Background Few trials have examined long-term outcomes of advance care planning (ACP) interventions. We examined the efficacy of an ACP intervention on preparation for end-of-life decision making for ...dialysis patients and surrogates and for surrogates’ bereavement outcomes. Study Design A randomized trial compared an ACP intervention (Sharing Patient’s Illness Representations to Increase Trust SPIRIT) to usual care alone, with blinded outcome assessments. Setting & Participants 420 participants (210 dyads of prevalent dialysis patients and their surrogates) from 20 dialysis centers. Intervention Every dyad received usual care. Those randomly assigned to SPIRIT had an in-depth ACP discussion at the center and a follow-up session at home 2 weeks later. Outcomes & Measurements Primary outcomes: preparation for end-of-life decision making, assessed for 12 months, included dyad congruence on goals of care at end of life, patient decisional conflict, surrogate decision-making confidence, and a composite of congruence and surrogate decision-making confidence. Secondary outcomes: bereavement outcomes, assessed for 6 months, included anxiety, depression, and posttraumatic distress symptoms completed by surrogates after patient death. Results Primary outcomes: adjusting for time and baseline values, dyad congruence (OR, 1.89; 95% CI, 1.1-3.3), surrogate decision-making confidence (β = 0.13; 95% CI, 0.01-0.24), and the composite (OR, 1.82; 95% CI, 1.0-3.2) were better in SPIRIT than controls, but patient decisional conflict did not differ between groups (β = −0.01; 95% CI, −0.12 to 0.10). Secondary outcomes: 45 patients died during the study. Surrogates in SPIRIT had less anxiety (β = −1.13; 95% CI, −2.23 to −0.03), depression (β = −2.54; 95% CI, −4.34 to −0.74), and posttraumatic distress (β = −5.75; 95% CI, −10.9 to −0.64) than controls. Limitations Study was conducted in a single US region. Conclusions SPIRIT was associated with improvements in dyad preparation for end-of-life decision making and surrogate bereavement outcomes.
Aim: To test the extent to which the vertical structure of tropical forests is determined by environment, forest structure or biogeographical history. Location: Pan-tropical. Methods: Using height ...and diameter data from 20,497 trees in 112 non-contiguous plots, asymptotic maximum height (H AM ) and height—diameter relationships were computed with nonlinear mixed effects (NLME) models to: (1) test for environmental and structural causes of differences among plots, and (2) test if there were continental differences once environment and structure were accounted for; persistence of differences may imply the importance of biogeography for vertical forest structure. NLME analyses for floristic subsets of data (only/excluding Fabaceae and only/excluding Dipterocarpaceae individuals) were used to examine whether family-level patterns revealed biogeographical explanations of cross-continental differences. Results: H AM and allometry were significantly different amongst continents. H AM was greatest in Asian forests (58.3 ± 7.5 m, 95% CI), followed by forests in Africa (45.1 ± 2.6 m), America (35.8 ± 6.0 m) and Australia (35.0 ± 7.4 m), and height—diameter relationships varied similarly; for a given diameter, stems were tallest in Asia, followed by Africa, America and Australia. Precipitation seasonality, basal area, stem density, solar radiation and wood density each explained some variation in allometry and H AM yet continental differences persisted even after these were accounted for. Analyses using floristic subsets showed that significant continental differences in H AM and allometry persisted in all cases. Main conclusions: Tree allometry and maximum height are altered by environmental conditions, forest structure and wood density. Yet, even after accounting for these, tropical forest architecture varies significantly from continent to continent. The greater stature of tropical forests in Asia is not directly determined by the dominance of the family Dipterocarpaceae, as on average non-dipterocarps are equally tall. We hypothesise that dominant large-statured families create conditions in which only tall species can compete, thus perpetuating a forest dominated by tall individuals from diverse families.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NMLJ, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Immunoglobulin light chain (AL) amyloidosis is a disorder of clonal plasma cells characterized by deposition of amyloid fibrils in a variety of tissues, leading to end-organ injury. Renal or cardiac ...involvement is most common, though any organ outside the central nervous system can develop amyloid deposition, and symptomatic presentations may consequently vary. The variability and subtlety of initial clinical presentations may contribute to delayed diagnoses, and organ involvement is often quite advanced and symptomatic by the time a diagnosis is established. Additionally, while organ function can improve with plasma-cell-directed therapy, such improvement lags behind hematologic response. Consequently, highly effective supportive care, including symptom management, is essential to improve quality of life and to maximize both tolerance of therapy and likelihood of survival. Considering the systemic nature of the disease, close collaboration between clinicians is essential for effective management.
Nephrology ranks next to last in career choices among US medical school graduates. The American Society of Nephrology established a Workforce Committee to help address this issue. Surveys of US ...medical students indicate that experiences during kidney pathophysiology courses in the preclerkship years may impact their decision to consider a career in nephrology. In October of 2011, preclinical kidney physiology and pathophysiology course directors at US medical schools were surveyed about teaching methods, curricular content, resources, and institutional support for teaching to identify what worked well and what impairs their teaching efforts. A Listserv of these educators, the American Society of Nephrology Renal Educators Listserv, was used to electronically administer the survey. Course leaders from 62 of 114 (54.4%) surveyed medical schools responded. Most of these educators are nephrologists, but physiologists and other clinicians also lead courses; 60% of course directors noted that lectures are videotaped, resulting in decreased attendance. A range of resources is used: 68% use audience response systems, 16% use the simulation center, and none of the educators indicated use of social media (such as Twitter or Facebook); 50% of respondents receive no remuneration, and 68% receive no full-time equivalent for their efforts. Audience response systems, virtual microscopy, and flash animations were identified as valuable teaching tools. Course directors, during subsequent dialogue on the American Society of Nephrology Renal Educators Listserv, have cited incorporation of case scenarios and integration of clinical exposure during preclinical years as methods that inspired interest. Hopefully, adoption of such approaches will ultimately serve to stimulate interest in nephrology.
Ethylene glycol is highly toxic and represents an important cause of poisonings worldwide. Toxicity can result in central nervous system dysfunction, cardiovascular compromise, elevated anion gap ...metabolic acidosis and acute kidney injury. Many states have passed laws requiring addition of the bittering agent, denatonium benzoate, to ethylene glycol solutions to reduce severity of exposures. The objectives of this study were to identify differences between unintentional and intentional exposures and to evaluate the utility of denatonium benzoate as a deterrent.
Using the National Poison Data System, we performed a retrospective analysis of reported cases of ethylene glycol exposures from January 2006 to December 2013. Outcome classification was summed for intentionality and used as a basis for comparison of effect groups. There were 45,097 cases of ethylene glycol exposures resulting in 154 deaths. Individuals more likely to experience major effects or death were older, male, and presented with more severe symptoms requiring higher levels of care. Latitude and season did not correlate with increased exposures; however, there were more exposures in rural areas. Denatonium benzoate use appeared to have no effect on exposure severity or number.
Deaths due to ethylene glycol exposure were uncommon; however, there were major clinical effects and more exposures in rural areas. Addition of denatonium benzoate was not associated with a reduction in exposures. Alternative means to deter ingestion are needed. These findings suggest the need to consider replacing ethylene glycol with alternative and less toxic agents.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This study evaluated 1-year linear trajectories of patient-reported dimensions of quality of life among patients receiving dialysis.
Longitudinal observational study.
227 patients recruited from 12 ...dialysis centers.
Sociodemographic and clinical characteristics.
Participants completed an hour-long interview monthly for 12 months. Each interview included patient-reported outcome measures of overall symptoms (Edmonton Symptom Assessment System), physical functioning (Activities of Daily Living/Instrumental Activities of Daily Living), cognitive functioning (Patient’s Assessment of Own Functioning Inventory), emotional well-being (Center for Epidemiologic Studies Depression Scale, State Anxiety Inventory, and Positive and Negative Affect Schedule), and spiritual well-being (Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale). For each dimension, linear and generalized linear mixed-effects models were used. Linear trajectories of the 5 dimensions were jointly modeled as a multivariate outcome over time.
Although dimension scores fluctuated greatly from month to month, overall symptoms, cognitive functioning, emotional well-being, and spiritual well-being improved over time. Older compared with younger participants reported higher scores across all dimensions (all P<0.05). Higher comorbidity scores were associated with worse scores in most dimensions (all P<0.01). Nonwhite participants reported better spiritual well-being compared with their white counterparts (P<0.01). Clustering analysis of dimension scores revealed 2 distinctive clusters. Cluster 1 was characterized by better scores than those of cluster 2 in nearly all dimensions at baseline and by gradual improvement over time.
Study was conducted in a single region of the United States and included mostly patients with high levels of function across the dimensions of quality of life studied.
Multidimensional patient-reported quality of life varies widely from month to month regardless of whether overall trajectories improve or worsen over time. Additional research is needed to identify the best approaches to incorporate patient-reported outcome measures into dialysis care.
Subjective cognitive impairment negatively affects daily functioning, health‐related quality of life, and health care consumption, and is predictive of future cognitive decline in many patient ...populations. However, no subjective measures of multidimensional cognitive functioning have been evaluated for dialysis patients. Our purposes were to examine (1) the association between patient‐reported (subjective) cognitive functioning and objective cognitive functioning and (2) the relationships between subjective and objective cognitive functioning and everyday functioning of dialysis patients. We used baseline data from an ongoing longitudinal observational study of trajectories in dialysis patients' multidimensional quality of life. One hundred thirty‐five patients completed a telephone‐based neuropsychological battery (Brief Test of Adult Cognition by Telephone, a measure of objective cognitive functioning), a measure of subjective cognitive functioning (Patient's Assessment of Own Functioning Inventory), and measures of everyday functioning (Activities of Daily Living ADL and Instrumental Activities of Daily Living IADL scales). After controlling for age and education, there was a modest correlation (r = 0.33, P > 0.001) between subjective and objective cognitive functioning. Multivariate logistic regression models showed subjective, but not objective, cognitive functioning was a significant predictor of both ADLs and IADLs. The findings suggest the potential clinical value of subjective measures of cognitive functioning, not to replace objective measures or diagnostic tests, but rather to optimize the meaningfulness of clinical assessment and management.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract Context There are few data on the frequency and current management of clinical ethical issues related to care of seriously ill dialysis patients in free-standing dialysis facilities. ...Objectives To examine the extent of clinical ethical challenges experienced by care providers in free-standing facilities and their perceptions about how those issues are managed. Methods A total of 183 care providers recruited from 15 facilities in North Carolina completed a survey regarding the occurrence and management of ethical issues in the past year. Care plan meetings were observed at four of the facilities for three consecutive months. Also, current policies and procedures at each of the facilities were reviewed. Results The two most frequently experienced challenges involved dialyzing frail patients with multiple comorbidities and caring for disruptive/difficult patients. The most common ways of managing ethical issues were discussions in care plan meetings ( n = 47) or discussions with the clinic manager ( n = 47). Although policies were in place to guide management of some of the challenges, respondents were often not aware of those policies. Also, although participants reported that ethical issues related to dialyzing undocumented immigrants were fairly common, no facility had a policy for managing this challenge. Participants suggested that all staff obtain training in clinical ethics and communication skills, facilities develop ethics teams, and there be clear policies to guide management of ethical challenges. Conclusion The scope of ethical challenges was extensive, how these challenges were managed varied widely, and there were limited resources for assistance. Multifaceted efforts, encompassing endeavors at the individual, facility, organization, and national levels, are needed to support staff in improving the management of ethical challenges in dialysis facilities.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Treatment with vitamin D sterols can lower plasma parathyroid hormone (PTH) in many patients with secondary hyperparathyroidism due to end-stage renal disease, but hypercalcemia, hyperphosphatemia, ...or both often develop during treatment. As such, alternative therapeutic approaches to managing excess PTH secretion are needed. Calcimimetic agents directly inhibit PTH secretion by activating the calcium-sensing receptor in the parathyroid glands, but clinical experience with them is limited. Fifty-two hemodialysis patients with secondary hyperparathyroidism were given single orally administered doses of the calcimimetic agent AMG 073 ranging from 5 to 100 mg, or placebo. Plasma PTH levels decreased 2 h after 25-, 50-, 75-, or 100-mg doses, falling by a maximum of 43 +/- 29%, 40 +/- 36%, 54 +/- 28%, or 55 +/- 39%, respectively. Plasma PTH levels decreased in all patients given doses of > or =25 mg but did not change in those who received placebo. In patients treated with daily doses of 25 or 50 mg of AMG 073 for 8 d, plasma PTH levels declined for the first 3 to 4 d and remained below baseline values after 8 d of treatment. Serum calcium concentrations also decreased by 5 to 10% from pretreatment levels in patients given 50 mg of AMG 073 for 8 d, but values were unchanged in those who received lower doses. Serum phosphorus levels and values for the calcium-phosphorus ion product both decreased after treatment with AMG 073. Thus, 8 d of treatment with AMG 073 effectively lowers plasma PTH levels and improves several disturbances in mineral metabolism that have been associated with soft tissue and vascular calcification and with adverse cardiovascular outcomes in patients with end-stage renal disease.
Lung development and function arises from the interactions between diverse cell types and lineages. Using single-cell RNA sequencing (RNA-seq), we characterize the cellular composition of the lung ...during development and identify vast dynamics in cell composition and their molecular characteristics. Analyzing 818 ligand-receptor interaction pairs within and between cell lineages, we identify broadly interacting cells, including AT2, innate lymphocytes (ILCs), and basophils. Using interleukin (IL)-33 receptor knockout mice and in vitro experiments, we show that basophils establish a lung-specific function imprinted by IL-33 and granulocyte-macrophage colony-stimulating factor (GM-CSF), characterized by unique signaling of cytokines and growth factors important for stromal, epithelial, and myeloid cell fates. Antibody-depletion strategies, diphtheria toxin-mediated selective depletion of basophils, and co-culture studies show that lung resident basophils are important regulators of alveolar macrophage development and function. Together, our study demonstrates how whole-tissue signaling interaction map on the single-cell level can broaden our understanding of cellular networks in health and disease.
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•Single-cell signaling map of lung development identifies inter-lineage crosstalk•Lung-resident basophils are broadly interacting cells located near alveoli•Lung environment imprints the gene signature of basophils via IL33 and GM-CSF•Basophils regulate alveolar macrophage maturation and immunomodulation functions
A population of resident basophils regulates the development and function of alveolar macrophages to control lung homeostasis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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