Bariatric surgery results: reporting clinical characteristics and adverse outcomes from an integrated healthcare delivery system.

BACKGROUND: Limited data have been reported on bariatric surgery within a large, high-volume regional multicenter integrated healthcare delivery system. OBJECTIVES: Review clinical characteristics and short- and intermediate-term outcomes and adverse events from a bariatric surgery program within an integrated healthcare delivery system. SETTING: Single high-volume, multicenter regional integrated healthcare delivery system. METHODS: Adult patients who underwent primary bariatric surgery during 2010-2011 were reviewed. Clinical characteristics, outcomes, and weight loss results were extracted from the electronic medical record. RESULTS: A total of 2399 patients were identified within the study period. The 30-day rates of clinical outcomes for Roux-en-Y gastric bypass (RYGB; n = 1313) and sleeve gastrectomy (SG; n = 1018) were 2.9% for readmission, 3.0% for major complications, .8% for reoperation, and 0% for mortality. One-year and 2-year weight loss results were as follows: percent weight loss (%WL) was 31.4 (±SD 8.5) and 34.2±12.0% for SG and 34.1±9.3 and 39.1±11.9 for RYGB; percent excess weight loss (%EBWL) was 64.2±18.0 and 69.8±23.7 for SG and 68.0±19.3 and 77.8±23.7 for RYGB; percent excess body mass index loss (%EBMIL) was 72.9±21.0 and 77.7±22.4 for SG and 76.6±22.1% and 85.6±21.6 for RYGB. Follow-up for each procedure at 1 year was 76% for SG (n = 778) and 80% for RYGB (n = 1052) and at 2 years was 65% for SG (n = 659) and 67% for RYGB (n = 875). CONCLUSIONS: A large regional high-volume multicenter bariatric program within an integrated healthcare delivery system can produce excellent short-term results with low rates of short- and intermediate-term adverse outcomes.

Oral steroids for acute radiculopathy due to a herniated lumbar disk: a randomized clinical trial.

IMPORTANCE: Oral steroids are commonly used to treat acute sciatica due to a herniated disk but have not been evaluated in an appropriately powered clinical trial. OBJECTIVE: To determine if oral prednisone is more effective than placebo in improving function and pain among patients with acute sciatica. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled clinical trial conducted from 2008 to 2013 in a large integrated health care delivery system in Northern California. Adults (n=269) with radicular pain for 3 months or less, an Oswestry Disability Index (ODI) score of 30 or higher (range, 0-100; higher scores indicate greater dysfunction), and a herniated disk confirmed by magnetic resonance imaging were eligible. INTERVENTIONS: Participants were randomly assigned in a 2:1 ratio to receive a tapering 15-day course of oral prednisone (5 days each of 60 mg, 40 mg, and 20 mg; total cumulative dose = 600 mg; n = 181) or matching placebo (n = 88). MAIN OUTCOMES AND MEASURES: The primary outcome was ODI change at 3 weeks; secondary outcomes were ODI change at 1 year, change in lower extremity pain (measured on a 0-10 scale; higher scores indicate more pain), spine surgery, and Short Form 36 Health Survey (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) scores (0-100 scale; higher scores better). RESULTS: Observed baseline and 3-week mean ODI scores were 51.2 and 32.2 for the prednisone group and 51.1 and 37.5 for the placebo group, respectively. The prednisone-treated group showed an adjusted mean 6.4-point (95% CI, 1.9-10.9; P = .006) greater improvement in ODI scores at 3 weeks than the placebo group and a mean 7.4-point (95% CI, 2.2-12.5; P = .005) greater improvement at 52 weeks. Compared with the placebo group, the prednisone group showed an adjusted mean 0.3-point (95% CI, -0.4 to 1.0; P = .34) greater reduction in pain at 3 weeks and a mean 0.6-point (95% CI, -0.2 to 1.3; P = .15) greater reduction at 52 weeks. The prednisone group showed an adjusted mean 3.3-point (95% CI, 1.3-5.2; P = .001) greater improvement in the SF-36 PCS score at 3 weeks, no difference in the SF-36 PCS score at 52 weeks (mean, 2.5; 95% CI, -0.3 to 5.4; P = .08), no change in the SF-36 MCS score at 3 weeks (mean, 2.2; 95% CI, -0.4 to 4.8; P = .10), and an adjusted 3.6-point (95% CI, 0.6-6.7; P = .02) greater improvement in the SF-36 MCS score at 52 weeks. There were no differences in surgery rates at 52-week follow-up. Having 1 or more adverse events at 3-week follow-up was more common in the prednisone group than in the placebo group (49.2% vs 23.9%; P < .001). CONCLUSIONS AND RELEVANCE: Among patients with acute radiculopathy due to a herniated lumbar disk, a short course of oral steroids, compared with placebo, resulted in modestly improved function and no improvement in pain. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00668434.

Higher levels of cystatin C are associated with worse cognitive function in older adults with chronic kidney disease: the chronic renal insufficiency cohort cognitive study.

OBJECTIVES: To determine the association between cognition and levels of cystatin C in persons with chronic kidney disease (CKD). DESIGN: Prospective observational study. SETTING: Chronic Renal Insufficiency Cohort Cognitive Study. PARTICIPANTS: Individuals with a baseline cognitive assessment completed at the same visit as serum cystatin C measurement (N = 821; mean age 64.9, 50.6% male, 48.6% white). MEASUREMENTS: Levels of serum cystatin C were categorized into tertiles; cognitive function was assessed using six neuropsychological tests. Scores on these tests were compared across tertiles of cystatin C using linear regression and logistic regression to examine the association between cystatin C level and cognitive performance (1 standard deviation difference from the mean). RESULTS: After multivariable adjustment for age, race, education, and medical comorbidities in linear models, higher levels of cystatin C were associated with worse cognition on the modified Mini-Mental State Examination, Buschke Delayed Recall, Trail-Making Test Part (Trails) A and Part B, and Boston Naming (P < .05 for all). This association remained statistically significant for Buschke Delayed Recall (P = .01) and Trails A (P = .03) after additional adjustment for estimated glomerular filtration rate (eGFR). The highest tertile of cystatin C was associated with greater likelihood of poor performance on Trails A (odds ratio (OR) = 2.17, 95% confidence interval (CI) = 1.16-4.06), Trails B (OR = 1.89, 95% CI = 1.09-3.27), and Boston Naming (OR = 1.85, 95% CI = 1.07-3.19) than the lowest tertile after multivariate adjustment in logistic models. CONCLUSION: In individuals with CKD, higher serum cystatin C levels were associated with worse cognition and greater likelihood of poor cognitive performance on attention, executive function, and naming. Cystatin C is a marker of cognitive impairment and may be associated with cognition independent of eGFR.

Effect of medical oncologists' attitudes on accrual to clinical trials in a community setting.

PURPOSE: Oncology clinical trials (OCTs) are crucial in evaluating new cancer treatments, but only 2% to 3% of US adult patients with cancer enter OCTs. This study assessed barriers to participation in clinical trials among oncologists in a large integrated health care delivery system with an active clinical trials program. Although many studies have identified major physician barriers to enrollment, few have examined how these barriers affect actual trial accrual. METHODS: Using information from a mailed survey, we examined the effect of oncologists' attitudes, beliefs, experiences, sociodemographic factors, and practice characteristics on clinical trial accrual in the 2 years following the survey. We identified relationships between these variables and subsequent clinical trial accrual using correlations and mixed effects models. RESULTS: A construct combining questions that assessed oncologist attitudes, beliefs, and experiences substantially influenced OCT enrollment (r = .51; P < .0001). This construct included awareness of open clinical trials and specific eligible patients, as well as the practice of initiating a discussion about OCTs with most eligible patients. This broad concept of awareness had the greatest correlation with enrollment and mediated the effect on enrollment of other values and beliefs, such as welcoming a patient's initiation of a trial discussion and valuing the support of research nurses and coordinators. CONCLUSION: Even in a health care setting with an active clinical trials program, substantial research personnel, infrastructure support, and widespread access to trials among oncologists and patients, oncologists' participation remains quite variable. Oncologist values, beliefs, and awareness of clinical trials play an important role in OCT accrual.

Prevalence of childhood and adolescent overweight and obesity from 2003 to 2010 in an integrated health care delivery system.

An observational study of the Kaiser Permanente Northern California (KPNC) BMI coding distributions was conducted to ascertain the trends in overweight and obesity prevalence among KPNC members aged 2-19 between the periods of 2003-2005 and 2009-2010. A decrease in the prevalence of overweight (-11.1% change) and obesity (-3.6% change) and an increase in the prevalence of healthy weight (+2.7% change) were demonstrated. Children aged 2-5 had the greatest improvement in obesity prevalence (-11.5% change). Adolescents aged 12-19 were the only age group to not show a decrease in obesity prevalence. Of the racial and ethnic groups, Hispanics/Latinos had the highest prevalence of obesity across all age groups. The KPNC prevalence of overweight and obesity compares favorably to external benchmarks, although differences in methodologies limit our ability to draw conclusions. Physician counseling as well as weight management programs and sociodemographic factors may have contributed to the overall improvements in BMI in the KPNC population. Physician training, practice tools, automated BMI reminders and performance feedback improved the frequency and quality of physician counseling. BMI screening and counseling at urgent visits, in addition to well-child care visits, increased the reach and dose of physician counseling.

Effectiveness and reach of the FLU-FIT program in an integrated health care system: a multisite randomized trial.

OBJECTIVES: We tested the effectiveness of offering home fecal immunochemical tests (FITs) during influenza vaccination clinics to increase colorectal cancer screening (CRCS). METHODS: In a clinical trial at Kaiser Permanente Northern California influenza clinics in Redwood City, Richmond, South San Francisco, Union City, and Fresno, we randomly assigned influenza clinic dates to intervention (FIT offered) or control (FIT not offered) and compared subsequent CRCS activity. RESULTS: Clinic staff provided FITs to 53.9% (1805/3351) of intervention patients aged 50 to 75 years. In the intent-to-treat analysis, 26.9% (900/3351) and 11.7% (336/2884) of intervention and control patients completed an FIT, respectively, within 90 days of vaccination (P ≤ .001). The adjusted odds ratio for completing FIT in the intervention versus the control arm was 2.75 (95% confidence interval = 2.40, 3.16). In the per protocol analysis, 35.4% (648/1830) of patients given FIT and 13.3% (588/4405) of patients not given FIT completed FIT within 90 days of vaccination (P ≤ .001). CONCLUSIONS: This intervention may increase CRCS among those not reached by other forms of CRCS outreach. Future research should include the extent to which these programs can be disseminated and implemented nationally.

Validation of the Kidney Disease Quality of Life Short Form 36 (KDQOL-36) US Spanish and English versions in a cohort of Hispanics with chronic kidney disease.

OBJECTIVE: Evaluate the reliability and validity of the Kidney Disease Quality of Life Short Form 36 (KDQOL-36) in Hispanics with mild-to-moderate chronic kidney disease (CKD). DESIGN: Cross-sectional SETTING: Chronic Renal Insufficiency Cohort Study PARTICIPANTS: 420 Hispanic (150 English- and 270 Spanish-speakers), and 409 non-Hispanic White individuals, matched by age (mean 57 years), sex (60% male), kidney function (mean estimated glomerular filtration rate 36ml/min/1.73m2), and diabetes (70%). METHODS: To measure construct validity, we selected instruments, comorbidities, and laboratory tests related to at least one KDQOL-36 subscale. Reliability was determined by calculating Cronbach's alpha. RESULTS: Reliability of each KDQOL-36 subscale [SF-12 Physical Component Summary (PCS) and Mental Component Summary (MCS), Symptoms/Problems, Burden of Kidney Disease and Effects of Kidney Disease] was very good (Cronbach's alpha >0.8). Construct validity was supported by expected negative correlation between MCS scores and the Beck Depression Inventory in all three subgroups (r=-0.56 to -0.61, P<.0001). There was inverse correlation between the Symptoms/ Problems subscale and the Patient Symptom Form (r= -0.70 to -0.77, P<.0001). We also found significant, positive correlation between the PCS score and a physical activity survey (r=+0.29 to +0.38, P< or =.003); and between the PCS and MCS scores and the Kansas City Questionnaire (r= +0.31 to +0.64, P<.0001). Reliability and validity were similar across all racial/ethnic groups analyzed separately. CONCLUSION: Our findings support the use of the KDQOL-36 as a measure of HRQOL in this cohort of US Hispanics with CKD.

Retinopathy and cognitive impairment in adults with CKD.

BACKGROUND: Retinal microvascular abnormalities have been associated with cognitive impairment, possibly serving as a marker of cerebral small-vessel disease. This relationship has not been evaluated in persons with chronic kidney disease (CKD), a condition associated with increased risk of both retinal pathology and cognitive impairment. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: 588 participants 52 years or older with CKD in the Chronic Renal Insufficiency Cohort (CRIC) Study. PREDICTOR: Retinopathy graded using the Early Treatment Diabetic Retinopathy Study severity scale and diameters of retinal vessels. OUTCOMES: Neuropsychological battery of 6 cognitive tests. MEASUREMENTS: Logistic regression models were used to evaluate the association of retinopathy, individual retinopathy features, and retinal vessel diameters with cognitive impairment (≤1 SD from the mean), and linear regression models were used to compare cognitive test scores across levels of retinopathy, adjusting for age, race, sex, education, and medical comorbid conditions. RESULTS: The mean age of the cohort was 65.3±5.6 (SD) years, 51.9% were nonwhite, and 52.6% were men. The prevalence of retinopathy was 30.1%, and the prevalence of cognitive impairment was 14.3%. Compared with those without retinopathy, participants with retinopathy had an increased likelihood of cognitive impairment on executive function (35.1% vs 11.5%; OR, 3.4 [95% CI, 2.0-6.0]), attention (26.7% vs 7.3%; OR, 3.0 [95% CI, 1.8-4.9]), and naming (26.0% vs 10.0%; OR, 2.1 [95% CI, 1.2-3.4]) after multivariable adjustment. Increased level of retinopathy also was associated with lower cognitive performance on executive function and attention. Microaneurysms were associated with cognitive impairment on some domains, but there were no significant associations with other retinal measures after multivariable adjustment. LIMITATIONS: Unknown temporal relationship between retinopathy and impairment. CONCLUSIONS: In adults with CKD, retinopathy is associated with poor performance on several cognitive domains, including executive function and attention. Evaluation of retinal microvascular abnormalities may be a promising tool for identifying patients with CKD who are at increased risk of cognitive impairment.

Patient awareness and knowledge of breast cancer-related lymphedema in a large, integrated health care delivery system.

Breast cancer patients have voiced dissatisfaction regarding their education on breast cancer-related lymphedema risk and risk reduction strategies from their clinicians. Informing patients about lymphedema can contribute to decrease their risk of developing the condition, or among those already affected, prevent it from progressing further. In this cross-sectional study, a lymphedema awareness score was calculated based on responses to a brief telephone interview conducted among 389 women diagnosed with invasive breast cancer at Kaiser Permanente Northern California from 2000 to 2008 and had a previous record of a lymphedema-related diagnosis or procedure in their electronic medical record. During the telephone interview, women self-reported a lymphedema clinical diagnosis, lymphedema symptoms but no lymphedema diagnosis, or neither a diagnosis nor symptoms, and responded to questions on lymphedema education and support services as well as health knowledge. Multivariable logistic regression [odds ratio (OR) and 95 % confidence interval (CI)] was used to determine the associations of selected sociodemographic and clinical factors with the odds of having lymphedema awareness (adequate vs. inadequate). The median (range) of the lymphedema awareness score was 4 (0-7). Compared with patients <50 years of age, patients 70+ years of age at breast cancer diagnosis had lower odds of adequate lymphedema awareness (OR 0.25; 95 % CI 0.07, 0.89), while patients 50-59 and 60-69 years had greater odds of adequate awareness although not statistically significant (OR 2.05; 95 % CI 0.88, 4.78 and OR 1.55; 95 % CI 0.60, 4.02, respectively; p for trend = 0.09). Higher educational level and greater health literacy were suggestive of adequate awareness yet were not significant. These results can help inform educational interventions to strengthen patient knowledge of lymphedema risk and risk reduction practices, particularly in an integrated health care delivery setting. With the growing population of breast cancer survivors, increasing patient awareness and education about lymphedema risk reduction and care after cancer diagnosis is warranted.

Placebo adherence and mortality in the Heart and Estrogen/Progestin Replacement Study.

BACKGROUND: Analyses from double-blind randomized trials have reported lower mortality among participants who were more adherent to placebo compared with those who were less adherent. We explored this phenomenon by analyzing data from the placebo arm of the Heart and Estrogen/Progestin Replacement Study (HERS), a randomized, double-blind, placebo-controlled trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Our primary aim was to measure and explain the association between adherence to placebo and total mortality among the placebo-allocated participants in the HERS. Secondary aims included assessment of the association between placebo adherence and cause-specific morbidity and mortality. METHODS: Participants with "higher placebo adherence" were defined as having taken at least 75% of their placebo study medication during each individual's participation in the study, whereas those with "lower placebo adherence" took less than 75%. The primary outcome was in-study all-cause mortality. RESULTS: More adherent participants had significantly lower total mortality compared with less adherent participants (hazard ratio, 0.52; 95% confidence interval, 0.29-0.93). Adjusting for available confounders did not change the magnitude or significance of the estimates. Analyses revealed that the association of higher adherence and mortality might be explained, in part, by time-dependent confounding. CONCLUSIONS: Analyses of the HERS data support a strong association between adherence to placebo study medication and mortality. Although probably not due to simple confounding by healthy lifestyle factors, the underlying mechanism for the association remains unclear. Further analyses of this association are necessary to explain this observation.

Adherence to placebo and mortality in the Beta Blocker Evaluation of Survival Trial (BEST).

BACKGROUND: Randomized controlled trials have reported lower mortality among patients who adhere to placebo compared with those who do not. We explored this phenomenon by reanalyzing data from the placebo arm of the Beta Blocker Evaluation of Survival Trial (BEST), a randomized, double-blind, placebo-controlled trial of bucindolol and mortality. AIMS: Our primary aim was to measure and explain the association between adherence to placebo and total mortality among the placebo-allocated participants in the BEST trial. Secondary aims included assessment of the association between placebo adherence and cause-specific mortality. METHODS: Participants with "higher placebo adherence" were defined as having taken at least 75% of their placebo study medication over the entire course of each individual's participation in the study, while those with "lower placebo adherence" took <75%. Primary outcome was in-study all-cause mortality. To account for confounding, we adjusted for all available modifiable, non-modifiable and psychosocial variables. RESULTS: Adherent participants had a significantly lower total mortality compared to less-adherent participants (HR=0.61, 95% Confidence Interval: 0.46-0.82). Adjusting for available confounders did not change the magnitude or significance of the estimates. When considering cause-specific mortality, CVD and pump failure showed similar associations. CONCLUSIONS: Analyses of the BEST trial data support a strong association between adherence to placebo study medication and total mortality. While probably not due to publication bias or simple confounding by healthy lifestyle factors, the underlying explanation for the association remains a mystery. Prospective examination of this association is necessary to better understand the underlying mechanism of this observation.

Clinician awareness and knowledge of breast cancer-related lymphedema in a large, integrated health care delivery setting.

Breast cancer survivors have reported dissatisfaction regarding their education on risk of breast cancer-related lymphedema (BCRL) from clinicians. We describe clinician knowledge and treatment referral of patients with BCRL among active oncologists, surgeons, and primary care physicians in the Kaiser Permanente Northern California Medical Care Program. A total of 887 oncologists, surgeons, and primary care clinicians completed a 10-minute web survey from May 2, 2010 to December 31, 2010 on BCRL knowledge, education, and referral patterns. A knowledge score of BCRL was calculated based on clinician responses. Multivariable regression models were used to determine the associations of selected covariates with BCRL knowledge score and clinician referral, respectively. Compared with primary care clinicians, oncologists had the highest mean score followed closely by surgeons (P < 0.0001). In multivariable analyses, being female, an oncologist or surgeon, and recently receiving BCRL materials were each significantly associated with higher BCRL knowledge scores. About 44% of clinicians (n = 381) indicated they had ever made a BCRL referral (100% oncologists, 79% surgeons, and 36% primary care clinicians). Clinicians with a higher knowledge score were more likely to make referrals. In stratified analyses by specialty, the significant associated factors remained for primary care but became non-significant for oncology and surgery. These results can inform educational interventions to strengthen clinician knowledge of the clinical management of BCRL, especially among primary care clinicians. With the growing number of breast cancer survivors, increasing clinician education about BCRL across all specialties is warranted.

The FLU-FIT program: an effective colorectal cancer screening program for high volume flu shot clinics.

OBJECTIVE: To determine whether offering home fecal immunochemical tests (FITs) to eligible patients during a high volume influenza vaccination clinic could lead to increased colorectal cancer screening (CRCS) rates in a managed care setting. STUDY DESIGN: Observational study. METHODS: During influenza vaccination clinics in 2008, trained staff provided FITs to patients who were eligible for CRCS (FLU-FIT group) (FLU indicates influenza vaccine). Screening outcomes for this cohort of patients were compared with those of a similar group of influenza clinic attendees who were not exposed to the intervention (FLUonly group). RESULTS: Among eligible participants in the FLU-only group (N = 4653), 13.7% completed FIT within 90 days of their influenza vaccine, and in the FLU-FIT group (N = 2812), 30.3% completed FIT (P <.0001). In the FLU-FIT group, 1447 (51.4%) were provided with a FIT kit, and 653 (45.1%) of these patients completed a FIT kit within 90 days. In multivariate analyses, FLU-FIT group participants were significantly more likely to complete FITs compared with FLU-only group participants (Odds Ratio = 2.76 [95% confidence interval, 2.45-3.11]). Overall, the CRCS rate for the FLU-only group increased from 51.5% to 56.3% (increase of 4.8 percentage points), compared with an increase from 49.2% to 63.2% (increase of 14.0 percentage points) in the FLU-FIT group (P lt;.0001 for change difference). CONCLUSIONS: The FLU-FIT Program is feasible to implement in a high volume influenza vaccination clinic conducted in a managed care setting and increases colorectal cancer screening activity among eligible influenza vaccination recipients who are reached with the intervention.

CKD in Hispanics: Baseline characteristics from the CRIC (Chronic Renal Insufficiency Cohort) and Hispanic-CRIC Studies.

BACKGROUND: Little is known regarding chronic kidney disease (CKD) in Hispanics. We compared baseline characteristics of Hispanic participants in the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic-CRIC (H-CRIC) Studies with non-Hispanic CRIC participants. STUDY DESIGN: Cross-sectional analysis. SETTING & PARTICIPANTS: Participants were aged 21-74 years with CKD using age-based estimated glomerular filtration rate (eGFR) at enrollment into the CRIC/H-CRIC Studies. H-CRIC included Hispanics recruited at the University of Illinois in 2005-2008, whereas CRIC included Hispanics and non-Hispanics recruited at 7 clinical centers in 2003-2007. FACTOR: Race/ethnicity. OUTCOMES: Blood pressure, angiotensin-converting enzyme (ACE)-inhibitor/angiotensin receptor blocker (ARB) use, and CKD-associated complications. MEASUREMENTS: Demographic characteristics, laboratory data, blood pressure, and medications were assessed using standard techniques and protocols. RESULTS: Of H-CRIC/CRIC participants, 497 were Hispanic, 1,650 were non-Hispanic black, and 1,638 were non-Hispanic white. Low income and educational attainment were nearly twice as prevalent in Hispanics compared with non-Hispanics (P < 0.01). Hispanics had self-reported diabetes (67%) more frequently than non-Hispanic blacks (51%) and whites (40%; P < 0.01). Blood pressure >130/80 mm Hg was more common in Hispanics (62%) than blacks (57%) and whites (35%; P < 0.05), and abnormalities in hematologic, metabolic, and bone metabolism parameters were more prevalent in Hispanics (P < 0.05), even after stratifying by entry eGFR. Hispanics had the lowest use of ACE inhibitors/ARBs among the high-risk subgroups, including participants with diabetes, proteinuria, and blood pressure >130/80 mm Hg. Mean eGFR was lower in Hispanics (39.6 mL/min/1.73 m(2)) than in blacks (43.7 mL/min/1.73 m(2)) and whites (46.2 mL/min/1.73 m(2)), whereas median proteinuria was higher in Hispanics (protein excretion, 0.72 g/d) than in blacks (0.24 g/d) and whites (0.12 g/d; P < 0.01). LIMITATIONS: Generalizability; observed associations limited by residual bias and confounding. CONCLUSIONS: Hispanics with CKD in the CRIC/H-CRIC Studies are disproportionately burdened with lower socioeconomic status, more frequent diabetes mellitus, less ACE-inhibitor/ARB use, worse blood pressure control, and more severe CKD and associated complications than their non-Hispanic counterparts.

Development of disability in chronic obstructive pulmonary disease: beyond lung function.

BACKGROUND: COPD is a major cause of disability, but little is known about how disability develops in this condition. METHODS: The authors analysed data from the Function, Living, Outcomes and Work (FLOW) Study which enrolled 1202 Kaiser Permanente Northern California members with COPD at baseline and re-evaluated 1051 subjects at 2-year follow-up. The authors tested the specific hypothesis that the development of specific non-respiratory impairments (abnormal body composition and muscle strength) and functional limitations (decreased lower extremity function, poor balance, mobility-related dyspnoea, reduced exercise performance and decreased cognitive function) will determine the risk of disability in COPD, after controlling for respiratory impairment (FEV(1) and oxygen saturation). The Valued Life Activities Scale was used to assess disability in terms of a broad range of daily activities. The primary disability outcome measure was defined as an increase in the proportion of activities that cannot be performed of 3.3% or greater from baseline to 2-year follow-up (the estimated minimal important difference). Multivariable logistic regression was used for analysis. RESULTS: Respiratory impairment measures were related to an increased prospective risk of disability (multivariate OR 1.75; 95% CI 1.26 to 2.44 for 1 litre decrement of FEV(1) and OR 1.57 per 5% decrement in oxygen saturation; 95% CI 1.13 to 2.18). Non-respiratory impairment (body composition and lower extremity muscle strength) and functional limitations (lower extremity function, exercise performance, and mobility-related dyspnoea) were all associated with an increased longitudinal risk of disability after controlling for respiratory impairment (p<0.05 in all cases). Non-respiratory impairment and functional limitations were predictive of prospective disability, above-and-beyond sociodemographic characteristics, smoking status and respiratory impairment (area under the receiver operating characteristic curve increased from 0.65 to 0.75; p<0.001). CONCLUSIONS: Development of non-respiratory impairment and functional limitations, which reflect the systemic nature of COPD, appear to be critical determinants of disablement. Prevention and treatment of disability require a comprehensive approach to the COPD patient.

Placebo adherence and its association with morbidity and mortality in the studies of left ventricular dysfunction.

BACKGROUND: A provocative finding from several double-blind clinical trials has been the association between greater adherence to placebo study medication and better health outcomes. We used data from the Studies of Left Ventricular Dysfunction (SOLVD) Treatment Trial (SOLVD-TT) and the SOLVD Prevention Trial (SOLVD-PT) to examine whether such associations could be validated and to examine several sources of bias and potential confounding. METHODS: Survival analytic methods were used to estimate the association between placebo adherence and several health outcomes, employing a number of modeling techniques to test for the existence of alternative explanations for the association. Higher adherence was defined as having taken ≥75% of prescribed study medication. RESULTS: Higher placebo adherence was associated with improved overall survival in both SOLVD-TT and SOLVD-PT [hazard ratio (HR) = 0.52, 95% confidence interval (CI): 0.35 to 0.79 and HR = 0.52, 95%CI: 0.38 to 0.71, respectively]. Associations were similar for fatal or non-fatal cardiovascular or coronary heart disease events. Adjustment for both modifiable and non-modifiable cardiac risk factors (including age, gender, diabetes, blood pressure, smoking, weight, alcohol use, and levels of education) had minimal effect on the strength of the association. Little evidence of bias was found as an explanation for this relationship. CONCLUSIONS: In these two trials, better adherence to placebo was associated with markedly superior health outcomes, including total in-study mortality and incident cardiovascular events. No important confounders were identified. These data suggest there may exist strong but unrecognized determinants of health outcomes for which placebo adherence is a marker.

Chronic kidney disease and cognitive function in older adults: findings from the chronic renal insufficiency cohort cognitive study.

OBJECTIVES: To investigate cognitive impairment in older, ethnically diverse individuals with a broad range of kidney function, to evaluate a spectrum of cognitive domains, and to determine whether the relationship between chronic kidney disease (CKD) and cognitive function is independent of demographic and clinical factors. DESIGN: Cross-sectional. SETTING: Chronic Renal Insufficiency Cohort Study. PARTICIPANTS: Eight hundred twenty-five adults aged 55 and older with CKD. MEASUREMENTS: Estimated glomerular filtration rate (eGFR, mL/min per 1.73 m(2)) was estimated using the four-variable Modification of Diet in Renal Disease equation. Cognitive scores on six cognitive tests were compared across eGFR strata using linear regression; multivariable logistic regression was used to examine level of CKD and clinically significant cognitive impairment (score < or =1 standard deviations from the mean). RESULTS: Mean age of the participants was 64.9, 50.4% were male, and 44.5% were black. After multivariable adjustment, participants with lower eGFR had lower cognitive scores on most cognitive domains (P<.05). In addition, participants with advanced CKD (eGFR<30) were more likely to have clinically significant cognitive impairment on global cognition (adjusted odds ratio (AOR) 2.0, 95% CI=1.1-3.9), naming (AOR=1.9, 95% CI=1.0-3.3), attention (AOR=2.4, 95% CI=1.3-4.5), executive function (AOR=2.5, 95% CI=1.9-4.4), and delayed memory (AOR=1.5, 95% CI=0.9-2.6) but not on category fluency (AOR=1.1, 95% CI=0.6-2.0) than those with mild to moderate CKD (eGFR 45-59). CONCLUSION: In older adults with CKD, lower level of kidney function was associated with lower cognitive function on most domains. These results suggest that older patients with advanced CKD should be screened for cognitive impairment.

Mesenchymal stem cell allograft in revision foot and ankle surgery: a clinical and radiographic analysis.

UNLABELLED: A review was conducted of 23 patients who underwent implantation of mesenchymal stem cell allograft for revision foot or ankle surgery. Composed of viable mesenchymal stem cells derived from cadaveric donor tissue, the graft had osteogenic, osteoinductive, and osteoconductive properties, and was capable of direct new bone formation at the site of implantation. In all of the cases, radiographic new bone formation was observed at the area of implantation and a 91.3% union rate was observed, and no evidence of graft rejection or complications associated with implantation were recorded. Wilcoxon rank sum tests were used to determine whether gender, diabetes, chronic renal insufficiency, neuropathy, number of previous surgeries, and smoking were associated with time to healing. Spearman's rank correlation coefficient was calculated in an effort to identify the influence of continuous numeric variables on the time to bone healing. Based on the outcomes observed in this retrospective study, it appears that mesenchymal stem cell allograft is a beneficial biological adjunct to bone healing, and serves as a suitable bone autograft substitute in revision foot and ankle surgery. LEVEL OF CLINICAL EVIDENCE: 4.

COPD as a systemic disease: impact on physical functional limitations.

PURPOSE: Although chronic obstructive pulmonary disease (COPD) has a major impact on physical health, the specific impact of COPD on physical functional limitations has not been characterized clearly. We aimed to elucidate the physical functional limitations that are directly attributable to COPD compared to a matched referent group without the condition. METHODS: We used the Function, Living, Outcomes, and Work (FLOW) cohort study of adults with COPD (n=1202) and referent subjects matched by age, sex, and race (n=302) to study the impact of COPD on the risk of a broad array of functional limitations using validated measures: lower extremity function (Short Physical Performance Battery [SPPB]), submaximal exercise performance (Six Minute Walk Test [SMWT]), standing balance (Functional Reach Test), skeletal muscle strength (manual muscle testing with dynamometry), and self-reported functional limitation (standardized item battery). Multivariate analysis was used to control for confounding by age, sex, race, height, educational attainment, and cigarette smoking. RESULTS: COPD was associated with poorer lower extremity function (mean SPPB score decrement for COPD vs referent -1.0 points; 95% CI, -1.25 to -0.73 pts) and less distance walked during the SMWT (-334 feet; 95% CI, -384 to -282 ft). COPD also was associated with weaker muscle strength in every muscle group tested, including both the upper and lower extremities (P<.0001 in all cases) and with a greater risk of self-reported functional limitation (OR 6.4; 95% CI, 3.7 to 10.9). CONCLUSIONS: A broad array of physical functional limitations were specifically attributable to COPD. COPD affects a multitude of body systems remote from the lung.

Cardiology clinical trial participation in community-based healthcare systems: obstacles and opportunities.

BACKGROUND: The objective of our study was to examine cardiologists' and organizational leaders' interest in clinical trial participation and perceived barriers and facilitators to participation within ten diverse non-profit healthcare delivery systems. Trials play a pivotal role in advancing knowledge about the safety and efficacy of cardiovascular interventions and tests. Although cardiovascular trials successfully enroll patients, recruitment challenges persist. Community-based health systems could be an important source of participants and investigators, but little is known about community cardiologists' experiences with trials. METHODS: We interviewed 25 cardiology and administrative leaders and mailed questionnaires to all 280 cardiologists at 10 U.S. healthcare organizations. RESULTS: The survey received a 73% response rate. While 60% of respondents had not participated in any trials in the past year, nearly 75% wanted greater participation. Cardiologists reported positive attitudes toward trial participation; more than half agreed that trials were their first choice of therapy for patients, if available. Almost all leaders described their organizations as valuing research but not necessarily trials. Major barriers to participation were lack of physician time and insufficient skilled research nurses. CONCLUSIONS: Cardiologists have considerable interest in trial participation. Major obstacles to increased participation are lack of time and effective infrastructure to support trials. These results suggest that community-based health systems are a rich source for cardiovascular research but additional funding and infrastructure are needed to leverage this resource.