Risk prediction to inform surveillance of chronic kidney disease in the US Healthcare Safety Net: a cohort study.

BackgroundThe capacity of electronic health record (EHR) data to guide targeted surveillance in chronic kidney disease (CKD) is unclear. We sought to leverage EHR data for predicting risk of progressing from CKD to end-stage renal disease (ESRD) to help inform surveillance of CKD among vulnerable patients from the healthcare safety-net.MethodsWe conducted a retrospective cohort study of adults (n = 28,779) with CKD who received care within 2 regional safety-net health systems during 1996-2009 in the Western United States. The primary outcomes were progression to ESRD and death as ascertained by linkage with United States Renal Data System and Social Security Administration Death Master files, respectively, through September 29, 2011. We evaluated the performance of 3 models which included demographic, comorbidity and laboratory data to predict progression of CKD to ESRD in conditions commonly targeted for disease management (hypertension, diabetes, chronic viral diseases and severe CKD) using traditional discriminatory criteria (AUC) and recent criteria intended to guide population health management strategies.ResultsOverall, 1730 persons progressed to end-stage renal disease and 7628 died during median follow-up of 6.6 years. Performance of risk models incorporating common EHR variables was highest in hypertension, intermediate in diabetes and chronic viral diseases, and lowest in severe CKD. Surveillance of persons who were in the highest quintile of ESRD risk yielded 83-94 %, 74-95 %, and 75-82 % of cases who progressed to ESRD among patients with hypertension, diabetes and chronic viral diseases, respectively. Similar surveillance yielded 42-71 % of ESRD cases among those with severe CKD. Discrimination in all conditions was universally high (AUC ≥0.80) when evaluated using traditional criteria.ConclusionsRecently proposed discriminatory criteria account for varying risk distribution and when applied to common clinical conditions may help to inform surveillance of CKD in diverse populations

Heart failure and social determinants of health in Thailand: An integrative review

© 2019 Background: Heart failure is a highly burdensome syndrome and is rapidly increasing in prevalence in low and middle-income countries and outcomes are influenced at the level of the patient, provider and health system. Understanding heart failure beyond a biomedical perspective and the relationship between health outcomes and social determinants of health is critical for informing policy development and improving health outcomes. Aim: To identify the social determinants of health for improving health outcomes for individuals with heart failure in Thailand. Method: This integrative review included studies published between January 1, 2008, and March 31, 2016 in both the Thai and English language identified through searching Scopus, PubMed, and CINAHL. Results: Six experimental, eight descriptive and two qualitative studies were identified met the inclusion and exclusion criteria. The majority of study participants were elderly, female, had low-education and income levels, were participating in a universal coverage scheme and living in a rural setting. All interventions were delivered at the level of the individual, focusing on education to improve knowledge, self-care, and functional status. Findings showed an improvement in health outcomes which were moderated by social determinants of health such as gender and income. Conclusion: As the burden of heart failure increases in Thailand and other emerging economies, developing culturally appropriate, affordable and acceptable models of intervention considering social determinants of health is necessary

Medication Adherence Interventions for Cardiovascular Disease in Low- and Middle-Income Countries: A Systematic Review.

Purpose: The burden of cardiovascular diseases (CVD) is high in low- and middle-income countries (LMICs). Medications are integral to the management and control of CVD; however, suboptimal adherence impacts health outcomes. This systematic review aims to critically examine interventions targeted at improving medication adherence among persons with CVD in LMICs. Methods: In this systematic review, we searched online databases PubMed, Embase, and CINAHL for studies that evaluated a medication adherence intervention for CVD, reported adherence as an outcome measure, were conducted in LMICs and reported the strategy or tool used to measure adherence. We included articles published in English, available in full text, peer-reviewed, and published between 2010 and 2020. Results: We included 45 articles in this review. The majority of the studies implemented counseling and educational interventions led by nurses, pharmacists, or community health workers. Many of the studies delivered medication-taking reminders in the form of phone calls, text messages, short message services (SMS), and in-phone calendars. Multi-component interventions were more effective than unifocal interventions. Interventions involving technology, such as mobile phone calls, electronic pillboxes, and interactive phone SMS reminders, were more effective than generic reminders. The outcomes reported in the studies varied based on the complexity and combination of strategies. When interventions were implemented at both the patient level, such as reminders, and at the provider level, such as team-based care, the effect on medication adherence was larger. Conclusion: In LMICs, medication adherence interventions among persons with CVD included a combination of patient education, reminders, fixed-dose combination therapy and team-based care approach were generally more effective than singular interventions. Among patients who had CVD, the medication adherence interventions were found to be moderately effective. Future studies focusing on improving medication adherence in LMICs should consider non-physician-led interventions and appropriately adapt the interventions to the local context

Placing Poverty in Context: A Case Study

The “poverty-in-context” approach to understanding poverty is shaped by the needs and priorities of a particular context, and it can be used as the basis for identifying pro-poor projects in local strategies such as City Development Plans. A key argument for the introduction of the City Development Plans initiative (2007–2012) in India was to move away from national conceptions of and responses to poverty and to instead focus on engaging with local understandings of poverty. Through a case study of the City Development Plan initiative in Trivandrum, the capital city of the Kerala state in southern India, we argue that an understanding of poverty at the local level did not accommodate contextual needs and priorities; consequently, we develop a poverty-in-context approach based on semi-structured qualitative interviews with various stakeholders in the case study area. The article concludes by suggesting how in the future a poverty-in-context approach might be used to shape pro-poor policy in general and preparation of City Development Plans in particular

Detection of Drug-Induced Acute Kidney Injury in Humans Using Urinary KIM-1, miR-21,-200c, and-423

Drug-induced acute kidney injury (AKI) is often encountered in hospitalized patients. Although serum creatinine (SCr) is still routinely used for assessing AKI, it is known to be insensitive and nonspecific. Therefore, our objective was to evaluate kidney injury molecule 1 (KIM-1) in conjunction with microRNA (miR)-21, -200c, and -423 as urinary biomarkers for drug-induced AKI in humans. In a cross-sectional cohort of patients (n = 135) with acetaminophen (APAP) overdose, all 4 biomarkers were significantly (P < .004) higher not only in APAP-overdosed (OD) patients with AKI (based on SCr increase) but also in APAP-OD patients without clinical diagnosis of AKI compared with healthy volunteers. In a longitudinal cohort of patients with malignant mesothelioma receiving intraoperative cisplatin (Cp) therapy (n = 108) the 4 biomarkers increased significantly (P < .0014) over time after Cp administration, but could not be used to distinguish patients with or without AKI. Evidence for human proximal tubular epithelial cells (HPTECs) being the source of miRNAs in urine was obtained first, by in situ hybridization based confirmation of increase in miR-21 expression in the kidney sections of AKI patients and second, by increased levels of miR-21, -200c, and -423 in the medium of cultured HPTECs treated with Cp and 4-aminophenol (APAP degradation product). Target prediction analysis revealed 1102 mRNA targets of miR-21, -200c, and -423 that are associated with pathways perturbed in diverse pathological kidney conditions. In summary, we report noninvasive detection of AKI in humans by combining the sensitivity of KIM-1 along with mechanistic potentials of miR-21, -200c, and -423

Reduced functional measure of cardiovascular reserve predicts admission to critical care unit following kidney transplantation

Background: There is currently no effective preoperative assessment for patients undergoing kidney transplantation that is able to identify those at high perioperative risk requiring admission to critical care unit (CCU). We sought to determine if functional measures of cardiovascular reserve, in particular the anaerobic threshold (VO2AT) could identify these patients. Methods: Adult patients were assessed within 4 weeks prior to kidney transplantation in a University hospital with a 37-bed CCU, between April 2010 and June 2012. Cardiopulmonary exercise testing (CPET), echocardiography and arterial applanation tonometry were performed. Results: There were 70 participants (age 41.7614.5 years, 60% male, 91.4% living donor kidney recipients, 23.4% were desensitized). 14 patients (20%) required escalation of care from the ward to CCU following transplantation. Reduced anaerobic threshold (VO2AT) was the most significant predictor, independently (OR = 0.43; 95% CI 0.27–0.68; p,0.001) and in the multivariate logistic regression analysis (adjusted OR = 0.26; 95% CI 0.12–0.59; p = 0.001). The area under the receiveroperating- characteristic curve was 0.93, based on a risk prediction model that incorporated VO2AT, body mass index and desensitization status. Neither echocardiographic nor measures of aortic compliance were significantly associated with CCU admission. Conclusions: To our knowledge, this is the first prospective observational study to demonstrate the usefulness of CPET as a preoperative risk stratification tool for patients undergoing kidney transplantation. The study suggests that VO2AT has the potential to predict perioperative morbidity in kidney transplant recipients

Total and corrected antioxidant capacity in hemodialyzed patients

BACKGROUND: Oxidative stress may play a critical role in the vascular disease of end stage renal failure and hemodialysis patients. Studies, analyzing either discrete analytes and antioxidant substances, or the integrated total antioxidant activity of human plasma during hemodialysis, give contradictory results. METHODS: Recently, we have introduced a new automated method for the determination of Total Antioxidant Capacity (TAC) of human plasma. We have serially measured TAC and corrected TAC (cTAC: after subtraction of the interactions due to endogenous uric acid, bilirubin and albumin) in 10 patients before the onset of the dialysis session, 10 min, 30 min, 1 h, 2 h and 3 h into the procedure and after completion of the session. RESULTS: Our results indicate that TAC decreases, reaching minimum levels at 2 h. However, corrected TAC increases with t(1/2 )of about 30 min. We then repeated the measurements in 65 patients undergoing dialysis with different filters (36 patients with ethylene vinyl alcohol copolymer resin filter -Eval-, 23 patients with two polysulfone filters -10 with F6 and 13 with PSN140-, and 6 patients with hemophan filters). Three specimens were collected (0, 30, 240 min). The results of this second group confirm our initial results, while no significant difference was observed using either filter. CONCLUSIONS: Our results are discussed under the point of view of possible mechanisms of modification of endogenous antioxidants, and the interaction of lipid- and water-soluble antioxidants

In Deadly Time: The Lasting On of Waste in Mayhew’s London

This paper examines the temporal dimension of waste in Henry Mayhew’s London Labour and the London Poor as an instance of how modernity has produced a largely hidden domain of the non-identical and indeterminate. Through a consideration of the phenomena of uselessness, decay and poverty I argue that the temporal dimension of waste is constituted as a corrosive or malign ‘Deadly Time.’ In placing such emphasis on time directed towards death, I aim to show that Mayhew’s undisciplined researches can be seen as a valuable source for understanding why modern thinking struggles to come to terms with waste

Aberrant DNA hypermethylation of the ITIH5 tumor suppressor gene in acute myeloid leukemia

Epigenetic mechanisms such as DNA hypermethylation and modifications of histone amino acids are known to play an important role in the control of gene expression both in normal human development and tumorigenesis. Hypermethylation of CpG islands within promoter regions of tumor suppressor genes is associated with transcriptional inactivation and represents, in addition to genetic aberrations, an important mechanism of gene silencing in the pathogenesis of human cancer. Inter-α-trypsine inhibitors (ITIs) are a family of serine protease inhibitors consisting of one light chain (bikunin) and two heavy chains (ITI heavy chains, ITIHs). ITIHs stabilize the extracellular matrix (ECM) by interacting with hyaluronic acid, which is a major ECM component. Hypermethylation in the upstream region of the promoter-associated CpG island of ITIH5, the most recently described member of the ITIH family, has been previously detected in breast cancer and was associated with an adverse outcome. In this study, we determined the DNA methylation status of the promoter region near the transcription start site of the ITIH5 tumor suppressor gene in leukemia cell lines and primary samples from patients with acute myeloid leukemia (AML) as well as the potential use of demethylating agents to restore a demethylated state of the promoter. Aberrant ITIH5 promoter hypermethylation occurred in 15 of 104 (14.4%) diagnostic AML samples. There were no statistically significant correlations between the ITIH5 methylation status and clinical prognostic parameters. Our results indicate that aberrant ITIH5 promoter hypermethylation is a novel epigenetic event in AML

Lack of association between mutations of gene-encoding mitochondrial D310 (displacement loop) mononucleotide repeat and oxidative stress in chronic dialysis patients in Taiwan

<p>Abstract</p> <p>Background</p> <p>Mitochondria (mt) are highly susceptible to reactive oxygen species (ROS). In this study, we investigated the association between a region within the displacement loop (D-loop) in mtDNA that is highly susceptible to ROS and oxidative stress markers in chronic dialysis patients. We enrolled 184 chronic dialysis patients and 213 age-matched healthy subjects for comparison. Blood levels of oxidative stress markers, such as thiobarbituric acid reactive substances (TBARS) and free thiol, and the mtDNA copy number were determined. A mononucleotide repeat sequence (CCCC...CCCTCCCCCC) between nucleotides 303 and 316-318 (D310) was identified in mtDNA.</p> <p>Results</p> <p>Depending on alterations in the D310 mononucleotide repeat, subjects were categorized into 4 subgroups: 7-C, 8-C, 9 or 10-C, and T-to-C transition. Oxidative stress was higher in chronic dialysis patients, evidenced by higher levels of TBARS and mtDNA copy number, and a lower level of free thiol. The distribution of 7-C, 8-C, and 9-10C in dialysis and control subjects was as follows: 7-C (38% <it>vs. </it>31.5%), 8-C (35.3% <it>vs. </it>43.2%), and 9-10C (24.5% <it>vs. </it>22.1%). Although there were significant differences in levels of TBARS, free thiol, and the mtDNA copy number in the D310 repeat subgroups (except T-to-C transition) between dialysis patients and control subjects, post hoc analyses within the same study cohort revealed no significant differences.</p> <p>Conclusion</p> <p>Although oxidative stress was elevated in chronic dialysis patients and resulted in a compensatory increase in the mtDNA copy number, homopolymeric C repeats in the mtDNA region (D310), susceptible to ROS, were not associated with oxidative stress markers in these patients.</p