Perspectives of emergency department physicians and nurses on reasons for preventable emergency department visits by patients with cancer.

BACKGROUND: Patients with cancer frequently visit the emergency department (ED) for medical care, yet approximately half of ED visits for patients with cancer are thought to be preventable. Preventable ED visits are associated with increased healthcare costs and poor patient experiences and outcomes. The voices of ED providers who work with patients with cancer in their everyday practices have not been solicited as it pertains to preventable visits. OBJECTIVES: The purpose of this study is to describe the perspectives of ED physicians and nurses on reasons for preventable ED visits by patients with cancer. METHODS: A qualitative descriptive design guided the study. We conducted 23 semi-structured interviews with ED physicians and nurses to query them about their perspectives on the reasons for preventable ED visits by patients with cancer. Content analysis was conducted to list and describe the reasons they discussed. RESULTS: Participants identified five "medical" and five "non-medical" causes of preventable ED visits. Medical reasons included uncontrolled cancer pain, gastrointestinal symptoms, anemia, fever, and on-going undiagnosed signs and symptoms. Non-medical reasons include patient hesitancy to contact primary care providers, lack of availability or responsiveness of primary providers, lack of access, lack of care coordination, and fears about diagnosis and treatment. CONCLUSION: The voices of ED providers should be included in discussions about the problem of preventable ED visits by patients with cancer. The reasons supplied by the participants suggest that solutions to the problem will need to occur at the patient, provider, system, and societal levels.

The impact of fear of cancer recurrence on healthcare utilization among long-term breast cancer survivors recruited through ECOG-ACRIN trials.

OBJECTIVE: To examine the relationship between fear of cancer recurrence (FCR) and healthcare utilization among long-term breast cancer survivors (BCS). METHODS: In a cross-sectional survey study, 505 younger survivors (YS: ≤45 years) and 622 older survivors (OS: 55-70 years) 3-8 years from diagnosis completed a questionnaire assessing demographics, medical history, FCR, and healthcare utilization. Healthcare utilization consisted of breast cancer (BC) and non-BC-related routine and nonroutine utilization. RESULTS: YS had significantly higher FCR than OS (p < 0.01). Independent of age, FCR was significantly associated with all three types of BC-related utilization (p < 0.05). In the multivariate models, we found a significant, positive interaction effect between FCR and increased comorbidities on nonroutine BC appointments (p = 0.01) and BC-related emergency room visits (p = 0.03). Additionally, comorbidities were associated with non-BC-related utilization (p < 0.01), and nonwhites were more likely to utilize nonroutine resources, both BC and non-BC-related (p < 0.01). CONCLUSIONS: Increased FCR has been associated with hypervigilance among survivors and may lead to increased healthcare utilization. YS are at higher risk for increased FCR and psychosocial concerns, which may lead to overutilization. Providers should be aware that higher FCR may be related to increased use of healthcare resources and that these patients might be better served with supportive resources to increase quality of life and decrease inappropriate utilization. While this study provides increased evidence of the relationship between FCR and healthcare utilization, interventions are needed for survivors at risk to address unmet needs, especially as life expectancy increases among BCS.

Effects of depressive symptomatology on cancer-related symptoms during oral oncolytic treatment.

OBJECTIVE: This manuscript assesses association between depressive symptoms and symptoms from cancer and its treatment during the first 12 weeks of a new oral oncolytic treatment. METHODS: This secondary analysis used data from a recently completed trial of an intervention to improve adherence to oral oncolytic treatment and manage symptoms. Following the initiation of the new oral oncolytic medication, 272 patients were interviewed at intake and weeks 4, 8, and 12 to assess depressive symptoms, and symptoms from cancer and its treatment. Depressive symptoms were measured using the Center for Epidemiologic Studies-Depression (CES-D20). The summed index of 18 cancer-related and treatment-related symptoms as well as the number of symptoms above threshold at intake, weeks 4, 8, and 12 were related to intake and time-varying CES-D20 using linear mixed effects models. RESULTS: Depressive symptomatology was a significant predictor of cancer-related and treatment-related symptoms at all-time points, but the strength of this relationship was greatest at the time of oral oncolytic agent initiation and at week 4. The strength of this relationship was the same for both summed symptom severity index and the number of symptoms above threshold, and using either intake or time-varying CES-D20. CONCLUSION: Introducing strategies to treat and manage symptoms of depression along with other symptoms might have added benefits among patients who start a new oral oncolytic treatment and report modest to higher levels of depressive symptoms. Assessments for the impact of strategies to lower depressive symptoms can be taken within the first 4 weeks.

Do treatment patterns alter beliefs cancer patients hold regarding oral oncolytic agents?

OBJECTIVE: Cancer patients, particularly those prescribed with oral oncolytic medications, face treatment side effects and temporary and permanent stoppages of treatment. This research examines how events during treatment affect patients' beliefs regarding oral oncolytic medications. METHODS: A total of 272 cancer patients initiating 1 of 28 oral oncolytic agents were followed for 12 weeks. Assessments of Beliefs About Medications Questionnaire, symptoms, physical function, and depression measures were performed during telephone interviews at intake (medication start) and 4, 8, and 12 weeks. Electronic medical record audits identified dates of temporary and permanent medication stoppages. Linear mixed-effects models were used for longitudinal analyses of the Beliefs About Medications Questionnaire scores in relation to patient characteristics, symptom severity, and medication stoppages. RESULTS: Over the initial 12 weeks, beliefs about the necessity of oral medications have increased, concerns have decreased, and interference of medications with daily lives has increased. Permanent stoppage of a medication predicted significant declines in beliefs about its necessity over time. Male patients, those less educated, those reporting higher symptom severity, and those experiencing temporary stoppages had greater concerns. Interference of medications with daily life was higher for males, increased with higher symptom severity, and differed by drug category. CONCLUSIONS: Patients' beliefs in the necessity of their oral medication were affected only by a permanent drug stoppage. Symptom severity, education, and patient sex affected patients' beliefs about their concerns with their medications and the interference medications posed for their daily lives. Interventions may need to target the distinct dimensions of beliefs during treatment with oral oncolytic agents.

Challenges to the design and testing supportive interventions for cancer patients treated with oral oncolytic agents.

Conducting research into supportive care for patients as they initiate treatment with oral oncolytic agents poses numerous new challenges. Some of these medications have very complex dosing schedules and produce symptoms that patients need to manage at home with less reliance on oncology clinicians. We describe lessons learned from a multi-site trial designed to improve adherence to these medications and self-management of symptoms among patients newly prescribed oral oncolytic agents. Identifying these challenges can assist researchers to improve the integrity of their future supportive care trials.

The Association between Relationship Satisfaction Concordance and Breast Cancer Survivors' Physical and Psychosocial Well-Being.

The purpose of this article is to examine the association of relationship satisfaction concordance between breast cancer survivors (BCSs) and their partners with matched controls on physical and psychosocial outcomes. Dyads of BCSs, age-matched controls, and partners were recruited as part of a larger, cross-sectional QOL survey study. Relationship concordance was measured by the ENRICH marital satisfaction score, with each dyad's score equaling the absolute value of the difference in satisfaction between survivor/control and their partner (lower score = greater concordance). Dependent variables for survivors/controls were social constraint, physical function, depression, fatigue, attention function, and sleep disturbance. Relationship satisfaction and concordance were used as the primary independent variables, while controlling for dyad category, race, education, income, and age within multiple linear regression models. The sample consisted of 387 dyads (220 BCSs, 167 controls). Relationship satisfaction concordance ranged from 0 to 53.4 (mean = 10.2). The BCS dyads had significantly worse concordance (11.1) than the controls (9.1) (p = 0.050). Within the multiple regression models, lower concordance was significantly associated with increased social constraint (p = 0.029), increased depression (p = 0.038), and increased fatigue (p = 0.006). Poor relationship satisfaction and concordance were significantly associated with poor physical and psychosocial outcomes. The maintenance of relationships should remain a focus through difficulties of cancer and into survivorship for survivors, partners, and providers.

Comparative effectiveness of two interventions to increase colorectal cancer screening among females living in the rural Midwest.

PURPOSE: To assess the comparative effectiveness of a tailored, interactive digital video disc (DVD) intervention versus DVD plus patient navigation (PN) intervention versus usual care (UC) on the uptake of colorectal cancer (CRC) screening among females living in Midwest rural areas. METHODS: As part of a larger study, 663 females (ages 50-74) living in rural Indiana and Ohio and not up-to-date (UTD) with CRC screening at baseline were randomized to one of three study groups. Demographics , health status/history, and beliefs and attitudes about CRC screening were measured at baseline. CRC screening was assessed at baseline and 12 months from medical records and self-report. Multivariable logistic regression was used to determine whether females in each group were UTD for screening and which test they completed. RESULTS: Adjusted for covariates, females in the DVD plus PN group were 3.5× more likely to complete CRC screening than those in the UC group (odds ratio [OR] 3.62; 95% confidence interval [CI]: 2.09, 6.47) and baseline intention to receive CRC screening (OR 3.45, CI: 2.21,5.42) at baseline. Adjusting for covariates, there was no difference by study arm whether females who became UTD for CRC screening chose to complete a colonoscopy or fecal occult blood test/fecal immunochemical test. CONCLUSIONS: Many females living in the rural Midwest are not UTD for CRC screening. A tailored intervention that included an educational DVD and PN improved knowledge, addressed screening barriers, provided information about screening test options, and provided support was more effective than UC and DVD-only to increase adherence to recommended CRC screening.

Cancer-Related Symptom Frameworks Using a Biopsychosocial-Spiritual Perspective: A Scoping Review.

BACKGROUND: Research to understand and manage cancer-related symptoms continues to advance, yet work that more fully adopts a biopsychosocial-spiritual view of symptoms is needed. OBJECTIVE: The purpose of this article is to review existing frameworks that have the potential to guide research on cancer-related symptoms, to explore the characteristics of each framework, and to appraise each using a biopsychosocial-spiritual lens. METHODS: A scoping review was conducted to identify available frameworks that could be applied to guide cancer-related symptom research and to assess their characteristics. Research questions and criteria were formulated at the outset, followed by identifying relevant publications detailing novel frameworks, charting data, and collating results. Upon identification of available frameworks, each was appraised for alignment with a standard definition of "biopsychosocial-spiritual." RESULTS: Eleven frameworks were identified to guide cancer-related symptom research. All were developed in the United States, led by nurse scientists, including symptom experiences as well as their antecedents and outcomes, and could be applied to one or more concurrent cancer-related symptoms. While all 11 frameworks included biopsychosocial dimensions, only 4 included spirituality. CONCLUSIONS: Four biopsychosocial-spiritual frameworks offer unique insight to support advancement of cancer-related symptom research and practice from a holistic perspective. This foundational work could lead to development and validation of new frameworks and modification of existing frameworks to more closely align with a biopsychosocial-spiritual view of cancer-related symptoms. This review offers a starting point to carefully and explicitly adopt frameworks in research and practice with increased emphasis on considering spiritual dimensions of symptoms.

A qualitative analysis of cancer-related patient care in the emergency department.

OBJECTIVES: Due to an increasing incidence of new cancer diagnoses in the United States and longer survivorship, a growing number of patients with cancer receive care in emergency departments (EDs). This trend places an increasing burden on already crowded EDs, and experts are concerned these patients do not receive optimal care. The purpose of this study was to describe the experiences of ED physicians and nurses who care for patients with cancer. This information can inform strategies to improve oncology care for patients in ED settings. METHODS: We used a qualitative descriptive design to summarize to the experiences of ED physicians and nurses (n = 23) caring for patients with cancer. We conducted individual, semistructured interviews to query participants about their perspectives on care for oncology patients in the ED. RESULTS: Physician and nurse participants identified 11 challenges and suggested three potential strategies to improve care. The challenges included the following: risk of infection, poor communication between ED staff and other providers, poor communication between oncology or primary care providers and patients, poor communication between ED providers and patients, difficult disposition decisions, new cancer diagnoses, complex pain management, allocation of limited resources, lack of cancer-specific skills among providers, poor care coordination, and evolving end-of-life decisions. The solutions included the following: patient education, education for ED providers, and improved care coordination. CONCLUSIONS: Physicians and nurses experience challenges stemming from three overarching types of factors: illness factors, communication factors, and system-level factors. Solutions for the challenges of providing oncology care in the ED call for new strategies at the levels of the patient, provider, institution, and health care system.

Comparative Effectiveness of 2 Interventions to Increase Breast, Cervical, and Colorectal Cancer Screening Among Women in the Rural US: A Randomized Clinical Trial.

Importance: Women living in rural areas have lower rates of breast, cervical, and colorectal cancer screening compared with women living in urban settings. Objective: To assess the comparative effectiveness of (1) a mailed, tailored digital video disc (DVD) intervention; (2) a DVD intervention plus telephonic patient navigation (DVD/PN); and (3) usual care with simultaneously increased adherence to any breast, cervical, and colorectal cancer screening that was not up to date at baseline and to assess cost-effectiveness. Design, Setting, and Participants: This randomized clinical trial recruited and followed up women from rural Indiana and Ohio (community based) who were not up to date on any or all recommended cancer screenings. Participants were randomly assigned between November 28, 2016, and July 1, 2019, to 1 of 3 study groups (DVD, DVD/PN, or usual care). Statistical analyses were completed between August and December 2021 and between March and September 2022. Intervention: The DVD interactively assessed and provided messages for health beliefs, including risk of developing the targeted cancers and barriers, benefits, and self-efficacy for obtaining the needed screenings. Patient navigators counseled women on barriers to obtaining screenings. The intervention simultaneously supported obtaining screening for all or any tests outside of guidelines at baseline. Main Outcomes and Measures: Receipt of any or all needed cancer screenings from baseline through 12 months, including breast, cervical, and colorectal cancer, and cost-effectiveness of the intervention. Binary logistic regression was used to compare the randomized groups on being up to date for all and any screenings at 12 months. Results: The sample included 963 women aged 50 to 74 years (mean [SD] age, 58.6 [6.3] years). The DVD group had nearly twice the odds of those in the usual care group of obtaining all needed screenings (odds ratio [OR], 1.84; 95% CI, 1.02-3.43; P = .048), and the odds were nearly 6 times greater for DVD/PN vs usual care (OR, 5.69; 95% CI, 3.24-10.5; P < .001). The DVD/PN intervention (but not DVD alone) was significantly more effective than usual care (OR, 4.01; 95% CI, 2.60-6.28; P < .001) for promoting at least 1 (ie, any) of the needed screenings at 12 months. Cost-effectiveness per woman who was up to date was $14 462 in the DVD group and $10 638 in the DVD/PN group. Conclusions and Relevance: In this randomized clinical trial of rural women who were not up to date with at least 1 of the recommended cancer screenings (breast, cervical, or colorectal), an intervention designed to simultaneously increase adherence to any or all of the 3 cancer screening tests was more effective than usual care, available at relatively modest costs, and able to be remotely delivered, demonstrating great potential for implementing an evidence-based intervention in remote areas of the midwestern US. Trial Registration: ClinicalTrials.gov Identifier: NCT02795104.

Aromatase inhibitors in obese breast cancer patients are not associated with increased plasma estradiol levels.

Obesity, in postmenopausal women, has been associated to a higher breast cancer incidence and worst prognosis. Some studies suggested a decrease in aromatase inhibitors (AI) efficacy in obese postmenopausal breast cancer patients, although estradiol levels were not measured. The purpose of the present study was to verify if estradiol levels are measurable in postmenopausal women under AI. If achievable, the goal is to compare the estradiol levels in lean versus obese postmenopausal women under AI treatment for non-metastatic breast cancer. Postmenopausal women were recruited in accordance to one of these four groups: lean [body mass index (BMI) of 18-25 kg/m(2)] under AI (n = 30), obese (BMI ≥ 30 kg/m(2)) under AI (n = 30), lean AI-naïve (n = 10), and obese AI-naïve (n = 10). Lean and obese women were matched according to their age. Estradiol levels were measured in plasma using an ELISA. The Wilcoxon signed-rank test was used to assess the significance of the differences between the groups. Estradiol levels in postmenopausal women under AI varied from 0 to 94.65 pg/ml with a median value of 0.98 pg/ml. Obese AI-naïve women had higher estradiol levels than lean AI-naïve women (p = 0.03). There was no difference in estradiol levels between lean and obese women under AI (p = 0.76). Despite very low plasma levels, it is possible to measure the estradiol levels in postmenopausal women under AI treatment. Our results suggest that the known impact of obesity on recurrence risk in women under AI treatment may not be due to incomplete aromatase inhibition. Further works are needed to examine closely the aromatase-independent pathways that are linking obesity to breast cancer risk and recurrence.

Impact of a Personal Health Record Intervention Upon Surveillance Among Colorectal Cancer Survivors: Feasibility Study.

BACKGROUND: There are currently an estimated 1.5 million individuals living in the United States with colorectal cancer (CRC), and although the 5-year survival rate has increased, survivors are at risk for recurrence, particularly within the first 2-3 years after treatment. National guidelines recommend continued surveillance after resection to identify recurrence early on. Adherence among survivors ranges from 23% to 94%. Novel interventions are needed to increase CRC survivors' knowledge and confidence in managing their cancer and thus to increase adherence to follow-up surveillance. OBJECTIVE: The objective of this study is to develop and test the feasibility and efficacy of a stand-alone, web-based personal health record (PHR) to increase surveillance adherence among CRC survivors, with patient beliefs about surveillance as secondary outcomes. METHODS: A pre- and postintervention feasibility trial was conducted testing the efficacy of the colorectal cancer survivor (CRCS)-PHR, which had been previously developed using an iterative, user-centered design approach. RESULTS: The average age of the sample was 58 (SD 9.9) years, with 57% (16/28) male and the majority married (20/28, 71%) and employed full-time (15/28, 54%). We observed a significant increase in adherence to colonoscopy (before: 11/21, 52% vs after: 18/21, 86%; P=.005) and CEA (14/21, 67% vs 20/21, 95%; P=.01), as well as a slight increase in CT scans (14/21, 67% vs 18/21, 86%; P=.10). The only significant impact on secondary outcome (patient beliefs) was benefits of CEA test (P=.04), as most of the beliefs were high at baseline. CONCLUSIONS: This feasibility study lays the groundwork for continued development of the CRCS-PHR to increase CRC surveillance. Patient-centered technologies, such as the CRCS-PHR, represent an important potential approach to improving the receipt of guideline-concordant care and follow-up surveillance, and not just for CRC survivors. Researchers should continue to develop patient-centered health technologies with clinician implementation in mind to increase patient self-efficacy and surveillance adherence.

Increasing breast, cervical, and colorectal cancer screening among rural women: Baseline characteristics of a randomized control trial.

BACKGROUND: Rural women suffer disproportionately from breast, cervical, and colorectal cancer mortality compared to those in urban areas. Screening behaviors for these three cancers share many similar beliefs and barriers. Unfortunately, published interventions have not attempted to simultaneously bring women up to date with screening for three cancers (breast, cervical, and colorectal) even though multiple behavior change interventions are effective. The aim of this randomized controlled study was to compare the effectiveness of a mailed interactive and tailored DVD vs. DVD plus telephonic patient navigation (DVD + PN) vs. Usual Care (UC) to increase the percentage of rural women (aged 50-74) up to date for breast, cervical, and colorectal cancer screening. METHODS: Nine hundred eighty-three participants needing one, two, or three cancer screening tests were consented and randomized to one of three groups. Prior to randomization, women were assessed for baseline characteristics including sociodemographics, health status, and cancer screening test beliefs. Screening status was assessed by medical record review. RESULTS: At baseline, the average age of participants was 58.6 years. Nineteen percent of the sample was not up to date with screenings for all three cancers. Colorectal cancer had the highest percentage of women (69%) who were not up to date with screening followed by cervical (57%) and then breast cancer (41%). Sixty percent of women reported receiving a reminder for mammography; 30%, for cervical cancer screening; 15% for colonoscopy; and 6% for FOBT/FIT. DISCUSSION: Increasing adherence to colorectal cancer screening may be the most urgent need among all screening tests. This clinical trial is registered at clinicaltrials.gov with identifier NCT02795104.

The Effect of Two Interventions to Increase Breast Cancer Screening in Rural Women.

Guideline-based mammography screening is essential to lowering breast cancer mortality, yet women residing in rural areas have lower rates of up to date (UTD) breast cancer screening compared to women in urban areas. We tested the comparative effectiveness of a tailored DVD, and the DVD plus patient navigation (PN) intervention vs. Usual Care (UC) for increasing the percentage of rural women (aged 50 to 74) UTD for breast cancer screening, as part of a larger study. Four hundred and two women who were not UTD for breast cancer screening, eligible, and between the ages of 50 to 74 were recruited from rural counties in Indiana and Ohio. Consented women were randomly assigned to one of three groups after baseline assessment of sociodemographic variables, health status, beliefs related to cancer screening tests, and history of receipt of guideline-based screening. The mean age of participants was 58.2 years with 97% reporting White race. After adjusting for covariates, 54% of women in the combined intervention (DVD + PN) had a mammogram within the 12-month window, over 5 times the rate of becoming UTD compared to UC (OR = 5.11; 95% CI = 2.57, 10.860; p < 0.001). Interactions of the intervention with other variables were not significant. Significant predictors of being UTD included: being in contemplation stage (intending to have a mammogram in the next 6 months), being UTD with other cancer screenings, having more disposable income and receiving a reminder for breast screening. Women who lived in areas with greater Area Deprivation Index scores (a measure of poverty) were less likely to become UTD with breast cancer screening. For rural women who were not UTD with mammography screening, the addition of PN to a tailored DVD significantly improved the uptake of mammography. Attention should be paid to certain groups of women most at risk for not receiving UTD breast screening to improve breast cancer outcomes in rural women.

Tyrosine phosphatase MEG2 modulates murine development and platelet and lymphocyte activation through secretory vesicle function.

MEG2, a protein tyrosine phosphatase with a unique NH2-terminal lipid-binding domain, binds to and is modulated by the polyphosphoinositides PI(4,5)P2 and PI(3,4,5)P3. Recent data implicate MEG2 in vesicle fusion events in leukocytes. Through the genesis of Meg2-deficient mice, we demonstrate that Meg2-/- embryos manifest hemorrhages, neural tube defects including exencephaly and meningomyeloceles, cerebral infarctions, abnormal bone development, and >90% late embryonic lethality. T lymphocytes and platelets isolated from recombination activating gene 2-/- mice transplanted with Meg2-/- embryonic liver-derived hematopoietic progenitor cells showed profound defects in activation that, in T lymphocytes, was attributable to impaired interleukin 2 secretion. Ultrastructural analysis of these lymphocytes revealed near complete absence of mature secretory vesicles. Taken together, these observations suggest that MEG2-mediated modulation of secretory vesicle genesis and function plays an essential role in neural tube, vascular, and bone development as well as activation of mature platelets and lymphocytes.

Control of vesicle fusion by a tyrosine phosphatase.

The tyrosine phosphatase PTP-MEG2 is targeted by its amino-terminal Sec14p homology domain to the membrane of secretory vesicles. There it regulates vesicle size by promoting homotypic vesicle fusion by a mechanism that requires its catalytic activity. Here, we identify N-ethylmaleimide-sensitive factor (NSF), a key regulator of vesicle fusion, as a substrate for PTP-MEG2. PTP-MEG2 reduced the phosphotyrosine content of NSF and co-localized with NSF and syntaxin 6 in intact cells. Furthermore, endogenous PTP-MEG2 co-immunoprecipitated with endogenous NSF. Phosphorylation of NSF at Tyr 83, as well as an acidic substitution at the same site, increased its ATPase activity and prevented alphaSNAP binding. Conversely, expression of a Y83F mutant of NSF caused spontaneous fusion events. Our results suggest that the molecular mechanism by which PTP-MEG2 promotes secretory vesicle fusion involves the local release of NSF from a tyrosine-phosphorylated, inactive state. This represents a novel mechanism for localized regulation of NSF and the first demonstrated role for a protein tyrosine phosphatase in the regulated secretory pathway.

Predictors of depression outcomes in adults with cancer: A 12 month longitudinal study.

OBJECTIVES: The prevalence of depression in patients with cancer ranges from 8% to 24% within the first year of receiving a cancer diagnosis. Identifying predictors of depression outcomes may facilitate tailored or more intensive treatment in patient subgroups with a poorer prognosis for depression improvement. The objective of this study was to determine predictors of depression severity and improvement over 12 months among adults with cancer. METHODS: Longitudinal analysis of data from the Indiana Cancer Pain and Depression trial was performed in 309 patients (n = 309) with cancer-related depression. Depression outcomes were assessed at baseline, 1, 3, 6, and 12 months and included depression severity (Hopkins Symptom Checklist-20) and global improvement (Depression Global Rating of Improvement (DGRI)). Multivariable repeated measures analyses, adjusting for treatment group, baseline depression, and time point, were conducted to determine symptom (pain), demographic, and clinical predictors of depression outcomes over 12 months. RESULTS: Pain was particularly important, with a clinically meaningful reduction in pain predicting a 12-24% greater odds of depression global improvement. Other factors that independently predicted better depression outcomes over 12 months included female sex, newly-diagnosed or maintainence/disease-free cancer, fewer comorbid medical conditions, and higher socioeconomic status. As expected, the three covariates adjusted for in the model (treatment group, passage of time, and baseline depression severity) also predicted depression outcomes. CONCLUSION: Pain as well as several demographic and clinical factors predict depression outcomes over 12 months. These findings may help identify patient subgroups requiring closer monitoring and more intensive or tailored depression treatment. Trial Registration clinicaltrials.gov Identifier: NCT00313573.

Presence and Distress of Chemotherapy-Induced Peripheral Neuropathy Symptoms in Upper Extremities of Younger and Older Breast Cancer Survivors.

PURPOSE: The purposes of this study were to determine whether the presence of upper extremity chemotherapy-induced peripheral neuropathy (CIPN) symptoms (burning, pins/needles, numbness, pain, and skin crawls) among breast cancer survivors (BCS) varied according to age (≤45 years or 55-70 years) and to examine age group differences in upper extremity CIPN symptom distress. METHODS: The study was a secondary analysis of younger (n=505) and older (n=622) BCS. Inclusion criteria were age of ≤45 years or 55-70 years; patient at 3-8 years postdiagnosis; patient received the chemotherapy regimen of paclitaxel, doxorubicin, and cyclophosphamide; and patient did not have recurrence. The Symptom Survivor Checklist was used to assess presence and distress of upper extremity CIPN symptoms. Analyses explored whether age group predicted CIPN symptom presence and distress while controlling for sociodemographic and medical variables. RESULTS: Older BCS reported fewer pins/needles, numbness, and pain symptoms (odds ratios: 0.623-0.751). Heart disease (odds ratios: 1.59-1.70) and progesterone-negative breast cancer (odds ratio: 0.663) were significantly associated with one or more CIPN symptoms. Symptom distress ratings did not differ by age groups; both age groups indicated distress from CIPN symptoms, with 25% or more reporting distress as "moderately" or "quite a bit." CONCLUSIONS: Younger BCS reported more upper extremity CIPN symptoms. BCS in both groups continued to report bothersome CIPN symptoms years after treatment. Study findings will assist clinicians in identifying BCS at higher risk for upper extremity CIPN as well as inform development of appropriate tailored interventions to mitigate these symptoms and facilitate restoration to age-related baseline function, thereby improving quality of life for BCS.

Dysfunctional cystic fibrosis transmembrane conductance regulator inhibits phagocytosis of apoptotic cells with proinflammatory consequences.

Cystic fibrosis (CF) is caused by mutated CF transmembrane conductance regulator (CFTR) and is characterized by robust airway inflammation and accumulation of apoptotic cells. Phagocytosis of apoptotic cells (efferocytosis) is a pivotal regulator of inflammation, because it prevents postapoptotic necrosis and actively suppresses release of a variety of proinflammatory mediators, including IL-8. Because CF is associated with accumulation of apoptotic cells, inappropriate levels of IL-8, and robust inflammation, we sought to determine whether CFTR deficiency specifically impairs efferocytosis and its regulation of inflammatory mediator release. Here we show that CFTR deficiency directly interferes with efferocytosis by airway epithelium, an effect that is not due to altered binding of apoptotic cells to epithelial cells or altered expression of efferocytosis receptors. In contrast, expression of RhoA, a known negative regulator of efferocytosis, is substantially increased in CFTR-deficient cells, and inhibitors of RhoA or its downstream effector Rho kinase normalize efferocytosis in these cells. Impaired efferocytosis appears to be mediated through an amiloride-sensitive ion channel, because amiloride restores phagocytic competency in CFTR-deficient cells. Finally, ineffective efferocytosis in CFTR-deficient cells appears to have proinflammatory consequences, because apoptotic cells enhance IL-8 release by these cells, but not by wild-type controls. Therefore, in CF, dysregulated efferocytosis may lead to accumulation of apoptotic cells and impaired regulation of the inflammatory response and, ultimately, may suggest a new therapeutic target.

Use of fluorescent probes to detect lipid signaling intermediates in macrophages.

To fulfill their function in host defense, professional phagocytes such as neutrophils and macrophages exhibit the ability to ingest (phagocytose), kill, and dispose of pathogenic microorganisms. Recent studies have provided strong evidence for the importance of membrane lipids such as polyphosphoinositides in these processes. In turn, reversible phosphorylation events, involving protein and lipid kinases and phosphatases, regulate signaling pathways involving metabolism of membrane lipids. Our ability to study lipid signaling events has been greatly facilitated by the development of fluorescent molecular imaging techniques. In particular, the expression of recombinant fusions of derivatives of the jellyfish-derived green fluorescent proteins (GFP) coupled to reporter molecules enables real-time monitoring of signaling events in live cells. Here, we discuss methods to monitor alterations in membrane polyphosphoinositides involved in signaling events regulating phagocytosis. To illustrate the use of this technology, we will focus on the role of protein tyrosine phosphatase MEG2 in phagocytosis and its modulation by phosphatidylinositol-3,4,5-triphosphate (PIP3). This approach enables investigators to ascertain the involvement of lipid intermediates in diverse signaling pathways.