Inhaled Fluticasone Furoate for Outpatient Treatment of Covid-19.

BACKGROUND: The effectiveness of inhaled glucocorticoids in shortening the time to symptom resolution or preventing hospitalization or death among outpatients with mild-to-moderate coronavirus disease 2019 (Covid-19) is unclear. METHODS: We conducted a decentralized, double-blind, randomized, placebo-controlled platform trial in the United States to assess the use of repurposed medications in outpatients with confirmed coronavirus disease 2019 (Covid-19). Nonhospitalized adults 30 years of age or older who had at least two symptoms of acute infection that had been present for no more than 7 days before enrollment were randomly assigned to receive inhaled fluticasone furoate at a dose of 200 µg once daily for 14 days or placebo. The primary outcome was the time to sustained recovery, defined as the third of 3 consecutive days without symptoms. Key secondary outcomes included hospitalization or death by day 28 and a composite outcome of the need for an urgent-care or emergency department visit or hospitalization or death through day 28. RESULTS: Of the 1407 enrolled participants who underwent randomization, 715 were assigned to receive inhaled fluticasone furoate and 692 to receive placebo, and 656 and 621, respectively, were included in the analysis. There was no evidence that the use of fluticasone furoate resulted in a shorter time to recovery than placebo (hazard ratio, 1.01; 95% credible interval, 0.91 to 1.12; posterior probability of benefit [defined as a hazard ratio >1], 0.56). A total of 24 participants (3.7%) in the fluticasone furoate group had urgent-care or emergency department visits or were hospitalized, as compared with 13 participants (2.1%) in the placebo group (hazard ratio, 1.9; 95% credible interval, 0.8 to 3.5). Three participants in each group were hospitalized, and no deaths occurred. Adverse events were uncommon in both groups. CONCLUSIONS: Treatment with inhaled fluticasone furoate for 14 days did not result in a shorter time to recovery than placebo among outpatients with Covid-19 in the United States. (Funded by the National Center for Advancing Translational Sciences and others; ACTIV-6 ClinicalTrials.gov number, NCT04885530.).

Bayesian transition models for ordinal longitudinal outcomes.

Ordinal longitudinal outcomes are becoming common in clinical research, particularly in the context of COVID-19 clinical trials. These outcomes are information-rich and can increase the statistical efficiency of a study when analyzed in a principled manner. We present Bayesian ordinal transition models as a flexible modeling framework to analyze ordinal longitudinal outcomes. We develop the theory from first principles and provide an application using data from the Adaptive COVID-19 Treatment Trial (ACTT-1) with code examples in R. We advocate that researchers use ordinal transition models to analyze ordinal longitudinal outcomes when appropriate alongside standard methods such as time-to-event modeling.

High tissue-sodium associates with systemic inflammation and insulin resistance in obese individuals.

BACKGROUND AND AIMS: High sodium intake is associated with obesity and insulin resistance, and high extracellular sodium content may induce systemic inflammation, leading to cardiovascular disease. In this study, we aim to investigate whether high tissue sodium accumulation relates with obesity-related insulin resistance and whether the pro-inflammatory effects of excess tissue sodium accumulation may contribute to such association. METHODS AND RESULTS: In a cross-sectional study of 30 obese and 53 non-obese subjects, we measured insulin sensitivity determined as glucose disposal rate (GDR) using hyperinsulinemic euglycemic clamp, and tissue sodium content using 23Na magnetic resonance imaging. Median age was 48 years, 68% were female and 41% were African American. Median (interquartile range) BMI was 33 (31.5, 36.3) and 25 (23.5, 27.2) kg/m2 in the obese and non-obese individuals, respectively. In obese individuals, insulin sensitivity negatively correlated with muscle (r = -0.45, p = 0.01) and skin sodium (r = -0.46, p = 0.01). In interaction analysis among obese individuals, tissue sodium had a greater effect on insulin sensitivity at higher levels of high-sensitivity C-reactive protein (p-interaction = 0.03 and 0.01 for muscle and skin Na+, respectively) and interleukin-6 (p-interaction = 0.024 and 0.003 for muscle and skin Na+, respectively). In interaction analysis of the entire cohort, the association between muscle sodium and insulin sensitivity was stronger with increasing levels of serum leptin (p-interaction = 0.01). CONCLUSIONS: Higher muscle and skin sodium are associated with insulin resistance in obese patients. Whether high tissue sodium accumulation has a mechanistic role in the development of obesity-related insulin resistance through systemic inflammation and leptin dysregulation remains to be examined in future studies. CLINICALTRIALS: gov registration: NCT02236520.

Effect of Fluvoxamine vs Placebo on Time to Sustained Recovery in Outpatients With Mild to Moderate COVID-19: A Randomized Clinical Trial.

Importance: The effectiveness of fluvoxamine to shorten symptom duration or prevent hospitalization among outpatients with mild to moderate symptomatic COVID-19 is unclear. Objective: To evaluate the efficacy of low-dose fluvoxamine (50 mg twice daily) for 10 days compared with placebo for the treatment of mild to moderate COVID-19 in the US. Design, Setting, and Participants: The ongoing Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV-6) platform randomized clinical trial was designed to test repurposed medications in outpatients with mild to moderate COVID-19. A total of 1288 participants aged 30 years or older with test-confirmed SARS-CoV-2 infection and experiencing 2 or more symptoms of acute COVID-19 for 7 days or less were enrolled between August 6, 2021, and May 27, 2022, at 91 sites in the US. Interventions: Participants were randomized to receive 50 mg of fluvoxamine twice daily for 10 days or placebo. Main Outcomes and Measures: The primary outcome was time to sustained recovery (defined as the third day of 3 consecutive days without symptoms). There were 7 secondary outcomes, including a composite outcome of hospitalization, urgent care visit, emergency department visit, or death through day 28. Results: Among 1331 participants who were randomized (median age, 47 years [IQR, 38-57 years]; 57% were women; and 67% reported receiving ≥2 doses of a SARS-CoV-2 vaccine), 1288 completed the trial (674 in the fluvoxamine group and 614 in the placebo group). The median time to sustained recovery was 12 days (IQR, 11-14 days) in the fluvoxamine group and 13 days (IQR, 12-13 days) in the placebo group (hazard ratio [HR], 0.96 [95% credible interval, 0.86-1.06], posterior P = .21 for the probability of benefit [determined by an HR >1]). For the composite outcome, 26 participants (3.9%) in the fluvoxamine group were hospitalized, had an urgent care visit, had an emergency department visit, or died compared with 23 participants (3.8%) in the placebo group (HR, 1.1 [95% credible interval, 0.5-1.8], posterior P = .35 for the probability of benefit [determined by an HR <1]). One participant in the fluvoxamine group and 2 participants in the placebo group were hospitalized; no deaths occurred in either group. Adverse events were uncommon in both groups. Conclusions and Relevance: Among outpatients with mild to moderate COVID-19, treatment with 50 mg of fluvoxamine twice daily for 10 days, compared with placebo, did not improve time to sustained recovery. These findings do not support the use of fluvoxamine at this dose and duration in patients with mild to moderate COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04885530.

Effect of Higher-Dose Ivermectin for 6 Days vs Placebo on Time to Sustained Recovery in Outpatients With COVID-19: A Randomized Clinical Trial.

Importance: It is unknown whether ivermectin, with a maximum targeted dose of 600 µg/kg, shortens symptom duration or prevents hospitalization among outpatients with mild to moderate COVID-19. Objective: To evaluate the effectiveness of ivermectin at a maximum targeted dose of 600 µg/kg daily for 6 days, compared with placebo, for the treatment of early mild to moderate COVID-19. Design, Setting, and Participants: The ongoing Accelerating COVID-19 Therapeutic Interventions and Vaccines 6 (ACTIV-6) platform randomized clinical trial was designed to evaluate repurposed therapies among outpatients with mild to moderate COVID-19. A total of 1206 participants older than 30 years with confirmed COVID-19 experiencing at least 2 symptoms of acute infection for less than or equal to 7 days were enrolled at 93 sites in the US from February 16, 2022, through July 22, 2022, with follow-up data through November 10, 2022. Interventions: Participants were randomly assigned to receive ivermectin, with a maximum targeted dose of 600 µg/kg (n = 602) daily, or placebo (n = 604) for 6 days. Main Outcomes and Measures: The primary outcome was time to sustained recovery, defined as at least 3 consecutive days without symptoms. The 7 secondary outcomes included a composite of hospitalization, death, or urgent/emergent care utilization by day 28. Results: Among 1206 randomized participants who received study medication or placebo, the median (IQR) age was 48 (38-58) years, 713 (59.1%) were women, and 1008 (83.5%) reported receiving at least 2 SARS-CoV-2 vaccine doses. The median (IQR) time to sustained recovery was 11 (11-12) days in the ivermectin group and 11 (11-12) days in the placebo group. The hazard ratio (posterior probability of benefit) for improvement in time to recovery was 1.02 (95% credible interval, 0.92-1.13; P = .68). Among those receiving ivermectin, 34 (5.7%) were hospitalized, died, or had urgent or emergency care visits compared with 36 (6.0%) receiving placebo (hazard ratio, 1.0 [95% credible interval, 0.6-1.5]; P = .53). In the ivermectin group, 1 participant died and 4 were hospitalized (0.8%); 2 participants (0.3%) were hospitalized in the placebo group and there were no deaths. Adverse events were uncommon in both groups. Conclusions and Relevance: Among outpatients with mild to moderate COVID-19, treatment with ivermectin, with a maximum targeted dose of 600 µg/kg daily for 6 days, compared with placebo did not improve time to sustained recovery. These findings do not support the use of ivermectin in patients with mild to moderate COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04885530.

Higher-Dose Fluvoxamine and Time to Sustained Recovery in Outpatients With COVID-19: The ACTIV-6 Randomized Clinical Trial.

Importance: The effect of higher-dose fluvoxamine in reducing symptom duration among outpatients with mild to moderate COVID-19 remains uncertain. Objective: To assess the effectiveness of fluvoxamine, 100 mg twice daily, compared with placebo, for treating mild to moderate COVID-19. Design, Setting, and Participants: The ACTIV-6 platform randomized clinical trial aims to evaluate repurposed medications for mild to moderate COVID-19. Between August 25, 2022, and January 20, 2023, a total of 1175 participants were enrolled at 103 US sites for evaluating fluvoxamine; participants were 30 years or older with confirmed SARS-CoV-2 infection and at least 2 acute COVID-19 symptoms for 7 days or less. Interventions: Participants were randomized to receive fluvoxamine, 50 mg twice daily on day 1 followed by 100 mg twice daily for 12 additional days (n = 601), or placebo (n = 607). Main Outcomes and Measures: The primary outcome was time to sustained recovery (defined as at least 3 consecutive days without symptoms). Secondary outcomes included time to death; time to hospitalization or death; a composite of hospitalization, urgent care visit, emergency department visit, or death; COVID-19 clinical progression scale score; and difference in mean time unwell. Follow-up occurred through day 28. Results: Among 1208 participants who were randomized and received the study drug, the median (IQR) age was 50 (40-60) years, 65.8% were women, 45.5% identified as Hispanic/Latino, and 76.8% reported receiving at least 2 doses of a SARS-CoV-2 vaccine. Among 589 participants who received fluvoxamine and 586 who received placebo included in the primary analysis, differences in time to sustained recovery were not observed (adjusted hazard ratio [HR], 0.99 [95% credible interval, 0.89-1.09]; P for efficacy = .40]). Additionally, unadjusted median time to sustained recovery was 10 (95% CI, 10-11) days in both the intervention and placebo groups. No deaths were reported. Thirty-five participants reported health care use events (a priori defined as death, hospitalization, or emergency department/urgent care visit): 14 in the fluvoxamine group compared with 21 in the placebo group (HR, 0.69 [95% credible interval, 0.27-1.21]; P for efficacy = .86) There were 7 serious adverse events in 6 participants (2 with fluvoxamine and 4 with placebo) but no deaths. Conclusions and Relevance: Among outpatients with mild to moderate COVID-19, treatment with fluvoxamine does not reduce duration of COVID-19 symptoms. Trial Registration: ClinicalTrials.gov Identifier: NCT04885530.

Effect of Ivermectin vs Placebo on Time to Sustained Recovery in Outpatients With Mild to Moderate COVID-19: A Randomized Clinical Trial.

Importance: The effectiveness of ivermectin to shorten symptom duration or prevent hospitalization among outpatients in the US with mild to moderate symptomatic COVID-19 is unknown. Objective: To evaluate the efficacy of ivermectin, 400 µg/kg, daily for 3 days compared with placebo for the treatment of early mild to moderate COVID-19. Design, Setting, and Participants: ACTIV-6, an ongoing, decentralized, double-blind, randomized, placebo-controlled platform trial, was designed to evaluate repurposed therapies in outpatients with mild to moderate COVID-19. A total of 1591 participants aged 30 years and older with confirmed COVID-19, experiencing 2 or more symptoms of acute infection for 7 days or less, were enrolled from June 23, 2021, through February 4, 2022, with follow-up data through May 31, 2022, at 93 sites in the US. Interventions: Participants were randomized to receive ivermectin, 400 µg/kg (n = 817), daily for 3 days or placebo (n = 774). Main Outcomes and Measures: Time to sustained recovery, defined as at least 3 consecutive days without symptoms. There were 7 secondary outcomes, including a composite of hospitalization or death by day 28. Results: Among 1800 participants who were randomized (mean [SD] age, 48 [12] years; 932 women [58.6%]; 753 [47.3%] reported receiving at least 2 doses of a SARS-CoV-2 vaccine), 1591 completed the trial. The hazard ratio (HR) for improvement in time to recovery was 1.07 (95% credible interval [CrI], 0.96-1.17; posterior P value [HR >1] = .91). The median time to recovery was 12 days (IQR, 11-13) in the ivermectin group and 13 days (IQR, 12-14) in the placebo group. There were 10 hospitalizations or deaths in the ivermectin group and 9 in the placebo group (1.2% vs 1.2%; HR, 1.1 [95% CrI, 0.4-2.6]). The most common serious adverse events were COVID-19 pneumonia (ivermectin [n = 5]; placebo [n = 7]) and venous thromboembolism (ivermectin [n = 1]; placebo [n = 5]). Conclusions and Relevance: Among outpatients with mild to moderate COVID-19, treatment with ivermectin, compared with placebo, did not significantly improve time to recovery. These findings do not support the use of ivermectin in patients with mild to moderate COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04885530.

Perioperative Blood Transfusions Are Associated With Worse Overall Survival But Not Disease-Free Survival After Curative Rectal Cancer Resection: A Propensity Score-Matched Analysis.

BACKGROUND: The effects of blood transfusions on oncologic outcomes after surgery remain inconclusive. Thus, we examined the association between receiving a perioperative blood transfusion and oncologic outcomes in patients undergoing curative rectal cancer resection. OBJECTIVE: The purpose of this study was to assess the association between receiving a perioperative blood transfusion with disease-free and overall survival in patients undergoing curative resection of clinical stage I to III rectal cancer. We hypothesized that blood transfusion is associated with worse disease-free and overall survival in this patient cohort. DESIGN: This was a retrospective cohort study using a propensity score-matched analysis. SETTINGS: The study involved 6 tertiary academic medical centers in the United States contributing to the United States Rectal Cancer Consortium. PATIENTS: Patients who underwent curative resection for rectal cancer from 2010 to 2018 were included. MAIN OUTCOME MEASURES: The primary outcome was disease-free survival. The secondary outcomes were overall survival, intensive care unit length of stay, hospital length of stay, surgical site infection, and readmission. RESULTS: Of the 924 patients eligible for matching, 312 patients were matched, including 100 patients who received a transfusion and 212 who did not. In a propensity score-matched analysis, receiving a perioperative blood transfusion was not associated with worse 5-year disease-free survival (transfused, 78%; not transfused, 83%; p = 0.32) but was associated with worse 5-year overall survival (transfused 65% vs not transfused 86%; p < 0.001) and increased hospital length of stay (transfused, 9.9 d; not transfused, 7.6 d; p = 0.001). LIMITATIONS: Despite propensity matching, confounding may remain. Propensity matching may limit the power to detect a difference in disease-free survival. CONCLUSIONS: Receiving a perioperative blood transfusion is not associated with worse disease-free survival but is associated with worse overall survival. Such findings are important for clinicians and patients to understand when considering perioperative blood transfusions. See Video Abstract at http://links.lww.com/DCR/B531. LAS TRANSFUSIONES DE SANGRE PERIOPERATORIAS SE ASOCIAN CON UNA PEOR SOBREVIDA GLOBAL, PERO NO CON LA SOBREVIDA LIBRE DE ENFERMEDAD POSTERIOR A LA RESECCIN CURATIVA DEL CNCER DE RECTO UN PUNTAJE DE PROPENSIN POR ANLISIS DE CONCORDANCIA: ANTECEDENTES:El impacto de las transfusiones de sangre en los resultados oncológicos posteriores a la cirugía no son concluyentes. Por lo anterior, estudiamos la asociación entre recibir una transfusión de sangre perioperatoria y los resultados oncológicos en pacientes llevados a resección curativa de cáncer de recto.OBJETIVO:El propósito de este estudio fue evaluar la asociación entre recibir una transfusión de sangre perioperatoria con la sobrevida libre de enfermedad y la sobrevida general en pacientes llevados a resección curativa de cáncer de recto en estadio clínico I-III. Nuestra hipótesis es que la transfusión de sangre se asocia con una peor sobrevida global y libre de enfermedad en esta cohorte de pacientes.DISEÑO:Es un estudio de cohorte retrospectivo que utilizó un puntaje de propensión por análisis de concordancia.AMBITO:El estudio se realizó en seis centros médicos académicos de tercer nivel en los Estados Unidos que contribuían al Consorcio de Cáncer de Recto de los Estados Unidos.PACIENTES:Se incluyeron pacientes que fueron llevados a resección curativa por cáncer de recto entre 2010 y 2018.PRINCIPALES VARIABLES EVALUADAS:El objeitvo principal fue la sobrevida libre de enfermedad. Los objetivos secundarios fueron la sobrevida global, el tiempo de estancia en la unidad de cuidados intensivos, el tiempo de la estancia hospitalaria, la infección del sitio quirúrgico y el reingreso.RESULTADOS:De los 924 pacientes elegibles para el emparejamiento, se emparejaron 312 pacientes, incluidos 100 pacientes que recibieron una transfusión y 212 que no. En el puntaje de propensión por análisis de concordancia, recibir una transfusión de sangre perioperatoria no se asoció con una peor sobrevida libre de enfermedad a 5 años (TRANSFUSIÓN 78%; NO TRANSFUSIÓN 83%; p = 0,32), pero se asoció con una peor sobrevida global a 5 años (TRANSFUSION 65% vs NO TRANSFUSION 86%; p <0,001) y aumento de la estancia hospitalaria (TRANSFUSIÓN 9,9 días; NO TRANSFUSION 7,6 días; p = 0,001).LIMITACIONES:A pesar de la concordancia de propensión, pueden existir desviaciones. El emparejamiento de propensión puede limitar el poder para detectar una diferencia en la sobrevida libre de enfermedad.CONCLUSIONES:Recibir una transfusión de sangre perioperatoria no se asocia con una peor sobrevida libre de enfermedad, pero sí con una peor sobrevida global. Es importante que los médicos y los pacientes comprendan estos hallazgos al considerar las transfusiones de sangre perioperatorias. Consulte Video Resumen en http://links.lww.com/DCR/B531. (Traducción-Dr Lisbeth Alarcon-Bernes).

Robotic-assisted and laparoscopic hernia repair: real-world evidence from the Americas Hernia Society Quality Collaborative (AHSQC).

BACKGROUND: Ventral hernia repair (VHR) is a commonly performed procedure and is especially prevalent in patients who have undergone previous open abdominal surgery: up to 28% of patients who have undergone laparotomy will develop a ventral hernia. There is increasing interest in robotic-assisted VHR (RVHR) as a minimally invasive approach to VHR not requiring myofascial release and in RVHR outcomes relative to outcomes associated with laparoscopic VHR (LVHR). We hypothesized real-world evidence from the Americas Hernia Society Quality Collaborative (AHSQC) database will indicate comparable clinical outcomes from RVHR and LVHR approaches not employing myofascial release. METHODS: Retrospective, comparative analysis of prospectively collected data describing laparoscopic and robotic-assisted elective ventral hernia repair procedures reported in the multi-institutional AHSQC database. A one-to-one propensity score matching algorithm identified comparable groups of patients to adjust for potential selection bias that could result from surgeon choice of repair approach. RESULTS: Matched data describe preoperative characteristics and perioperative outcomes in 615 patients in each group. The following significant differences were observed among the 11 outcomes that were pre-specified. Operative time tended to be longer for the RVHR group compared to the LVHR group (p < 0.001). Length of stay differed between the two groups; while both groups had a median length of stay of 0, stay lengths tended to be longer in the LVHR group (p < 0.001). Rates of conversion to laparotomy were fewer for the RVHR group: < 1% and 2%, respectively (p = 0.007). Through 30 days, there were fewer RVHR patient-clinic visits (p = 0.038). CONCLUSION: Both RVHR and LVHR perioperative results compare favorably with each other in most measures. Differences favored RVHR in terms of shorter LOS, fewer conversions to laparotomy, and fewer postoperative clinic visits; differences favored LVHR in terms of shorter operative times.

Body mass index and chronic kidney disease outcomes after acute kidney injury: a prospective matched cohort study.

BACKGROUND: Acute kidney injury (AKI) and obesity are independent risk factors for chronic kidney disease (CKD). This study aimed to determine if obesity modifies risk for CKD outcomes after AKI. METHODS: This prospective multisite cohort study followed adult survivors after hospitalization, with or without AKI. The primary outcome was a combined CKD event of incident CKD, progression of CKD and kidney failure, examined using time-to-event Cox proportional hazards models, adjusted for diabetes status, age, pre-existing CKD, cardiovascular disease status and intensive care unit admission, and stratified by study center. Body mass index (BMI) was added as an interaction term to examine effect modification by body size. RESULTS: The cohort included 769 participants with AKI and 769 matched controls. After median follow-up of 4.3 years, among AKI survivors, the rate of the combined CKD outcome was 84.7 per1000-person-years with BMI ≥30 kg/m2, 56.4 per 1000-person-years with BMI 25-29.9 kg/m2, and 72.6 per 1000-person-years with BMI 20-24.9 kg/m2. AKI was associated with a higher risk of combined CKD outcomes; adjusted-HR 2.43 (95%CI 1.87-3.16), with no evidence that this was modified by BMI (p for interaction = 0.3). After adjustment for competing risk of death, AKI remained associated with a higher risk of the combined CKD outcome (subdistribution-HR 2.27, 95%CI 1.76-2.92) and similarly, there was no detectable effect of BMI modifying this risk. CONCLUSIONS: In this post-hospitalization cohort, we found no evidence for obesity modifying the association between AKI and development or progression of CKD.

Effects of long-term intradialytic oral nutrition and exercise on muscle protein homeostasis and markers of mitochondrial content in patients on hemodialysis.

Patients with end-stage kidney disease on maintenance hemodialysis commonly develop protein-energy wasting, a syndrome characterized by nutritional and metabolic abnormalities. Nutritional supplementation and exercise are recommended to prevent protein-energy wasting. In a 6-mo prospective randomized, open-label, clinical trial, we reported that the combination of resistance exercise and nutritional supplementation does not have an additive effect on lean body mass measured by dual-energy X-ray absorptiometry. To provide more mechanistic data, we performed a secondary analysis where we hypothesized that the combination of nutritional supplementation and resistance exercise would have additive effects on muscle protein accretion by stable isotope protein kinetic experiments, muscle mass by MRI, and mitochondrial content markers in muscle. We found that 6 mo of nutritional supplementation during hemodialysis increased muscle protein net balance [baseline: 2.5 (-17.8, 13.0) µg·100 mL-1·min-1 vs. 6 mo: 43.7 (13.0, 98.5) µg·100 mL-1·min-1, median (interquartile range), P = 0.04] and mid-thigh fat area [baseline: 162.3 (104.7, 226.6) cm2 vs. 6 mo: 181.9 (126.3, 279.2) cm2, median (interquartile range), P = 0.04]. Three months of nutritional supplementation also increased markers of mitochondrial content in muscle. Although the study is underpowered to detected differences, the combination of nutritional supplementation and exercise failed to show further benefit in protein accretion or muscle cross-sectional area. We conclude that long-term nutritional supplementation increases the skeletal muscle anabolic effect, the fat cross-sectional area of the thigh, and markers of mitochondrial content in skeletal muscle.

Nephrology Provider Surprise Question Response and Hospitalizations in Older Adults with Advanced CKD.

BACKGROUND: Older adults with advanced non-dialysis-dependent chronic kidney disease (NDD-CKD) face a high risk of hospitalization and related adverse events. METHODS: This prospective cohort study followed nephrology clinic patients ≥60 years old with NDD-CKD stages 4-5. After an eligible patient's office visit, study staff asked the patient's provider to rate the patient's risk of death within the next year using the surprise question ("Would you be surprised if this patient died in the next 12 months?") with a 5-point Likert scale response (1, "definitely not surprised" to 5, "very surprised"). We used a statewide database to ascertain hospitalization during follow-up. RESULTS: There were 488 patients (median age 72 years, 51% female, 17% black) with median estimated glomerular filtration rate 22 mL/min/1.73 m2. Over a median follow-up of 2.1 years, the rates of hospitalization per 100 person-years in the respective response groups were 41 (95% confidence interval [CI]: 34-50), "very surprised"; 65 (95% CI: 55-76), "surprised"; 98 (95% CI: 85-113), "neutral"; 125 (95% CI: 107-144), "not surprised"; and 120 (95% CI: 94-151), "definitely not surprised." In a fully adjusted cumulative probability ordinal regression model for proportion of follow-up time spent hospitalized, patients whose providers indicated that they would be "definitely not surprised" if they died spent a greater proportion of follow-up time hospitalized compared with those whose providers indicated that they would be "very surprised" (odds ratio 2.4, 95% CI: 1.0-5.7). There was a similar association for time to first hospitalization. CONCLUSION: Nephrology providers' responses to the surprise question for older patients with advanced NDD-CKD were independently associated with proportion of future time spent hospitalized and time to first hospitalization. Additional studies should examine how to use this information to provide patients with anticipatory guidance on their possible clinical trajectory and to target potentially preventable hospitalizations.

Tissue sodium stores in peritoneal dialysis and hemodialysis patients determined by 23-sodium magnetic resonance imaging.

BACKGROUND: Tissue sodium content in patients on maintenance hemodialysis (MHD) and peritoneal dialysis (PD) were previously explored using 23Sodium magnetic resonance imaging (23NaMRI). Larger studies would provide a better understanding of sodium stores in patients on dialysis as well as the factors influencing this sodium accumulation. METHODS: In this cross-sectional study, we quantified the calf muscle and skin sodium content in 162 subjects (10 PD, 33 MHD patients, and 119 controls) using 23NaMRI. Plasma levels of interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP) were measured to assess systemic inflammation. Sixty-four subjects had repeat 23NaMRI scans that were analyzed to assess the repeatability of the 23NaMRI measurements. RESULTS: Patients on MHD and PD exhibited significantly higher muscle and skin sodium accumulation compared to controls. African American patients on dialysis exhibited greater muscle and skin sodium content compared to non-African Americans. Multivariable analysis showed that older age was associated with both higher muscle and skin sodium. Male sex was also associated with increased skin sodium deposition. Greater ultrafiltration was associated with lower skin sodium in patients on PD (Spearman's rho=-0.68, P = 0.035). Higher plasma IL-6 and hsCRP levels correlated with increased muscle and skin sodium content in the overall study population. Patients with higher baseline tissue sodium content exhibited greater variability in tissue sodium stores on repeat measurements. CONCLUSIONS: Our findings highlight greater muscle and skin sodium content in dialysis patients compared to controls without kidney disease. Tissue sodium deposition and systemic inflammation seen in dialysis patients might influence one another bidirectionally.

Comparing pathologic outcomes for robotic versus laparoscopic Surgery in rectal cancer resection: a propensity adjusted analysis of 7616 patients.

BACKGROUND: Margin negative resection of rectal cancer with minimally invasive techniques remains technically challenging. Robotic surgery has potential advantages over traditional laparoscopy. We hypothesize that the difference in the rate of negative margin status will be < 6% between laparoscopic and robotic approach. METHODS: The National Cancer Database (2010-2014) was queried for adults with locally advanced rectal cancer who underwent neoadjuvant chemoradiation and curative resection to conduct an observational retrospective cohort study of a prospectively maintained database. Patients were grouped by either robotic (ROB) or laparoscopic (LAP) approach in an intent-to-treat analysis. Primary outcome was negative margin status, defined as a composite of circumferential resection margin and distal margin. Secondary outcomes included length of stay (LOS), readmission, 90-day mortality, and overall survival. RESULTS: 7616 patients with locally advanced rectal cancer who underwent minimally invasive resection were identified. 2472 (32%) underwent attempted robotic approach. The overall conversion rate was 13% and was increased in the laparoscopic group [LAP: 15% vs. ROB: 8%; OR 0.47; 95% CI (0.39, 0.57)]. Differences in margin negative resection rate were within the prespecified range of practical equivalence (LAP: 93% vs.: ROB 94%; 95% CI (0.69, 1.06); [Formula: see text] = 1). For secondary outcomes, there was no difference in 30-day readmission [LAP: 9% vs.: ROB 8%; 95% CI (0.84, 1.24)] and 90-day mortality [LAP: 1% vs.: ROB 1%; 95% CI (0.38, 1.24)]. While the median LOS was 5 days in both groups, the mean LOS was 0.6 (95% CI: 0.24, 0.89) days shorter in the robotic group. CONCLUSION: This robust analysis supports either robotic or laparoscopic approach for resection of locally advanced rectal cancer from a margin perspective. Both have similar readmission and 5-year overall survival rates. Patients undergoing robotic surgery have a 0.6-day decrease in LOS and decreased conversion rate.

Serious Illness Treatment Preferences for Older Adults with Advanced CKD.

BACKGROUND: Patient-centered care for older adults with CKD requires communication about patient's values, goals of care, and treatment preferences. Eliciting this information requires tools that patients understand and that enable effective communication about their care preferences. METHODS: Nephrology clinic patients age ≥60 years with stage 4 or 5 nondialysis-dependent CKD selected one of four responses to the question, "If you had a serious illness, what would be important to you?" Condensed versions of the options were, "Live as long as possible;" "Try treatments, but do not suffer;" "Focus on comfort;" or "Unsure." Patients also completed a validated health outcome prioritization tool and an instrument determining the acceptability of end-of-life scenarios. Patient responses to the three tools were compared. RESULTS: Of the 382 participants, 35% (n=134) selected "Try treatments, but do not suffer;" 33% (n=126) chose "Focus on comfort;" 20% (n=75) opted for "Live as long as possible;" and 12% (n=47) selected "Unsure." Answers were associated with patients' first health outcome priority and acceptability of end-of-life scenarios. One third of patients with a preference to "Focus on comfort" reported that a life on dialysis would not be worth living compared with 5% of those who chose "Live as long as possible" (P<0.001). About 90% of patients agreed to share their preferences with their providers. CONCLUSIONS: Older adults with advanced CKD have diverse treatment preferences and want to share them. A single treatment preference question correlated well with longer, validated health preference tools and may provide a point of entry for discussions about patient's treatment goals.

Racial disparities in end-stage renal disease in a high-risk population: the Southern Community Cohort Study.

INTRODUCTION: The Southern Community Cohort Study is a prospective study of low socioeconomic status (SES) blacks and whites from the southeastern US, where the burden of end-stage renal disease (ESRD) and its risk factors are high. We tested whether the 2.4-fold elevated risk of ESRD we previously observed in blacks compared to whites was explained by differences in baseline kidney function. METHODS: We conducted a case-cohort study of incident ESRD cases (n = 737) with stored blood and a probability sampled subcohort (n = 4238) and calculated estimated glomerular filtration rate (eGFR) from serum creatinine. 86% of participants were enrolled from community health centers in medically underserved areas and 14% from the general population in 12 states in the southeastern United States. Incident ESRD after entry into the cohort was ascertained by linkage of the cohort with the US Renal Data System (USRDS). RESULTS: Median (25th, 75th percentile) eGFR at baseline was 63.3 (36.0, 98.2) ml/min/1.73m2 for ESRD cases and 103.2 (86.0, 117.9) for subcohort. Black ESRD cases had higher median (25th, 75th) eGFR [63.3 (35.9, 95.9)] compared to whites [59.1 (39.4, 99.2)]. In multivariable Cox models accounting for sampling weights, baseline eGFR was a strong predictor of ESRD risk, and an interaction with race was detected (P = 0.029). The higher ESRD risk among blacks relative to whites persisted (hazard ratio: 2.58; 95% confidence interval: 1.65, 4.03) after adjustment for eGFR. CONCLUSION: In this predominantly lower SES cohort, the racial disparity in ESRD risk is not explained by differences in baseline kidney function.

Health Outcome Priorities of Older Adults with Advanced CKD and Concordance with Their Nephrology Providers' Perceptions.

BACKGROUND: Older adults with advanced CKD have significant pain, other symptoms, and disability. To help ensure that care is consistent with patients' values, nephrology providers should understand their patients' priorities when they make clinical recommendations. METHODS: Patients aged ≥60 years with advanced (stage 4 or 5) non-dialysis-dependent CKD receiving care at a CKD clinic completed a validated health outcome prioritization tool to ascertain their health outcome priorities. For each patient, the nephrology provider completed the same health outcome prioritization tool. Patients also answered questions to self-rate their health and completed an end-of-life scenarios instrument. We examined the associations between priorities and self-reported health status and between priorities and acceptance of common end-of-life scenarios, and also measured concordance between patients' priorities and providers' perceptions of priorities. RESULTS: Among 271 patients (median age 71 years), the top health outcome priority was maintaining independence (49%), followed by staying alive (35%), reducing pain (9%), and reducing other symptoms (6%). Nearly half of patients ranked staying alive as their third or fourth priority. There was no relationship between patients' self-rated health status and top priority, but acceptance of some end-of-life scenarios differed significantly between groups with different top priorities. Providers' perceptions about patients' top health outcome priorities were correct only 35% of the time. Patient-provider concordance for any individual health outcome ranking was similarly poor. CONCLUSIONS: Nearly half of older adults with advanced CKD ranked maintaining independence as their top heath outcome priority. Almost as many ranked being alive as their last or second-to-last priority. Nephrology providers demonstrated limited knowledge of their patients' priorities.

Metabolic Effects of Diet and Exercise in Patients with Moderate to Severe CKD: A Randomized Clinical Trial.

CKD is steadily increasing along with obesity worldwide. Furthermore, obesity is a proinflammatory risk factor for progression of CKD and cardiovascular disease. We tested the hypothesis that implementation of caloric restriction and aerobic exercise is feasible and can improve the proinflammatory metabolic milieu in patients with moderate to severe CKD through a pilot, randomized, 2×2 factorial design trial. Of 122 participants consented, 111 were randomized to receive caloric restriction and aerobic exercise, caloric restriction alone, aerobic exercise alone, or usual care. Of those randomized, 42% were women, 25% were diabetic, and 91% were hypertensive; 104 started intervention, and 92 completed the 4-month study. Primary outcomes were a change from baseline in absolute fat mass, body weight, plasma F2-isoprostane concentrations, and peak oxygen uptake (VO2 peak). Compared with usual care, the combined intervention led to statistically significant decreases in body weight and body fat percentage. Caloric restriction alone also led to significant decreases in these measures, but aerobic exercise alone did not. The combined intervention and each independent intervention also led to significant decreases in F2-isoprostane and IL-6 concentrations. No intervention produced significant changes in VO2 peak, kidney function, or urine albumin-to-creatinine ratio. In conclusion, 4-month dietary calorie restriction and aerobic exercise had significant, albeit clinically modest, benefits on body weight, fat mass, and markers of oxidative stress and inflammatory response in patients with moderate to severe CKD. These results suggest healthy lifestyle interventions as a nonpharmacologic strategy to improve markers of metabolic health in these patients.

Insulin resistance is a significant determinant of sarcopenia in advanced kidney disease.

Maintenance hemodialysis (MHD) patients display significant nutritional abnormalities. Insulin is an anabolic hormone with direct effects on skeletal muscle (SM). We examined the anabolic actions of insulin, whole-body (WB), and SM protein turnover in 33 MHD patients and 17 participants without kidney disease using hyperinsulinemic-euglycemic-euaminoacidemic (dual) clamp. Gluteal muscle biopsies were obtained before and after the dual clamp. At baseline, WB protein synthesis and breakdown rates were similar in MHD patients. During dual clamp, controls had a higher increase in WB protein synthesis and a higher suppression of WB protein breakdown compared with MHD patients, resulting in statistically significantly more positive WB protein net balance [2.02 (interquartile range [IQR]: 1.79 and 2.36) vs. 1.68 (IQR: 1.46 and 1.91) mg·kg fat-free mass-1·min-1 for controls vs. for MHD patients, respectively, P < 0.001]. At baseline, SM protein synthesis and breakdown rates were higher in MHD patients versus controls, but SM net protein balance was similar between groups. During dual clamp, SM protein synthesis increased statistically significantly more in controls compared with MHD patients ( P = 0.03), whereas SM protein breakdown decreased comparably between groups. SM net protein balance was statistically significantly more positive in controls compared with MHD patients [67.3 (IQR: 46.4 and 97.1) vs. 15.4 (IQR: -83.7 and 64.7) µg·100 ml-1·min-1 for controls and MHD patients, respectively, P = 0.03]. Human SM biopsy showed a positive correlation between glucose and leucine disposal rates, phosphorylated AKT to AKT ratio, and muscle mitochondrial markers in controls but not in MHD patients. Diminished response to anabolic actions of insulin in the stimulated setting could lead to muscle wasting in MHD patients.

Factors associated with recurrence and mortality in central line-associated bloodstream infections: a retrospective cohort study.

BACKGROUND: Central line-associated bloodstream infections (CLABSIs) are associated with increased mortality, hospital length of stay, and cost. Antimicrobial treatment guidelines for CLABSIs are primarily based on expert opinion. We hypothesized that shorter antimicrobial treatment duration is associated with decreased 60-day recurrence-free survival. METHODS: A retrospective cohort study of all adults with hospital-acquired CLABSIs (HA-CLABSIs) over 5 years at a single tertiary care academic hospital was performed. The time from the end of effective antimicrobial treatment until recurrence of infection or mortality, censored at 60 days after the end of antimicrobial treatment, represented the primary outcome. Effective antimicrobial treatment was defined as the administration of at least one antimicrobial to which the causative organism was sensitive. RESULTS: A total of 366 cases met eligibility criteria. The median Sequential Organ Failure Assessment (SOFA) score was 6 (interquartile range (IQR) 4-8). Patients were treated for a median of 15 (IQR 10-20) days with effective antimicrobials. The incidence of 60-day mortality or recurrence after completion of the antimicrobial course was 22.1% (81 patients). In a Cox proportional-hazards model, antimicrobial treatment duration (hazard ratio (HR) = 0.35; 95% confidence interval (CI) 0.26-0.48), SOFA score (HR = 1.16; 95% CI 1.09-1.22), and age (HR = 1.021; 95% CI = 1.004-1.037) were associated with mortality or recurrence. The effect of antimicrobial treatment duration appeared to plateau after 15 days. CONCLUSIONS: Longer antimicrobial treatment duration in patients with HA-CLABSIs is associated with improved recurrence-free survival during the first 60 days after infection. This effect appears to plateau after 15 days of treatment. Prospective studies are needed to definitively determine the optimal antimicrobial treatment duration for CLABSIs.