Moraska, Amanda R.

Background: The increasing prevalence of heart failure (HF) and high associated costs has spurred investigation of factors related to adverse outcomes in these patients. Reports to date present discrepant evidence regarding the link between depression and HF outcomes, and only scarce data related to healthcare utilization in the form of emergency department (ED) visits are available. Purpose: To evaluate the relationship of depression with healthcare utilization and death among HF patients in the community. Methods: Residents of Olmsted, Dodge, and Fillmore, MN counties with HF were prospectively recruited between October 2007 and December 2010, and completed a 9-item Patient Health Questionnaire (PHQ-9) for depression categorized as: none-minimal (PHQ-9 score 0-4), mild (5-9), or moderate-severe (≥10). Anderson-Gill models were used to determine if depression predicted hospitalizations and ED visits while proportional hazards regression estimated hazard ratios for death. Results: Among 411 HF patients (mean age 73±13, 58% male), 15% had moderate-severe depression, 27% mild, and 58% none-minimal. Over a mean follow-up of 1.5 years, 613 hospitalizations, 786 ED visits, and 75 deaths occurred. The risk of all adverse outcomes increased stepwise with increasing severity of depression (Table). After adjustment for key clinical characteristics, moderate-severe depression was associated with nearly a 2-fold increased risk of hospitalization and ED visits, and almost a 4-fold increased risk of death. These results are independent of coexisting comorbidities. Conclusions: Depression is frequent among HF patients in the community and independently predicts a significant increase in the use of healthcare resources and mortality. Greater attention to the recognition and management of depression in HF may improve clinical outcomes and decrease healthcare utilization and expenditures in these patients. Hazard Ratios (95%CI) for Hospitalizations and All-Cause Mortality by Severity of Depression None-Minimal Mild Moderate-Severe P for trend Hospitalizations Crude 1.00 (ref) 1.23 (0.91-1.66) 2.01 (1.39-2.89) <0.001 Fully-Adjusted * 1.00 (ref) 1.15 (0.86-1.54) 1.93 (1.37-2.71) 0.001 Emergency Department Visits Crude 1.00 (ref) 1.42 (1.03-1.96) 1.99 (1.42-2.79) <0.001 Fully-Adjusted * 1.00 (ref) 1.39 (1.00-1.93) 1.98 (1.40-2.79) <0.001 All-Cause Mortality Crude 1.00 (ref) 1.53 (0.87-2.68) 3.33 (1.95-5.70) <0.001 Fully-Adjusted * 1.00 (ref) 1.55 (0.88-2.74) 3.84 (2.21-6.68) <0.001 * Adjusted for age, sex, and Charlson comorbidity index

Objective: To determine among community heart failure (HF) patients whether frailty is associated with an increased risk of hospitalization, emergency department (ED) visits and death, independently of comorbidities. Background: Frailty is associated with adverse outcomes in some populations; however the prognostic value of frailty among HF patients is not fully documented, particularly for healthcare utilization. Methods: Olmsted, Dodge and Fillmore County residents with HF between 10/2007 and 12/2010 were prospectively recruited to undergo frailty assessment. Frailty was defined as 3 or more of the following: unintentional weight loss >10 lbs. in 1 year, physical exhaustion, weak grip strength, and slowness and low activity measured by the SF-12 physical component score. Intermediate frailty was defined as having 1-2 components. To account for repeated events, Anderson-Gill modeling was used to determine if frailty predicted hospitalization or ED visits. Cox proportional hazards regression examined associations between frailty and death. Results: Among 409 patients (mean age 73±13, 58% male), 19% were frail and 55% had intermediate frailty. Within one year, 449 hospitalizations, 523 ED visits and 34 deaths occurred. There was a positive graded association between frailty and hospitalization and ED visits (Table). After adjustment for age, sex, ejection fraction and comorbidity, frailty was associated with an 80% increased risk of hospitalization and a 60% increased risk of ED visits. Frailty was also associated with more than a 2-fold increased risk of death after adjustment. Conclusion: In the community, frailty is prevalent and is a strong and independent predictor of hospitalizations, ED visits and death among HF patients. As it is independent from coexisting comorbidities, frailty defines new avenues for intervention and should be formally assessed clinically. Hazard Ratios (95% CI) for Hospitalizations, Emergency Department Visits and Death by Frailty Status Not Frail Intermediate Frail Frail P for trend Hospitalization Crude 1.00 1.46 (1.05-2.02) 2.15 (1.45-3.19) <0.001 Fully-adjusted 1.00 1.29 (0.94-1.77) 1.82 (1.22-2.73) 0.005 Emergency Department Visits Crude 1.00 1.59 (1.14-2.21) 1.88 (1.22-2.90) 0.002 Fully-adjusted 1.00 1.46 (1.05-2.05) 1.58 (1.01-2.48) 0.034 Death Crude 1.00 1.40 (0.73-2.69) 3.98 (2.01-7.90) <0.001 Fully-adjusted 1.00 0.87 (0.44-1.73) 2.42 (1.19-4.95) 0.003

Background— The increasing prevalence of heart failure (HF) and high associated costs have spurred investigation of factors leading to adverse outcomes in patients with HF. Studies to date report inconsistent evidence on the link between depression and outcomes with only limited data on emergency department and outpatient visits. Methods and Results— Olmsted, Dodge, and Fillmore county, Minnesota residents with HF were prospectively recruited between October 2007 and December 2010 and completed a 1-time 9-item Patient Health Questionnaire for depression categorized as: none to minimal (Patient Health Questionnaire score, 0–4), mild (5–9), or moderate to severe (≥10). Andersen-Gill models were used to determine whether depression predicted hospitalizations and emergency department visits, whereas negative binomial regression models explored the association of depression with outpatient visits. Cox proportional hazards regression characterized the relationship between depression and all-cause mortality. Among 402 patients with HF (mean age, 73±13 years; 58% men), 15% had moderate to severe depression, 26% mild, and 59% none to minimal depression. During a mean follow-up of 1.6 years, 781 hospitalizations, 1000 emergency department visits, 15 515 outpatient visits, and 74 deaths occurred. After adjustment, moderate to severe depression was associated with nearly a 2-fold increased risk of hospitalization (hazard ratio, 1.79; 95% confidence interval, 1.30–2.47) and emergency department visits (hazard ratio, 1.83; 95% confidence interval, 1.34–2.50), a modest increase in outpatient visits (rate ratio, 1.20; 95% confidence interval, 1.00–1.45), and a 4-fold increase in all-cause mortality (hazard ratio, 4.06; 95% confidence interval, 2.35–7.01). Conclusions— In this prospective cohort study, depression independently predicted an increase in the use of healthcare resources and mortality. Greater recognition and management of depression in HF may optimize clinical outcomes and resource utilization.

PurposeFatigue is one of the most common symptoms experienced by patients with cancer. This trial was developed to evaluate the efficacy of long-acting methylphenidate for improving cancer-related fatigue and to assess its toxicities.Patients and MethodsAdults with cancer were randomly assigned in a double-blinded manner to receive methylphenidate (target dose, 54 mg/d) or placebo for 4 weeks. The Brief Fatigue Inventory was the primary outcome measure, while secondary outcome measures included a Symptom Experience Diary (SED), the Short Form-36 (SF-36) Vitality Subscale, a linear analog self-assessment, the Pittsburgh Sleep Quality Index, and the Subject Global Impression of Change.ResultsIn total, 148 patients were enrolled. Using an area under the serum concentration-time curve analysis, there was no evidence that methylphenidate, as compared with placebo, improved the primary end point of cancer-related fatigue in this patient population (P = .35). Comparisons of secondary end points, including clinically significant changes in quality-of-life variables and cancer-related fatigue change from baseline, were similarly negative. However, a subset analysis suggested that patients with more severe fatigue and/or with more advanced disease did have some fatigue improvement with methylphenidate (eg, in patients with stage III or IV disease, the mean improvement in usual fatigue was 19.7 with methylphenidate v 2.1 with placebo; P = .02). There was a significant difference in self-reported toxicities (SED), with increased levels of nervousness and appetite loss in the methylphenidate arm.ConclusionThis clinical trial was unable to support the primary prestudy hypothesis that the chosen long-acting methylphenidate product would decrease cancer-related fatigue.