Luca Neri

Incidence and risk factors for diarrhea following kidney transplantation and association with graft loss and mortality.

BACKGROUND Gastrointestinal complications after kidney transplantation are associated with inferior graft outcomes. We examined the incidence, risk factors, and outcomes of posttransplantation diarrhea. STUDY DESIGN Historic cohort study. SETTING & PARTICIPANTS We examined first kidney transplant recipients in the United States from 1995 to 2002, with follow-up through December 2002. Recipients of multiple organs were excluded. We limited our study population to Medicare beneficiaries. PREDICTORS Recipient, donor, and transplant characteristics were ascertained by means of US Renal Data System database inquiry. OUTCOMES Incidence of diarrhea, graft loss, and death after transplantation. First episodes of diarrhea after transplantation were ascertained by using International Classification of Disease, Ninth Revision, Clinical Modification codes using Medicare billing data. Cause of diarrhea was classified as infectious or not and according to specific cause. Graft loss and death were ascertained from the date of the first diarrhea episode. RESULTS We enrolled 41,442 patients. Mean follow-up was 758 +/- 399 days. We observed 7,103 diarrhea cases and 8,104 graft losses (4,201 deaths). The 3-year cumulative incidence of diarrhea was 22%, with 18% diagnosed as noninfectious diarrhea with an unspecified cause. Using multivariate Cox proportional hazards analysis, factors associated with increased risk of unspecified noninfectious diarrhea were female sex (hazard ratio [HR], 1.40; 95% confidence interval, 1.33 to 1.48), type 1 diabetes (HR, 1.20; 95% confidence interval, 1.06 to 1.37), and regimens containing tacrolimus and mycophenolate mofetil (HR, 1.37; 95% confidence interval, 1.28 to 1.46). Unspecified noninfectious diarrhea was associated with increased risk of graft failure (HR, 2.13; 95% confidence interval, 1.98 to 2.28) and patient death (HR, 2.04; 95% confidence interval, 1.85 to 2.24). LIMITATIONS Use of claims data to ascertain patient characteristics and events; inability to make causal inference based on retrospective designs. CONCLUSIONS Regimens containing tacrolimus and mycophenolate mofetil were associated with increased risk of noninfectious diarrhea. Episodes of noninfectious diarrhea doubled the hazard of graft loss and patient death.

Obesity and cardiac risk after kidney transplantation: Experience at one center and comprehensive literature review

Background. The cardiac implications of obesity in kidney transplant recipients are not well-described. Methods. We examined associations of body mass index (BMI) at transplant with posttransplant cardiac risk among 1102 renal allograft recipients at a single center in 1991 to 2004. Cumulative posttransplant incidences of congestive heart failure (CHF), atrial fibrillation (AF), myocardial infarction, and a composite of these cardiac diagnoses were estimated by the Kaplan-Meier method. Bivariate (hazards ratio) and covariate (adjusted hazards ratio) relationships of BMI increments with cardiac risk were modeled by Cox’s regression. We also systematically reviewed the literature on BMI and cardiac events after transplant. Results. In the local data, 5-year cumulative incidence of any cardiac diagnosis rose from 8.67% to 29.35% across the lowest to highest BMI quartiles (P=0.02), driven primarily by increases in CHF and AF. In contrast, the rate of myocardial infarction did not differ by BMI quartile (P=0.56). Each 5 U BMI increase predicted 25% higher risk of the cardiac composite (hazards ratio 1.25, 95% CI 1.07–1.47, P=0.005), a relationship that persisted with significance after covariate adjustment (adjusted hazards ratio 1.19, 95% CI 1.00–1.43, P=0.049). BMI independently predicted cardiac risk in subcohorts with pretransplant heart disease and with nondiabetic renal failure. Data from 26 original articles support BMI as a risk factor for posttransplant CHF and AF, whereas findings for coronary/ischemic outcomes are inconsistent and predominantly negative. Conclusions. High BMI at transplant predicts increased cardiac risk, especially of CHF and AF. Further research should examine whether obesity treatment modifies cardiac risk after kidney transplantation.

Early outcomes of thymoglobulin and basiliximab induction in kidney transplantation: Application of statistical approaches to reduce bias in observational comparisons

Background. Retrospective comparison of treatment-related kidney transplant outcomes may be facilitated by multivariable statistical adjustments and case-matching. Methods. We studied Organ Procurement and Transplantation Network registry data for kidney transplants in 2001 to 2005 managed with thymoglobulin, basiliximab, or no antibody induction and discharge maintenance immunosuppression regimens of tacrolimus and mycophenolate mofetil. The primary outcome was the 6 month, Food and Drug Administration-approved composite endpoint of rejection, graft failure, or death. Outcomes according to induction exposure were compared using logistic regression analysis, exposure likelihood matching, and outcome risk score matching. Results. All statistical approaches demonstrated lower rates of the 6-month triple endpoint with thymoglobulin compared with basiliximab when steroids were present, with approximately 22% adjusted, relative reduction by logistic regression analysis and 3% absolute reductions by matching approaches. When steroids were absent, risk reduction among thymoglobulin versus basiliximab-treated patients was of larger magnitude but borderline statistical significance. Triple endpoint incidence was lower with both induction regimens compared with no induction across methods. Estimated sample sizes necessary to detect the observed differences between induction types in the presence of steroids in a prospective trial ranged from 1600 to nearly 7000 patients. Conclusions. Consistency across statistical approaches suggests superiority of thymoglobulin compared with basiliximab or no antibody induction therapy for 6-month kidney transplant outcomes in the modern immunosuppression era. As the sample sizes necessary to power a prospective superiority trial are likely prohibitive, studies such as these provide clinically relevant information that may not be otherwise attainable.

Regimen Complexity and Prescription Adherence in Dialysis Patients

Objectives: Poor medication adherence is common in end-stage renal disease and may cause suboptimal outcomes and increased healthcare costs. We assessed the association between regimen complexity, perceived burden of oral therapy (BOT) and medication adherence in a large sample of hemodialysis (HD) patients. Methods: 1,238 HD patients in 54 Italian centers participated. Data were collected on patients’ socio-demographic characteristics, perceived BOT, quality of life, healthcare satisfaction, social support and medication adherence with a self-administered questionnaire. Data on medication regimen, comorbidities, hospitalizations, and transplant listing status were provided by the nursing staff. We estimated the adjusted association of regimen complexity, BOT and medication adherence with logistic regression. Results: There were 789 (64%) men and the median age was 67 years. Mean daily burden was 9.7 tablets and 48% of patients were adherent to medication prescriptions. The number of tablets prescribed in the medication regimen was associated to adherence likelihood after adjustment for possible confounders. Perceived BOT moderated the association between tablet count and self-reported adherence. Conclusion: Poor adherence was very common in our sample. Reducing tablet burden might help patients be adherent. However, our results suggest that modulating regimen complexity might be ineffective if patients’ negative attitudes toward medications are not addressed concurrently.

Joint Association of Hyperuricemia and Reduced GFR on Cardiovascular Morbidity: A Historical Cohort Study Based on Laboratory and Claims Data From a National Insurance Provider

BACKGROUND Hyperuricemia is common in patients with chronic kidney disease (CKD). We assessed the relationship of increased serum uric acid levels with cardiovascular risk across levels of kidney function. STUDY DESIGN Historical cohort study. SETTING & PARTICIPANTS Study data were drawn from administrative records of a national private health insurer (2003-2006). We included all adult beneficiaries with concurrently measured serum creatinine and serum uric acid. Patients with acute kidney failure or undergoing renal replacement therapy at baseline were excluded. PREDICTORS Serum uric acid concentration and estimated glomerular filtration rate (eGFR). OUTCOMES & MEASUREMENTS Cardiovascular diagnoses (myocardial infarction, subacute coronary heart disease, heart failure, cerebrovascular disease, or peripheral arterial disease) ascertained from billing claims. Cox proportional hazard models were used to test the association of predictors with cardiovascular morbidity. Models were adjusted for sociodemographic characteristics, selected comorbid conditions, and laboratory results. RESULTS In 148,217 eligible patients, mean eGFR was 84 mL/min/1.73 m(2) and the prevalence of CKD stages 3-5 was 6.0%. Hyperuricemia (serum uric acid >7 mg/dL) was found in 15.6% of patients. The 40-month cumulative incidence of cardiovascular events (mean follow-up, 15.3 months) was 8.1%. Cardiovascular risk was associated independently with uric acid level, and this association was stronger in patients with lower eGFRs. LIMITATIONS Observational design, lack of information for mortality and potential confounders, single creatinine and uric acid assessment. CONCLUSIONS Serum uric acid concentration was an independent correlate of cardiovascular morbidity, and this association was stronger in patients with severely decreased eGFR. This investigation provides a rationale for further study of serum uric acid-lowering interventions on cardiovascular risk in the general population and patients with CKD.

Combined effects of ascorbic acid and phosphate on rat VSMC osteoblastic differentiation

BACKGROUND Ascorbic acid (AA) supplementation has been suggested to afford erythropoietin hyporesponsiveness and high levels of ferritin in haemodialysis (HD) patients. However, little is known about the possible side effects of this policy on vascular calcification (VC). VC, induced by a high-phosphate and uraemic milieu, is characterized by a passive deposition of calcium-phosphate (Ca-P) and an active transformation of vascular smooth muscle cells (VSMCs) in osteoblastic-like cells. The aim of these studies was to characterize the combined effects of AA and P on VC. MATERIALS AND METHODS Rat VSMCs were challenged with inorganic P (Pi) and AA, and Ca deposition analysis was performed to quantify VC. To investigate VSMC osteoblastic differentiation, we analysed α-actin protein content and core-binding factor alpha-1 (Cbfα1/RUNX2) messenger RNA (mRNA) expression. RESULTS When incubated with 5 mM Pi, VSMCs showed a significant increase in Ca deposition compared to control cells. Interestingly, the addition of AA in the calcification medium resulted in a dose-dependent increase in Pi-induced Ca deposition. At the same time, the combined effect of AA and Pi on VSMCs resulted in the reduction of α-actin protein content and in a 4-fold increase of Cbfα1/RUNX2 mRNA expression. CONCLUSIONS We demonstrated that AA combined with Pi increases Ca deposition in rat VSMCs. The role of AA as cofactor in osteoblastic differentiation was demonstrated by phenotypic changes in VSMCs and enhanced bone mineralization key gene expression. These in vitro preliminary data suggest a potential role for AA combined with Pi in worsening VC.

Conventional vs. daylight methyl aminolevulinate photodynamic therapy for actinic keratosis of the face and scalp: an intra-patient, prospective, comparison study in Italy

Daylight photodynamic therapy (DL‐PDT) with methyl aminolevulinate (MAL) is a simplified PDT procedure that was recently shown in a few trials to be effective for grade I actinic keratosis (AK), with improved tolerability and reduced time of clinical attendance as compared to conventional PDT (c‐PDT).

Constipation severity is associated with productivity losses and healthcare utilization in patients with chronic constipation

Objective We sought to evaluate the association between constipation severity, productivity losses and healthcare utilization in a national sample of Italian patients with chronic non-organic constipation (CC) Methods We enrolled 878 outpatients with CC. Clinical and demographic data were collected by physicians during clinical examinations. Patients completed a self-administered questionnaire (Patient Assessment of Constipation-Symptoms, PAC-SYM; Work Productivity and Activity Impairment; healthcare utilization, and Symptoms Checklist 90 Revised – Somatization Scale, SCL-90 R). Results Mean PAC-SYM score was 1.62 ± 0.69. Mean weekly sick time due to constipation was 2.7 ± 8.6 h and productivity losses due to presenteeism was 19.7% ± 22.3%. Adjusted productivity losses in patients with severe CC (PAC-SYM score 2.3–4.0) compared to patients with mild symptoms (PAC-SYM score 0.0–1.0) was Italian Purchase Power Parity US

Stress and sleep in nurses employed in “3 × 8” and “2 × 12” fast rotating shift schedules

6160. Constipation severity (PAC-SYM quintiles) was associated with higher healthcare utilization (RRPAC-SYM 4/01.84; p-value for linear trend <0.01). After adjustment for somatization scores, the association of constipation severity with productivity losses and healthcare utilization rates was attenuated yet statistically significant. Conclusions We observed a graded increase in productivity losses and healthcare utilization with increasing constipation severity. Further studies should evaluate whether significant savings might be achieved with regimens aimed at reducing the constipation severity.

Italian expert consensus for the management of actinic keratosis in immunocompetent patients

We compared two “3 × 8” shift rotas with backward rotation and quick return (morning and night shift in the same day) in a 5- or 6-day shift cycle, and a “2 × 12” shift rota with forward rotation in a 5-d shift cycle. A total of 294 nurses (72.6% women, mean age 33.8) were examined in a survey on work-related stress, including the Standard Shiftwork Index. Ten nurses per each shift roster recorded their activity and rest periods by actigraphy, rated sleepiness and sleep quality, and collected salivary cortisol throughout the whole shift cycle. Nurses engaged in the “2 × 12” rota showed lower levels of sleep disturbances and, according to actigraphy, sleep duration was more balanced and less fragmented than in the “3 × 8” rosters. The counter-clockwise shift rotation and quick return of “3 × 8” schedules reduce possibility of sleep and recovery. The insertion of a morning shift before the day with quick return increases night sleep by about 1 h. Nurses who take a nap during the night shift require 40% less sleep in the morning after. The “2 × 12” clockwise roster, in spite of 50% increased length of shift, allows a better recovery and more satisfying leisure times, thanks to longer intervals between work periods. Sleepiness increased more during the night than day shifts in all rosters, but without significant difference between 8-h and 12-h rosters. However, the significantly higher level at the start of the night shift in the “3 × 8” rotas points out that the fast backward rotation with quick return puts the subjects in less efficient operational conditions. Some personal characteristics, such as morningness, lability to overcome drowsiness, flexibility of sleeping habits and age were significantly associated to sleep disturbances in nurses engaged in the “3 × 8” rotas, but not in the “2 × 12” schedule.