Parathyroidectomy and the Development of New Depression Among Adults With Primary Hyperparathyroidism.

Importance: Primary hyperparathyroidism (PHPT) is a common endocrine disorder associated with neuropsychiatric symptoms. Although parathyroidectomy has been associated with improvement of preexisting depression among adults with PHPT, the effect of parathyroidectomy on the development of new depression is unknown. Objective: To determine the effect of early parathyroidectomy on the incidence of new depression among adults with PHPT compared with nonoperative management. Design, Setting, and Participants: Analyzed data included observational national Veterans Affairs data from adults with a new diagnosis of PHPT from 2000 through 2019 using target trial emulation with cloning, a biostatistical method that uses observational data to emulate a randomized clinical trial. New depression rates were compared between those treated with early parathyroidectomy vs nonoperative management using an extended Cox model with time-varying inverse probability censoring weighting, adjusted for patient demographics, comorbidities, and depression risk factors. Eligible adults with a new biochemical diagnosis of PHPT, excluding those with past depression diagnoses, residing in an assisted living/nursing facility, or with Charlson Comorbidity Index score higher than 4 were included. These data were analyzed January 4, 2023, through June 15, 2023. Exposure: Early parathyroidectomy (within 1 year of PHPT diagnosis) vs nonoperative management. Main Outcome: New depression, including among subgroups according to patient age (65 years or older; younger than 65 years) and baseline serum calcium (11.3 mg/dL or higher; less than 11.3 mg/dL). Results: The study team identified 40 231 adults with PHPT and no history of depression of whom 35896 were male (89%) and the mean (SD) age was 67 (11.3) years. A total of 3294 patients underwent early parathyroidectomy (8.2%). The weighted cumulative incidence of depression was 11% at 5 years and 18% at 10 years among patients who underwent parathyroidectomy, compared with 9% and 18%, respectively, among nonoperative patients. Those treated with early parathyroidectomy experienced no difference in the adjusted rate of new depression compared with nonoperative management (hazard ratio, 1.05; 95% CI, 0.94-1.17). There was also no estimated effect of early parathyroidectomy on new depression in subgroup analyses based on patient age or serum calcium. Conclusions: In this study, there was no difference in the incidence of new depression among adults with PHPT treated with early parathyroidectomy vs nonoperative management, which is relevant to preoperative discussions about the benefits and risks of operative treatment.

Clonal hematopoiesis of indeterminate potential is associated with reduced risk of cognitive impairment in patients with chronic kidney disease.

INTRODUCTION: Clonal hematopoiesis of indeterminate potential (CHIP) and dementia disproportionately burden patients with chronic kidney disease (CKD). The association between CHIP and cognitive impairment in CKD patients is unknown. METHODS: We conducted time-to-event analyses in up to 1452 older adults with CKD from the Chronic Renal Insufficiency Cohort who underwent CHIP gene sequencing. Cognition was assessed using four validated tests in up to 6 years mean follow-up time. Incident cognitive impairment was defined as a test score one standard deviation below the baseline mean. RESULTS: Compared to non-carriers, CHIP carriers were markedly less likely to experience impairment in attention (adjusted hazard ratio [HR] [95% confidence interval {CI}] = 0.44 [0.26, 0.76], p = 0.003) and executive function (adjusted HR [95% CI] = 0.60 [0.37, 0.97], p = 0.04). There were no significant associations between CHIP and impairment in global cognition or verbal memory. DISCUSSION: CHIP was associated with lower risks of impairment in attention and executive function among CKD patients. HIGHLIGHTS: Our study is the first to examine the role of CHIP in cognitive decline in CKD. CHIP markedly decreased the risk of impairment in attention and executive function. CHIP was not associated with impairment in global cognition or verbal memory.

Clonal hematopoiesis of indeterminate potential contributes to accelerated chronic kidney disease progression.

Background: Clonal hematopoiesis of indeterminate potential (CHIP) is a common inflammatory condition of aging that causes myriad end-organ damage. We have recently shown associations for CHIP with acute kidney injury and with kidney function decline in the general population, with stronger associations for CHIP driven by mutations in genes other than DNMT3A (non- DNMT3A CHIP). Longitudinal kidney function endpoints in individuals with pre-existing chronic kidney disease (CKD) and CHIP have been examined in two previous studies, which reported conflicting findings and were limited by small sample sizes. Methods: In this study, we examined the prospective associations between CHIP and CKD progression events in four cohorts of CKD patients (total N = 5,772). The primary outcome was a composite of 50% kidney function decline or kidney failure. The slope of eGFR decline was examined as a secondary outcome. Mendelian randomization techniques were then used to investigate potential causal effects of CHIP on eGFR decline. Finally, kidney function was assessed in adenine-fed CKD model mice having received a bone marrow transplant recapitulating Tet2 -CHIP compared to controls transplanted wild-type bone marrow. Results: Across all cohorts, the average age was 66.4 years, the average baseline eGFR was 42.6 ml/min/1.73m 2 , and 24% had CHIP. Upon meta-analysis, non- DNMT3A CHIP was associated with a 59% higher relative risk of incident CKD progression (HR 1.59, 95% CI: 1.02-2.47). This association was more pronounced among individuals with diabetes (HR 1.29, 95% CI: 1.03-1.62) and with baseline eGFR ≥ 30 ml/min/1.73m (HR 1.80, 95% CI: 1.11-2.90). Additionally, the annualized slope of eGFR decline was steeper among non- DNMT3A CHIP carriers, relative to non-carriers (ß -0.61 ± 0.31 ml/min/1.73m 2 , p = 0.04). Mendelian randomization analyses suggested a causal role for CHIP in eGFR decline among individuals with diabetes. In a dietary adenine mouse model of CKD, Tet2 -CHIP was associated with lower GFR as well as greater kidney inflammation, tubular injury, and tubulointerstitial fibrosis. Conclusion: Non- DNMT3A CHIP is a potentially targetable novel risk factor for CKD progression.

Heterogeneous Treatment Effects of Intensive Glycemic Control on Kidney Microvascular Outcomes and Mortality in ACCORD.

SIGNIFICANCE STATEMENT: Identifying and quantifying treatment effect variation across patients is the fundamental challenge of precision medicine. Here we quantify heterogeneous treatment effects of intensive glycemic control in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, considering three outcomes of interest-a composite kidney outcome (driven by macroalbuminuria), all-cause mortality, and first assisted hypoglycemic event. We demonstrate that the effects of intensive glycemic control vary with risk of kidney failure, as predicted by the kidney failure risk equation (KFRE). Participants at highest risk of kidney failure gain the largest absolute kidney benefit of intensive glycemic control but also experience the largest absolute risk of death and hypoglycemic events. Our findings illustrate the value of identifying clinically meaningful treatment heterogeneity, particularly when treatments have different effects on multiple end points. OBJECTIVE: Clear criteria to individualize glycemic targets in patients with type II diabetes are lacking. In this post hoc analysis of the ACCORD, we evaluate whether the KFRE can identify patients for whom intensive glycemic control confers more benefit in preventing kidney microvascular outcomes. RESEARCH DESIGN AND METHODS: We divided the ACCORD trial population into quartiles on the basis of 5-year kidney failure risk using the KFRE. We estimated conditional treatment effects within each quartile and compared them with the average treatment effect in the trial. The treatment effects of interest were the 7-year restricted mean survival time (RMST) differences between intensive and standard glycemic control arms on ( 1 ) time-to-first development of severely elevated albuminuria or kidney failure and ( 2 ) all-cause mortality. RESULTS: We found evidence that the effect of intensive glycemic control on kidney microvascular outcomes and all-cause mortality varies with baseline risk of kidney failure. Patients with elevated baseline risk of kidney failure derived the most from intensive glycemic control in reducing kidney microvascular outcomes (7-year RMST difference of 114.8 [95% confidence interval 58.1 to 176.4] versus 48.4 [25.3 to 69.6] days in the entire trial population) However, this same patient group also experienced a shorter time to death (7-year RMST difference of -56.7 [-100.2 to -17.5] v. -23.6 [-42.2 to -6.6] days). CONCLUSIONS: We found evidence of heterogenous treatment effects of intensive glycemic control on kidney microvascular outcomes in ACCORD as a function of predicted baseline risk of kidney failure. Patients with higher kidney failure risk experienced the most pronounced reduction in kidney microvascular outcomes but also experienced the highest risk of all-cause mortality.

"Diving in the deep-end and swimming": a mixed methods study using normalization process theory to evaluate a learning collaborative approach for the implementation of palliative care practices in hemodialysis centers.

BACKGROUND: Normalization Process Theory (NPT) is an implementation theory that can be used to explain how and why implementation strategies work or not in particular circumstances. We used it to understand the mechanisms that lead to the adoption and routinization of palliative care within hemodialysis centers. METHODS: We employed a longitudinal, mixed methods approach to comprehensively evaluate the implementation of palliative care practices among ten hemodialysis centers participating in an Institute for Healthcare Improvement Breakthrough- Series learning collaborative. Qualitative methods included longitudinal observations of collaborative activities, and interviews with implementers at the end of the study. We used an inductive and deductive approach to thematic analysis informed by NPT constructs (coherence, cognitive participation, collective action, reflexive monitoring) and implementation outcomes. The NoMAD survey, which measures NPT constructs, was completed by implementers at each hemodialysis center during early and late implementation. RESULTS: The four mechanisms posited in NPT had a dynamic and layered relationship during the implementation process. Collaborative participants participated because they believed in the value and legitimacy of palliative care for patients receiving hemodialysis and thus had high levels of cognitive participation at the start. Didactic Learning Sessions were important for building practice coherence, and sense-making was solidified through testing new skills in practice and first-hand observation during coaching visits by an expert. Collective action was hampered by limited time among team members and practical issues such as arranging meetings with patients. Reflexive monitoring of the positive benefit to patient and family experiences was key in shifting mindsets from disease-centric towards a patient-centered model of care. NoMAD survey scores showed modest improvement over time, with collective action having the lowest scores. CONCLUSIONS: NPT was a useful framework for understanding the implementation of palliative care practices within hemodialysis centers. We found a nonlinear relationship among the mechanisms which is reflected in our model of implementation of palliative care practices through a learning collaborative. These findings suggest that the implementation of complex practices such as palliative care may be more successful through iterative learning and practice opportunities as the mechanisms for change are layered and mutually reinforcing. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04125537 . Registered 14 October 2019 - Retrospectively registered.

Heterogeneous treatment effects of intensive glycemic control on kidney microvascular outcomes in ACCORD.

Objective: Clear criteria to individualize glycemic targets are lacking. In this post-hoc analysis of the Action to Control Cardiovascular Risk in Diabetes trial (ACCORD), we evaluate whether the kidney failure risk equation (KFRE) can identify patients who disproportionately benefit from intensive glycemic control on kidney microvascular outcomes. Research design and methods: We divided the ACCORD trial population in quartiles based on 5-year kidney failure risk using the KFRE. We estimated conditional treatment effects within each quartile and compared them to the average treatment effect in the trial. The treatment effects of interest were the 7-year restricted-mean-survival-time (RMST) differences between intensive and standard glycemic control arms on (1) time-to-first development of severely elevated albuminuria or kidney failure and (2) all-cause mortality. Results: We found evidence that the effect of intensive glycemic control on kidney microvascular outcomes and all-cause mortality varies with baseline risk of kidney failure. Patients with elevated baseline risk of kidney failure benefitted the most from intensive glycemic control on kidney microvascular outcomes (7-year RMST difference of 115 v. 48 days in the entire trial population) However, this same patient group also experienced shorter times to death (7-year RMST difference of -57 v. -24 days). Conclusions: We found evidence of heterogenous treatment effects of intensive glycemic control on kidney microvascular outcomes in ACCORD as a function of predicted baseline risk of kidney failure. Patients with higher kidney failure risk experienced the most pronounced benefits of treatment on kidney microvascular outcomes but also experienced the highest risk of all-cause mortality.

Blood Pressure, Incident Cognitive Impairment, and Severity of CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.

RATIONALE & OBJECTIVE: Hypertension is a known risk factor for dementia and cognitive impairment. There are limited data on the relation of systolic blood pressure (SBP) and diastolic blood pressure (DBP) with incident cognitive impairment in adults with chronic kidney disease. We sought to identify and characterize the relationship among blood pressure, cognitive impairment, and severity of decreased kidney function in adults with chronic kidney disease. STUDY DESIGN: Longitudinal cohort study. SETTING & PARTICIPANTS: 3,768 participants in the Chronic Renal Insufficiency Cohort (CRIC) Study. EXPOSURE: Baseline SBP and DBP were examined as exposure variables, using continuous (linear, per 10-mm Hg higher), categorical (SBP<120 [reference], 120 to 140,>140mm Hg; DBP<70 (reference), 70 to 80, > 80mm Hg) and nonlinear terms (splines). OUTCOME: Incident cognitive impairment defined as a decline in Modified Mini-Mental State Examination (3MS) score to greater than 1 standard deviation below the cohort mean. ANALYTICAL APPROACH: Cox proportional hazard models adjusted for demographics as well as kidney disease and cardiovascular disease risk factors. RESULTS: The mean age of participants was 58±11 (SD) years, estimated glomerular filtration rate (eGFR) was 44mL/min/1.73m2 ± 15 (SD), and the median follow-up time was 11 (IQR, 7-13) years. In 3,048 participants without cognitive impairment at baseline and with at least 1 follow-up 3MS test, a higher baseline SBP was significantly associated with incident cognitive impairment only in the eGFR>45mL/min/1.73m2 subgroup (adjusted hazard ratio [AHR], 1.13 [95% CI, 1.05-1.22] per 10mm Hg higher SBP]. Spline analyses, aimed at exploring nonlinearity, showed that the relationship between baseline SBP and incident cognitive impairment was J-shaped and significant only in the eGFR>45mL/min/1.73m2 subgroup (P=0.02). Baseline DBP was not associated with incident cognitive impairment in any analyses. LIMITATIONS: 3MS test as the primary measure of cognitive function. CONCLUSIONS: Among patients with chronic kidney disease, higher baseline SBP was associated with higher risk of incident cognitive impairment specifically in those individuals with eGFR>45mL/min/1.73m2. PLAIN-LANGUAGE SUMMARY: High blood pressure is a strong risk factor for dementia and cognitive impairment in studies of adults without kidney disease. High blood pressure and cognitive impairment are common in adults with chronic kidney disease (CKD). The impact of blood pressure on the development of future cognitive impairment in patients with CKD remains unclear. We identified the relationship between blood pressure and cognitive impairment in 3,076 adults with CKD. Baseline blood pressure was measured, after which serial cognitive testing was performed over 11 years. Fourteen percent of participants developed cognitive impairment. We found that a higher baseline systolic blood pressure was associated with an increased risk of cognitive impairment. We found that this association was stronger in adults with mild-to-moderate CKD compared with those with advanced CKD.

Risk of Permanent Hypoparathyroidism Requiring Calcitriol Therapy in a Population-Based Cohort of Adults Older Than 65 Undergoing Total Thyroidectomy for Graves' Disease.

Objective: Total thyroidectomy for Graves' disease (GD) is associated with rapid treatment of hyperthyroidism and low recurrence rates. However, it carries the risk of surgical complications including permanent hypoparathyroidism, which contributes to long-term impaired quality of life. The objective of this study was to determine the incidence of permanent hypoparathyroidism requiring calcitriol therapy among a population-based cohort of older adults undergoing total thyroidectomy for GD in the United States. Methods: We performed a population-based cohort study using 100% Medicare claims from beneficiaries older than 65 years with GD who underwent total thyroidectomy from 2007 to 2017. We required continuous enrollment in Medicare Parts A, B, and D for 12 months before and after surgery to ensure access to comprehensive claims data. Patients were excluded if they had a preoperative diagnosis of thyroid cancer or were on long-term preoperative calcitriol. Our primary outcome was permanent hypoparathyroidism, which was identified based on persistent use of calcitriol between 6 and 12 months following thyroidectomy. We used multivariable logistic regression to identify characteristics associated with permanent hypoparathyroidism, including patient age, sex, race/ethnicity, neighborhood disadvantage, Charlson-Deyo Comorbidity Index, urban or rural residence, and frailty. Results: We identified 4650 patients who underwent total thyroidectomy for GD during the study period and met the inclusion criteria (mean age = 72.8 years [standard deviation = 5.5], 86% female, and 79% white). Among this surgical cohort, 104 (2.2% [95% confidence interval, CI = 1.8-2.7%]) patients developed permanent hypoparathyroidism requiring calcitriol therapy. Patients who developed permanent hypoparathyroidism were on average older (mean age 74.1 vs. 72.8 years) than those who did not develop permanent hypoparathyroidism (p = 0.04). On multivariable regression, older age was the only patient characteristic associated with permanent hypoparathyroidism (odds ratio age ≥76 years = 1.68 [CI = 1.13-2.51] compared with age 66-75 years). Conclusions: The risk of permanent hypoparathyroidism requiring calcitriol therapy among this national, U.S. population-based cohort of older adults with GD treated with total thyroidectomy was low, even when considering operations performed by a heterogeneous group of surgeons. These findings suggest that the risk of hypoparathyroidism should not be a deterrent to operative management for GD in older adults who are appropriate surgical candidates.

Racial Disparities in Health Beliefs and Advance Care Planning Among Patients Receiving Maintenance Dialysis.

CONTEXT: Among people receiving maintenance dialysis, little is known about racial disparities in the occurrence of prognostic discussions, beliefs about future health, and completion of advance care planning (ACP) documents. OBJECTIVES: We examined whether Black patients receiving maintenance dialysis differ from White patients in prognostic discussions, beliefs about future health, and completion of ACP-related documents. METHODS: We surveyed adult patients receiving maintenance dialysis from seven dialysis units in Cleveland, Ohio, and hospitalized patients at a tertiary care hospital in Cleveland. Of the 450 patients who were asked to participate in the study, 423 (94%) agreed. We restricted the current secondary analyses to include only Black (n=285) and White (n=114) patients. The survey assessed patients' knowledge of their kidney disease, attitudes toward chronic kidney disease (CKD) treatment, preferences for end-of-life (EoL) care, the patient-reported occurrence of prognostic discussions, experiences with kidney therapy decision making, sentiments of dialysis regret, beliefs about health over the next 12 months, and advance care planning. We used stepwise logistic regression to determine if race was associated with the occurrence of prognostic discussions, beliefs about future health, and completion of an ACP-related document, while controlling for potential confounders. RESULTS: We found no significant difference in the frequency of prognostic discussions between Black (11.9%) versus White patients (7%) (P=0.15). However, Black patients (19%) had lower odds of believing that their health would worsen over the next 12 months (OR 0.22, CI 0.12, 0.44) and reporting completion of any ACP-related document (OR 0.5, CI 0.32, 0.81) compared to White patients CONCLUSION: Racial differences exist in beliefs about future health and completion of ACP-related documents. Systemic efforts to investigate differences in health beliefs and address racial disparities in the completion of ACP-related documents are needed.

Vitamin K Status and Cognitive Function in Adults with Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort.

Vitamin K is linked to cognitive function, but studies in individuals with chronic kidney disease (CKD), who are at risk for vitamin K insufficiency and cognitive impairment, are lacking. The cross-sectional association of vitamin K status biomarkers with cognitive performance was evaluated in ≥55-y-old adults with CKD (N = 714, 49% female, 44% black). A composite score of a cognitive performance test battery, calculated by averaging the z scores of the individual tests, was the primary outcome. Vitamin K status was measured using plasma phylloquinone and dephospho-uncarboxylated matrix Gla protein [(dp)ucMGP]. Participants with low plasma (dp)ucMGP, reflecting higher vitamin K status, had better cognitive performance than those in the two higher (dp)ucMGP categories based on the composite outcome (P = 0.03), whereas it did not significantly differ according to plasma phylloquinone categories (P = 0.08). Neither biomarker was significantly associated with performance on individual tests (all P > 0.05). The importance of vitamin K to cognitive performance in adults with CKD remains to be clarified.

The Impact of Care Partners on the Mobility of Older Adults Receiving Hemodialysis.

Rationale & Objective: Many older adults receiving hemodialysis have mobility limitations and rely on care partners, yet data are sparse regarding the support provided by care partners. Our aim was to examine how care partners support the mobility of an older adult receiving hemodialysis. Study Design: Qualitative study. Setting & Participants: Using purposive sampling, we recruited persons aged 60 years or more receiving maintenance hemodialysis and care partners aged 18 years or more who were providing support to an older adult receiving hemodialysis. We conducted in-person semi-structured interviews about mobility with each individual. Analytical Approach: We conducted descriptive and focused coding of interview transcripts and employed thematic analysis. Our outcome was to describe perceived mobility supports provided by care partners using qualitative themes. Results: We enrolled 31 older adults receiving hemodialysis (42% women, 68% Black) with a mean age of 73 ± 8 years and a mean dialysis duration of 4.6 ± 3.5 years. Of these, 87% of patients used assistive devices and 90% had care partners. We enrolled 12 care partners (75% women, 33% Black) with a mean age of 54 ± 16 years. From our patient and care partner interviews, we found three themes: (1) what care partners see, (2) what care partners do, and (3) what care partners feel. Regarding what they see, care partners witness a decline in patient mobility. Regarding what they do, care partners guide and facilitate activities and manage others who also assist. Regarding what they feel, care partners respect the patient's autonomy but experience frustration and worry about the patient's future mobility. Limitations: Modest sample size; single geographic area. Conclusions: In older adults receiving hemodialysis, care partners observe a decline in mobility and provide support for mobility. They respect the patient's autonomy but worry about future mobility losses. Future research should incorporate care partners in interventions that address mobility in older adults receiving hemodialysis.

Association of Proximal Tubular Secretory Clearance with Long-Term Decline in Cognitive Function.

BACKGROUND: People with chronic kidney disease (CKD) are at high risk for cognitive impairment and progressive cognitive decline. Retention of protein-bound organic solutes that are normally removed by tubular secretion is hypothesized to contribute to cognitive impairment in CKD. METHODS: We followed 2362 participants who were initially free of cognitive impairment and stroke in the prospective Chronic Renal Insufficiency Cohort (CRIC) Study. We estimated tubular secretory clearance by the 24-hour kidney clearances of eight endogenous solutes that are primarily eliminated by tubular secretion. CRIC study investigators assessed participants' cognitive function annually using the Modified Mini-Mental State (3MS) Examination. Cognitive decline was defined as a sustained decrease of more than five points in the 3MS score from baseline. Using Cox regression models adjusted for potential confounders, we analyzed associations between secretory solute clearances, serum solute concentrations, and cognitive decline. RESULTS: The median number of follow-up 3MS examinations was six per participant. There were 247 incident cognitive decline events over a median of 9.1 years of follow-up. Lower kidney clearances of five of the eight secretory solutes (cinnamoylglycine, isovalerylglycine, kynurenic acid, pyridoxic acid, and tiglylglycine) were associated with cognitive decline after adjustment for baseline eGFR, proteinuria, and other confounding variables. Effect sizes ranged from a 17% to a 34% higher risk of cognitive decline per 50% lower clearance. In contrast, serum concentrations of the solutes were not associated with cognitive decline. CONCLUSIONS: Lower kidney clearances of secreted solutes are associated with incident global cognitive decline in a prospective study of CKD, independent of eGFR. Further work is needed to determine the domains of cognition most affected by decreased secretory clearance and the mechanisms of these associations.

Video Images about Decisions for Ethical Outcomes in Kidney Disease (VIDEO-KD): the study protocol for a multi-centre randomised controlled trial.

INTRODUCTION: Older patients with advanced chronic kidney disease (CKD) often are inadequately prepared to make informed decisions about treatments including dialysis and cardiopulmonary resuscitation. Further, evidence shows that patients with advanced CKD do not commonly engage in advance care planning (ACP), may suffer from poor quality of life, and may be exposed to end-of-life care that is not concordant with their goals. We aim to study the effectiveness of a video intervention on ACP, treatment preferences and other patient-reported outcomes. METHODS AND ANALYSIS: The Video Images about Decisions for Ethical Outcomes in Kidney Disease trial is a multi-centre randomised controlled trial that will test the effectiveness of an intervention that includes a CKD-related video decision aid followed by recording personal video declarations about goals of care and treatment preferences in older adults with advancing CKD. We aim to enrol 600 patients over 5 years at 10 sites. ETHICS AND DISSEMINATION: Regulatory and ethical aspects of this trial include a single Institutional Review Board mechanism for approval, data use agreements among sites, and a Data Safety and Monitoring Board. We intend to disseminate findings at national meetings and publish our results. TRIAL REGISTRATION NUMBER: NCT04347629.

Association of Intensive vs Standard Blood Pressure Control With Cerebral Blood Flow: Secondary Analysis of the SPRINT MIND Randomized Clinical Trial.

IMPORTANCE: Antihypertensive treatments benefit cerebrovascular health and cognitive function in patients with hypertension, but it is uncertain whether an intensive blood pressure target leads to potentially harmful cerebral hypoperfusion. OBJECTIVE: To investigate the association of intensive systolic blood pressure (SBP) control vs standard control with whole-brain cerebral blood flow (CBF). DESIGN, SETTING, AND PARTICIPANTS: This substudy of the Systolic Blood Pressure Intervention Trial (SPRINT) randomized clinical trial compared the efficacy of 2 different blood pressure-lowering strategies with longitudinal brain magnetic resonance imaging (MRI) including arterial spin labeled perfusion imaging to quantify CBF. A total of 1267 adults 50 years or older with hypertension and increased cardiovascular risk but free of diabetes or dementia were screened for the SPRINT substudy from 6 sites in the US. Randomization began in November 2010 with final follow-up MRI in July 2016. Analyses were performed from September 2020 through December 2021. INTERVENTIONS: Study participants with baseline CBF measures were randomized to an intensive SBP target less than 120 mm Hg or standard SBP target less than 140 mm Hg. MAIN OUTCOMES AND MEASURES: The primary outcome was change in whole-brain CBF from baseline. Secondary outcomes were change in gray matter, white matter, and periventricular white matter CBF. RESULTS: Among 547 participants with CBF measured at baseline, the mean (SD) age was 67.5 (8.1) years and 219 (40.0%) were women; 315 completed follow-up MRI at a median (IQR) of 4.0 (3.7-4.1) years after randomization. Mean whole-brain CBF increased from 38.90 to 40.36 (difference, 1.46 [95% CI, 0.08-2.83]) mL/100 g/min in the intensive treatment group, with no mean increase in the standard treatment group (37.96 to 37.12; difference, -0.84 [95% CI, -2.30 to 0.61] mL/100 g/min; between-group difference, 2.30 [95% CI, 0.30-4.30; P = .02]). Gray, white, and periventricular white matter CBF showed similar changes. The association of intensive vs standard treatment with CBF was generally similar across subgroups defined by age, sex, race, chronic kidney disease, SBP, orthostatic hypotension, and frailty, with the exception of an indication of larger mean increases in CBF associated with intensive treatment among participants with a history of cardiovascular disease (interaction P = .05). CONCLUSIONS AND RELEVANCE: Intensive vs standard antihypertensive treatment was associated with increased, rather than decreased, cerebral perfusion, most notably in participants with a history of cardiovascular disease. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01206062.

Content of Tele-Palliative Care Consultations with Patients Receiving Dialysis.

Background: Little is known about the content of communication in palliative care telehealth conversations in the dialysis population. Understanding the content and process of these conversations may lead to insights about how palliative care improves quality of life. Methods: We conducted a qualitative analysis of video recordings obtained during a pilot palliative teleconsultation program. We recruited patients receiving dialysis from five facilities affiliated with an academic medical center. Palliative care clinicians conducted teleconsultation using a wall-mounted screen with a camera mounted on a pole and positioned mid-screen in the line of sight to facilitate direct eye contact. Patients used an iPad that was attached to an IV pole positioned next to the dialysis chair. Conversations were coded using a preexisting framework of themes and content from the Serious Illness Conversation Guide (SICG) and revised Edmonton Symptom Assessment System-Renal. Results: We recruited 39 patients to undergo a telepalliative care consultation while receiving dialysis, 34 of whom completed the teleconsultation. Specialty palliative care clinicians (3 physicians and 1 nurse practitioner) conducted 35 visits with 34 patients. Median (interquartile range) duration of conversation was 42 (28-57) minutes. Most frequently discussed content included sources of strength (91%), critical abilities (88%), illness understanding (85%), fears and worries (85%), what family knows (85%), fatigue (77%), and pain (65%). Process features such as summarizing statements (85%) and making a recommendation (82%) were common, whereas connectional silence (56%), and emotion expression (21%) occurred less often. Conclusions: Unscripted palliative care conversations in outpatient dialysis units through telemedicine exhibited many domains recommended by the SICG, with less frequent discussion of symptoms. Emotion expression was uncommon for these conversations that occurred in an open setting.

Nephrology Referral Based on Laboratory Values, Kidney Failure Risk, or Both: A Study Using Veterans Affairs Health System Data.

RATIONALE & OBJECTIVE: Current guidelines for nephrology referral are based on laboratory criteria. We sought to evaluate whether nephrology referral patterns reflect current clinical practice guidelines and to estimate the change in referral volume if they were based on the estimated risk of kidney failure. STUDY DESIGN: Observational cohort. SETTING & PARTICIPANTS: Retrospective study of 399,644 veterans with chronic kidney disease (October 1, 2015 through September 30, 2016). EXPOSURE: Laboratory referral criteria based on Veterans Affairs/Department of Defense guidelines, categories of predicted risk for kidney failure using the Kidney Failure Risk Equation, and the combination of laboratory referral criteria and predicted risk. OUTCOME: Number of patients identified for referral. ANALYTICAL APPROACH: We evaluated the number of patients who were referred and their predicted 2-year risk for kidney failure. For each exposure, we estimated the number of patients who would be identified for referral. RESULTS: There were 66,276 patients who met laboratory indications for referral. Among these patients, 11,752 (17.7%) were referred to nephrology in the following year. The median 2-year predicted risk of kidney failure was 1.5% (interquartile range, 0.3%-4.7%) among all patients meeting the laboratory referral criteria. If referrals were restricted to patients with a predicted risk of ≥1% in addition to laboratory indications, the potential referral volume would be reduced from 66,276 to 38,229 patients. If referrals were based on predicted risk alone, a 2-year risk threshold of 1% or higher would identify a similar number of patients (72,948) as laboratory-based criteria with median predicted risk of 2.3% (interquartile range, 1.4%-4.6%). LIMITATIONS: Missing proteinuria measurements. CONCLUSIONS: The current laboratory-based guidelines for nephrology referral identify patients who are, on average, at low risk for progression, most of whom are not referred. As an alternative, referral based on a 2-year kidney failure risk exceeding 1% would identify a similar number of patients but with a higher median risk of kidney failure.

Risk of Fracture Among Older Adults With Primary Hyperparathyroidism Receiving Parathyroidectomy vs Nonoperative Management.

Importance: Primary hyperparathyroidism (PHPT) contributes to the development and progression of osteoporosis in older adults. The effectiveness of parathyroidectomy for reducing fracture risk in older adults is unknown. Objective: To compare the incidence of clinical fracture among older adults with PHPT treated with parathyroidectomy vs nonoperative management. Design, Setting, and Participants: This was a population-based, longitudinal cohort study of all Medicare beneficiaries with PHPT from 2006 to 2017. Multivariable, inverse probability weighted Cox proportional hazards and Fine-Gray competing risk regression models were constructed to determine the association of parathyroidectomy vs nonoperative management with incident fracture. Data analysis was conducted from February 17, 2021, to September 14, 2021. Main Outcomes and Measures: The primary outcome was clinical fracture at any anatomic site not associated with major trauma during the follow-up period. Results: Among the 210 206 Medicare beneficiaries with PHPT (mean [SD] age, 75 [6.8] years; 165 637 [78.8%] women; 183 433 [87.3%] White individuals), 63 136 (30.0%) underwent parathyroidectomy within 1 year of diagnosis, and 147 070 (70.0%) were managed nonoperatively. During a mean (SD) follow-up period of 58.5 (35.5) months, the unadjusted incidence of fracture was 10.2% in patients treated with parathyroidectomy. During a mean (SD) follow-up of 52.5 (33.8) months, the unadjusted incidence of fracture was 13.7% in patients observed nonoperatively. On multivariable analysis, parathyroidectomy was associated with lower adjusted rates of any fracture (hazard ratio [HR], 0.78; 95% CI, 0.76-0.80]) and hip fracture (HR, 0.76; 95% CI, 0.72-0.79). At 2, 5, and 10 years, parathyroidectomy was associated with adjusted absolute fracture risk reduction of 1.2% (95% CI, 1.0-1.4), 2.8% (95% CI, 2.5-3.1), and 5.1% (95% CI, 4.6-5.5), respectively, compared with nonoperative management. On subgroup analysis, there were no significant differences in the association of parathyroidectomy with fracture risk by age group, sex, frailty, history of osteoporosis, or meeting operative guidelines. Fine-Gray competing risk regression confirmed parathyroidectomy was associated with a lower probability of any fracture and hip fracture when accounting for the competing risk of death (HR, 0.84; 95% CI, 0.82-0.85; and HR, 0.83; 95% CI, 0.80-0.85, respectively). Conclusions and Relevance: This longitudinal cohort study found that parathyroidectomy was associated with a lower risk of any fracture and hip fracture among older adults with PHPT, suggesting a clinically meaningful benefit of operative management in this population.