Kidney disease progression and all-cause mortality across estimated glomerular filtration rate and albuminuria categories among patients with vs. without type 2 diabetes.

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.

Fall Ascertainment and Development of a Risk Prediction Model Using Electronic Medical Records.

OBJECTIVES: To examine the use of electronic medical record (EMR) data to ascertain falls and develop a fall risk prediction model in an older population. DESIGN: Retrospective longitudinal study using 10 years of EMR data (2004-2014). A series of 3-year cohorts included members continuously enrolled for a minimum of 3 years, requiring 2 years pre-fall (no previous record of a fall) and a 1-year fall risk period. SETTING: Kaiser Permanente Hawaii, an ambulatory setting. PARTICIPANTS: A total of 57 678 adults, age 60 years and older. MEASUREMENTS: Initial EMR searches were guided by current literature and geriatricians to understand coding sources of falls as our outcome. Falls were captured by two coding sources: International Classification of Diseases, Ninth Revision (ICD-9) codes (E880-889) and/or a fall listed as a "primary reason for visit." A comprehensive list of EMR predictors of falls were included into prediction models enabling statistical subset selection from many variables and modeling by logistic regression. RESULTS: Although 72% of falls in the training data set were coded as "primary reason for visit," 22% of falls were coded as ICD-9 and 6% coded as both. About 80% were reported in face-to-face encounters (eg, emergency department). A total of 2164 individuals had a fall in the risk period. Using the 13 key predictors (age, comorbidities, female sex, other mental disorder, walking issues, Parkinson's disease, urinary incontinence, depression, polypharmacy, psychotropic and anticonvulsant medications, osteoarthritis, osteoporosis) identified through LASSO regression, the final model had a sensitivity of 67%, specificity of 69%, positive predictive value of 8%, negative predictive value of 98%, and area under the curve of .74. CONCLUSION: This study demonstrated how the EMR can be used to ascertain falls and develop a fall risk prediction model with moderate sensitivity/specificity. Concurrent work with clinical providers to enhance fall documentation will improve the ability of the EMR to capture falls and consequently may improve the model to predict fall risk.

Balancing Adherence and Expense: The Cost-Effectiveness of Two-Sample vs One-Sample Fecal Immunochemical Test.

Colorectal cancer (CRC) causes more than 50,000 deaths each year in the United States but early detection through screening yields survival gains; those diagnosed with early stage disease have a 5-year survival greater than 90%, compared to 12% for those diagnosed with late stage disease. Using data from a large integrated health system, this study evaluates the cost-effectiveness of fecal immunochemical testing (FIT), a common CRC screening tool. A probabilistic decision-analytic model was used to examine the costs and outcomes of positive test results from a 1-FIT regimen compared with a 2-FIT regimen. The authors compared 5 diagnostic cutoffs of hemoglobin concentration for each test (for a total of 10 screening options). The principal outcome from the analysis was the cost per additional advanced neoplasia (AN) detected. The authors also estimated the number of cancers detected and life-years gained from detecting AN. The following costs were included: program management of the screening program, patient identification, FIT kits and their processing, and diagnostic colonoscopy following a positive FIT. Per-person costs ranged from $33 (1-FIT at 150ng/ml) to $92 (2-FIT at 50ng/ml) across screening options. Depending on willingness to pay, the 1-FIT 50 ng/ml and the 2-FIT 50 ng/ml are the dominant strategies with cost-effectiveness of $11,198 and $28,389, respectively, for an additional AN detected. The estimates of cancers avoided per 1000 screens ranged from 1.46 to 4.86, depending on the strategy and the assumptions of AN to cancer progression.

Automated telephone calls to enhance colorectal cancer screening: economic analysis.

OBJECTIVES: To estimate the cost-effectiveness of an automated telephone intervention for colorectal cancer screening from a managed care perspective, using data from a pragmatic randomized controlled trial. METHODS: Intervention patients received calls for fecal occult blood testing (FOBT) screening. We searched patients' electronic medical records for any screening (defined as FOBT, flexible sigmoidoscopy, double-contrast barium enema, or colonoscopy) during follow-up. Intervention costs included project implementation and management, telephone calls, patient identification, and tracking. Screening costs included FOBT (kits, mailing, and processing) and any completed screening tests during follow-up. We estimated the incremental cost-effectiveness ratio (ICER) of the cost per additional screen. RESULTS: At 6 months, average costs for intervention and control patients were $37 (25% screened) and $34 (19% screened), respectively. The ICER at 6 months was $42 per additional screen, less than half what other studies have reported. Cost-effectiveness probability was 0.49, 0.84, and 0.99 for willingness-to-pay thresholds of $40, $100, and $200, respectively. Similar results were seen at 9 months. A greater increase in FOBT testing was seen for patients aged >70 years (45/100 intervention, 33/100 control) compared with younger patients (25/100 intervention, 21/100 control). The intervention was dominant for patients aged >70 years and was $73 per additional screen for younger patients. It increased screening rates by about 6% and costs by $3 per patient. CONCLUSIONS: At willingness to pay of $100 or more per additional screening test, an automated telephone reminder intervention can be an optimal use of resources.

Incidence and demography of femur fractures with and without atypical features.

The case definition, community incidence, and characteristics of atypical femoral shaft fractures (FSFs) are poorly understood. This retrospective study utilized electronic medical records and radiograph review among women ≥50 years of age and men ≥65 years of age from January 1996 to June 2009 at Kaiser Permanente Northwest to describe the incidence rates and characteristics of subgroups of femur fractures. Fractures were categorized based on the American Society for Bone and Mineral Research (ASBMR) as atypical fracture major features (AFMs) (low force, shaft location, transverse or short oblique, noncomminuted) and AFMs with additional minor radiograph features (AFMms) (beaking, cortical thickening, or stress fracture). There were 5034 fractures in the study. The incidence rates of FSFs (without atypical features) and AFMs appeared flat (cumulative incidence: 18.2 per 100,000 person-years, 95% CI = 16.0-20.7; 5.9 per 100,000 person-years, 95% CI = 4.6-7.4; respectively) with 1,271,575 person-years observed. The proportion of AFMs that were AFMms increased over time. Thirty percent of AFMs had any dispensing of a bisphosphonate prior to the fracture, compared to 15.8% of the non-atypical FSFs. Years of oral glucocorticosteroid dispensing appeared highest in AFM and AFMm fractures. Those with AFMs only were older and had a lower frequency of bisphosphonate dispensing compared to those with AFMms. We conclude that rates of FSFs, with and without atypia, were low and stable over 13.5 years. Patients with only AFMs appear to be different from those with AFMms; it may be that only the latter group is atypical. There appear to be multiple associated risk factors for AFMm fractures.

Patient Barriers to Mammography Identified During a Reminder Program.

Background: Patient mammogram reminders are effective at increasing screening, but patient barriers remain. We evaluated patient characteristics and reported barriers for their association with mammogram completion after a reminder program. Methods: This retrospective cohort study used data from electronic records and a subgroup survey. Participants were female Kaiser Permanente Northwest health maintenance organization (HMO) members aged 50-69 who were 20 months past their last mammogram (index date) and had received a reminder intervention (n = 4708). A mailed survey was completed by 340 of 667 (50.2%) women who received it. The intervention was a "mammogram due soon" postcard 20 months after the last mammogram, followed by up to two automated phone calls and one live call for nonresponders. The outcome was mammogram completion at 10 months after index date. Results: Characteristics associated with lower mammogram completion rates were aged <60 (odds ratio [OR] 0.69, p < 0.0001), health plan membership <5 years (OR 0.81, p = 0.019), family income <$40,000/year (OR 0.77, p = 0.018), and obesity (OR 0.67, p < 0.0001). Obese women were more likely than nonobese women to report "too much pain" from mammograms (31.3% vs.18.8%, p < 0.01). Younger women were more likely to endorse that they were "too busy" (19.1% vs. 6.4%, p < 0.001) and had more worries about mammogram accuracy (2.5 vs. 2.3 on a 5-point scale, p < 0.05). Pain mediated the relationship between obesity and mammogram completion rates (indirect effect = -0.111, p = 0.008). Conclusions: Important barriers to mammogram completion remain even after an effective mammogram reminder system among insured patients. Tailored interventions are necessary to overcome these barriers.

Automated telephone calls improved completion of fecal occult blood testing.

BACKGROUND: Although colorectal cancer (CRC) prognosis is improved by early diagnosis, screening rates remain low. OBJECTIVE: To determine the effect of an automated telephone intervention on completion of fecal occult blood testing (FOBT). RESEARCH DESIGN: In this randomized controlled trial conducted at Kaiser Permanente Northwest, a not-for-profit health maintenance organization, 5905 eligible patients aged 51 to 80, at average risk for CRC and due for CRC screening, were randomly assigned to an automated telephone intervention (n = 2943) or usual care (UC; n = 2962). The intervention group received up to three 1-minute automated telephone calls that provided a description and health benefits of FOBT. During the call, patients could request that an FOBT kit be mailed to their home. Those who requested but did not return the cards received an automated reminder call. Cox proportional hazard method was used to determine the independent effect of automated telephone calls on completion of an FOBT, after adjusting for age, sex, and prior CRC screening. RESULTS: By 6 months after call initiation, 22.5% in the intervention and 16.0% in UC had completed an FOBT. Those in the intervention group were significantly more likely to complete an FOBT (hazard ratio, 1.31; 95% confidence interval, 1.10-1.56) compared with UC. Older patients (aged 71-80 vs. aged 51-60) were also more likely to complete FOBT (hazard ratio, 1.48; 95% confidence interval, 1.07-2.04). CONCLUSIONS: Automated telephone calls increased completion of FOBT. Further research is needed to evaluate automated telephone interventions among diverse populations and in other clinical settings.

Effect of a multimodal reminder program on repeat mammogram screening.

BACKGROUND: Patient mammogram reminders are effective but have not been fully implemented in practice to improve routine screening. The effectiveness of implementation and maintenance phases of a multimodal reminder program that incorporated automated calls capable of efficiently reaching large numbers of women was evaluated to improve repeat mammography screening. DESIGN: A quasi-experimental study was conducted in 2008 using electronic medical record data during three time periods: pre-reminder phase (2004), post-reminder implementation phase (2006), and post-reminder maintenance phase (January 1-July 1, 2007). SETTING/PARTICIPANTS: Participants were female Kaiser Permanente Northwest HMO members aged 42 years or more who were 20 months past their last mammogram (index date) (N=35,104). The intervention program targeted women aged 50-69 years. Women aged 42-49 years (for whom clinical guidelines also recommend mammography) not targeted by the program constituted the primary comparison group (CG1). INTERVENTION: A "mammogram due soon" postcard was mailed to participants 20 months after their last mammogram, followed by up to two automated phone calls and one live call for nonresponders. MAIN OUTCOME MEASURES: The outcome measure was the time until participants received a mammogram in the 10 months following the index date. RESULTS: Pre-reminder, 63.4% of targeted women completed a mammogram; this number increased to 75.4% in the post-reminder implementation phase; 80.6% completed a mammogram in the maintenance phases. After controlling for demographics and clinic visits, intervention women were 1.51 times more likely to complete a mammogram (CI=1.40, 1.62) post-reminder implementation, compared to CG1. The effect was maintained in 2007 (hazard ratio 1.81, CI=1.65, 1.99). CONCLUSIONS: The study found that this multimodal reminder system could be effectively implemented and maintained in a large health system. If widely implemented, this intervention could substantially improve community mammography screening.

Role of endothelial NO synthase phosphorylation in cerebrovascular protective effect of recombinant erythropoietin during subarachnoid hemorrhage-induced cerebral vasospasm.

BACKGROUND AND PURPOSE: In the present study, the effect of subarachnoid hemorrhage (SAH) on the phosphorylation of endothelial NO synthase (eNOS) and the ability of recombinant erythropoietin (Epo) to augment this vasodilator mechanism in the spastic arteries were studied. METHODS: Recombinant adenoviral vectors (10(9) plaque-forming units per animal) encoding genes for human Epo (AdEpo), and beta-galactosidase were injected immediately after injection of autologous arterial blood into the cisterna magna (day 0) of rabbits. Cerebral angiography was performed on day 0 and day 2, and basilar arteries were harvested for Western blots, measurement of cGMP levels, and analysis of vasomotor functions. RESULTS: Injection of autologous arterial blood into cisterna magna resulted in significant vasospasm of the basilar arteries. Despite the narrowing of arterial diameter and reduced expression of eNOS, expressions of phosphorylated protein kinase B (Akt) and phosphorylated eNOS were significantly increased in spastic arteries. Gene transfer of AdEpo reversed the vasospasm. AdEpo-transduced basilar arteries demonstrated significant augmentation of the endothelium-dependent relaxations to acetylcholine, whereas the relaxations to an NO donor, 2-(N,N-diethylamino)diazenolate-2-oxide sodium salt, were not affected. Transduction with AdEpo further increased the expression of phosphorylated Akt and eNOS and elevated basal levels of cGMP in the spastic arteries. CONCLUSIONS: Phosphorylation of eNOS appears to be an adaptive mechanism activated during development of vasospasm. The vascular protective effect of Epo against cerebral vasospasm induced by SAH may be mediated in part by phosphorylation of Akt/eNOS.

Preoperative aspirin therapy is associated with improved postoperative outcomes in patients undergoing coronary artery bypass grafting.

BACKGROUND: Aspirin is beneficial in the setting of atherosclerotic cardiovascular disease. There are limited data evaluating preoperative aspirin administration preceding coronary artery bypass grafting and associated postoperative outcomes. METHODS AND RESULTS: Using prospectively collected data from 1636 consecutive patients undergoing first-time isolated coronary artery bypass surgery at our institution from January 2000 through December 2002, we evaluated the association between aspirin usage within the 5 days preceding coronary bypass surgery and risk of adverse in-hospital postoperative events. A logistic regression model, which included propensity scores, was used to adjust for remaining differences between groups. Overall, there were 36 deaths (2.2%) and 48 adverse cerebrovascular events (2.9%) in the postoperative hospitalization period. Patients receiving preoperative aspirin (n=1316) had significantly lower postoperative in-hospital mortality compared with those not receiving preoperative aspirin [1.7% versus 4.4%; adjusted odds ratio (OR), 0.34; 95% CI, 0.15 to 0.75; P=0.007]. Rates of postoperative cerebrovascular events were similar between groups (2.7% versus 3.8%; adjusted OR, 0.67; 95% CI, 0.32 to 1.50; P=0.31). Preoperative aspirin therapy was not associated with an increased risk of reoperation for bleeding (3.5% versus 3.4%; P=0.96) or requirement for postoperative blood product transfusion (adjusted OR, 1.17; 95% CI, 0.88 to 1.54; P=0.28). CONCLUSIONS: Aspirin usage within the 5 days preceding coronary artery bypass surgery is associated with a lower risk of postoperative in-hospital mortality and appears to be safe without an associated increased risk of reoperation for bleeding or need for blood product transfusion.