Shotgun proteomics of homogenate milk reveals dynamic changes in protein abundances between colostrum, transitional, and mature milk of swine.

Milk is an easily digestible source of nutrients and bioactive factors, its composition reflects the neonate's needs, and changes from colostrum to transitional and mature milk. Our objective was to measure milk fat, lactose, total carbohydrate, and protein content in parallel with global proteome of homogenate milk samples to characterize changes across the three phases of swine lactation. Milk samples were collected from multiparous sows (n = 9) on postnatal day 0 (D0; colostrum), 3 (D3; early transitional), 7 (D7; late transitional), and 14 (D14; mature). On D3, percent fat (16 ± 2.1) and lactose (3.8 ± 0.3) were higher (P < 0.05) than on D0 (10 ± 3.9 and 1.5 ± 0.3, respectively). Levels of fat and lactose were not different between D3 and D14. Percent total protein decreased (P < 0.05) between D0 (11 ± 2.1) and D3 (5 ± 0.7), but there was no significant change in percent protein between D3 and D14. Total carbohydrates increased (P < 0.05) between D3 (944 ± 353 µg/mL) and D14 (1,150 ± 462 µg/mL). Quantitative proteomic analysis using liquid chromatography tandem mass spectrometry (LC-MS/MS) of homogenate D0, D3, and D14 milk samples (n = 6) identified 772 protein groups which corresponded to 501 individual protein-coding genes. A total of 207 high confidence proteins were detected in n = 3 sows/day. Of the high confidence proteins, 81 proteins were common among all 3 days of lactation. Among the proteins that decreased between the days (false discovery rate; FDR < 0.05) were multiple apolipoproteins and XDH which decreased between D0 to D3. Proteins that increased across the days (FDR < 0.05) were complement factors and 14-3-3 proteins (YWHAQ, YWHAE). Our data provide a good characterization of milk proteome changes that likely reflect mammary function as well as the neonate's phase-specific developmental needs. This data may be useful in developing approaches to enhance the health and welfare of swine.

Facility-Level Variation in Dialysis Use and Mortality Among Older Veterans With Incident Kidney Failure.

Importance: Current guidelines lack consensus regarding the treatment of patients who may not benefit from dialysis; this lack of consensus may be associated with the substantial variation in dialysis use and outcomes across health care facilities. Objective: To assess the degree to which variation in dialysis use and mortality was associated with patient rather than facility characteristics and to distinguish which features identified the US Department of Veterans Affairs (VA) facilities with high rates of dialysis use. Design, Setting, and Participants: This cohort study analyzed data of veterans with stage 3 or 4 chronic kidney disease that progressed to kidney failure between January 1, 2011, and December 31, 2014. These patients received care from VA facilities across the US. Data sources included laboratory and administrative records from the VA, Medicare, and United States Renal Data System. Data analysis was conducted from August 1, 2019, to September 1, 2020. Exposures: The primary exposure was the VA facility in which patients received most of their care before the onset of incident kidney failure defined as the first occurrence of either a sustained estimated glomerular filtration rate of less than 15 mL/min/1.73 m2 or the initiation of maintenance dialysis. Main Outcomes and Measures: The primary outcomes were dialysis use and mortality within 2 years of incident kidney failure. Median rate ratio was used to quantify facility-level variation, and variance partition coefficient was used to quantify the sources of unexplained variation. Results: The cohort included 8695 older veterans with a mean (SD) age of 78.8 (7.5) years who were predominantly male (8573 [99%]) and White (6102 [70%]) individuals treated at 108 VA facilities. The observed frequency of dialysis use across facilities ranged from 25.0% to 81.4%, with a median (interquartile range [IQR]) rate of 51.7% (48.4%-60.0%). The observed frequency of mortality across facilities ranged from 27.2% to 60.0%, with a median (IQR) rate of 45.2% (41.2%-48.6%). The median rate ratio (adjusted for multiple patient and facility characteristics) was 1.40 for dialysis use and 1.08 for mortality. The unexplained variation in both outcomes mainly derived from patient characteristics rather than facility characteristics. No correlation was found between dialysis use and mortality at the facility level (correlation coefficient = 0.03). Conclusions and Relevance: This study found sizable variation in dialysis use for older adults that was poorly correlated with facility-level mortality rates and was not accounted for by differences in measured patient and facility characteristics. These findings suggest opportunities to improve the degree to which dialysis use practices align with the values, goals, and preferences of older adults with kidney failure.

Prevention and management of CVD in LMICs: why do ethnicity, culture, and context matter?

BACKGROUND: Low- and middle-income countries now experience the highest prevalence and mortality rates of cardiovascular disease. MAIN TEXT: While improving the availability and delivery of proven, effective therapies will no doubt mitigate this burden, we posit that studies evaluating cardiovascular disease risk factors, management strategies and service delivery, in diverse settings and diverse populations, are equally critical to improving outcomes in low- and middle-income countries. Focusing on examples drawn from four cardiovascular diseases - coronary artery disease, stroke, diabetes and kidney disease - we argue that ethnicity, culture and context matter in determining the risk factors for disease as well as the comparative effectiveness of medications and other interventions, particularly diet and lifestyle interventions. CONCLUSION: We believe that a host of cohort studies and randomized control trials currently being conducted or planned in low- and middle-income countries, focusing on previously understudied race/ethnic groups, have the potential to increase knowledge about the cause(s) and management of cardiovascular diseases across the world.

Medical Record Documentation of Goals-of-Care Discussions Among Older Veterans With Incident Kidney Failure.

RATIONALE & OBJECTIVE: Elicitation and documentation of patient preferences is at the core of shared decision making and is particularly important among patients with high anticipated mortality. The extent to which older patients with incident kidney failure undertake such discussions with their providers is unknown and its characterization was the focus of this study. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: A random sample of veterans 67 years and older with incident kidney failure receiving care from the US Veterans Health Administration between 2005 and 2010. EXPOSURES: Demographic and facility characteristics, as well as predicted 6-month mortality risk after dialysis initiation and documentation of resuscitation preferences. OUTCOMES: Documented discussions of dialysis treatment and supportive care. ANALYTICAL APPROACH: We reviewed medical records over the 2 years before incident kidney failure and up to 1 year afterward to ascertain the frequency and timing of documented discussions about dialysis treatment, supportive care, and resuscitation. Logistic regression was used to identify factors associated with these documented discussions. RESULTS: The cohort of 821 veterans had a mean age of 80.9±7.2 years, and 37.2% had a predicted 6-month mortality risk>20% with dialysis. Documented discussions addressing dialysis treatment and resuscitation were present in 55.6% and 77.1% of patients, respectively. Those addressing supportive care were present in 32.4%. The frequency of documentation varied by mortality risk and whether the patient ultimately started dialysis. In adjusted analyses, the frequency and pattern of documentation were more strongly associated with geographic location and receipt of outpatient nephrology care than with patient demographic or clinical characteristics. LIMITATIONS: Documentation may not fully reflect the quality and content of discussions, and generalizability to nonveteran patients is limited. CONCLUSIONS: Among older veterans with incident kidney failure, discussions of dialysis treatment are decoupled from other aspects of advance care planning and are suboptimally documented, even among patients at high risk for mortality.

Acute Kidney Injury in Children Hospitalized With Diarrheal Illness in the United States.

OBJECTIVES: To determine the incidence, correlates, and consequences of acute kidney injury (AKI) among children hospitalized with diarrheal illness in the United States. METHODS: Using data from Kids' Inpatient Database in 2009 and 2012, we studied children hospitalized with a primary diagnosis of diarrheal illness (weighted N = 113 195). We used the International Classification of Diseases, Ninth Revision, Clinical Modification, diagnosis codes 584.5 to 584.9 to capture AKI. We calculated the incidence, correlates, and consequences (mortality, length of stay [LOS], and costs) of AKI associated with hospitalized diarrheal illness using stepwise logistic regression and generalized linear models. RESULTS: The average incidence of AKI in children hospitalized with diarrheal illness was 0.8%. Hospital location and teaching status were associated with the odds of AKI, as were older age, solid organ transplant, hypertension, chronic kidney disease, and rheumatologic and hematologic conditions. The development of AKI in hospitalized diarrheal illness was associated with an eightfold increase in the odds of in-hospital mortality (odds ratio 8.0; 95% confidence interval [CI] 4.2-15.4). AKI was associated with prolonged LOS (mean increase 3.0 days; 95% CI 2.3-3.8) and higher hospital cost (mean increase $9241; 95% CI $4661-$13 820). CONCLUSIONS: Several demographic factors and comorbid conditions are associated with the risk of AKI in children hospitalized with diarrheal illness. Although rare, development of AKI in this common pediatric condition is associated with increased mortality, LOS, and hospital cost.

Early detection of chronic kidney disease in low-income and middle-income countries: development and validation of a point-of-care screening strategy for India.

INTRODUCTION: Although deaths due to chronic kidney disease (CKD) have doubled over the past two decades, few data exist to inform screening strategies for early detection of CKD in low-income and middle-income countries. METHODS: Using data from three population-based surveys in India, we developed a prediction model to identify a target population that could benefit from further CKD testing, after an initial screening implemented during home health visits. Using data from one urban survey (n=8698), we applied stepwise logistic regression to test three models: one comprised of demographics, self-reported medical history, anthropometry and point-of-care (urine dipstick or capillary glucose) tests; one with demographics and self-reported medical history and one with anthropometry and point-of-care tests. The 'gold-standard' definition of CKD was an estimated glomerular filtration rate <60 mL/min/1.73 m2 or urine albumin-to-creatinine ratio ≥30 mg/g. Models were internally validated via bootstrap. The most parsimonious model with comparable performance was externally validated on distinct urban (n=5365) and rural (n=6173) Indian cohorts. RESULTS: A model with age, sex, waist circumference, body mass index and urine dipstick had a c-statistic of 0.76 (95% CI 0.75 to 0.78) for predicting need for further CKD testing, with external validation c-statistics of 0.74 and 0.70 in the urban and rural cohorts, respectively. At a probability cut-point of 0.09, sensitivity was 71% (95% CI 68% to 74%) and specificity was 70% (95% CI 69% to 71%). The model captured 71% of persons with CKD and 90% of persons at highest risk of complications from untreated CKD (ie, CKD stage 3A2 and above). CONCLUSION: A point-of-care CKD screening strategy using three simple measures can accurately identify high-risk persons who require confirmatory kidney function testing.

Paying for Hemodialysis in Kerala, India: A Description of Household Financial Hardship in the Context of Medical Subsidy.

INTRODUCTION: Many low- and middle-income countries are implementing strategies to increase dialysis availability as growing numbers of people reach end-stage renal disease. Despite efforts to subsidize care, the economic sustainability of chronic dialysis in these settings remains uncertain. We evaluated the association of medical subsidy with household financial hardship related to hemodialysis in Kerala, India, a state with high penetrance of procedure-based subsidies for patients on dialysis. METHODS: Patients on maintenance hemodialysis at 15 facilities in Kerala were administered a questionnaire that ascertained demographics, dialysis details, and household finances. We estimated direct and indirect costs of hemodialysis, and described the use of medical subsidy. We evaluated whether presence of subsidy (private, charity, or government-sponsored) was associated with lower catastrophic health expenditure (defined as ≥40% of nonsubsistence expenditure spent on dialysis) or distress financing. RESULTS: Of the 835 patients surveyed, 759 (91%) reported their households experienced catastrophic health expenditure, and 644 (77%) engaged in distress financing. Median dialysis-related expenditure was 80% (25th-75th percentile: 60%-90%) of household nonsubsistence expenditure. Government subsidies were used by 238 (29%) of households, 139 (58%) of which were in the lowest income category. Catastrophic health expenditure was present in 215 (90%) of households receiving government subsidy and 332 (93%) without subsidy. CONCLUSIONS: Provision of medical subsidy in Kerala, India was not associated with lower rates of household financial hardship related to long-term hemodialysis therapy. Transparent counseling on impending costs and innovative strategies to mitigate household financial distress are necessary for persons with end-stage renal disease in resource-limited settings.

Acute Kidney Injury Due to Diarrheal Illness Requiring Hospitalization: Data from the National Inpatient Sample.

BACKGROUND: Diarrheal illness is a major reason for hospitalization, but data on consequent acute kidney injury (AKI) are sparse. OBJECTIVE: To determine the incidence of AKI in infectious and non-infectious diarrheal illness requiring hospitalization and to identify correlates and outcomes of diarrhea-associated AKI. DESIGN: Using data from the 2012 National Inpatient Sample (NIS), we created a cohort of patients with a primary diagnosis of diarrheal illness. Diarrheal illness, disease correlates, and AKI were defined by ICD-9 diagnosis codes. We used logistic regression with backward variable selection to determine factors independently associated with AKI in infectious and non-infectious diarrheal illness, as well as to determine the association of AKI with in-hospital mortality. We used generalized linear models to assess differences in length of stay and costs of hospitalization. MAIN MEASURES: The primary outcome was AKI in hospitalized diarrheal illness. Secondary outcomes were in-hospital mortality, length of stay, and cost of hospitalization associated with AKI. KEY RESULTS: One in ten adults hospitalized with diarrheal illness experienced AKI, with higher incidence rates in older adults. Chronic kidney disease (CKD) and hypertension were associated with increased odds of AKI (all diarrhea OR 4.81, 95% CI 4.52 to 5.12 and OR 1.33, 95% CI 1.27 to 1.40, respectively). AKI in diarrheal illness was associated with substantial increase in mortality (OR 5.05, 95% CI 4.47 to 5.72), length of stay (mean increase 1.7 days [95% CI 1.6 to 1.8]), and cost of hospitalization (mean increase $4411 [95% CI 4023 to 4800]). CONCLUSION: Acute kidney injury is common and consequential among patients hospitalized for diarrheal illness. Persons with CKD and hypertension are the most susceptible, possibly due to diminished renal reserve and exacerbating effects of treatment with diuretics and renin-angiotensin-aldosterone system blockers. Proactive management of these unique pharmacologic and physiologic factors is necessary to prevent AKI in this vulnerable population.