Frailty and chronic kidney disease: associations and implications / Fragilidade e doença renal crônica: associações e implicações

ABSTRACT Introduction: Frailty and its association with chronic kidney disease (CKD) has been established previously. The present study examined this association further by studying the distribution of frailty among groups defined by different stages of the disease. It also identified associated health deficits and explored their association with estimated glomerular filtration rate (eGFR) and urine albumin creatinine ratio (UACR). Methods: A cross-sectional survey was conducted on 90 non-dialysis dependent CKD Stage 1-4 patients, recruited in three stratified groups of 30 participants each based on the stage of disease. Frailty was assessed using Fried's frailty criteria and associated health deficits were recorded using a pre-determined list. Depression was screened using a 4-point depression scale. Results: 21.1% of the participants were frail and 43.3% were pre-frail. The proportion of frailty in CKD groups A (Stages 1 and 2), B (Stage 3a), and C (Stages 3b and 4) was 10%, 13.3%, and 40%, respectively. The association of health deficits including co-morbidities, physical parameters, mental status, daily activities, etc. with UACR, eGFR, and CKD stages was not statistically significant. Nearly one in two frail participants was depressed compared with 14% among non-frail participants. Conclusion: The skewed distribution of 21% frail subjects identified in our study indicates an association between frailty and advancing kidney disease. Frail individuals had a lower eGFR, higher UACR, were more likely to be depressed, and had higher count of health deficits and poorer performance on Barthel Index of Activities of Daily Living and WHOQOL. Early identification of depression would improve care in these patients.

RESUMO Introdução: Fragilidade e sua associação com DRC foram estabelecidas anteriormente. O presente estudo aprofundou esta associação, estudando distribuição da fragilidade entre grupos definidos por diferentes estágios da doença. Também identificou déficits de saúde associados e explorou sua associação com taxa de filtração glomerular estimada (TFGe) e relação albumina/creatinina urinária (RAC). Métodos: Realizou-se uma pesquisa transversal em 90 pacientes com DRC Estágios 1-4 não dependentes de diálise, recrutados em três grupos estratificados de 30 participantes cada, conforme estágio da doença. Avaliou-se fragilidade usando os critérios de fragilidade de Fried e registraram-se os déficits de saúde associados usando uma lista pré-determinada. A depressão foi verificada utilizando a escala de depressão de 4 pontos. Resultados: 21,1% dos participantes eram frágeis e 43,3% eram pré-frágeis. A proporção de fragilidade nos grupos de DRC A (Estágios 1 e 2), B (Estágio 3a), e C (Estágios 3b e 4) foi de 10%, 13,3%, 40% respectivamente. A associação de déficits de saúde, incluindo comorbidades, parâmetros físicos, estado mental, atividades diárias etc. com RAC, TFGe e estágios da DRC não foi estatisticamente significativa. Cerca de um em cada dois participantes frágeis estava depressivo comparados com 14% entre não frágeis. Conclusão: A distribuição enviesada de 21% dos indivíduos frágeis identificados em nosso estudo indica associação entre fragilidade e doença renal progressiva. Indivíduos frágeis apresentaram menor TFGe, maior RAC, eram mais propensos a depressão, tinham maior índice de déficits de saúde e desempenho inferior no Índice de Atividades da Vida Diária de Barthel e WHOQOL. A identificação precoce da depressão melhoraria o atendimento desses pacientes.

Frailty and chronic kidney disease: associations and implications.

INTRODUCTION: Frailty and its association with chronic kidney disease (CKD) has been established previously. The present study examined this association further by studying the distribution of frailty among groups defined by different stages of the disease. It also identified associated health deficits and explored their association with estimated glomerular filtration rate (eGFR) and urine albumin creatinine ratio (UACR). METHODS: A cross-sectional survey was conducted on 90 non-dialysis dependent CKD Stage 1-4 patients, recruited in three stratified groups of 30 participants each based on the stage of disease. Frailty was assessed using Fried's frailty criteria and associated health deficits were recorded using a pre-determined list. Depression was screened using a 4-point depression scale. RESULTS: 21.1% of the participants were frail and 43.3% were pre-frail. The proportion of frailty in CKD groups A (Stages 1 and 2), B (Stage 3a), and C (Stages 3b and 4) was 10%, 13.3%, and 40%, respectively. The association of health deficits including co-morbidities, physical parameters, mental status, daily activities, etc. with UACR, eGFR, and CKD stages was not statistically significant. Nearly one in two frail participants was depressed compared with 14% among non-frail participants. CONCLUSION: The skewed distribution of 21% frail subjects identified in our study indicates an association between frailty and advancing kidney disease. Frail individuals had a lower eGFR, higher UACR, were more likely to be depressed, and had higher count of health deficits and poorer performance on Barthel Index of Activities of Daily Living and WHOQOL. Early identification of depression would improve care in these patients.

Impact of PAP therapy on hospitalization rates in Medicare beneficiaries with COPD and coexisting OSA.

OBJECTIVE: Growing evidence supports that patients with chronic obstructive pulmonary disease (COPD) and coexisting obstructive sleep apnea (OSA) have poor prognosis. This association is described as overlap syndrome. Positive airway pressure (PAP) therapy is now the preferred treatment for OSA. We hypothesized that use of PAP therapy in elderly patients with overlap syndrome would be associated with lower healthcare utilization. METHODS: In this retrospective cohort study, we analyzed data from 5% national sample of fee-for-service Medicare beneficiaries with a diagnosis of COPD who were newly started on PAP therapy in 2011. We examined the effect of PAP therapy on emergency room (ER) visits and hospitalizations for all-cause and COPD-related conditions in the 1 year pre- and 1 year post-initiation of PAP therapy. RESULTS: In year 2011, we identified 319 patients with overlap syndrome who were new users of PAP therapy. In this cohort of patients, hospitalization rates for COPD-related conditions were significantly lower in the 1 year post-initiation of PAP therapy compared to the 1-year pre-initiation period (19.4 vs 25.4%, P value = 0.03). However, ER visits (for any cause or COPD-related conditions) and hospitalization rates for any cause did not differ significantly in the pre- and post-initiation periods. PAP therapy was more beneficial in older adults, those with higher COPD complexity, and those with three or more comorbidities. CONCLUSION: Initiation of PAP therapy in elderly patients with overlap syndrome is associated with a reduction in hospitalization for COPD-related conditions, but not for all-cause hospitalizations and ER visits.

Validation of claims-based algorithms for pulmonary arterial hypertension.

Administrative claims studies do not adequately distinguish pulmonary arterial hypertension (PAH) from other forms of pulmonary hypertension (PH). Our aim is to develop and validate a set of algorithms using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes and electronic medical records (EMR), to identify patients with PAH. From January 2012 to August 2015, the EMRs of patients with ICD-9-CM codes for PH with an outpatient visit at the University of Texas Medical Branch were reviewed. Patients were divided into PAH or non-PAH groups according to EMR encounter diagnosis. Patient demographics, echocardiography, right heart catheterization (RHC) results, and PAH-specific therapies were assessed. RHC measurements were reviewed to categorize cases as hemodynamically determined PAH or not PAH. Weighted sensitivity, specificity, and positive and negative predictive values were calculated for the developed algorithms. A logistic regression analysis was conducted to determine how well the algorithms performed. External validation was performed at the University of Virginia Health System. The cohort for the development algorithms consisted of 683 patients with PH, PAH group (n = 191) and non-PAH group (n = 492). A hemodynamic diagnosis of PAH determined by RHC was recorded in the PAH (26%) and non-PAH (3%) groups. The positive predictive value for the algorithm that included ICD-9-CM and PAH-specific medications was 66.9% and sensitivity was 28.2% with a c-statistic of 0.66. The positive predictive value for the EMR-based algorithm that included ICD-9-CM, EMR encounter diagnosis, echocardiography, RHC, and PAH-specific medication was 69.4% and a c-statistic of 0.87. A validation cohort of 177 patients with PH examined from August 2015 to August 2016 using EMR-based algorithms yielded a similar positive predictive value of 62.5%. In conclusion, claims-based algorithms that included ICD-9-CM codes, EMR encounter diagnosis, echocardiography, RHC, and PAH-specific medications better-identified patients with PAH than ICD-9-CM codes alone.

RNA-Seq analysis of peripheral blood mononuclear cells reveals unique transcriptional signatures associated with disease progression in dengue patients.

Patients infected with Dengue virus usually present a mild, self-limiting febrile dengue infection (DI) that occasionally leads to a potentially lethal complication, called the severe dengue (DS). The ability to identify the prognostic markers of DS could allow an improved disease intervention and management. To identify the transcriptional signatures associated with the dengue disease progression, we carried out the high-throughput sequencing of the RNA isolated from the peripheral blood mononuclear cells (PBMCs) of the dengue patients of varying severity and compared with that in the patients with other febrile illnesses (OFIs) or the healthy controls. The transcriptional signatures that discriminated the DS patients from OFI and DI patients were broadly related to the pathways involving glycine, serine, and threonine metabolisms, extracellular matrix organization, ubiquitination, and cytokines and inflammatory response. Several upregulated genes in the inflammatory process (MPO, DEFA4, ELANE, AUZ1, CTSG, OLFM4, SLC16A14, and CRISP3) that were associated with the dengue disease progression are known to facilitate leukocyte-mediated migration, and neutrophil activation and degranulation process. High activity of MPO and ELANE in the plasma samples of the follow-up and recovered dengue patients, as well as and the presence of a larger amount of cell-free dsDNA in the DS patients, suggested an association of neutrophil-mediated immunity with dengue disease progression. Careful monitoring of some of these gene transcripts, and control of the activity of proteins encoded by them, may have a great translational significance for the prognosis and management of the dengue patients.

Process and Outcome Measures among COPD Patients with a Hospitalization Cared for by an Advance Practice Provider or Primary Care Physician.

OBJECTIVES: To examine the process and outcomes of care of COPD patients by Advanced Practice Providers (APPs) and primary care physicians. METHODS: We conducted a cross sectional retrospective cohort study of Medicare beneficiaries with COPD who had at least one hospitalization in 2010. We examined the process measures of receipt of spirometry evaluation, influenza and pneumococcal vaccine, use of COPD medications, and referral to a pulmonary specialist visit. Outcome measures were emergency department (ER) visit, number of hospitalizations and 30-day readmission in 2010. RESULTS: A total of 7,257 Medicare beneficiaries with COPD were included. Of these, 1,999 and 5,258 received primary care from APPs and primary care physicians, respectively. Patients in the APP group were more likely to be white, younger, male, residing in non-metropolitan areas and have fewer comorbidities. In terms of process of care measures, APPs were more likely to prescribe short acting bronchodilators (adjusted odds ratio [aOR] = 1.18, 95%Confidence Interval [CI] 1.05-1.32), oxygen therapy (aOR = 1.25, 95% CI 1.12-1.40) and consult a pulmonary specialist (aOR = 1.39, 95% CI 1.23-1.56), but less likely to give influenza and pneumococcal vaccinations. Patients receiving care from APPs had lower rates of ER visits for COPD (aOR = 0.84, 95%CI 0.71-0.98) and had a higher follow-up rate with pulmonary specialist within 30 days of hospitalization for COPD (aOR = 1.25, 95%CI 1.07-1.48) than those cared for by physicians. CONCLUSIONS: Compared to patients cared for by physicians, patients cared for by APPs were more likely to receive short acting bronchodilator, oxygen therapy and been referred to pulmonologist, however they had lower rates of vaccination probably due to lower age group. Patients cared for by APPs were less like to visit an ER for COPD compared to patients care for by physicians, conversely there was no differences in hospitalization or readmission for COPD between MDs and APPs.

Successful treatment of aortic root abscess in a patient with pulmonary arterial hypertension.

Continuous prostanoid infusion is an established treatment for pulmonary arterial hypertension that has led to improvements in symptoms, exercise tolerance, and survival. Patients with pulmonary arterial hypertension (PAH) who develop sepsis frequently experience clinical and hemodynamic deterioration associated with poor outcomes. Successful management of sepsis involves identification of the source of infection, early antimicrobial administration, judicious fluid resuscitation, and continuation of specific PAH therapies. We describe successful management of a patient with idiopathic PAH receiving chronic intravenous prostacyclin therapy who developed an aortic root abscess due to Clostridium perfringens requiring emergent aortic root repair. Management involved imaging studies, removal of potential sources with administration of intravenous antibiotics, and cautious fluid administration with hemodynamic monitoring. A multidisciplinary group led by a PAH specialist worked cohesively before, during, and after surgical intervention and achieved a successful outcome.

Esophageal dilations in eosinophilic esophagitis: a single center experience.

AIM: To diagnose the clinical and histologic features that may be associated with or predictive of the need for dilation and dilation related complications; examine the safety of dilation in patients with eosinophilic esophagitis (EoE). METHODS: The medical records of all patients diagnosed with EoE between January 2002 and July 2010 were retrospectively reviewed. Esophageal biopsies were reexamined by an experienced pathologist to confirm the diagnosis (≥ 15 eos/hpf per current guidelines). Patients were divided into 2 groups: patients who did not receive dilation therapy and those who did. Demographics, clinical history, the use of pharmacologic therapy, endoscopic and pathology findings, and the number of biopsies and dilations carried out, if any, and their locations were recorded for each patient. The dilation group was further examined based on the interval between diagnosis and dilation, and whether or not a complication occurred. RESULTS: Sixty-one patients were identified with EoE and 22 (36%) of them underwent esophageal dilations for stricture/narrowing. The peak eos/hpf was significantly higher in patients who received a dilation (P = 0.04). Four (18% of pts.) minor complications occurred: deep mucosal tear 1, and small mucosal tears 3. There were no cases of esophageal perforations. Higher peak eos/hpf counts were not associated with increased risk of complications. CONCLUSION: Esophageal dilation appears to be a safe procedure in EoE patients, carrying a low complication rate. No correlation was found between the peak of eosinophil count and complication rate. Complications can occur independently of the histologic features. The long-term outcome of EoE treatment, with or without dilation, needs to be determined.