ml/min/1.73m2 with normal to mildly increased albuminuria).Conclusions: Presence of albuminuria was associated with accelerated eGFR decline independent of T2D. Risk for adverse outcomes was remarkably high among patients with CKD and normal to mildly increased albuminuria levels. Independent of T2D or albuminuria, a substantial risk for adverse outcomes exists for CKD patients in a routine care setting. [ABSTRACT FROM AUTHOR]

Objective: Weight loss is recommended for overweight patients with diabetes but avoidance of weight gain may be a more realistic goal. We calculated the 4-year economic impact of maintaining body weight versus gaining weight.Research Design and Methods: Among 8,154 patients with type 2 diabetes, we calculated weight change as the difference between the first body weight measure in 2010 and the last measure in 2013 and calculated mean glycated hemoglobin (A1C) from all measurements from 2010 to 2013. We created four analysis groups: weight change <5% and A1C <7%; weight gain ≥5% and A1C <7%; weight change <5% and A1C ≥7%; and weight gain ≥5% and A1C ≥7%. We compared change in medical costs between 2010 and 2013, adjusted for demographic and clinical characteristics.Results: Patients who maintained weight within 5% of baseline experienced a reduction in costs of about $400 regardless of A1C. In contrast, patients who gained ≥5% of baseline weight and had mean A1C ≥7% had an increase in costs of $1,473 (P < 0.001). Those who gained >5% of their baseline weight with mean A1C <7% had a modest increase in costs ($387, NS).Conclusions: Patients who gained at least 5% of their baseline body weight and did not maintain A1C <7% over 4 years experienced a 14% increase in medical costs, whereas those who maintained good glycemic control had a mean cost increase of 3.3%. However, patients who maintained weight within 5% of baseline had costs that were ∼5% lower than baseline. Avoidance of weight gain may reduce costs in the long-term. [ABSTRACT FROM AUTHOR]

Introduction. Whether changes in adherence are associated with changes in HbA1c is assumed but not known. Methods. We conducted a observational study of 2,844 type 2 diabetes patients who initiated metformin as their first antihyperglycemic drug. Using HbA1c measures before, 6–12 months after, and up to 3 years after metformin initiation, we analyzed HbA1c change as a function of initial adherence and change in adherence. Results. Compared with no adherence, initial adherence of 50–79% was associated with an adjusted reduction in HbA1c of 0.45% while adherence ≥80% was associated with HbA1c reduction of 0.73%. Change from some initial adherence (1–79%) to total nonadherence was associated with 0.25% increase in HbA1c. Change from some to full adherence was associated with an HbA1c decrease of 0.15%. Those associations were accentuated among patients not in glycemic control: change from some to no adherence was associated with an HbA1c increase of 0.63% and change from some to full adherence was associated with an HbA1c decrease of 0.40%. Conclusions. Initial adherence to newly prescribed metformin therapy produces substantial HbA1c reduction. Among those with modest adherence but suboptimal glycemic control, the difference between moving to full adherence versus nonadherence results in lower HbA1c of one percentage point. [ABSTRACT FROM AUTHOR]

The article presents the study on the incidence and risk components for postprocedure venous thromboembolism (VTE) in podiatric surgery. Risk factors associated with VTE included prior VTE, use of hormone therapy or oral contraceptives, and obesity. Researchers of the study found a low overall risk of VTE in podiatric surgery, which could mean that routine prophylaxis is not justified, however those with two or more VTE risk factors should consider periprocedure prophylaxis.

Objective: To identify the characteristics associated with glycemic response to newly initiated insulin therapy.Research Design and Methods: We identified 1,139 type 2 diabetic patients who initiated insulin therapy between 1 January 2009 and 30 June 2010. Outcomes of interest were the proportion of patients achieving A1C <7% and mean change in A1C within 3-9 months.Results: Mean A1C at insulin initiation was 8.2 vs. 9.2% among those who did and did not attain A1C <7% (P < 0.001). Within a mean of 5 months, 464 (40.7%) patients attained A1C <7%. In multivariable analyses controlling for insulin regimen, dose, and oral agent use, preinsulin A1C was responsible for nearly all the explained variance in A1C change. Each one percentage point of preinsulin A1C reduced the probability of attaining <7% by 26% (odds ratio 0.74 [95% CI 0.68-0.80]).Conclusions: Insulin initiation at lower levels of A1C improves goal attainment and independently increases glycemic response. [ABSTRACT FROM AUTHOR]

OBJECTIVE--To identify the characteristics associated with glycemic response to newly initiated insulin therapy. RESEARCH DESIGN AND METHODS--We identified 1,139 type 2 diabetic patients who initiated insulin therapy between 1 January 2009 and 30 June 2010. Outcomes of interest were the proportion of patients achieving A1C <7% and mean change in A1C within 3-9 months. RESULTS--Mean A1C at insulin initiation was 8.2 vs. 9.2% among those who did and did not attain A1C <7% (P < 0.001). Within a mean of 5 months, 464 (40.7%) patients attained A1C <7%. In multivariable analyses controlling for insulin regimen, dose, and oral agent use, preinsulin A1C was responsible for nearly all the explained variance in A1C change. Each one percentage point of preinsulin A1C reduced the probability of attaining <7% by 26% (odds ratio 0.74 [95% CI 0.68-0.80]). CONCLUSIONS--Insulin initiation at lower levels of A1C improves goal attainment and independently increases glycemic response. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via the original article. [ABSTRACT FROM AUTHOR]