Ethnoracial Identity and Cognitive Impairment: A Community Study.

BACKGROUND: Identifying potentially modifiable risk factors associated with MCI in different ethnoracial groups could reduce MCI burden and health inequity in the population. METHODS: Among 2845 adults aged 65+ years, we investigated potential risk exposures including education, physical and mental health, lifestyle, and sensory function, and their cross-sectional associations with MCI. We compared proportions of exposures between Black and White participants and explored relationships among race, MCI, and exposures. Logistic regression modeled MCI as a function of each exposure in the overall sample adjusting for age, sex, educational level, and race, and investigating race*exposure interactions. RESULTS: Compared with White participants, Black participants had greater odds of MCI (OR 1.53; 95% CI, 1.13 to 2.06) and were more likely to report depressive symptoms, diabetes, and stroke, to have high blood pressure and BMI, and to be APOE - 4 carriers. Exposures associated with higher odds of MCI were diabetes, stroke, lifetime smoking, sleep disturbances, social isolation, loneliness, depression and anxiety symptoms, and vision and hearing loss. There were no significant interactions between race and any exposure. CONCLUSIONS: Black participants had 53% higher odds of MCI adjusting for age, sex, and education. The same exposures were associated with MCI in Black and White participants.

Impact of adherence to procalcitonin antibiotic prescribing guideline recommendations for low procalcitonin levels on antibiotic use.

BACKGROUND: The Procalcitonin Antibiotic Consensus Trial (ProACT) found provision of a procalcitonin antibiotic prescribing guideline to hospital-based clinicians did not reduce antibiotic use. Possible reasons include clinician reluctance to follow the guideline, with an observed 64.8% adherence rate. In this study we sought to determine the threshold adherence rate for reduction in antibiotic use, and to explore opportunities to increase adherence. METHODS: This study is a retrospective analysis of ProACT data. ProACT randomized 1656 patients presenting to 14 U.S. hospitals with suspected lower respiratory tract infection to usual care or provision of procalcitonin assay results and an antibiotic prescribing guideline to the treating clinicians. We simulated varying adherence to guideline recommendations for low procalcitonin levels and determined which threshold adherence rate could have resulted in rejection of the null hypothesis of no difference between groups at alpha = 0.05. We also performed sensitivity analyses within specific clinical settings and grouped patients initially prescribed antibiotics despite low procalcitonin into low, medium, and high risk of illness severity or bacterial infection. RESULTS: Our primary outcome was number of antibiotic-days by day 30 using an intention-to-treat approach and a null hypothesis of no difference in antibiotic use. We determined that an 84% adherence rate in the hospital setting (emergency department and inpatient) for low procalcitonin could have allowed rejection of the null hypothesis (3.7 vs 4.3 antibiotic-days, p = 0.048). The threshold adherence rate was 76% for continued guideline adherence after discharge. Even 100% adherence in the emergency department alone failed to reduce antibiotic-days. Of the 218 patients prescribed antibiotics in the emergency department despite low procalcitonin, 153 (70.2%) were categorized as low or medium risk. CONCLUSIONS: High adherence in the hospital setting to a procalcitonin antibiotic prescribing guideline is necessary to reduce antibiotic use in suspected lower respiratory tract infection. Continued guideline adherence after discharge and withholding of antibiotics in low and medium risk patients with low procalcitonin may offer impactful potential opportunities for antibiotic reduction. Trial registration Procalcitonin Antibiotic Consensus Trial (ProACT), ClinicalTrials.gov Identifier: NCT02130986. First posted May 6, 2014.

ProPACC: Protocol for a Trial of Integrated Specialty Palliative Care for Critically Ill Older Adults.

BACKGROUND: Each year, approximately one million older adults die in American intensive care units (ICUs) or survive with significant functional impairment. Inadequate symptom management, surrogates' psychological distress and inappropriate healthcare use are major concerns. Pioneering work by Dr. J. Randall Curtis paved the way for integrating palliative care (PC) specialists to address these needs, but convincing proof of efficacy has not yet been demonstrated. DESIGN: We will conduct a multicenter patient-randomized efficacy trial of integrated specialty PC (SPC) vs. usual care for 500 high-risk ICU patients over age 60 and their surrogate decision-makers from five hospitals in Pennsylvania. INTERVENTION: The intervention will follow recommended best practices for inpatient PC consultation. Patients will receive care from a multidisciplinary SPC team within 24 hours of enrollment that continues until hospital discharge or death. SPC clinicians will meet with patients, families, and the ICU team every weekday. SPC and ICU clinicians will jointly participate in proactive family meetings according to a predefined schedule. Patients in the control arm will receive routine ICU care. OUTCOMES: Our primary outcome is patient-centeredness of care, measured using the modified Patient Perceived Patient-Centeredness of Care scale. Secondary outcomes include surrogates' psychological symptom burden and health resource utilization. Other outcomes include patient survival, as well as interprofessional collaboration. We will also conduct prespecified subgroup analyses using variables such as PC needs, measured by the Needs of Social Nature, Existential Concerns, Symptoms, and Therapeutic Interaction scale. CONCLUSIONS: This trial will provide robust evidence about the impact of integrating SPC with critical care on patient, family, and health system outcomes.

Ambient fine particulate matter exposure and incident mild cognitive impairment and dementia.

BACKGROUND/OBJECTIVE: Poor air quality is implicated as a risk factor for cognitive impairment and dementia. Few studies have examined these associations longitudinally in well-characterized population-based cohorts with standardized annual assessment of both mild cognitive impairment (MCI) and dementia. We investigated the association between estimated ambient fine particulate matter (PM2.5 ) and risk of incident MCI and dementia in a post-industrial region known for historically poor air quality. SETTING/PARTICIPANTS: Adults aged 65+ years in a population-based cohort (n = 1572). MEASUREMENTS: Census tract level PM2.5 from Environmental Protection Agency (EPA) air quality monitors; Clinical Dementia Rating (CDR)®. DESIGN: We estimated ambient PM2.5 exposure (µg/m3 , single-year and 5-year averages) by geocoding participants' residential addresses to census tracts with daily EPA PM2.5 measurements from 2002 to 2014. Using Bayesian spatial regression modeling adjusted for age, sex, education, smoking history, and household income, we examined the association between estimated PM2.5 exposure and risk of incident MCI (CDR = 0.5) and incident dementia (CDR ≥ 1.0). RESULTS: Modeling estimated single-year exposure, each 1 µg/m3 higher ambient PM2.5 was associated with 67% higher adjusted risk of incident dementia (hazard ratio [HR] = 1.669, 95% credible interval [CI]: 1.298, 2.136) and 75% higher adjusted risk of incident MCI (HR = 1.746, 95% CI: 1.518, 2.032). Estimates were higher when modeling 5-year ambient PM2.5 exposure for incident dementia (HR = 2.082, 95% CI: 1.528, 3.015) and incident MCI (HR = 3.419, 95% CI: 2.806, 4.164). CONCLUSIONS: Higher estimated ambient PM2.5 was associated with higher risk of incident MCI and dementia, particularly when considering longer-term exposure, and independent of demographic characteristics and smoking history. Targeting poor air quality may be a reasonable population-wide intervention to reduce the risk of cognitive impairment in older adults, particularly in regions exceeding current recommendations for safe exposure to PM2.5 .

Insomnia symptoms and biomarkers of monocyte activation, systemic inflammation, and coagulation in HIV: Veterans Aging Cohort Study.

BACKGROUND: Insomnia may be a risk factor for cardiovascular disease in HIV (HIV-CVD); however, mechanisms have yet to be elucidated. METHODS: We examined cross-sectional associations of insomnia symptoms with biological mechanisms of HIV-CVD (immune activation, systemic inflammation, and coagulation) among 1,542 people with HIV from the Veterans Aging Cohort Study (VACS) Biomarker Cohort. Past-month insomnia symptoms were assessed by the item, "Difficulty falling or staying asleep?," with the following response options: "I do not have this symptom" or "I have this symptom and…" "it doesn't bother me," "it bothers me a little," "it bothers me," "it bothers me a lot." Circulating levels of the monocyte activation marker soluble CD14 (sCD14), inflammatory marker interleukin-6 (IL-6), and coagulation marker D-dimer were determined from blood specimens. Demographic- and fully-adjusted (CVD risk factors, potential confounders, HIV-related factors) regression models were constructed, with log-transformed biomarker variables as the outcomes. We present the exponentiated regression coefficient (exp[b]) and its 95% confidence interval (CI). RESULTS: We observed no significant associations between insomnia symptoms and sCD14 or IL-6. For D-dimer, veterans in the "Bothers a Lot" group had, on average, 17% higher D-dimer than veterans in the "No Difficulty Falling or Staying Asleep" group in the demographic-adjusted model (exp[b] = 1.17, 95%CI = 1.01-1.37, p = .04). This association was nonsignificant in the fully-adjusted model (exp[b] = 1.09, 95%CI = 0.94-1.26, p = .27). CONCLUSION: We observed little evidence of relationships between insomnia symptoms and markers of biological mechanisms of HIV-CVD. Other mechanisms may be responsible for the insomnia-CVD relationship in HIV; however, future studies with comprehensive assessments of insomnia symptoms are warranted.

Outcomes in refractory diffuse large B-cell lymphoma: results from a multicenter real-world study in China.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) patients refractory to rituximab-based immunochemotherapy have a dismal prognosis. However, the definition of refractory DLBCL remains inconsistent and no large cohort study data is available from Asian countries. To validate the definition and outcomes of refractory DLBCL in China, we conducted a multicenter, retrospective cohort study. METHODS: The REtrospective AnaLysis of Treatment REspoNse of refractory DLBCL (REAL-TREND) study was performed using real-world data from 8 centers in China. DLBCL patients with curative intent were included in the REAL-TREND dataset. Overall survival (OS) was estimated using the Kaplan-Meier method and compared by the log-rank test. Due to heterogeneity in response rates among different centers, the response rates of refractory patients were pooled using random-effect models. Multivariate survival analysis was performed using the Cox regression model. RESULTS: A total of 2778 DLBCL patients diagnosed between January, 2010 and December, 2015 were enrolled to this study. After validating previous definitions, the SCHOLAR-1 study was most suitable to define refractory DLBCL. The estimated 5-year cumulative incidence of refractory patients was 20% (95% confidence Interval [CI] = 18%-22%). After the determination of refractory disease, overall response rate and complete remission rate were 30% (95% CI = 22%-38%) and 9% (95% CI = 4%-15%), respectively. Patients with either no response to immunochemotherapy or relapse within 12 months after stem-cell transplantation had inferior survival with a median OS of 5.9 months (95% CI = 5.5-7.1 months) and 2-year OS rate of 16% (95% CI = 12%-20%). International prognostic index score 4-5 (hazard ratio [HR] = 2.22; 95% CI = 1.47-3.35), central nervous system relapse (HR = 1.43; 95% CI = 1.04-1.97), and best response status (HR = 2.68; 95% CI = 1.42-5.03 for partial remission. HR = 5.97, 95% CI = 3.21-11.11 for stable disease/progressive disease) were independent unfavorable prognostic factors. CONCLUSIONS: This is the first large-scale Asian cohort study focusing on outcomes of refractory DLBCL. The definition of the SCHOLAR-1 study identifies patients with homogenously inferior survival, thus is appropriate to select refractory DLBCL. Due to poor clinical outcomes in the rituximab era, patients with refractory DLBCL may be potential candidates for novel treatment modalities.

Exercise and the Risk of Mild Cognitive Impairment: Does the Effect Depend on Vascular Factors?

INTRODUCTION: Although exercise is associated with a lower risk for mild cognitive impairment (MCI), it is unclear whether its protective effect depends on the presence or absence of vascular factors. METHODS: In an exploratory study of data from a population-based cohort, 1254 participants aged 65+ years were followed for 10 years for incident MCI. The main effect of baseline total minutes of exercise per week (0 vs. 1 to 149 vs. 150+), and its interaction with several vascular factors, on risk for incident MCI was examined using Cox proportional hazards regression models, adjusting for demographics. RESULTS: Compared with no exercise, 1 to 149 minutes [hazard ratio (HR)=0.90; 95% confidence interval (95% CI), 0.69-1.16] and 150 or more minutes per week (HR=0.84; 95% CI, 0.66-1.07) of exercise lowered risk for incident MCI in a dose-dependent manner. The majority of interactions were not statistically significant, but risk reduction effect sizes of <0.75 suggested that exercise may have stronger effects among those without high cholesterol, never smoking, and not currently consuming alcohol; also, those with arrhythmia, coronary artery disease, and heart failure. Overall, there was a pattern of exercise being associated with lower MCI risk among those without vascular factors. CONCLUSIONS: Spending more time engaging in exercise each week may offer protection against MCI in late life, with some variation among those with different vascular conditions and risk factors. Our findings may help target subgroups for exercise recommendations and interventions, and also generate hypotheses to test regarding underlying mechanisms.

Predictors of Dementia in the Oldest Old: A Novel Machine Learning Approach.

BACKGROUND: Incidence of dementia increases exponentially with age; little is known about its risk factors in the ninth and 10th decades of life. We identified predictors of dementia with onset after age 85 years in a longitudinal population-based cohort. METHODS: On the basis of annual assessments, incident cases of dementia were defined as those newly receiving Clinical Dementia Rating (CDR) ≥1. We used a machine learning method, Markov modeling with hybrid density-based and partition-based clustering, to identify variables associated with subsequent incident dementia. RESULTS: Of 1439 participants, 641 reached age 85 years during 10 years of follow-up and 45 of these became incident dementia cases. Using hybrid density-based and partition-based, among those aged 85+ years, probability of incident dementia was associated with worse self-rated health, more prescription drugs, subjective memory complaints, heart disease, cardiac arrhythmia, thyroid disease, arthritis, reported hypertension, higher systolic and diastolic blood pressure, and hearing impairment. In the subgroup aged 85 to 89 years, risk of dementia was also associated with depression symptoms, not currently smoking, and lacking confidantes. CONCLUSIONS: An atheoretical machine learning method revealed several factors associated with increased probability of dementia after age 85 years in a population-based cohort. If independently validated in other cohorts, these findings could help identify the oldest-old at the highest risk of dementia.

Associations of Total, Cognitive/Affective, and Somatic Depressive Symptoms and Antidepressant Use With Cardiovascular Disease-Relevant Biomarkers in HIV: Veterans Aging Cohort Study.

OBJECTIVE: We sought to determine the associations of total, cognitive/affective, and somatic depressive symptoms and antidepressant use with biomarkers of processes implicated in cardiovascular disease in HIV (HIV-CVD). METHODS: We examined data from 1546 HIV-positive and 843 HIV-negative veterans. Depressive symptoms were assessed using the Patient Health Questionnaire-9, and past-year antidepressant use was determined from Veterans Affair pharmacy records. Monocyte (soluble CD14 [sCD14]), inflammatory (interleukin-6 [IL-6]), and coagulation (D-dimer) marker levels were determined from previously banked blood specimens. Linear regression models with multiple imputation were run to estimate the associations between depression-related factors and CVD-relevant biomarkers. RESULTS: Among HIV-positive participants, greater somatic depressive symptoms were associated with higher sCD14 (exp[b] = 1.02, 95% confidence interval [CI] = 1.00-1.03) and D-dimer (exp[b] = 1.06, 95% CI = 1.00-1.11) after adjustment for demographics and potential confounders. Further adjustment for antidepressant use and HIV factors slightly attenuated these relationships. Associations were also detected for antidepressant use, as selective serotonin reuptake inhibitor use was related to lower sCD14 (exp[b] = 0.95, 95% CI = 0.91-1.00) and IL-6 (exp[b] = 0.86, 95% CI = 0.76-0.96), and tricyclic antidepressant use was related to higher sCD14 (exp[b] = 1.07, 95% CI = 1.03-1.12) and IL-6 (exp[b] = 1.14, 95% CI = 1.02-1.28). Among HIV-negative participants, total, cognitive/affective, and somatic depressive symptoms were associated with higher IL-6, and tricyclic antidepressant use was related to higher sCD14. CONCLUSIONS: Our novel findings suggest that a) monocyte activation and altered coagulation may represent two pathways through which depression increases HIV-CVD risk and that b) tricyclic antidepressants may elevate and selective serotonin reuptake inhibitors may attenuate HIV-CVD risk by influencing monocyte and inflammatory activation.

The Development and Validation of Prostate Cancer-specific Physician-Hospital Networks.

OBJECTIVE: To develop prostate cancer-specific physician-hospital networks to define hospital-based units that more accurately group hospitals, providers, and the patients they serve. METHODS: Using Surveillance, Epidemiology, and End Results-Medicare, we identified men diagnosed with localized prostate cancer between 2007 and 2011. We created physician-hospital networks by assigning each patient to a physician and each physician to a hospital based on treatment patterns. We assessed content validity by examining characteristics of hospitals anchoring the physician-hospital networks and of the patients associated with these hospitals. RESULTS: We identified 42,963 patients associated with 344 physician-hospital networks. Networks anchored by a teaching hospital (compared to a nonteaching hospital) had higher median numbers of prostate cancer patients (117 [interquartile range {71-189} vs 82 {50-126}]) and treating physicians (7 [4-11] vs 4 [3-6]) (both P <0.001). On average, patients traveled farther to networks anchored by a teaching hospital (49 miles [standard deviation] [207] vs 41 [183]; P <.001). Hospitals known as high-volume centers for robotic prostatectomies, proton-beam therapy, and active surveillance had network rates for these procedures well above the mean. Hospitals known as safety net providers served higher proportions of minorities. CONCLUSION: We empirically developed prostate-cancer specific physician-hospital networks that exhibit content validity and are relevant from a clinical and policy perspective. They have the potential to become targets for policy interventions focused on improving the delivery of prostate cancer care.

The Influence of Stereotactic Body Radiation Therapy Adoption on Prostate Cancer Treatment Patterns.

PURPOSE: To our knowledge it is unknown whether stereotactic body radiation therapy of prostate cancer is a substitute for other radiation treatments or surgery, or for expanding the pool of patients who undergo treatment instead of active surveillance. MATERIALS AND METHODS: Using SEER (Surveillance, Epidemiology, and End Results)-Medicare we identified men diagnosed with prostate cancer between 2007 and 2011. We developed physician-hospital networks by identifying the treating physician of each patient based on the primary treatment received and subsequently assigning each physician to a hospital. We examined the relative distribution of prostate cancer treatments stratified by whether stereotactic body radiation therapy was performed in a network by fitting logistic regression models with robust SEs to account for patient clustering in networks. RESULTS: We identified 344 physician-hospital networks, including 30 (8.7%) and 314 (91.3%) in which stereotactic body radiation therapy was and was not performed, respectively. Networks in which that therapy was and was not done did not differ with time in the performance of robotic and radical prostatectomy, and active surveillance (all p >0.05). The relationship with intensity modulated radiation therapy did not show any consistent temporal pattern. In networks in which it was performed less intensity modulated radiation therapy was initially done but there were similar rates in later years. Brachytherapy trends differed among networks in which stereotactic body radiation therapy was vs was not performed with a lower brachytherapy rate in networks in which stereotactic body radiation therapy was done (p=0.03). CONCLUSIONS: Surgery and active surveillance rates did not differ in networks in which stereotactic body radiation therapy was vs was not performed but when that therapy was done there was a lower brachytherapy rate. Stereotactic body radiation therapy may represent more of an alternative to brachytherapy than to active surveillance.

Patterns of stereotactic body radiation therapy: The influence of lung cancer treatment on prostate cancer treatment.

INTRODUCTION: Technology availability and prior experience with novel cancer treatments may partially drive their use. We sought to examine this issue in the context of stereotactic body radiation therapy (SBRT) by studying how its use for an established indication (lung cancer) impacts its use for an emerging indication (prostate cancer). METHODS: Using SEER-Medicare from 2007 to 2011, we developed prostate cancer-specific physician-hospital networks. Our primary dependent variable was SBRT use for prostate cancer and our primary independent variable was SBRT use for lung cancer, both at the network level. To assess the influence of SBRT availability and experiential use, we generated predicted probabilities of SBRT use for prostate cancer stratified by a network's use of lung cancer SBRT, adjusting for network characteristics. To assess intensity of use, we examined the correlation between the proportion of prostate cancer patients and lung cancer patients receiving SBRT within a network. RESULTS: We identified 316 networks that served 41,034 prostate cancer and 83,433 lung cancer patients. A network was significantly more likely to use SBRT for prostate cancer if that network used SBRT for lung cancer (e.g., in 2011, odds ratio [OR] 12.7; 95% confidence interval [CI] 3.9-41.8). The Pearson's correlation between the proportion of prostate cancer patients and lung cancer patients receiving SBRT in a network was 0.34, which was not statistically significant (P = 0.12). CONCLUSIONS: SBRT availability and experiential use for lung cancer influences its use for prostate cancer, but intensity of use for one does not relate to intensity of use for the other.

Long-term Host Immune Response Trajectories Among Hospitalized Patients With Sepsis.

Importance: Long-term immune sequelae after sepsis are poorly understood. Objective: To assess whether abnormalities in the host immune response during hospitalization for sepsis persist after discharge. Design, Settings, and Participants: This prospective, multicenter cohort study enrolled and followed up for 1 year adults who survived a hospitalization for sepsis from January 10, 2012, to May 25, 2017, at 12 US hospitals. Exposures: Circulating levels of inflammation (interleukin 6 and high-sensitivity C-reactive protein [hs-CRP]), immunosuppression (soluble programmed death ligand 1 [sPD-L1]), hemostasis (plasminogen activator inhibitor 1 and D-dimer), endothelial dysfunction (E-selectin, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1), and oxidative stress biomarkers were measured at 5 time points during and after hospitalization for sepsis for 1 year. Individual biomarker trajectories and patterns of trajectories across biomarkers (phenotypes) were identified. Main Outcomes and Measures: Outcomes were adjudicated centrally and included all-cause and cause-specific readmissions and mortality. Results: A total of 483 patients (mean [SD] age, 60.5 [15.2] years; 265 [54.9%] male) who survived hospitalization for sepsis were included in the study. A total of 376 patients (77.8%) had at least 1 chronic disease, and their mean (SD) Sequential Organ Failure Assessment score was 4.2 (3.0). Readmissions were common (485 readmissions in 205 patients [42.5%]), and 43 patients (8.9%) died by 3 months, 56 patients (11.6%) died by 6 months, and 85 patients (17.6%) died by 12 months. Elevated hs-CRP levels were observed in 23 patients (25.8%) at 3 months, 26 patients (30.2%) at 6 months, and 23 patients (25.6%) at 12 months, and elevated sPD-L1 levels were observed in 45 patients (46.4%) at 3 months, 40 patients (44.9%) at 6 months, and 44 patients (49.4%) at 12 months. Two common phenotypes were identified based on hs-CRP and sPDL1 trajectories: high hs-CRP and sPDL1 levels (hyperinflammation and immunosuppression phenotype [326 of 477 (68.3%)]) and normal hs-CRP and sPDL1 levels (normal phenotype [143 of 477 (30.0%)]). These phenotypes had similar clinical characteristics and clinical course during hospitalization for sepsis. Compared with normal phenotype, those with the hyperinflammation and immunosuppression phenotype had higher 1-year mortality (odds ratio, 8.26; 95% CI, 3.45-21.69; P < .001), 6-month all-cause readmission or mortality (hazard ratio [HR], 1.53; 95% CI, 1.10-2.13; P = .01), and 6-month readmission or mortality attributable to cardiovascular disease (HR, 5.07; 95% CI, 1.18-21.84; P = .02) or cancer (HR, 5.15; 95% CI, 1.25-21.18; P = .02). These associations were adjusted for demographic characteristics, chronic diseases, illness severity, organ support, and infection site during sepsis hospitalization and were robust in sensitivity analyses. Conclusions and Relevance: In this study, persistent elevation of inflammation and immunosuppression biomarkers occurred in two-thirds of patients who survived a hospitalization for sepsis and was associated with worse long-term outcomes.

Optimism may moderate screening mammogram frequency in Medicare: A longitudinal study.

Higher trait optimism and/or lower cynical hostility are associated with healthier behaviors and lower risk of morbidity and mortality, yet their association with health care utilization has been understudied. Whether these psychological attitudes are associated with breast cancer screening behavior is unknown. To assess the association of optimism and cynical hostility with screening mammography in older women and whether sociodemographic factors acted as mediators of these relationships, we used Women's Health Initiative (WHI) observational cohort survey data linked to Medicare claims. The sample includes WHI participants without history of breast cancer who were enrolled in Medicare Parts A and B for ≥2 years from 2005-2010, and who completed WHI baseline attitudinal questionnaires (n = 48,291). We used survival modeling to examine whether screening frequency varied by psychological attitudes (measured at study baseline) after adjusting for sociodemographic characteristics, health conditions, and healthcare-related variables. Psychological attitudes included trait optimism (Life Orientation Test-Revised) and cynical hostility (Cook Medley subscale), which were self-reported at study baseline. Sociodemographic, health conditions, and healthcare variables were self-reported at baseline and updated through 2005 as available. Contrary to our hypotheses, repeated events survival models showed that women with the lowest optimism scores (i.e., more pessimistic tendencies) received 5% more frequent screenings after complete covariate adjustment (p < .01) compared to the most optimistic group, and showed no association between cynical hostility and frequency of screening mammograms. Sociodemographic factors did not appear to mediate the relationship between optimism and screenings. However, higher levels of education and higher levels of income were associated with more frequent screenings (both p < .01). We also found that results for optimism were primarily driven by women who were aged 75 or older after January 2009, when changes to clinical guidelines lead to uncertainty about risks and benefits of screening in this age group. The study demonstrated that lower optimism, higher education, and higher income were all associated with more frequent screening mammograms in this sample after repeated events survival modeling and covariate adjustment.

Accuracy of the Pediatric End-stage Liver Disease Score in Estimating Pretransplant Mortality Among Pediatric Liver Transplant Candidates.

Importance: Fair allocation of livers between pediatric and adult recipients is critically dependent on the accuracy of mortality estimates afforded by the Pediatric End-stage Liver Disease (PELD) and Model for End-stage Liver Disease, respectively. Widespread reliance on exceptions for pediatric recipients suggests that the 2 systems may not be comparable. Objective: To evaluate the accuracy of the PELD score in estimating 90-day pretransplant mortality among pediatric patients on the United Network for Organ Sharing (UNOS) waiting list. Design, Setting, and Participants: Patients who were listed from February 27, 2002, to March 31, 2014, for primary liver transplant were included in this retrospective analysis and were followed up for at least 2 years through June 17, 2016. The study analyzed 2 cohorts using the UNOS Standard Transplant Analysis and Research data files. The full cohort comprised 4298 patients (<18 years of age) who had chronic liver disease (excluding cancer). The reduced cohort (n = 2421) excluded patients receiving living donor transplantation or PELD exception points. Main Outcomes and Measures: Observed and expected 90-day pretransplant mortality rates evaluated at 10-point interval PELD levels. Results: Among the 4298 patients in the full cohort (mean [SD] age, 2.5 [4.2] years; 2251 [52.4%] female; 2201 [51.2%] white), PELD scores and mortality were concordant (C statistic, 0.8387 [95% CI, 0.8191-0.8584] for the full cohort and 0.8123 [95% CI, 0.7919-0.8327] for the reduced cohort). However, the estimated 90-day mortality using the PELD score underestimated the actual probability of death by as much as 17%. Conclusions and Relevance: With use of the PELD score, the ranking of risk among children was preserved, but direct comparisons between adult and pediatric candidates were not accurate. Children with chronic liver disease who are in need of transplant may be at a disadvantage compared with adults in a similar situation.

Net ultrafiltration intensity and mortality in critically ill patients with fluid overload.

BACKGROUND: Although net ultrafiltration (UFNET) is frequently used for treatment of fluid overload in critically ill patients with acute kidney injury, the optimal intensity of UFNET is unclear. Among critically ill patients with fluid overload receiving renal replacement therapy (RRT), we examined the association between UFNET intensity and risk-adjusted 1-year mortality. METHODS: We selected patients with fluid overload ≥ 5% of body weight prior to initiation of RRT from a large academic medical center ICU dataset. UFNET intensity was calculated as the net volume of fluid ultrafiltered per day from initiation of either continuous or intermittent RRT until the end of ICU stay adjusted for patient hospital admission body weight. We stratified UFNET as low (≤ 20 ml/kg/day), moderate (> 20 to ≤ 25 ml/kg/day) or high (> 25 ml/kg/day) intensity. We adjusted for age, sex, body mass index, race, surgery, baseline estimated glomerular filtration rate, oliguria, first RRT modality, pre-RRT fluid balance, duration of RRT, time to RRT initiation from ICU admission, APACHE III score, mechanical ventilation use, suspected sepsis, mean arterial pressure on day 1 of RRT, cumulative fluid balance during RRT and cumulative vasopressor dose during RRT. We fitted logistic regression for 1-year mortality, Gray's survival model and propensity matching to account for indication bias. RESULTS: Of 1075 patients, the distribution of high, moderate and low-intensity UFNET groups was 40.4%, 15.2% and 44.2% and 1-year mortality was 59.4% vs 60.2% vs 69.7%, respectively (p = 0.003). Using logistic regression, high-intensity compared with low-intensity UFNET was associated with lower mortality (adjusted odds ratio 0.61, 95% CI 0.41-0.93, p = 0.02). Using Gray's model, high UFNET was associated with decreased mortality up to 39 days after ICU admission (adjusted hazard ratio range 0.50-0.73). After combining low and moderate-intensity UFNET groups (n = 258) and propensity matching with the high-intensity group (n = 258), UFNET intensity > 25 ml/kg/day compared with ≤ 25 ml/kg/day was associated with lower mortality (57% vs 67.8%, p = 0.01). Findings were robust to several sensitivity analyses. CONCLUSIONS: Among critically ill patients with ≥ 5% fluid overload and receiving RRT, UFNET intensity > 25 ml/kg/day compared with ≤ 20 ml/kg/day was associated with lower 1-year risk-adjusted mortality. Whether tolerating intensive UFNET is just a marker for recovery or a mediator requires further research.

Children with Chronic Disease Bear the Highest Burden of Pediatric Sepsis.

OBJECTIVE: To describe the contemporary epidemiology of pediatric sepsis in children with chronic disease, and the contribution of chronic diseases to mortality. We examined the incidence and hospital mortality of pediatric sepsis in a nationally representative sample and described the contribution of chronic diseases to hospital mortality. STUDY DESIGN: We analyzed the 2013 Nationwide Readmissions Database using a retrospective cohort design. We included non-neonatal patients <19 years of age hospitalized with sepsis. We examined patient characteristics, the distribution of chronic disease, and the estimated national incidence, and described hospital mortality. We used mixed effects logistic regression to explore the association between chronic diseases and hospital mortality. RESULTS: A total of 16 387 admissions, representing 14 243 unique patients, were for sepsis. The national incidence was 0.72 cases per 1000 per year (54 060 cases annually). Most (68.6%) had a chronic disease. The in-hospital mortality was 3.7% overall-0.7% for previously healthy patients and 5.1% for patients with chronic disease. In multivariable analysis, oncologic, hematologic, metabolic, neurologic, cardiac and renal disease, and solid organ transplantation were associated with increased in-hospital mortality. CONCLUSIONS: More than 2 of 3 children admitted with sepsis have ≥1 chronic disease and these patients have a higher in-hospital mortality than previously healthy patients. The burden of sepsis in hospitalized children is greatest in pediatric patients with chronic disease.

Optimism predicts sustained vigorous physical activity in postmenopausal women.

Optimism and cynical hostility are associated with health behaviors and health outcomes, including morbidity and mortality. This analysis assesses their association with longitudinal vigorous physical activity (PA) in postmenopausal women of the Women's Health Initiative (WHI). Subjects include 73,485 women nationwide without history of cancer or cardiovascular disease (CVD), and no missing baseline optimism, cynical hostility, or PA data. The Life Orientation Test-Revised Scale measured optimism. A Cook Medley questionnaire subscale measured cynical hostility. Scale scores were divided into quartiles. Vigorous PA three times or more per week was assessed via self-report at study baseline (1994-1998) and through follow-up year 6. Descriptive analysis mapped lifetime trajectories of vigorous PA (recalled at ages 18, 25, 50; prospectively assessed at baseline, and 3 and 6 years later). Hierarchical generalized linear mixed models examined the prospective association between optimism, cynical hostility, and vigorous PA over 6 years. Models adjusted for baseline sociodemographic variables, psychosocial characteristics, and health conditions and behaviors. Vigorous PA rates were highest for most optimistic women, but fell for all women by approximately 60% between age 50 and study baseline. In adjusted models from baseline through year 6, most vs. least optimistic women were 15% more likely to exercise vigorously (p < 0.001). Cynical hostility was not associated with lower odds of longitudinal vigorous PA after adjustment. Results did not differ by race/ethnicity or socioeconomic status. Higher optimism is associated with maintaining vigorous PA over time in post-menopausal women, and may protect women's health over the lifespan.

Precision medicine for all? Challenges and opportunities for a precision medicine approach to critical illness.

All of medicine aspires to be precise, where a greater understanding of individual data will lead to personalized treatment and improved outcomes. Prompted by specific examples in oncology, the field of critical care may be tempted to envision that complex, acute syndromes could bend to a similar reductionist philosophy-where single mutations could identify and target our critically ill patients for treatment. However, precision medicine faces many challenges in critical care. These include confusion about terminology, uncertainty about how to divide patients into discrete groups, the challenges of multi-morbidity, scale, and the need for timely interventions. This review addresses these challenges and provides a translational roadmap spanning preclinical work to identify putative treatment targets, novel designs for clinical trials, and the integration of the electronic health record to implement precision critical care for all.