Evaluation of the modified FINDRISC to identify individuals at high risk for diabetes among middle-aged white and black ARIC study participants.

OBJECTIVE: To evaluate a modified Finnish Diabetes Risk Score (FINDRISC) for predicting the risk of incident diabetes among white and black middle-aged participants from the Atherosclerosis Risk in Communities (ARIC) study. RESEARCH DESIGN AND METHODS: We assessed 9754 ARIC cohort participants who were free of diabetes at baseline. Logistic regression and receiver operator characteristic (ROC) curves were used to evaluate a modified FINDRISC for predicting incident diabetes after 9 years of follow-up, overall and by race/gender group. The modified FINDRISC used comprised age, body mass index, waist circumference, blood pressure medication and family history. RESULTS: The mean FINDRISC (range, 2 [lowest risk] to 17 [highest risk]) for black women was higher (9.9 ± 3.6) than that for black men (7.6 ± 3.9), white women (8.0 ± 3.6) and white men (7.6 ± 3.5). The incidence of diabetes increased generally across deciles of FINDRISC for all 4 race/gender groups. ROC curve statistics for the FINDRISC showed the highest area under the curve for white women (0.77) and the lowest for black men (0.70). CONCLUSIONS: We used a modified FINDRISC to predict the 9-year risk of incident diabetes in a biracial US population. The modified risk score can be useful for early screening of incident diabetes in biracial populations, which may be helpful for early interventions to delay or prevent diabetes.

Socioeconomic status and the trajectory of self-rated health.

BACKGROUND: self-rated health (SRH) likely reflects both mental and physical health domains, and is assessed by asking individuals to describe their health status. Poor SRH is associated with disease incidence and subsequent mortality. Changes in SRH across time in persons with different incident diseases are uncharacterised. METHODS: SRH was assessed in the Atherosclerosis Risk in Communities study via annual telephone interviews over a median of 17.6 years. Individual quadratic growth models were used for repeated measures of SRH in persons who remained disease-free during follow-up (n = 11,188), as well as among those who were diagnosed with myocardial infarction (MI; n = 1,071), stroke (n = 809), heart failure (HF; n = 1,592) or lung cancer (n = 433) and those who underwent a cardiac revascularisation procedure (n = 1,340) during follow-up. RESULTS: among disease-free participants and across time, there was a trend for lowest mean SRH among persons living in low socioeconomic areas and highest mean SRH among persons living in high socioeconomic areas. Factors contributing to the decline in SRH over time included advanced age, lower educational attainment, smoking and obesity. CONCLUSION: addressing factors related to poor SRH trajectories among patients pre- and post-incident disease may favourably affect health outcomes among patients regardless of type of disease.

Ertugliflozin Compared to Other Anti-hyperglycemic Agents as Monotherapy and Add-on Therapy in Type 2 Diabetes: A Systematic Literature Review and Network Meta-Analysis.

INTRODUCTION: Ertugliflozin is a new sodium-glucose co-transporter-2 inhibitor (SGLT2i) for the treatment of type 2 diabetes mellitus. As there are no head-to-head trials comparing the efficacy of SGLT2is, the primary objective of this analysis was to indirectly compare ertugliflozin to other SGLT2i in patient populations with inadequately controlled glycated hemoglobin (HbA1c > 7.0%) and previously treated with either diet/exercise, metformin alone or metformin plus a dipeptidyl peptidase-4 inhibitor (DPP4i). METHODS: A systematic literature review (SLR) identified randomized controlled trials (RCTs) reporting outcomes at 24-26 weeks of treatment. Comparators to ertugliflozin were the SGLT2is canagliflozin, dapagliflozin and empagliflozin, with non-SGLT2i comparators also evaluated third-line [insulin and glucagon-like peptide-1 receptor agonists (GLP-1 RAs)]. Outcomes were change from baseline in HbA1c, weight and systolic blood pressure (SBP) as well as HbA1c < 7% and key safety events. Bayesian network meta-analysis was used to synthesize evidence. Results are presented as the median of the mean difference (MD) or as odds ratios with 95% credible intervals (CrI). RESULTS: In patients uncontrolled on diet/exercise, the efficacy of ertugliflozin 5 mg monotherapy was not significantly different from that of other low-dose SGLT2is in terms of HbA1c reduction, while ertugliflozin 15 mg was more effective than dapagliflozin 10 mg (MD - 0.36%, CrI - 0.65, - 0.08) and empagliflozin 25 mg (MD - 0.31%, CrI - 0.58, - 0.04). As add-on therapy to metformin, ertugliflozin 5 mg was more effective in lowering HbA1c than dapagliflozin 5 mg (MD - 0.22%, CrI - 0.42, - 0.02), and ertugliflozin 15 mg was more effective than dapagliflozin 10 mg (MD - 0.26%, CrI - 0.46, - 0.06) and empagliflozin 25 mg (MD - 0.23%, CrI - 0.44, - 0.03). Among patients uncontrolled on combination therapy metformin plus a DPP4i, no relevant RCTs with insulin were identified from the SLR. One study with a GLP-1 RA was included in a sensitivity analysis due to limited data. There were no differences between ertugliflozin 5 or 15 mg and other SGLT2is, with the exception of dapagliflozin 10 mg, which was significantly less effective when added to sitagliptin and metformin. Overall, there were no other significant differences for remaining efficacy and safety outcomes except for a lower SBP for canagliflozin 300 mg compared to ertugliflozin 15 mg in the diet/exercise population. CONCLUSIONS: Indirect comparisons for HbA1c reduction found that ertugliflozin 5 mg was more effective than dapagliflozin 5 mg when added to metformin monotherapy, whereas ertugliflozin 15 mg was more effective than dapagliflozin 10 mg and empagliflozin 25 mg when added to diet/exercise and to metformin monotherapy. The HbA1c reduction associated with ertugliflozin was no different than that associated with canagliflozin across all populations. FUNDING: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Pfizer Inc., New York, NY, USA.

Hospital length of stay for incident heart failure: Atherosclerosis Risk in Communities (ARIC) cohort: 1987-2005.

Heart failure (HF) accounts for 6.5 million hospital days per year. It remains unknown if socioeconomic factors are associated with hospital length of stay (LOS). We analyzed predictors of longer hospital LOS [mean (days), 95% confidence interval (CI)] among participants with incident hospitalized HF (n = 1,300) in the Atherosclerosis Risk in Communities (ARIC) cohort from 1987 to 2005. In a statistical model adjusted for median household income, age, gender, race/study community, education level, hypertension, alcohol use, smoking, Medicaid status, and Charlson comorbidity index score, Medicaid recipients experienced a longer LOS (7.5, 6.3-8.9) compared to non-Medicaid recipients (6.2, 5.7-6.7), and patients with a higher burden of comorbidity had a longer LOS (7.5, 6.4-8.6) compared to patients with a lower burden (6.2, 5.7-6.9). Median household income and education were not associated with longer LOS in multivariable models. Medicaid recipients and patients with more comorbid disease may not have the resources for adequate, comprehensive, out-of-hospital management of HF symptoms, and may require a longer LOS due to the need for more care during the hospitalization because of more severe HF. Data on out-of-hospital management of chronic diseases as well as HF severity are needed to further elucidate the mechanisms leading to longer LOS among subgroups of HF patients.

Differential associations of oral glucose tolerance test-derived measures of insulin sensitivity and pancreatic ß-cell function with coronary artery calcification and microalbuminuria in type 2 diabetes.

OBJECTIVE We evaluated relationships of oral glucose tolerance testing (OGTT)-derived measures of insulin sensitivity and pancreatic ß-cell function with indices of diabetes complications in a cross-sectional study of patients with type 2 diabetes who are free of overt cardiovascular or renal disease. RESEARCH DESIGN AND METHODS A subset of participants from the Penn Diabetes Heart Study (n = 672; mean age 59 ± 8 years; 67% male; 60% Caucasian) underwent a standard 2-h, 75-g OGTT. Insulin sensitivity was estimated using the Matsuda Insulin Sensitivity Index (ISI), and ß-cell function was estimated using the Insulinogenic Index. Multivariable modeling was used to analyze associations between quartiles of each index with coronary artery calcification (CAC) and microalbuminuria. RESULTS The Insulinogenic Index and Matsuda ISI had distinct associations with cardiometabolic risk factors. The top quartile of the Matsuda ISI had a negative association with CAC that remained significant after adjusting for traditional cardiovascular risk factors (Tobit ratio -0.78 [95% CI -1.51 to -0.05]; P = 0.035), but the Insulinogenic Index was not associated with CAC. Conversely, the highest quartile of the Insulinogenic Index, but not the Matsuda ISI, was associated with lower odds of microalbuminuria (OR 0.52 [95% CI 0.30-0.91]; P = 0.022); however, this association was attenuated in models that included duration of diabetes. CONCLUSIONS Lower ß-cell function is associated with microalbuminuria, a microvascular complication, while impaired insulin sensitivity is associated with higher CAC, a predictor of macrovascular complications. Despite these pathophysiological insights, the Matsuda ISI and Insulinogenic Index are unlikely to be translated into clinical use in type 2 diabetes beyond established clinical variables, such as obesity or duration of diabetes.

Socioeconomic status, Medicaid coverage, clinical comorbidity, and rehospitalization or death after an incident heart failure hospitalization: Atherosclerosis Risk in Communities cohort (1987 to 2004).

BACKGROUND: Among patients with heart failure (HF), early readmission or death and repeat hospitalizations may be indicators of poor disease management or more severe disease. METHODS AND RESULTS: We assessed the association of neighborhood median household income (nINC) and Medicaid status with rehospitalization or death in the Atherosclerosis Risk in Communities cohort study (1987 to 2004) after an incident HF hospitalization in the context of individual socioeconomic status and evaluated the relationship for modification by demographic and comorbidity factors. We used generalized linear Poisson mixed models to estimate rehospitalization rate ratios and 95% CIs and Cox regression to estimate hazard ratios (HRs) and 95% CIs of rehospitalization or death. In models controlling for race and study community, sex, age at HF diagnosis, body mass index, hypertension, educational attainment, alcohol use, and smoking, patients with a high burden of comorbidity who were living in low-nINC areas at baseline had an elevated hazard of all-cause rehospitalization (HR, 1.40; 95% CI, 1.10 to 1.77), death (HR, 1.36; 95% CI, 1.02 to 1.80), and rehospitalization or death (HR, 1.36; 95% CI, 1.08 to 1.70) as well as increased rates of hospitalization compared to those with a high burden of comorbidity living in high-nINC areas. Medicaid recipients with a low level of comorbidity had an increased hazard of all-cause rehospitalization (HR, 1.19; 95% CI, 1.05 to 1.36) and rehospitalization or death (HR, 1.21; 95% CI, 1.07 to 1.37) and a higher rate of repeat hospitalizations compared to non-Medicaid recipients. CONCLUSIONS: Comorbidity burden appears to influence the association among nINC, Medicaid status, and rehospitalization and death in patients with HF.

Matching donor to recipient in lung transplantation: How much does size matter?

OBJECTIVE: The impact of size matching between donor and recipient is unclear in lung transplantation. Therefore, we determined the relation of donor lung size to 1) posttransplant survival and 2) pulmonary function as measured by forced expiratory volume in 1 second. METHODS: From 1990 to 2006, 469 adults underwent lung transplantation with lungs from donors aged 7 to 70 years. Donor and recipient total lung capacities were calculated using established formulae (predicted total lung capacity), and actual recipient lung size was measured in the pulmonary function laboratory. Disparity between donor and recipient lung size was expressed as a ratio of donor predicted total lung capacity to recipient predicted total lung capacity-the predicted total lung capacity ratio-and predicted donor total lung capacity to actual recipient total lung capacity-the actual total lung capacity ratio. Survival was measured by multiphase hazard methodology and repeated measures of National Health and Nutrition Examination Survey-normalized forced expiratory volume in 1 second analyzed by temporal decomposition. RESULTS: Predicted total lung capacity ratio and actual total lung capacity ratio ranged widely, from 0.55 to 1.59 and 0.52 to 4.20, respectively. Overall survival was unaffected by predicted total lung capacity ratio (P = .3) or actual total lung capacity ratio (P = .5). Patients with emphysema and an actual total lung capacity ratio of 0.67 or less or 1.03 or greater had higher predicted mortality (P = .01). During the first posttransplant year, forced expiratory volume in 1 second increased and then gradually declined. Predicted total lung capacity ratio and actual total lung capacity ratio had a small impact on forced expiratory volume in 1 second, primarily in the late phase after transplant in a disease-specific manner. CONCLUSION: Size matching between donor and recipient using predicted total lung capacity ratio and actual total lung capacity ratio is an effective technique. Wide discrepancies in lung sizing do not affect overall posttransplant survival or pulmonary function. Therefore, a greater degree of lung size mismatch can likely be accepted, thereby improving patients' odds of undergoing transplantation.

Temporal pattern of transfusion and its relation to rejection after lung transplantation.

BACKGROUND: Blood transfusion has been shown to impact rejection after renal and cardiac transplantation, but it has not been studied after lung transplantation (LTx). In this study we assess: (1) patterns of transfusion, and (2) temporal interrelationships with histologic evidence of rejection. METHODS: From July 1998 to January 2006, 326 of 331 patients undergoing LTx had available for study both time-related post-operative blood transfusion data and their series of transbronchial biopsy evaluations of perivascular rejection grade (Grades A0 to A4). Longitudinal temporal decomposition for ordinal variables was used to characterize prevalence of rejection grade and simultaneously assess the influence of (a) red blood cell (RBC), (b) platelet and (c) plasma administration. RESULTS: Although peri-operative transfusion was common, transfusions continued at a low, steady rate throughout the life of LTx patients; patients received a total of 2,841 RBC units through follow-up. Immediately after LTx, the prevalence of Grade A0 rejection was 51%, and this increased to 84% by 6 months. RBC transfusion between biopsies was associated with lower histologic grade of rejection (70%, 73% and 77% with Grade A0 for 0, 1 and 12 units, respectively; p = 0.009), and this was particularly evident early after LTx. Histologic grade was not influenced by platelets or plasma. CONCLUSIONS: Transfusion requirements are high and continue throughout life after LTx; causes and effective treatment of persistent anemia should be sought. RBC transfusion appears to have an immunosuppressive effect, particularly early after transplant.

Spirometry after transplantation: how much better are two lungs than one?

BACKGROUND: The purpose of this study was to determine how much double lung transplantation improves lung function over single lung transplantation and to identify predictors of lung function after transplantation. METHODS: From February 1990 to November 2005, 463 adults underwent lung transplantation. Among 379 of these patients (82%), 6372 evaluations of postoperative normalized forced expiratory volume in 1 second (FEV(1)) and forced vital capacity (FVC) were analyzed using longitudinal temporal decomposition methods for repeated continuous measurements. We characterized the time course of postoperative spirometry, compared it between double and single lung transplantation, and identified its modulators. RESULTS: FEV(1) (% of predicted) was only somewhat better after double than single lung transplantation (65%, 58%, and 59% vs 51%, 43%, and 40% at 1, 3, and 5 years, p = 0.03), as was FVC (% of predicted) (67%, 68%, and 66% vs 62%, 56%, and 51%, p < 0.0001). Both FEV1% and FVC% increased sharply to 1 year. For double lung transplantation, these values persisted, with minimal decline to 5 years; but for single lung transplantation, they continuously declined to 5 years. Values for double lung transplantation remained higher than for single lung transplantation at all time points but never approached twice the value. Patients undergoing double lung transplantation for emphysema had the highest postoperative FEV1% and FVC%, but also the lowest values for single lung transplantation; the benefit of double lung transplantation was between these values for other diagnoses. CONCLUSIONS: Spirometry weakly favors double lung over single lung transplantation. The advantage of spirometry values alone may not justify double lung transplantation.

Early experience with lung transplantation using donors after cardiac death.

Lung transplantations that utilize donor organs after cardiac death (DCD) can substantially increase the number of available allografts for waiting recipients. Unfortunately, reported clinical outcomes are limited and widespread acceptance is slow. To further examine the potential of this modality, the results of 4 patients transplanted with DCD organs, implementing a protocol of controlled organ retrieval (Maastricht Classification III), were reviewed. There were no operative deaths; extracorporeal membrane oxygenation was required in 1 patient secondary to severe primary graft dysfunction. Three patients are alive and well at 4, 15 and 21 months; 1 patient died at 34 months with bronchiolitis obliterans syndrome, in part attributable to medication non-compliance.

Decortication after lung transplantation.

BACKGROUND: Compromise of a pulmonary allograft by restrictive or infectious pleural-space pathology may be amenable to surgical intervention; however, the role of decortication in this patient population has not yet been substantiated. To address this issue, indications and outcomes of decortication after lung transplantation were examined at our institution. METHODS: From February 1990 to December 2006, 553 patients underwent lung transplantation; postoperative decortications were performed 27 times in 24 patients (4.3%). RESULTS: Indications for decortication included presumed empyema (15), loculated effusion (7), hemothorax (3), and fibrothorax (2). Decortication was performed at a median of 81 days after transplantation (range, 12 days to 7.8 years). Complete lung reexpansion was achieved after 19 of 27 decortications (70%). Infection was cleared from the pleural space in 9 of 15 empyema patients (64%). Survivals at 1, 3, 6, and 12 months after decortication were 85%, 73%, 65%, and 60%, respectively. Operative mortality (30-day or in-hospital) was 23%, and median length of stay was 19 days. CONCLUSIONS: Decortication may alleviate the compromise of a transplanted lung by restrictive or infectious pleural-space disease, but operative risk is substantial.

Atrial fibrillation after lung transplantation: timing, risk factors, and treatment.

BACKGROUND: Atrial fibrillation (AF) is common after lung transplantation and can be challenging to manage. Objectives of this study were to determine prevalence and timing of perioperative AF, identify its risk factors, evaluate treatment strategies, assess return to sinus rhythm by hospital discharge, and investigate its impact on outcomes. METHODS: From March 1995 to January 2005, 333 patients underwent primary lung transplantation (exclusive of heart and lung transplantation). Data on timing, prevalence, management, and outcome were extracted from the Unified Transplant Registry and Cardiothoracic Anesthesia databases, supplemented with medical record review. Risk factors for AF were identified by logistic regression analysis, and bootstrap bagging was used for variable selection. RESULTS: AF developed postoperatively in 68 patients (20%), with the peak incidence 2 days after operation. Risk factors were older age (p = 0.0004), primary pulmonary hypertension (5 of 12 [42%] versus 63 of 321 [20%] for others, p = 0.006), and extremes of weight (p = 0.04). Pharmacologic treatment consisted of rate control agents only in 18 patients (27%), antiarrhythmics only in 5 (7.5%), and both in 44 (66%). Cardioversion was required in 24 (36%). Rhythm was recorded for 59 patients, and 55 (93%) were in sinus rhythm at discharge. Postoperative AF had no short-term or long-term survival impact. CONCLUSIONS: AF after lung transplantation is common, with occurrence peaking 2 days postoperatively. Older patients and those with primary pulmonary hypertension are at elevated risk. Treatment requires a combination of multiple pharmacologic agents and electrical cardioversion. Almost all patients are discharged in sinus rhythm, and prognosis is unaffected.

Lung transplantation for idiopathic pulmonary fibrosis.

BACKGROUND: Outcomes of lung transplantation for idiopathic pulmonary fibrosis (IPF) are thought to be worse than those for other indications, although the reasons are unknown. In addition, the choice of single versus double lung transplantation is unclear. To guide decision-making, we (1) compared survival of patients receiving transplantation for IPF with survival of patients receiving transplantation for non-IPF diagnoses, (2) identified risk factors for mortality after transplantation for IPF, and (3) ascertained whether double lung transplantation for IPF confers a survival advantage. METHODS: From February 1990 to November 2005, 469 patients underwent lung transplantation, 82 for IPF. Multiphase hazard modeling was used to identify risk factors, and propensity matching was used to compare survival of IPF and non-IPF patients and to assess the effect of single versus double lung transplantation. RESULTS: Survival estimates after transplantation for IPF were 95%, 73%, 56%, and 44% at 30 days and 1, 3, and 5 years, somewhat worse than for matched non-IPF patients (p = 0.03). Risk factors for mortality were earlier date of transplantation (p = 0.07), single lung transplantation (p = 0.03), and higher wedge pressure (p = 0.003). Survival for double versus single lung transplantation was 81% versus 67% at 1 year and 55% versus 34% at 5 years; however, among matched non-IPF patients, corresponding survivals were 88% versus 71% at 1 year and 72% versus 48% at 5 years (p = 0.3). CONCLUSIONS: Survival after lung transplantation for IPF is worse than after other indications for transplantation when multiple clinical variables are accounted for. Survival may be improved by double lung transplant.

Dialysis after lung transplantation: prevalence, risk factors and outcome.

BACKGROUND: Renal failure requiring dialysis after lung transplantation represents a major source of morbidity for patients and compromises their quality of life. We sought to ascertain the prevalence of dialysis after lung transplantation and to identify risk factors for its occurrence. We also assessed outcomes after institution of dialysis. METHODS: From our program's inception in February 1990 until January 2005, 425 patients underwent lung transplantation. Data on dialysis occurrence, timing, management and outcome were extracted from the Unified Transplant Database, patient follow-up and medical record review. RESULTS: Thirty-seven patients developed a need for dialysis, a prevalence of 0.6%, 4%, 9%, 13%, 16% and 19%, at 30 days and 1, 3, 5, 7 and 9 years after transplant, respectively. Lower creatinine clearance (p = 0.03) and greater recipient height (p = 0.0002) increased the risk for dialysis, whereas donor blood type O (p = 0.001) and head trauma as donor cause of death (p = 0.01) lowered it. Higher doses of calcineurin inhibitors correlated with the period of highest risk for dialysis. Median survival of patients requiring dialysis was 5 months, considerably lower than expected. Four patients underwent renal transplantation, 3 of whom were still alive 3, 6 and 9 months later. CONCLUSIONS: Dialysis after lung transplantation is common and cumulative over time. Risk factors for its development may be modifiable because they appear to be linked to nephrotoxicity secondary to immunosuppression. The low threshold for creatinine clearance appears to be 50 ml/min/1.73 m(2). Survival after institution of dialysis is poor, highlighting the need for prevention. Renal transplantation may be a reasonable therapeutic option.

Extended use of extracorporeal membrane oxygenation after lung transplantation.

OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) for severe graft failure after lung transplantation is accepted immediately postoperatively; extending its use is controversial. We evaluated our post-lung transplant ECMO experience, which included extended indication, to (1) determine its prevalence, risk factors, indications, and timing, (2) compare complications and outcomes of these patients with those not requiring it, and (3) identify risk factors, including indications, for mortality. METHODS: From February 1990 to October 2005, 474 patients underwent lung transplantation; postoperative ECMO support was instituted for severe graft failure 23 times in 22 patients (4.0%). Indications for ECMO and its timing were obtained by reviewing medical records and survival by systematic follow-up. RESULTS: No factor evaluated predicted severe graft failure leading to ECMO. The most common indication for ECMO was early graft failure (13 patients); however, it was also used for pneumonia or sepsis (6) and acute rejection (4). ECMO was initiated at a median arterial oxygen tension/inspired oxygen fraction of 59 at a median of 2 days postoperatively and was maintained for a median of 4 days. The most common complications were renal failure (57%) and bleeding (43%). ECMO was effective in salvaging patients with rejection and early graft failure (survival at 1, 3, 6, and 12 months: 62%, 54%, 49%, and 41%), but ineffective for pneumonia or sepsis (survival at these intervals: 9%, 4%, 4%, and 3%). CONCLUSIONS: ECMO can be extended beyond early severe graft failure to acute rejection and can be considered after the immediate postoperative period. Survival after ECMO in patients with pneumonia or sepsis is poor.