Analysis of retinal and choroidal microvascular changes using optical coherence tomography and optical coherence tomography angiography in patients with acute leukemia.

PURPOSE: Although leukemic retinopathy accounts for 80% of ocular complications in acute leukemia, its pathogenesis remains unclear. To evaluate changes in retinal and choroicapillaris and structural parameters in patients with acute leukemia, we analyzed the correlation between vascular perfusion metrics and laboratory parameters and assessed the changes after hematopoietic stem cell transplantation (HSCT). METHODS: Herein, 104 eyes of 52 patients aged 18 and above with acute leukemia were enrolled. 80 eyes of 40 healthy patients were recruited as control participants. All participants underwent optical coherence tomography (OCT) and OCT angiography (OCTA) at baseline. RESULTS: Patients with acute leukemia had a significantly thicker ganglion cell-inner plexiform layer (GCIPL) and lower circularity index than the control participants. Post-HSCT perfusion metrics did not differ significantly, but parafoveal thickness decreased significantly. During the active phase of acute leukemia, lower platelet levels were associated with significant GCIPL thickening and increased foveal avascular zone and perimeter. D-dimer levels positively correlated with GCIPL thickness. CONCLUSION: Patients with acute leukemia had subclinical retinal microvascular deficits on OCTA and GCIPL thickening on OCT, possibly associated with bone marrow function. GCIPL thickness may indicate acute ischemia in such patients. Further studies must elucidate their clinical and prognostic significance.

ß-Sitosterol Attenuates Dexamethasone-Induced Muscle Atrophy via Regulating FoxO1-Dependent Signaling in C2C12 Cell and Mice Model.

Sarcopenia refers to a decline in muscle mass and strength with age, causing significant impairment in the ability to carry out normal daily functions and increased risk of falls and fractures, eventually leading to loss of independence. Maintaining protein homeostasis is an important factor in preventing muscle loss, and the decrease in muscle mass is caused by an imbalance between anabolism and catabolism of muscle proteins. Although ß-sitosterol has various effects such as anti-inflammatory, protective effect against nonalcoholic fatty liver disease (NAFLD), antioxidant, and antidiabetic activity, the mechanism of ß-sitosterol effect on the catabolic pathway was not well known. ß-sitosterol was assessed in vitro and in vivo using a dexamethasone-induced muscle atrophy mice model and C2C12 myoblasts. ß-sitosterol protected mice from dexamethasone-induced muscle mass loss. The thickness of gastrocnemius muscle myofibers was increased in dexamethasone with the ß-sitosterol treatment group (DS). Grip strength and creatine kinase (CK) activity were also recovered when ß-sitosterol was treated. The muscle loss inhibitory efficacy of ß-sitosterol in dexamethasone-induced muscle atrophy in C2C12 myotube was also verified in C2C12 myoblast. ß-sitosterol also recovered the width of myotubes. The protein expression of muscle atrophy F-box (MAFbx) was increased in dexamethasone-treated animal models and C2C12 myoblast, but it was reduced when ß-sitosterol was treated. MuRF1 also showed similar results to MAFbx in the mRNA level of C2C12 myotubes. In addition, in the gastrocnemius and tibialis anterior muscles of mouse models, Forkhead Box O1 (FoxO1) protein was increased in the dexamethasone-treated group (Dexa) compared with the control group and reduced in the DS group. Therefore, ß-sitosterol would be a potential treatment agent for aging sarcopenia.

Regional Differences in the Diets of Adélie and Emperor Penguins in the Ross Sea, Antarctica.

To identify the dietary composition and characteristics of both Adélie (Pygoscelis adeliae) and Emperor (Aptenodytes forsteri) penguins at four breeding sites, we performed stable carbon (δ13C) and nitrogen (δ15N) isotope analysis of down samples taken from penguin chicks. Adélie Penguin chicks at Cape Hallett mostly fed on Antarctic krill (Euphausia superba; 65.5 ± 3.5%), a reflection of the prevalence of that species near Cape Hallett, and no significant differences were noted between 2017 and 2018. However, Adélie Penguin chicks at Inexpressible Island, located near Terra Nova Bay, fed on both Antarctic silverfish (Pleuragramma antarctica; 42.5%) and ice krill (Euphausia crystallorophias; 47%), reflecting the high biomass observed in Terra Nova Bay. Meanwhile, no significant difference was noted between the two breeding sites of the Emperor Penguin. Emperor Penguin chicks predominantly fed on Antarctic silverfish (74.5 ± 2.1%) at both breeding sites (Cape Washington and Coulman Island), suggesting that diet preference represents the main factor influencing Emperor Penguin foraging. In contrast, the diet of the Adélie Penguin reflects presumed regional differences in prey prevalence, as inferred from available survey data.

Prevalence of Macular Abnormalities Identified Only on Optical Coherence Tomography in Korean Patients Scheduled for Cataract Surgery.

PURPOSE: To assess the prevalence of macular abnormalities identified only on macular optical coherence tomography (OCT) which were not suspected by biomicroscopic fundus examination, and examine the clinical outcome of patients with these macular abnormalities during preoperative evaluation for cataract surgery in a large series of Korean patients.<br/>. METHODS: Macular OCT was performed on patients scheduled for routine cataract surgery by the same physician at Seoul St. Mary's Hospital, between June 2018 and November 2019. The patients' medical records were reviewed retrospectively to obtain demographic data and the results of preoperative evaluation before cataract surgery. Patients were divided into two groups based on the preoperative macular OCT. RESULTS: normal and abnormal OCT groups. RESULTS: Nine hundred eighty-seven eyes (698 patients) were included in this study. Macular OCT identified abnormalities in 44 eyes (4.5%) of 35 patients (5.0%). Twenty-one eyes (2.1%) had age-related macular degeneration, 20 eyes (2.0%) had epiretinal membrane, and three eyes (0.3%) had lamellar hole. Patients with macular abnormalities identified on macular OCT had a statistically significant higher mean age than those who had normal OCT findings (p < 0.001). Best-corrected visual acuity was worse in patients with abnormal macular OCT after cataract surgery (p = 0.048). CONCLUSIONS: In the preoperative evaluation for cataract surgery in Korean patients, one in every 20 patients had macular abnormalities identified only on macular OCT in spite of unremarkable macular findings on biomicroscopic funduscopy. Age was significantly higher in patients with abnormal macular OCT findings. Thus, inclusion of macular OCT examination in preoperative screening before routine cataract surgery would be beneficial.

Relationship between eyelid margin irregularity and meibomian gland dropout.

PURPOSE: To examine the relationship between lid margin abnormalities and meibomian gland loss in infrared meibography. METHODS: This study was a retrospective chart review of 170 patients with dry eye disease. A correlation analysis between eyelid margin abnormalities and meibomian gland dropout in infrared meibography was performed using data from 141 eyes. We graded the following eyelid margin abnormalities: irregular lid margin, vascular engorgement, plugging, anterior placement of the mucocutaneous junction, exposed terminal duct, and presence of tattoos. Multiple regression analyses were performed with meiboscore (meibomian gland dropout grade) as the dependent variable and age, sex, lid margin abnormality grades, and total grading score of lid margin abnormalities as the covariates. In addition, Meibomian glands structure were examined in those with eyelid margin dimpling using meibography in 25 eyes. RESULTS: In the multiple regression analysis, an irregular lid margin in the upper eyelid was associated with a higher meiboscore after controlling for age and sex (coefficients B = 1.379, p = 0.025). Other lid margin abnormalities did not significantly affect the meiboscore. In the lower eyelids, irregular lid margin (coefficients B = 0.602, p = 0.009) and total grading score of lid margin abnormality were associated with higher meiboscores (coefficients B = 0.100, p = 0.022). Of the 25 eyes with dimples, 21 (84%) showed focal or complete meibomian gland loss at the site. CONCLUSIONS: Lid margin abnormalities were found to be associated with meibomian gland dropout.

Prognostic factors of cytomegalovirus retinitis after hematopoietic stem cell transplantation.

PURPOSE: To identify the visual prognostic factors in patients with cytomegalovirus (CMV) retinitis after hematopoietic stem cell transplantation (HSCT). METHODS: This retrospective cohort study included 4241 patients who underwent HSCT from April 1, 2010 to March 31, 2019 at Seoul St. Mary's Hospital. Of them, 1063 patients presented CMV viremia, and 67 patients (93 eyes) were diagnosed with CMV retinitis. We enrolled 66 patients (91 eyes). The main outcomes included the initial best-corrected visual acuity (BCVA), BCVA at the diagnosis of retinitis and last visit, involved retinal zone, peak CMV DNA levels in the peripheral blood and aqueous humor, time between HSCT and the diagnosis of retinitis, time between the diagnosis of viremia and retinitis, complications, recurrence, survival, and so on. RESULTS: The mean BCVA (logarithm of the minimum angle of resolution) values before HSCT, at the time of retinitis diagnosis, and at the last visit were 0.041 ± 0.076, 0.262 ± 0.529, and 0.309 ± 0.547, respectively. Multiple regression analysis revealed that the involved zone (P = 0.001), time between HSCT and retinitis diagnosis (P = 0.019), and survival status (P = 0.001) were associated with the final visual acuity. CONCLUSIONS: The final visual prognosis was worse in patients with greater invasion of the central retinal zone, those with a longer interval between HSCT and the diagnosis of retinitis, and those who died. Prompt diagnosis of CMV retinitis through periodic fundus examinations of patients with CMV viremia can prevent severe vision loss. Once CMV viremia is confirmed, we recommend fundus examinations to be immediately performed and repeated every 2 weeks for at least 2 months, even if the CMV DNA titer in the peripheral blood becomes negative.

Attenuated Visual Function in Patients with Major Depressive Disorder.

BACKGROUND: We sought to investigate visual function, primarily, and structural changes in retinal ganglion cells, secondarily, in patients with major depressive disorder. METHODS: A total of 50 normal participants and 49 patients with major depressive disorder were included in this cross-sectional study. The participants underwent 24-2 standard automated perimetry and spectral-domain optical coherence tomography. RESULTS: The pattern standard deviation (PSD) in the visual field test was higher in the major depressive disorder patients than in the normal control subjects (P = 0.017). The patients with major depressive disorder showed reduced minimum ganglion cell-inner plexiform layer (GCIPL) thickness relative to the normal control participants (P = 0.015). The average score on the Hamilton Depression Rating scale showed a significant correlation with the PSD, minimum GCIPL thickness, and inferior GCIPL thickness (r = 0.265, P = 0.009; r = -0.239, P = 0.017; and r = -0.204, P = 0.043, respectively). The multivariate analysis of factors associated with PSD showed old age and a high Hamilton Depression Rating score to be relevant (P = 0.002 and 0.028, respectively). CONCLUSIONS: Visual function was decreased and the GCIPL thickness was reduced in major depressive disorder patients. The retinal neurodegenerative process in depression might be considered in patients with depression.

Novel Optical Coherence Tomography Parameters as Prognostic Factors for Stage 3 Epiretinal Membranes.

PURPOSE: We aimed to describe the visual prognosis of eyes with ectopic inner foveal layers (EIFLs) after epiretinal membrane (ERM) surgery. METHODS: This retrospective study enrolled patients diagnosed with stage 3 ERM based on the EIFL staging scheme who underwent ERM surgery with a minimum follow-up period of 12 months. Central foveal thickness (CFT), EIFL thickness, and the length of the ellipsoid zone defect were evaluated at baseline and at 1 month, 6 months, and 12 months after surgery based on pre- and postoperative swept-source optical coherence tomography (OCT) images. The association of EIFL thickness and other OCT parameters with pre- and postoperative best-corrected visual acuity (BCVA) was analyzed. RESULTS: Sixty-nine eyes with stage 3 ERMs were analyzed. Preoperative BCVA was correlated with preoperative CFT (r = 0.517, p < 0.001) and preoperative EIFL thickness (r = 0.652, p < 0.001). At 12 months, postoperative BCVA was correlated negatively with preoperative CFT (r = 0.470, p=0.016) and preoperative EIFL thickness (r = 0.582, p=0.004). The improvement in BCVA was not associated with postoperative reduction in CFT (p=0.06), although it was significantly associated with postoperative reduction in EIFL thickness (r = 0.635, p=0.007). CONCLUSIONS: EIFL thickness should be considered a negative prognostic factor for postoperative anatomical and functional recovery in patients with stage 3 ERMs.

Investigating conflict in ICUs-is the clinicians' perspective enough?

OBJECTIVE: Most studies have assessed conflict between clinicians and surrogate decision makers in ICUs from only clinicians' perspectives. It is unknown if surrogates' perceptions differ from clinicians'. We sought to determine the degree of agreement between physicians and surrogates about conflict and to identify predictors of physician-surrogate conflict. DESIGN: Prospective cohort study. SETTING: Four ICUs of two hospitals in San Francisco, California. PATIENTS: Two hundred and thirty surrogate decision makers and 100 physicians of 175 critically ill patients. MEASUREMENTS: Questionnaires addressing participants' perceptions of whether there was physician-surrogate conflict, as well as attitudes and preferences about clinician-surrogate communication; κ scores to quantify physician-surrogate concordance about the presence of conflict; and hierarchical multivariate modeling to determine predictors of conflict. MAIN RESULTS: Either the physician or surrogate identified conflict in 63% of cases. Physicians were less likely to perceive conflict than surrogates (27.8% vs 42.3%; p = 0.007). Agreement between physicians and surrogates about conflict was poor (κ = 0.14). Multivariable analysis with surrogate-assessed conflict as the outcome revealed that higher levels of surrogates' satisfaction with physicians' bedside manner were associated with lower odds of conflict (odds ratio, 0.75 per 1 point increase in satisfaction; 95% CI, 0.59-0.96). Multivariable analysis with physician-assessed conflict as the outcome revealed that the surrogate having felt discriminated against in the healthcare setting was associated with higher odds of conflict (odds ratio, 17.5; 95% CI, 1.6-190.1) while surrogates' satisfaction with physicians' bedside manner was associated with lower odds of conflict (0-10 scale; odds ratio, 0.76 per 1 point increase; 95% CI, 0.58-0.99). CONCLUSIONS: Conflict between physicians and surrogates is common in ICUs. There is little agreement between physicians and surrogates about whether physician-surrogate conflict has occurred. Further work is needed to develop reliable and valid methods to assess conflict. In the interim, future studies should assess conflict from the perspective of both clinicians and surrogates.

Discussion of treatment trials in intensive care.

PURPOSE: This study aimed to characterize whether and how the option of a treatment trial is discussed with surrogates in intensive care units. MATERIALS AND METHODS: We audio-recorded 72 family conferences for 72 patients at high risk for death or severe functional impairment in 5 intensive care units in San Francisco, California. We analyzed transcripts to develop a coding framework for whether and how trials were discussed. RESULTS: Trials were offered in 15% of conferences. We identified 2 types: (1) time-limited trials, defined as continuing all intensive, life-sustaining treatments, with a plan to reassess after a defined time period based on prespecified clinical milestones, and (2) symptom-limited trials, defined as using basic medical care aimed at survival (rather than purely comfort-focused treatment) once ventilatory support is withdrawn, with a plan to reassess based on patient symptoms. Clinicians frequently did not inform surrogates about key elements of the trial such as criteria by which the effectiveness of the trial would be evaluated and possible next steps based on trial results. CONCLUSIONS: In this cohort of critically ill patients, trials were infrequently and incompletely discussed. Additional work is needed to improve communication about treatment trials and evaluate their impact on patient and family outcomes.

Association between physicians' beliefs and the option of comfort care for critically ill patients.

PURPOSE: For critically ill patients at high risk of death, reasonable treatment options include attempts at life prolongation and treatment focused on comfort. Little is known about whether and how physicians present the option of comfort care to surrogates. This study assessed how comfort care is presented to surrogates and whether physicians' beliefs are associated with whether comfort care is presented as an option. METHODS: Mixed-methods study of 72 audio-recorded family conferences about treatment decisions in five ICUs at two hospitals in San Francisco, California. One hundred sixty-nine family members and 54 physicians participated. Patients were at high risk of death or severe functional impairment. Transcripts of audio-recorded conferences were coded to identify whether physicians offered comfort care as an alternative to life-sustaining treatment and to characterize the stated risks and benefits. Physicians completed a questionnaire indicating the strength of their belief that life support should be foregone. RESULTS: The inpatient mortality rate was 72 %. Using a broad definition of comfort-oriented treatment, this option was presented in 56 % (95 % CI, 44-67 %) of conferences. In clustered multivariate models, the only independent predictor of offering comfort care as an option was the strength of the physician's belief that life support should be foregone [OR 1.38 (1.14-1.66), p = 0.01]. CONCLUSIONS: Clinicians did not explicitly inform surrogates about the option of comfort-oriented treatment in roughly half of clinician-family meetings. Physicians who more strongly believe that the appropriate goal of care is life prolongation are less likely to inform surrogates about the option of comfort care.

Light and the outcome of the critically ill: an observational cohort study.

INTRODUCTION: Light before and during acute illness has been associated with both benefit and harm in animal models and small human studies. Our objective was to determine the associations of light duration (photoperiod) and intensity (insolation) before and during critical illness with hospital mortality in ICU patients. Based on the 'winter immunoenhancement' theory, we tested the hypothesis that a shorter photoperiod before critical illness is associated with improved survival. METHODS: We analyzed data from 11,439 patients admitted to 8 ICUs at the University of Pittsburgh Medical Center between June 30, 1999 and July 31, 2004. Daily photoperiod and insolation prior to and after ICU admission were estimated for each patient by using data provided by the United States Naval Observatory and National Aeronautics and Space Administration and direct measurement of light gradient from outside to bedside for each ICU room. Our primary outcome was hospital mortality. The association between light and risk of death was analyzed using multivariate analyses, adjusting for potential confounders, including severity of illness, case mix, and ICU type. RESULTS: The cohort had an average APACHE III of 52.9 and a hospital mortality of 10.7%. In total, 128 ICU beds were analyzed; 108 (84%) had windows. Pre-illness photoperiod ranged from 259 to 421 hours in the prior month. A shorter photoperiod was associated with a reduced risk of death: for each 1-hour decrease, the adjusted OR was 0.997 (0.994 to 0.999, p = 0.03). In the ICU, there was near complete (99.6%) degradation of natural light from outside to the ICU bed. Thus, light exposure once in the ICU approached zero; the 24-hour insolation was 0.005 ± 0.003 kWh/m² with little diurnal variation. There was no association between ICU photoperiod or insolation and mortality. CONCLUSIONS: Consistent with the winter immunoenhancement theory, a shorter photoperiod in the month before critical illness is associated with a reduced risk of death. Once in the ICU, patients are exposed to near negligible natural light despite the presence of windows. Further studies are warranted to determine the underlying mechanisms and whether manipulating light exposure, before or during ICU admission, can enhance survival.

Identifying family members who may struggle in the role of surrogate decision maker.

UNLABELLED: Although acting as a surrogate decision maker can be highly distressing for some family members of intensive care unit patients, little is known about whether there are modifiable risk factors for the occurrence of such difficulties. OBJECTIVES: To identify: 1) factors associated with lower levels of confidence among family members to function as surrogates and 2) whether the quality of clinician-family communication is associated with the timing of decisions to forego life support. METHODS: We conducted a prospective study of 230 surrogate decision makers for incapacitated, mechanically ventilated patients at high risk of death in four intensive care units at University of California San Francisco Medical Center from 2006 to 2007. Surrogates completed a questionnaire addressing their perceived ability to act as a surrogate and the quality of their communication with physicians. We used clustered multivariate logistic regression to identify predictors of low levels of perceived ability to act as a surrogate and a Cox proportional hazard model to determine whether quality of communication was associated with the timing of decisions to withdraw life support. RESULTS: There was substantial variability in family members' confidence to act as surrogate decision makers, with 27% rating their perceived ability as 7 or lower on a 10-point scale. Independent predictors of lower role confidence were the lack of prior experience as a surrogate (odds ratio 2.2, 95% confidence interval [1.04-4.46], p=.04), no prior discussions with the patient about treatment preferences (odds ratio 3.7, 95% confidence interval [1.79-7.76], p<.001), and poor quality of communication with the ICU physician (odds ratio 1.2, 95% confidence interval [1.09-1.35] p<.001). Higher quality physician-family communication was associated with a significantly shorter duration of life-sustaining treatment among patients who died (ß=0.11, p=.001). CONCLUSIONS: Family members without prior experience as a surrogate and those who had not engaged in advanced discussions with the patient about treatment preferences were at higher risk to report less confidence in carrying out the surrogate role. Better-quality clinician-family communication was associated with both more confidence among family members to act as surrogates and a shorter duration of use of life support among patients who died.

Surrogate decision makers' interpretation of prognostic information: a mixed-methods study.

BACKGROUND: Little is known about why surrogate decision makers for patients with advanced illness often have overly optimistic expectations about prognosis. OBJECTIVE: To determine how surrogates interpret prognostic statements and to explore factors influencing surrogates' interpretations of grim prognostic information. DESIGN: Multicenter, mixed-methods study. SETTING: Intensive care units of 3 hospitals in San Francisco, California. PARTICIPANTS: 80 surrogates of critically ill patients. MEASUREMENTS: Participants recorded their interpretation of 16 prognostic statements using a standard probability scale. Generalized estimating equations were used to determine whether participants interpreted statements more optimistically as the expressed probability of survival decreased. Fifteen surrogates whose responses exhibited this trend participated in a semistructured interview. RESULTS: Participants' interpretations of prognostic statements expressing a low risk for death were relatively accurate, but interpretations of statements conveying a high risk for death were more optimistic than the actual meaning (P < 0.001; generalized estimating equation model). Interpretations of the statement "90% chance of surviving" did not differ from the actual meaning, but interpretations of "5% chance of surviving" were more optimistic and showed substantial variability (median, 90% [interquartile range, 90% to 95%; P = 0.11] vs. 15% [interquartile range, 5% to 40%; P < 0.001], respectively). Two main themes from the interviews explained this trend: surrogates' need to register optimism in the face of a poor prognosis and surrogates' belief that patient attributes unknown to the physician would lead to better-than-predicted outcomes. LIMITATION: Surrogates' interpretations were elicited in an experimental setting rather than during actual clinician-surrogate conversations. CONCLUSION: Inaccurate interpretations of physicians' prognostications by surrogates arise partly from optimistic biases rather than simply from misunderstandings. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute.

Anti-inflammatory medication adherence, healthcare utilization and expenditures among Medicaid and children's health insurance program enrollees with asthma.

BACKGROUND: Underuse of controller therapy among Medicaid-enrolled children is common and leads to more emergency department (ED) visits and hospitalizations. However, there is little evidence about the relationship between medication adherence, outcomes and costs once controller therapy is initiated. OBJECTIVE: This study examined the relationship between adherence to two commonly prescribed anti-inflammatory medications, inhaled corticosteroids (ICS) and leukotriene inhibitors (LI), and healthcare utilization and expenditures among children enrolled in Medicaid and the Children's Health Insurance Program in Florida and Texas in the US. METHODS: The sample for this retrospective observational study consisted of 18,456 children aged 2-18 years diagnosed with asthma, who had been continuously enrolled for 24 months during 2004-7 and were on monotherapy with ICS or LI. State administrative enrolment files were linked to medical claims data. Children were grouped into three adherence categories based on the percentage of days per year they had prescriptions filled (medication possession ratio). Bivariate and multivariable regression analyses that adjusted for the children's demographic and health characteristics were used to examine the relationship between adherence and ED visits, hospitalizations, and expenditures. RESULTS: Average adherence was 20% for ICS-treated children and 28% for LI-treated children. Children in the highest adherence category had lower odds of an ED visit than those in the lowest adherence category (p<0.001). We did not detect a statistically significant relationship between adherence and hospitalizations; however, only 3.7% of children had an asthma-related hospitalization. Overall asthma care expenditures increased with greater medication adherence. CONCLUSIONS: Although greater adherence was associated with lower rates of ED visits, higher medication expenditures outweighed the savings. The overall low adherence rates suggest that quality improvement initiatives should continue to target adherence regardless of the class of medication used. However, low baseline hospitalization rates may leave little opportunity to significantly decrease costs through better disease management, without also decreasing medication costs.

Do physicians disclose uncertainty when discussing prognosis in grave critical illness?

OBJECTIVE: Even when critically ill patients are almost certain to die from their illnesses, there is generally an element of prognostic uncertainty. Little is known about how physicians handle this uncertainty in conversations with surrogate decision makers. We sought to evaluate whether and how physicians discuss prognostic uncertainty with surrogate decision makers of patients who are highly likely, but not certain, to die. DESIGN: We audiotaped and transcribed discussions between clinicians and surrogate decision makers at two major California teaching hospitals from 2006 through 2008. Physicians completed a questionnaire addressing their prognostic estimates for patients' survival to hospital discharge. PARTICIPANTS: We included physicians and surrogates of 12 incapacitated, critically ill patients. MEASUREMENTS: We analyzed transcripts of discussions in which physicians' estimates of patients' chances of hospital survival were 1% to 5%; we coded whether physicians disclosed the prognostic uncertainty and, if so, how they conveyed that death was highly likely but not certain. RESULTS: Physicians' estimates of short-term survival were 1% to 5% for 12 of the 70 patients enrolled in the original study. In 8 of 12 cases, physicians conveyed prognostic uncertainty by using probabilistic language or by an explicit mention of uncertainty. In four cases, physicians made at least one statement that either implied or was ambiguous about whether death was certain. CONCLUSION: We observed variability in how physicians handle prognostic uncertainty in their discussions with surrogates of patients who are highly likely, but not certain, to die, including some circumstances in which physicians stated or implied that death was certain.

An empirical study of surrogates' preferred level of control over value-laden life support decisions in intensive care units.

RATIONALE: Despite ongoing ethical debate concerning who should control decisions to discontinue life support for incapacitated, critically ill patients, the perspectives of surrogate decision makers are poorly understood. OBJECTIVES: To determine (1) what degree of decisional authority surrogates prefer for value-sensitive life support decisions compared with more technical biomedical decisions, and (2) what predicts surrogates' preferences for more control over life support decisions. METHODS: This was a prospective study of 230 surrogate decision makers for incapacitated, mechanically ventilated patients at high risk of death. Surrogates reported their preferred degree of decisional authority using the Degner Control Preferences Scale for two types of decisions: a value-sensitive decision about whether to discontinue life support and a decision regarding which antibiotic to prescribe for an infection. MEASUREMENTS AND MAIN RESULTS: The majority of surrogates (55%, 127/230; 95% confidence interval, 49-62%) preferred to have final control over the value-sensitive life support decision; 40% (91/230) wished to share control equally with the physician; 5% (12/230) of surrogates wanted the physician to make the decision. Surrogates preferred significantly more control over the value-sensitive life support decision compared with the technical decision about choice of antibiotics (P < 0.0001). Factors independently associated with surrogates' preference for more control over the life support decision were: less trust in the intensive care unit physician, male sex, and non-Catholic religious affiliation. CONCLUSIONS: Surrogates vary in their desire for decisional authority for value-sensitive life support decisions, but prefer substantially more authority for this type of decision compared with technical, medical judgments. Low trust in physicians is associated with surrogates preferring more control of life support decisions.

Anti-inflammatory medication adherence and cost and utilization of asthma care in a commercially insured population.

OBJECTIVE: The authors hypothesized that adherence to anti-inflammatory treatment could reduce overall cost of asthma care, as higher spending on drugs would be offset by reductions in hospital and emergency care. METHODS: A retrospective observational study using 2 years of claims data for 41,234 commercially insured asthmatics on monotherapy with either leukotriene inhibitors (LI) or inhaled corticosteriods (ICS). Patients were grouped into adherence quartiles based on the percentage of days per year they had prescriptions filled (medication possession ratio). The relationship between adherence and four outcomes was examined: ( 1 ) emergency department (ED) visits, ( 2 ) hospitalizations, ( 3 ) nondrug net payments for asthma care, ( 4 ) total net payments for asthma care (including drug costs). Multivariate and logistic regression models adjusting for demographics, comorbidities, and measures of past asthma utilization were used. RESULTS: Adherence rates were low with a median medication possession ratio of 39% for LI and 15% for ICS. Both ED and hospital use was negatively associated with adherence to LI. Patients in the lowest quartile experienced 80 (95% confidence interval (CI) = 62-102) ED visits and 34 (95% CI = 22-52) admissions per 1000 patient-years compared to 36 (95% CI = 27-49) ED visits and 13 (95% CI = 8-22) admissions in the highest quartile. In contrast, ED visits and hospital admissions did not differ significantly between adherence groups for ICS. Total payments for asthma care increased significantly with higher adherence for both LI and ICS patients. Comparing the lowest and highest adherence quartile, payments per person per month increased significantly from $65.11 (95% CI = $57.02-$73.20) to $147.46 (95% CI = $139.48-$155.44) for patients on LI and from $38.71 (95% CI = $29.52-$47.90) to 93.13 (95% CI = $83.70-$102.56) for patients on ICS. The only subgroup, for which overall asthma payments did not increase with better adherence, were patients with past ED visit or hospital admission on LI. CONCLUSIONS: In this observational study, treatment with LI, but not with ICS, appears to improve disease control, as evidenced by the reduction in the incidence of ED visits and hospitalizations in patients on LI. Savings generated by this reduction in high-cost events don't offset the increased payments for drugs in more adherence patients, except for selected high-risk patients.