Developing and testing models to predict mortality in the general population.

We have previously proposed an approach using information collected from published reports to generate prediction models. The goal of this project was to validate this technique to develop and test various prediction models. A risk indicator (R) is calculated as a linear combination of the hazard ratios for the following predictors: age, male gender, diabetes, albuminuria, and either CKD, CVD or both. We developed a linear and two exponential expressions to predict the probability of the outcome of 2-year mortality and compared to actual outcome in the target dataset from NHANES. The risk indicator demonstrated good performance with area under ROC curve of 0.84. The linear and two exponential expressions generated similar predictions in the lower categories of risk indicator (R ≤ 6). However, in the groups with higher R value, the linear expression tends to predict lower, and the exponential expressions higher, probabilities than the observed outcome. A Combined model which averaged the linear and logistic expressions was shown to approximate the actual outcome data the best. A simple technique (named Woodpecker™) allows derivation functional prediction models and risk stratification tools from reports of clinical outcome studies and their application to new populations by using only summary statistics of the new population.

Distinct Pattern of Metastases in Patients with Invasive Lobular Carcinoma of the Breast.

BACKGROUND: Invasive lobular carcinoma (ILC) comprises around 10 - 15% of invasive breast cancers. Few prior studies have demonstrated a unique pattern of metastases between ILC and the more common invasive ductal carcinoma (IDC). To our knowledge, such data is limited to first sites of distant recurrence. We aimed to perform a comparison of the metastatic pattern of ILC and IDC at first distant recurrence as well as over the entire course of metastatic disease. METHODS: We used a prospectively collated database of patients with metastatic breast cancer. Breast cancer recurrence or metastases were classified into various sites and a descriptive analysis was performed. RESULTS: Among 761 patients, 88 (11.6%) were diagnosed with ILC and 673 (88.4%) with IDC. Patients with ILC showed more frequent metastases to the bone (56.8 vs. 37.7%, p = 0.001) and gastrointestinal (GI) tract (5.7 vs. 0.3%, p < 0.001) as first site of distant recurrence, and less to organs such as lung (5.7 vs. 24.2%, p < 0.001) and liver (4.6 vs. 11.4%, p = 0.049). Over the entire course of metastatic disease, more patients with ILC had ovarian (5.7 vs. 2.1%, p = 0.042) and GI tract metastases (8.0 vs. 0.6%, p < 0.001), also demonstrating reduced tendency to metastasize to the liver (20.5 vs. 49.0%, p < 0.001) and lung (23.9 vs. 51.9%, p < 0.001). All associations but bone held after sensitivity analysis on hormonal status. Although patients presenting with ILC were noted to have more advanced stage at presentation, recurrence-free survival in these patients was increased (4.8 years vs. 3.2 years, p = 0.017). However, overall survival was not (2.5 vs. 2.0 years, p = 0.75). CONCLUSION: After accounting for hormone receptor status, patients with IDC had greater lung/pleura and liver involvement, while patients with ILC had a greater propensity to develop ovarian and GI metastases both at first site and overall. Clinicians can use this information to provide more directed screening for metastases; it also adds to the argument that these two variants of breast cancer should be managed as unique diseases.

Prevalence and determinants of end-of-life chemotherapy use in patients with metastatic breast cancer.

Cessation of chemotherapy in the last few weeks of life could be an important quality-of-care benchmark. Proportion of metastatic breast cancer patients who receive end-of-life chemotherapy is not well described. We aimed to determine the prevalence and determinants of end-of-life chemotherapy use in patients with metastatic breast cancer. A retrospective cohort study using a prospectively collated database of patients with metastatic breast cancer who died between January 1, 2010, and September 30, 2014, was conducted. End-of-life chemotherapy (EOLC) use was defined as receipt of chemotherapy within 2 weeks of death (EOLC2) and receipt of chemotherapy within 4 weeks of death (EOLC4). Patients who did not receive any chemotherapy in the last 4 weeks before death were categorized as non-EOLC. We identified 274 patients with metastatic breast cancer, of whom 28 received EOLC2 (10.2%) and 62 received EOLC4 (22.6%). In comparison with non-EOLC, patients receiving EOLC4 were younger and had greater disease burden. Patients in EOLC4 group received more number of lines of chemotherapy. In a multivariable analysis, younger age at metastatic disease and greater number of metastatic organ systems involved were predictors of end-of-life chemotherapy use. Prevalence of the use of end-of-life chemotherapy in our cohort was higher than previously described. More end-of-life chemotherapy was used in younger women, and those with greater disease burden. Earlier initiation of end-of-life discussions may be targeted to such patients.

Prevalence of Triple-Negative Breast Cancer in India: Systematic Review and Meta-Analysis.

PURPOSE: There is considerable variation in prevalence rates of triple-negative breast cancer (TNBC) reported by various studies from India. We performed a systematic review and literature-based meta-analysis of these studies. METHODS: We searched databases of Medline, Scopus, EMBASE, and Web of Science for studies that reported on the prevalence of TNBC in India that were published between January 1, 1999, and December 31, 2015. We extracted relevant information from each study by using a standardized form. We pooled study-specific estimates by using random-effects meta-analysis to provide summary estimates. We explored sources of heterogeneity by using subgroup analyses and metaregression. RESULTS: Data were obtained from 17 studies that involved 7,237 patients with breast cancer. Overall combined prevalence of TNBC was 31% (95% CI, 27% to 35%). There was substantial heterogeneity across the studies (I2 of 91% [95% CI, 88% to 94%]; P < .001) that was not explained by available study level characteristics, including study location, definition of human epidermal growth factor receptor 2 or estrogen receptor, mean age of participants, proportion of patients with premenopausal cancer, grade 3 disease, or tumor size > 5 cm. Overall combined prevalence of hormone receptor-positive and human epidermal growth factor receptor 2-positive breast cancer was 48% (95% CI, 42% to 54%) and 27% (95% CI, 24% to 31%), respectively. There was no evidence of publication bias. CONCLUSION: Prevalence of TNBC in India is considerably higher compared with that seen in Western populations. As many as as one in three women with breast cancer could have triple-negative disease. This finding has significant clinical relevance as it may contribute to poor outcomes in patients with breast cancer in India. Additional research is needed to understand the determinants of TNBC in India.

Case report on renal failure reversal in lambda chain multiple myeloma with bortezomib and dexamethasone.

Renal failure (RF) reversal in multiple myeloma (MM) is associated with an improved prognosis. Light chain myeloma, serum creatinine (SCr) > 4 mg/dL, extensive proteinuria, early infections, and certain renal biopsy findings are associated with lower rates of RF reversal. Our patient is a 67-year-old female with multiple poor prognostic factors for RF reversal who demonstrated a rapid renal response with bortezomib and dexamethasone (BD) regimen. She presented initially with altered mental status. On exam, she appeared lethargic and dehydrated and had generalized tenderness. She had been taking ibuprofen as needed for pain for a few weeks. Labs showed a white cell count-18,900/µL with no bandemia, hemoglobin 10.8 gm/dL, potassium-6.7 mEq/L, bicarbonate-15 mEq/L, blood urea nitrogen-62 mg/dL, SCr-5.6 mg/dL (baseline: 1.10), and corrected calcium-11.8 mg/dL. A rapid flu test was positive. Imaging studies were unremarkable. Her EKG showed sinus tachycardia and her urinalysis was unremarkable. The unexplained RF in an elderly individual in conjunction with hypercalcemia and anemia prompted a MM work-up; eventually, lambda variant MM was diagnosed. An immediate (4 days) renal response defined as 50% reduction in SCr was noticed after initiation of the BD regimen.

Recipient's unemployment restricts access to renal transplantation.

Equitable distribution of a scarce resource such as kidneys for transplantation can be a challenging task for transplant centers. In this study, we evaluated the association between recipient's employment status and access to renal transplantation in patients with end-stage renal disease (ESRD). We used data from the United States Renal Data System (USRDS). The primary variable of interest was employment status at ESRD onset. Two outcomes were analyzed in Cox model: (i) being placed on the waiting list for renal transplantation or being transplanted (whichever occurred first); and (ii) first transplant in patients who were placed on the waiting list. We analyzed 429 409 patients (age of ESRD onset 64.2 ± 15.2 yr, 55.0% males, 65.1% White). Compared with patients who were unemployed, patients working full time were more likely to be placed on the waiting list/transplanted (HR 2.24, p < 0.001) and to receive a transplant once on the waiting list (HR 1.65, p < 0.001). Results indicate that recipient's employment status is strongly associated with access to renal transplantation, with unemployed and partially employed patients at a disadvantage. Adding insurance status to the model reduces the effect size, but the association still remains significant, indicating additional contribution from other factors.

The role of initial hemodialysis vascular access in the outcome of subsequent kidney transplantation.

The role of initial hemodialysis vascular access in the subsequent kidney transplant outcome is unclear. Study population was derived from the United States Renal Data System and included adult patients with end-stage renal disease who started HD 1/1/2005-9/1/2009 and subsequently received at least one kidney transplant. Primary outcome variables were death-censored graft loss and all-cause recipient mortality. Among the study population (n = 17 157), 12 428 (72.4%) patients were initiated on HD with a catheter, 4090 (23.8%) patients with an arterio-venous fistula (AVF), and 639 (13.7%) patients with an arterio-venous graft (AVG). The rate of death-censored kidney allograft loss in AVF and AVG groups was not significantly different from the catheter group (HR, 0.82; p = 0.07 and HR, 0.68; p = 0.13, respectively). All-cause mortality of patients initiated on HD with AVG (HR, 0.761; p = 0.21) was not significantly different compared to those with catheters. However, all-cause mortality in the AVF group was lower compared to patients initiated on HD with catheters (HR, 0.65; p = 0.001). AVF used at the initiation of HD was associated with lower rate of all-cause mortality after kidney transplantation compared to the catheter. The type of initial vascular access for hemodialysis was not associated with kidney allograft survival.

Education is associated with reduction in racial disparities in kidney transplant outcome.

In this study, we hypothesized that higher level of education might be associated with reduced racial disparities in renal transplantation outcomes. We used data from the United States Renal Data System (September 1, 1990-September 1, 2007) (n=79,223) and analyzed two outcomes, graft loss and recipient mortality, using Cox models. Compared with whites, African Americans had increased risk of graft failure (HR, 1.48; p<0.001) and recipient mortality (HR, 1.06; p=0.004). Compared with recipients who graduated from college, all other education groups had inferior graft survival. Specifically, compared with college-graduated individuals, African Americans who never finished high school had the highest risk of graft failure (HR, 1.45; p<0.001), followed by high school graduates (HR, 1.27; p<0.001) and those with some college education (HR, 1.18; p<0.001). A similar trend was observed in whites. In African Americans (compared with whites), the highest risk of graft failure was associated with individuals who did not complete high school (HR, 1.96; p<0.001) followed by high school graduates (HR, 1.47; p<0.001), individuals with some college education (HR, 1.45; p<0.001), and college graduates (HR, 1.39; p<0.001). A similar trend was observed with recipient mortality. In sum, higher education was associated with reduced racial disparities in graft and recipient survival.

Association between initial type of hemodialysis access used in the elderly and mortality.

We hypothesized that certain subpopulations (elderly and those with greater comorbidity) may not have significant benefit from "fistula first" initiative. A cohort of incident hemodialysis patients from 2005 to 2007, who were ≥70 years old, was derived from the United States Renal Data System. Primary variable of interest was type of vascular access used at first outpatient hemodialysis (i.e., fistula, graft, or central catheter), with primary outcome of all-cause mortality (time to death measured from the first outpatient hemodialysis). A cohort of 82,202 patients was stratified by age (70 to ≤80, 81 to ≤90, and >90). Each group demonstrated a survival benefit with the use of an arterio-venous fistula compared with catheter (hazard ratio [HR] 0.56 [P < 0.001], HR 0.55 [P < 0.001], and HR 0.69 [P = 0.007], respectively). Comparing graft to with a catheter, both groups, 70 to ≤80 and 81 to ≤90, had significant benefit compared with catheter (HR 0.73, P < 0.001 and HR 0.74, P < 0.001, respectively). However, significance was lost in those ≥90 (HR 0.83, P = 0.354). When substratified by comorbidity, those 81 to ≤90 years old with a history of malignancy or peripheral vascular disease also did not reach significant benefit compared with a catheter (HR 0.88, P = 0.423 and HR 0.85, P = 0.221, respectively). While specific subgroups in the hemodialysis population exist where use of fistulas and grafts at time of dialysis initiation is not of proven statistical benefit to survival, elderly hemodialysis patients with comorbidities still appear to benefit from the use of fistulas and grafts.

Social adaptability index predicts overall mortality in patients with diabetes.

BACKGROUND: A quantifiable assessment of socioeconomic status and its bearing on clinical outcome in patients with diabetes is lacking. The social adaptability index (SAI) has previously been validated in the general population and in patients with chronic kidney disease, including those on dialysis and with kidney transplant. We hypothesize that SAI could be used in diabetes practice to identify a disadvantaged population at risk for inferior outcomes. METHODS: The NHANES-3 database of patients who have diabetes was analyzed. The association of the SAI (calculated as the linear combination of indicators of education status, employment, income, marital status, and substance abuse) with patient survival was evaluated using Cox model. RESULTS: The study population consisted of 1634 subjects with diabetes mellitus with mean age of 61.9±15.3 years; 40.9% males; 38.5% white, 27.7% African American, and 31.3% Mexican American. The highest SAI was in whites (6.9±2.5), followed by Mexican Americans (6.5±2.3), and then African Americans (6.1±2.6) (ANOVA, P<.001). SAI was higher in subjects living in metropolitan areas (6.8±2.6) compared to the rural population (6.3±2.4) (T test, P<.001). Also, SAI was greater in males (7.1±2.4) than in females (6.1±2.4) (T test, P<.001). SAI had significant association with survival (hazard ratio 0.9, P<.001) in the entire study population and in most of the subgroups (divided by race, sex, and urban/rural location). Furthermore, SAI divided into tertiles (≤5, 6 to 8, >8) demonstrated a significant and "dose-dependent" association with survival. CONCLUSION: Social adaptability index is associated with mortality in the diabetic population and is useful in identifying individuals who are at risk for inferior outcomes.

Social adaptability index predicts kidney transplant outcome: a single-center retrospective analysis.

BACKGROUND: Social adaptability index (SAI) is the composite index of socioeconomic status based upon employment status, education level, marital status, substance abuse and income. It has been used in the past to define populations at higher risk for inferior clinical outcomes. The objective of this retrospective study was to evaluate the association of the SAI with renal transplant outcome. METHODS: We used data from the clinical database at the Beth Israel Deaconess Medical Center Transplant Institute, supplemented with data from United Network for Organ Sharing for the years 2001-09. The association between SAI and graft loss and recipient mortality in renal transplant recipients was studied using Cox model in the entire study population as well as in the subgroups based on age, race, sex and diabetes status. RESULTS: We analyzed 533 end-stage renal disease patients (mean age at transplant 50.8 ± 11.8 years, 52.2% diabetics, 58.9% males, 71.1% White). Higher SAI on a continuous scale was associated with decreased risk of graft loss [hazard ratio (HR) 0.89, P < 0.05, per 1 point increment in the SAI] and decreased risk of recipient mortality (HR 0.84, P < 0.01, per 1 point increment in the SAI). Higher SAI was also significantly associated with decreased risk for graft loss/recipient mortality in some study subgroups (age 41-65 years, males, non-diabetics). CONCLUSIONS: SAI has an association with graft and recipient survival in renal transplant recipients. It can be helpful in identifying patients at higher risk for inferior transplant outcome as a target population for potential intervention.

Association of education level with dialysis outcome.

The impact of education on health care outcome has been studied in the past, but its role in the dialysis population is unclear. In this report, we evaluated this association. We used the United States Renal Data System data of end-stage renal disease patients aged 18 years. Education level at the time of end-stage renal disease onset was the primary variable of interest. The outcome of the study was patient mortality. We used four categories of education level: 0 = less than 12 years of education; 1 = high school graduate; 2 = some college; 3 = college graduate. Subgroups based on age, race, sex, donor type, and diabetic status were also analyzed. After adjustments for covariates in the Cox model, using individuals with less than 12 years of education as a reference, patients with college education showed decreased mortality with hazard ratio of 0.81 (95% confidence interval 0.69­0.95), P = 0.010. In conclusion, we showed that higher education level is associated with improved survival of patients on dialysis.

Effect of education on racial disparities in access to kidney transplantation.

Higher education level might result in reduced disparities in access to renal transplantation. We analyzed two outcomes: (i) being placed on the waiting list or transplanted without listing and (ii) transplantation in patients who were placed on the waiting list. We identified 3224 adult patients with end-stage renal disease (ESRD) in United States Renal Data System with education information available (mean age of ESRD onset of 57.1 ± 16.2 yr old, 54.3% men, 64.2% white, and 50.4% diabetics). Compared to whites, fewer African Americans graduated from college (10% vs. 16.7%) and a higher percentage never graduated from the high school (38.6% vs. 30.8%). African American race was associated with reduced access to transplantation (hazard ratio [HR] 0.70, p < 0.001 for wait-listing/transplantation without listing; HR 0.58, p < 0.001 for transplantation after listing). African American patients were less likely to be wait-listed/transplanted in the three less-educated groups: HR 0.67 (p = 0.005) for those never completed high school, HR 0.76 (p = 0.02) for high school graduates, and HR 0.65 (p = 0.003) for those with partial college education. However, the difference lost statistical significance in those who completed college education (HR 0.75, p = 0.1). In conclusion, in comparing white and African American candidates, racial disparities in access to kidney transplantation do exist. However, they might be alleviated in highly educated individuals.

Social Adaptability Index predicts access to kidney transplantation.

Identifying the group of subjects prone to disparities in access to kidney transplantation is important for developing potential interventions. Data from the United States Renal Data System (January 1, 1990-September 1, 2007; n = 3407) were used to study association between the Social Adaptability Index (SAI; based upon employment, marital status, education, income, and substance abuse) and outcomes (time to being placed on the waiting list and time to being transplanted once listed). Patients were 56.9 ± 16.1 yr old, 54.2% men, 64.2% white, and 50.4% had diabetes. SAI was higher in whites (7.4 ± 2.4) than African Americans (6.5 ± 2.6) [ANOVA, p < 0.001] and greater in men (7.4 ± 2.4) than in women (6.7 ± 2.5) [T-test, p < 0.001]. In multivariate model, greater SAI (range 0-12) was associated with increased likelihood of being placed on the waiting list (hazard ratio [HR] 1.19 [95% CI 1.15-1.23] per each point of increase in SAI, p < 0.001) and greater likelihood of receiving a transplant once listed (HR of 1.06 [95% CI 1.03-1.09] per point of increase in SAI, p < 0.001). Similar trends were observed in most of the subgroups (based upon race, sex, diabetic status, age, comorbidities, and donor type). SAI is associated with access to renal transplantation in patients with end-stage renal disease; it may be used to indentify individuals at risk of healthcare disparities.

Impact of substance abuse on access to renal transplantation.

BACKGROUND: With an ever-increasing demand for kidneys and limited supply pool, it is essential to understand the balance between utility and equity in transplant access. The goal of this project was to evaluate the association between recipient's substance abuse and renal transplant access in patients with end-stage renal disease (ESRD). METHODS: We used data from the United States Renal Data System. The primary variables of interest were abuse of alcohol, tobacco, or illicit drugs based on information from Centers for Medicare & Medicaid Services form 2728. We analyzed three outcomes in Cox model: (1) being placed on the waiting list for renal transplantation or transplanted (whichever occurred first); (2) first transplant in patients who were placed on the waiting list; and (3) graft loss or mortality after transplant. In addition, we performed subgroup analysis based on age, race, sex, diabetic status, and donor type. RESULTS: We analyzed 1,077,699 patients (age of ESRD onset 62.9±15.5 years, 54.1% males, 64.2% white, and 29.7% African American). When compared with those with no substance abuse, abusing all three substances was associated with reduced transplant access (hazard ratio 0.39, P<0.001 for wait listing/transplant; hazard ratio 0.67, P=0.019 for transplant). This trend was similar in most subgroups studied. CONCLUSION: We demonstrated that patients with ESRD abusing or dependent on tobacco, alcohol, or illicit drugs are less likely to be placed on the waiting list for kidney transplant; and once on the list are less likely to be transplanted. The possible utility justifications for such disparity and potential interventions are discussed.

Association between social adaptability index and survival of patients with chronic kidney disease.

BACKGROUND: While individual socioeconomic factors have been associated with clinical outcome, a composite index has not been developed. In this project, we tested the hypothesis that Social Adaptability Index (SAI) based on employment, education, income, marital status and substance abuse is associated with survival in chronic kidney disease (CKD) patients. METHODS: This is a retrospective cohort study of patients with CKD stage 2 or greater. We used the Third National Health and Nutrition Examination Survey (NHANES III) cohort data between 1988 and 1994 including those 18 years or older. Our primary variable of interest is SAI. Each component of SAI (employment status, education, marital status, and substance abuse) has been graded on the scale of 0-3, income has been graded on the scale 0-1. Age, sex, race, diabetes, co-morbidity index, body mass index (BMI), geographic location, haemoglobin, serum creatinine, serum albumin, serum cholesterol and Hba1c were used as covariates in multivariate analysis. The outcome of the study is patient's mortality. The time to death was calculated as time between the first interview by NHANES and death. RESULTS: We analysed 13 400 subjects with mean age of 50.6 ± 20-53.6% males, 44.4% white, 29.7% African American and 22.1% Mexican American-with 8.5% having diabetes, with an average number of co-morbid conditions of 2.7 ± 1.1. Lower SAI is associated with greater stage of CKD. Higher SAI was associated with decreased mortality [hazard ratio (HR) 0.88, P < 0.001, 95% confidence interval (CI) 0.86-0.89]. When SAI quintiles were analysed, we demonstrated a 'dose-dependent' association between SAI and survival. Subgroup analysis showed that this association of SAI and survival was present in all studied subgroups. The limitations of the study include retrospective design, potential misreporting and misclassification, and reverse causality. CONCLUSION: We demonstrated that SAI has a strong and clinically significant association with mortality in CKD patients.