Donald R. Sullivan

An Opportunistic Infection Associated With Ruxolitinib, a Novel Janus Kinase 1,2 Inhibitor

We report a case of Cryptococcus neoformans pneumonia in a patient taking ruxolitinib, a janus kinase 1,2 inhibitor approved for the treatment of myelofibrosis. We hypothesize that ruxolitinib contributed to this infection through its effects on cell-mediated immunity. Clinicians should be aware of the potential for intracellular or opportunistic infections associated with this novel drug class.

Patient-Centered Outcomes among Lung Cancer Screening Recipients with Computed Tomography: A Systematic Review

Introduction: Lung cancer screening using low-dose computed tomography (LDCT) is now widely recommended for adults who are current or former heavy smokers. It is important to evaluate the impact of screening on patient-centered outcomes. Among current and former smokers eligible for lung cancer screening, we sought to determine the consequences of screening with LDCT, and subsequent results, on patient-centered outcomes such as quality of life, distress, and anxiety. Methods: We searched the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews (through the fourth Quarter 2012), MEDLINE (2000 to May 31, 2013), reference lists of articles, and Scopus for relevant English-language studies and systematic reviews. To evaluate the effect of LDCT screening on patient-centered outcomes, we included only randomized controlled trials (RCTs) involving asymptomatic adults. To evaluate the association of particular results and/or recommendations from a screening LDCT with patient-centered outcomes, we included results from RCTs as well as from cohort studies. Results: A total of 8215 abstracts were reviewed. Five publications from two European RCTs and one publication from a cohort study conducted in the United States met inclusion criteria. The process of LDCT lung cancer screening was associated with short-term psychologic discomfort in many people but did not affect distress, worry, or health-related quality of life. False-positive results were associated with short-term increases in distress that returned to levels that were similar to those among people with negative results. Negative results were associated with short-term decreases in distress. Conclusions: As lung cancer screening is implemented in the general population, it will be important to evaluate its association with patient-centered outcomes. People considering lung cancer screening should be aware of the possibility of distress caused by false-positive results. Clinicians may want to consider tailoring communication strategies that can decrease the distress associated with these results.

Recognizing, Naming, and Measuring a Family Intensive Care Unit Syndrome

Most major decisions in the intensive care unit (ICU) regarding goals of care are shared by clinicians and someone other than the patient. Multicenter clinical trials focusing on improved communication between clinicians and these surrogate decision makers have not reported consistently improved outcomes. We suggest that acquired maladaptive reasoning may contribute importantly to failure of the intervention strategies tested to date. Surrogate decision makers often suffer significant psychological morbidity in the form of stress, anxiety, depression, and post-traumatic stress disorder. Family members in the ICU also suffer cognitive blunting and sleep deprivation. Their decision-making abilities are eroded by anticipatory grief and cognitive biases, while personal and family conflicts further impact their decision making. We propose recognizing a family ICU syndrome to describe the morbidity and associated decision-making impairment experienced by many family members of patients with acute critical illness (in the ICU) and chronic critical illness (in the long-term, acute care hospital). Research rigorously using models of compromised decision making may help elucidate both mechanisms of impairment and targets for intervention. Better quantifying compromised decision making and its relationship to poor outcomes will allow us to formulate and advance useful techniques. The use of decision aids and improving ICU design may provide benefit now and in the near future. In measuring interventions targeting cognitive barriers, clinically significant outcomes, such as time to decision, should be considered. Statistical approaches, such as survival models and rank statistic testing, will increase our power to detect differences in our interventions.

Learned helplessness among families and surrogate decision-makers of patients admitted to medical, surgical, and trauma ICUs

BACKGROUND We sought to determine the prevalence of and clinical variables associated with learned helplessness, a psychologic state characterized by reduced motivation, difficulty in determining causality, and depression, in family members of patients admitted to ICUs. METHODS We conducted an observational survey study of a prospectively defined cohort of family members, spouses, and partners of patients admitted to surgical, medical, and trauma ICUs at a large academic medical center. Two validated instruments, the Learned Helplessness Scale and the Perceived Stress Scale, were used, and self-report of patient clinical characteristics and subject demographics were collected. RESULTS Four hundred ninety-nine family members were assessed. Of these, 238 of 460 (51.7%) had responses consistent with a significant degree of learned helplessness. Among surrogate decision-makers, this proportion was 50% (92 of 184). Characteristics associated with significant learned helplessness included grade or high school education (OR, 3.27; 95% CI, 1.29-8.27; P = .01) and Perceived Stress Scale score > 18 (OR, 4.15; 95% CI, 2.65-6.50; P < .001). The presence of a patient advance directive or do not resuscitate (DNR) order was associated with reduced odds of significant learned helplessness (OR, 0.56; 95% CI, 0.32-0.98; P = .05). CONCLUSIONS The majority of family members of patients in the ICU experience significant learned helplessness. Risk factors for learned helplessness include lower educational levels, absence of an advance directive or DNR order, and higher stress levels among family members. Significant learned helplessness in family members may have negative implications in the collaborative decision-making process.

'I still don't know diddly': a longitudinal qualitative study of patients' knowledge and distress while undergoing evaluation of incidental pulmonary nodules.

Background:Hundreds of thousands of incidental pulmonary nodules are detected annually in the United States, and this number will increase with the implementation of lung cancer screening. The lengthy period for active pulmonary nodule surveillance, often several years, is unique among cancer regimens. The psychosocial impact of longitudinal incidental nodule follow-up, however, has not been described.Aims:We sought to evaluate the psychosocial impact of longitudinal follow-up of incidental nodule detection on patients.Methods:Veterans who participated in our previous study had yearly follow-up qualitative interviews coinciding with repeat chest imaging. We used conventional content analysis to explore their knowledge of nodules and the follow-up plan, and their distress.Results:Seventeen and six veterans completed the year one and year two interviews, respectively. Over time, most patients continued to have inadequate knowledge of pulmonary nodules and the nodule follow-up plan. They desired and appreciated more information directly from their primary care provider, particularly about their lung cancer risk. Distress diminished over time for most patients, but it increased around the time of follow-up imaging for some, and a small number reported severe distress.Conclusions:In settings in which pulmonary nodules are commonly detected, including lung cancer screening programmes, resources to optimise patient-centred communication strategies that improve patients’ knowledge and reduce distress should be developed.

Treatment Receipt and Outcomes among Lung Cancer Patients with Depression

AIMS Among lung cancer patients, depression has been associated with increased mortality, although the mechanisms are unknown. We evaluated the association of depression with mortality and receipt of cancer therapies among depressed veterans with lung cancer. MATERIALS AND METHODS A retrospective, cohort study of lung cancer patients in the Veterans Affairs-Northwest Health Network from 1995 to 2010. Depression was defined by ICD-9 coding within 24 months before lung cancer diagnosis. Multivariable Cox proportional analysis and logistic regression were used. RESULTS In total, 3869 lung cancer patients were evaluated; 14% had a diagnosis of depression. A diagnosis of depression was associated with increased mortality among all stage lung cancer patients (hazard ratio = 1.14, 95% confidence interval: 1.03-1.27, P = 0.01). Among early-stage (I and II) non-small cell lung cancer (NSCLC) patients, the hazard ratio was 1.37 (95% confidence interval: 1.12-1.68, P = 0.003). There was no association of depression diagnosis with surgery (odds ratio = 0.83, 95% confidence interval: 0.56-1.22, P = 0.34) among early-stage NSCLC patients. A depression diagnosis was not associated with mortality (hazard ratio = 1.02, 95% confidence interval: 0.89-1.16, P = 0.78) or chemotherapy (odds ratio = 1.07, 95% confidence interval: 0.83-1.39, P = 0.59) or radiation (odds ratio = 1.04, 95% confidence interval: 0.81-1.34, P = 0.75) receipt among advanced-stage (III and IV) NSCLC patients. Increased utilisation of health services for depression was associated with increased mortality among depressed patients. CONCLUSIONS Depression is associated with increased mortality in lung cancer patients and this association is higher among those with increased measures of depression care utilisation. Differences in lung cancer treatment receipt are probably not responsible for the observed mortality differences between depressed and non-depressed patients. Clinicians should recognise the significant effect of depression on lung cancer survival.

Depression symptom trends and health domains among lung cancer patients in the CanCORS study

OBJECTIVES Among lung cancer patients depression symptoms are common and impact outcomes. The aims of this study were to determine risk factors that contribute to persistent or new onset depression symptoms during lung cancer treatment, and examine interactions between depression symptoms and health domains that influence mortality. MATERIALS AND METHODS Prospective observational study in five healthcare systems and 15 Veterans Affairs medical centers. Patients in the Cancer Care Outcomes Research and Surveillance (CanCORS) Consortium with lung cancer were eligible. The 8-item Center for Epidemiologic Studies Depression (CES-D) scale was administered at baseline and follow-up. Scores ≥4 indicated elevated depressive symptoms. Health domains were measured using validated instruments. We applied logistic regression and Cox proportional hazards modeling to explore the association between depression symptoms, health domains, and mortality. RESULTS Of 1790 participants, 38% had depression symptoms at baseline and among those still alive, 31% at follow-up. Risk factors for depression symptoms at follow-up included younger age (OR=2.81), female sex (OR=1.59), low income (OR=1.45), not being married (OR=1.74) and current smoking status (OR=1.80); high school education was associated with reduced odds of depression symptoms at follow-up, compared with lesser educational attainment (OR=0.74) (all p values <0.05). Patients with depression symptoms had worse health-related quality of life, vitality, cancer-specific symptoms, and social support than patients without depression symptoms (all p<0.001). The association between depression symptoms and increased mortality is greater among patients with more lung cancer symptoms (p=0.008) or less social support (p=0.04). CONCLUSIONS Patient risk factors for depression symptoms at follow-up were identified and these subgroups should be targeted for enhanced surveillance. Patients with depression symptoms suffer across all health domains; however, only more lung cancer symptoms or less social support are associated with worse mortality among these patients. These potentially modifiable health domains suggest targets for possible intervention in future studies.

Randomized, double-blind, placebo-controlled study of methylphenidate for the treatment of depression in SSRI-treated cancer patients receiving palliative care.

To determine the effectiveness of methylphenidate for depression treatment in patients with advanced cancer.

Association of patient characteristics with chemotherapy receipt among depressed and non‐depressed patients with non‐small cell lung cancer

Lung cancer patients suffer considerable morbidity and mortality along with substantial psychological distress [1]. Lung cancer patients with diagnoses of depression experience greater mortality than their non-depressed peers [2], but the causes of this increased mortality are not well understood. For patients with advanced stage non-small cell lung cancer (NSCLC), platinum-based chemotherapy prolongs survival, improves symptom control, and yields superior quality of life compared to best supportive care [3]. The utilization of chemotherapy and patient factors impacting its receipt have not been characterized in depressed patients. The National Comprehensive Cancer Network (NCCN) has established Clinical Practice Guidelines for the treatment of lung cancer [3]. Previous studies have revealed that patients’ age and comorbidities affect receipt of recommended therapies [4], which is in accordance with guidelines. Other patient characteristics, such as black race, reduce the likelihood of chemotherapy receipt and represent an important treatment disparity [5–7]. It is unclear to what extent patients’ psychological comorbidities, such as a diagnosis of depression, influence utilization of guideline recommended chemotherapy. In addition, interactions between patient characteristics, such as race and depression, and their impact on chemotherapy receipt have not been explored. We examined chemotherapy receipt among lung cancer patients with a diagnosis of depression, including an analysis of patient risk factors associated with reduced receipt, in order to determine if differences in receipt may contribute to increased mortality.

Military Factors Associated with Smoking in Veterans

Introduction Given the high prevalence of smoking among Veterans and the economic, social, and clinical implications, it is important to understand the factors that contribute to smoking in order to focus efforts to mitigate these factors and improve smoking cessation efforts among Veterans. The availability of research on smoking in Veterans compared with civilians is limited given the military-specific differences in their life course. We aimed to identify military-specific factors combined with sociodemographic factors for ever smoking and current smoking among Veterans to inform future interventions. Materials and Methods We used data from the 2010 National Survey of Veterans, the most current, to analyze the association of sociodemographic and military-specific factors with ever versus never smoking, and current versus past smoking using multiple variable logistic regression models (IRB#4125). Results Among 8,618 respondents, the proportions of current, past, and never smokers were 17%, 48%, and 34%, respectively. Sociodemographic factors associated with ever smoking were female gender, educational attainment of less than a bachelors degree, and being divorced/separated/widowed. Military-specific factors associated with ever smoking were exposure to dead/dying/wounded soldiers during service, and past, current, and unsure enrollment in Veterans Affairs healthcare. Never smoking was associated with Hispanic ethnicity, income over