Assessment of renal allograft rejection with diffusion tensor imaging.

OBJECTIVES: To investigate the value of DTI in differentiation of renal allograft rejection from well-functioning stable allograft, using fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values. METHODS: In this prospective study, 22 transplant recipients with well-functioning stable allograft (group A) and 20 patients with renal allograft rejection (group B + C) were recruited over a period of 19 months from January 2018 to July 2019. DTI-MRI was performed in all the patients, and FA and ADC values were measured in cortical and medullary regions of the transplanted kidney. On biopsy, graft rejection was classified as acute (group B) (n = 7) and chronic graft rejection (group C) (n = 13) based on the BANNF scoring system. Statistical analysis was performed using STATA v.14.0. RESULTS: Statistically significant difference between group A and group B + C was noted for cortical (p < 0.001), and medullary (p = 0.003) FA values, and cortical (p = 0.020), and medullary (p = 0.046) ADC values. Cortical(p < 0.001) and Medullary(p = 0.020) FA values showed statistically significant difference between group A and group C, and cortical FA value(p = 0.012) also showed statistically significant difference between group B and group C. AUC (to differentiate between renal allograft rejection and well-functioning stable allograft) for cortical, and medullary FA values and cortical and medullary ADC values were 0.853(p < 0.001), 0.757(p = 0.004), 0.709(p = 0.021) and 0.736(p = 0.009), respectively. CONCLUSION AND ADVANCES IN KNOWLEDGE: DTI is a promising functional MRI technique for the non-invasive assessment of renal allograft function. Diffusion parameters, such as FA and ADC values, can be useful in the differentiation of renal allograft rejection from well-functioning stable allograft.

Assessment of Risk Factors and Outcome of Early Versus Late Cytomegalovirus Infection Infection in Living-related D+/R + Renal Allograft Recipients.

Introduction: Cytomegalovirus infection (CMV) in a kidney transplant recipient (KTR) is a serious complication resulting in increased morbidity, mortality and reduced graft survival. There is limited data on early (within 3 months posttransplant) CMV infection (ECMVI) vs. late CMV infection (LCMVI) in patients not receiving CMV prophylaxis. In India, majority of kidney transplants are D + R + combination. This study aimed to compare the risk factors and outcome of ECMVI vs. LCMVI in living related post-KTR. Methods: This was a single-center ambispective study of adult KTR from living donor between January 2001 and December 2015 who had CMV infection. This study had two cohorts: retrospective and prospective. Retrospective cohort included all KTR from January 2001 to September 2014. Prospective cohort included KTR who received transplants from October 2014 to December 2015. Of both cohorts, patients with early and late CMV infection were included. All patients received triple-drug immunosuppression. CMV infection was diagnosed when KTR had detectable CMV copies > 500/mL. In the prospective cohort, CMV PCR was done at 45 days, 3, 6, 9 and 12 months in all patients. Patients with CMV were treated on conventional lines. All patients were followed up till June 2016. Results: Of 2175 retrospective cohort, 97 and of the 155 prospective cohorts 75 had CMV infection, total being 172 CMV infections. Of these, 90 patients had ECNVI and 82 LCMVI. Induction was used in 48.8% in ECMVI group vs. 35.3% in LCMVI group (p = 0.02). CNI toxicity was present prior to CMV infection in 15 (17.4%) in ECMVI as compared to 14 (17.9%) in LCMVI (P = 0.93). In the ECMVI, 6 (6.6%) had acute rejection as compared to 13 (15.8%) in the LCMVI (P = 0.05). While asymptomatic CMV infection was more common in early (63.3% vs 37.8%, P = 0.001), symptomatic CMV without tissue diagnosis was more common in late (54.8% vs. 31.1%, P = 0.002). Total duration of post-transplant follow-up was 22.8 ± 22.1 months in ECMVI as compared to 49.7 + 40.9 months in the LCMVI (P < 0.001). The serum creatinine at last follow-up was 1.9 ± 1.6 mg/dL in ECMVI group and 2.4 ± 2.0 mg/dL in LCMVI (P = 0.02). Conclusion: In D+/R + living renal transplant recipients, without routine CMV prophylaxis, late CMV infection had more tissue invasive disease and is associated with inferior graft function on long-term follow-up.

Psychometric assessment of the health-related productivity questionnaire (HRPQ) among women with endometriosis.

Objective: Endometriosis impacts health-related quality of life. The objective was to assess the validity and responsiveness of the Health-Related Productivity Questionnaire, version 2 (HRPQ). Methods: Outcome measures (Endometriosis Health Profile-30; pain scales; and global assessment) from Elaris Endometriosis I and II clinical trials (EM-I, EM-II) were used. Validity testing using Cohen's conventions was assessed. Known-groups validity was evaluated using generalized linear models comparing clinical responders, assessment of change, and the endometriosis impact. The effect size (ES) and standard error of means were calculated to evaluate responsiveness. Results: 871 and 815 women participated in the EM-I and EM-II trials. The total hours of lost work among employed women were 16.5 (±11.4) hours per week for EM-I and 15.2 (±11.3) for EM-II. The total hours of lost work among the household group were 8.3 (±8.7) hours for EM-I and 8.4 (±9.0) hours for EM-II. HRPQ discriminated between all known group assessments tested. Correlations for the HRPQ compared to other measures were small to moderate. Moderate to large ES was observed and the ability of the HRPQ to detect change was strong using patient-reported impressions. Conclusion: The HRPQ is a valid and responsive tool for evaluating patient-reported productivity at work and at home among women with endometriosis.

National Patterns of Emergency Department Use for Women with Endometriosis, 2006-2015.

Introduction: Endometriosis is a burdensome chronic condition for which conservative management is often recommended when indicated. Nonetheless, some women seek care for endometriosis in the emergency department (ED). We evaluated trends in ED visits for endometriosis from 2006 to 2015. Materials and Methods: Nationally representative estimates of ED visits for endometriosis by women aged 18-49 were extracted from the Health Care Utilization Project Nationwide Emergency Department Sample into three cohorts by calendar years 2006-2007, 2010-2011, and 2014-Q3 2015. Visits with a principal diagnosis code of endometriosis (International Classification of Disease, 9th Edition, Clinical Modification, code 617.x) were included. Patient and hospital characteristics were compared across cohorts using analysis of variance. Trends in the proportion of ED visits ending in inpatient admission and in mean charges (2015 USD) were assessed using generalized linear models controlling for patient and hospital characteristics. Results: The annual number of ED visits nationally was stable at ∼15,000 visits per year during 2006-2015. From 2006-2007 to 2014-2015, the composition of ED visits shifted away from private pay (42.0% vs. 35.3%) and uninsured (23.6% vs. 16.6%) to Medicaid (26.7% vs. 40.1%) and became more concentrated in metro-teaching hospitals (33.9% vs. 51.9%) (p < 0.001 for all). Inpatient admission rates declined from 20.1% to 9.2% (p < 0.001). Mean ED charges increased from $2458 to $4953 (p < 0.001). Conclusion: During 2006-2015, the number of ED visits for endometriosis remained stable, the inpatient admission/transfer rate declined by half, and mean charges per visit doubled.

Health Care Utilization and Costs Associated with Endometriosis Among Women with Medicaid Insurance.

BACKGROUND: Endometriosis is a painful chronic inflammatory disease caused by endometrial tissue implanting and growing outside the uterus, resulting in pelvic pain symptoms and subfertility. Treatment imposes a substantial economic burden on the patient and health care system. OBJECTIVE: To evaluate direct health care utilization and costs among women newly diagnosed with endometriosis compared with age-matched controls in a U.S. Medicaid population. METHODS: This retrospective cohort study used deidentified health care claims from the 2007-2015 MarketScan Multi-State Medicaid Database. Women (aged 18-49 years) newly diagnosed with endometriosis (ICD-9-CM 617.xx) during January 2008 through September 2014 were identified (date of first diagnosis = index date). Age-matched women without endometriosis (controls) were selected from the database and assigned index dates matching the distribution for endometriosis patients. Direct health care resource utilization (HCRU) and costs (medical and pharmacy) over the 12-month post-index period (2015 U.S. dollars) were computed by service category (hospitalization, emergency room visits, outpatient services, and prescriptions) and compared between study cohorts using the chi-square test for proportions and t-test for continuous variables. RESULTS: The final sample included 15,615 endometriosis patients and 86,829 matched controls. HCRU during the 12-month post-index follow-up period was significantly higher for endometriosis cases compared with controls in all measured categories. Hospital admissions occurred among 33.1% of cases and 7.2% of controls, and 65.8% of endometriosis patients were admitted for endometriosis-related surgery. Emergency room visits occurred in 71.5% of cases, and 42.2% of controls. Mean (SD) office visits were 10.4 (8.5) for endometriosis patients and 5.1 (6.9) for controls. Endometriosis patients had significantly more prescription claims than controls, 45.9 (42.0) versus 25.1 (39.1). Mean total direct health care costs were $13,670 ($29,843) for cases versus $5,779 ($23,614) for controls. All differences between cases and controls were significant at P < 0.001. CONCLUSIONS: Health care costs and resource utilization in all measured categories were higher among endometriosis cases than controls. The economic burden of endometriosis among patients with Medicaid insurance is substantial, underscoring the unmet medical need for earlier diagnosis and cost-effective treatments. DISCLOSURES: This study was funded by AbbVie and conducted by Truven Health Analytics, an IBM Company. AbbVie participated in developing the study design, data analysis and interpretation, manuscript writing and revisions, and approval for publication. Soliman and Vora are employees of AbbVie and may own AbbVie stock/stock options. Surrey has served in a consulting role on research to AbbVie and is on the speaker bureau for Ferring Laboratories. Bonafede and Nelson are employees of Truven Health Analytics, an IBM Company, which received compensation from AbbVie for the overall conduct of the study and preparation of the manuscript. Agarwal has served in a consulting role on research to AbbVie. Preliminary results of this study were previously presented in a podium session at the 2017 American Society for Reproductive Medicine Scientific Congress and Expo; October 28-November 1, 2017; San Antonio, TX.

Cost-effectiveness of elagolix versus leuprolide acetate for treating moderate-to-severe endometriosis pain in the USA.

AIM: To assess the cost-effectiveness of elagolix versus leuprolide acetate in women with moderate to severe endometriosis pain. METHODS: A Markov model was developed. The efficacy of leuprolide acetate was derived from statistical prediction models using elagolix trial data. Model inputs were extracted from Phase III clinical trials and published literature. RESULTS: Compared with leuprolide acetate, elagolix generated positive net monetary benefit (NMB) assuming a payer's willingness-to-pay threshold of US$100,000 per quality-adjusted life year over a 1-year time horizon: US$5660 for elagolix 150 mg and US$6443 for elagolix 200 mg. The 2-year NMBs were also positive. CONCLUSION: Elagolix was cost effective versus leuprolide acetate in the management of moderate to severe endometriosis pain over 1- and 2-year time horizons. Results were robust in sensitivity analyses.

Infection is the chief cause of mortality and non-death censored graft loss in the first year after renal transplantation in a resource limited population: A single centre study.

AIM: Few studies have assessed the impact of infections after renal transplantation (RTX) in low and middle income countries. This single centre study aimed to delineate the profile and impact of infections requiring hospitalization (IRH) occurring in the first year after RTX in India. METHOD: Patients who underwent RTX between July 2012 and June 2015 were followed up for 12 months after transplantation. RESULTS: 60.2% of the 387 patients studied had at least one IRH and total 492 infections were diagnosed. The most common were urinary tract (30.3%), gastrointestinal (17.1%) and pulmonary (11.2%) infections. Viral aetiology (33.3%) was most frequent, followed by bacterial (23.6%), parasitic (5.1%), tuberculosis (4.5%), and fungal infections (3.9%). 86.4% deaths were due to infections. One year patient and graft survival were inferior among recipients with IRH compared to those with no IRH: 91.8% vs. 98.1% (log rank = 0.010) and 90.1% vs. 97.4% (log rank = 0.006) respectively. Average monthly income per family member <5000 Rupees (75 USD), NODAT, and acute rejection were independent risk factors for IRH. CONCLUSION: The profile of IRH is unique involving opportunistic, community-acquired and endemic infections seen in this country. It is the predominant cause of mortality and graft loss in the first year after RTX. Poor economic status is an important determinant of IRH in our population.

How to advocate for the inclusion of chronic kidney disease in a national noncommunicable chronic disease program.

Many countries are developing or refining national strategies for noncommunicable chronic disease (NCD) prevention and control. Chronic kidney disease (CKD) is a cause and consequence of other NCDs; CKD acts as a risk multiplier for all four key NCDs as specified by the World Health Organization; CKD is associated with high health-care costs; CKD is readily identifiable; and treatment of CKD is cost-effective and improves outcomes. These observations argue in favor of including CKD in national NCD programs. The purpose of this article is to outline key steps in advocating for the inclusion of CKD in national NCD strategies.

Ezetimibe 5 and 10 mg for lowering LDL-C: potential billion-dollar savings with improved tolerability.

OBJECTIVE: To compare the clinical efficacy of ezetimibe 5 mg (prescribed as a 10-mg tablet split in half) with a whole 10-mg tablet. STUDY DESIGN: From January 2003 through July 2005, all Bronx Veterans Administration ezetimibe prescriptions were for 10 mg. In August 2005, it was mandated that all new ezetimibe prescriptions be 5 mg, prescribed as a 10-mg tablet split in half. METHODS: The impact of the 2 ezetimibe dosing strategies on percent lowering of low-density lipoprotein cholesterol (LDL-C) and achievement of National Cholesterol Education Program Adult Treatment Panel III (ATP III) goals was assessed in all patients prescribed ezetimibe 5 or 10 mg. RESULTS: A total of 272 patients were prescribed ezetimibe; 86 received 5 mg and 186 received 10 mg. Of those 272 patients, 197 had evaluable baseline and posttreatment LDL-C (55 taking the 5-mg dose and 142 taking the 10-mg dose). The effects of ezetimibe 5 and 10 mg on all lipid parameters were similar. Ezetimibe 10 mg reduced LDL-C by 26.1%, whereas 5 mg reduced LDL-C by 25.8%. The percentages of patients achieving goal LDL-C were similar: 61.8% (5 mg) and 60.5% (10 mg). CONCLUSION: These data strongly suggest that ezetimibe 5 mg and ezetimibe 10 mg are clinically equivalent with respect to LDL-C reduction and achievement of ATP III LDL-C goals. Widespread adoption of this low-dose strategy could result in a potential cost savings of more than a billion dollars annually, with a potential reduction in hepatotoxicity.

Prevention of chronic kidney and vascular disease: toward global health equity--the Bellagio 2004 Declaration.

Chronic kidney disease (CKD) not only reflects target organ injury in systemic vascular disease in the general population and in association with diabetes, hypertension, and smoking, but it is recognized as one of the major risk factors in the pathogenesis and outcome of cardiovascular disease. Recent surveys have revealed that the prevalence of CKD, particularly the hidden mild form (mildly elevated levels of serum creatinine or urinary albumin excretion), is surprisingly high in the general population. In recent years, the global epidemic of type 2 diabetes has led to an alarming increase in the number of patients with CKD. Most patients with CKD (over 50 million individuals worldwide) succumb to cardiovascular events, while each year over 1 million develop end-stage renal failure, which requires costly treatment and in many countries of the world, unaffordable renal replacement therapy by chronic dialysis or renal transplantation. Alarmed by the immense challenge to human morbidity and the economic burden of CKD and ensuing systemic cardiovascular disease, the International Society of Nephrology convened a multidisciplinary group of expert physicians and public health leaders from around the world to develop strategies to delay and avert this bleak future by effective prevention of CKD based on awareness, early detection, and effective treatment.

Chronic kidney disease and its prevention in India.

Chronic kidney disease (CKD) is an important, chronic, noncommunicable disease epidemic that affects the world, including India. Because of the absence of a renal registry in India, the true magnitude of CKD/end-stage renal disease (ESRD) is unknown. Two community-based studies, although methodologically different, have shown a prevalence of chronic renal failure of 0.16% and 0.79%. The cost of maintenance hemodialysis for a single session varies between 10 US dollars to 40 between government-run and private hospitals. The average cost of erythropoetin is approximately 150 US dollars to 200 per month. The cost of chronic ambulatory peritoneal dialysis with "Y" set at 3 exchanges per week, which most patients in India do, is US 400 US dollars per month. The cost of a renal transplant (RT) procedure is approximately US 700 US dollars to 800 in the government sector and 6000 US dollars in the private sector. The cost of immunosuppression with basic triple immunosuppression drugs (cyclosporine, steroid, and azathioprin) is US 250 US dollars per month. There are hardly any state-funded medical treatment and medical insurance facilities for CKD and ESRD patients in India. India has nearly 700 nephrologists and approximately 400 dialysis units with 1000 dialysis stations, with the majority being in the private sector. A maximum of 2% of patients can be subjected to maintenance hemodialysis. Until now, approximately 3000 patients have been initiated on chronic ambulatory peritoneal dialysis. India has approximately 100 RT centers, mostly in private setup, and not more than 3000 to 4000 RTs are performed annually. Thus, only 3% to 5% of all patients with ESRD in India get some form of renal replacement therapy. Thus, planning for prevention of CKD on a long-term basis is the only practical solution for India. It appears that even in India, diabetes and hypertension are responsible for 40% to 50% of all cases of chronic renal failure. Screening for these 2 diseases and CKD is simple and easy to perform. The best approach will be to start screening for CKD in a high-risk group, like first-degree relatives of patients with diabetes, hypertension, and CKD, and simultaneously making a platform to run the program through the existing health care system of the country. The key issue of funding the program needs to be explored. Initial funding may come from international agencies like the World Health Organization, World Bank, and International Society of Nephrology, along with support from the country itself. Ultimately, funding has to be sustained from our own existing health care system.