Prospective evaluation of functional brain activity and oxidative damage in breast cancer: changes in task-induced deactivation during a working memory task.

Cancer-related cognitive dysfunction is an important issue for breast cancer survivors. Previous research has identified both cross-sectional and longitudinal alterations in brain function related to cancer status and treatment. In this study, we prospectively collected functional magnetic resonance imaging data in breast cancer cases treated with adjuvant chemotherapy and in controls with no cancer history during a working memory task. Data and blood specimens were collected immediately prior to the start of treatment (baseline) and following completion of treatment (follow-up), and at yoked intervals for controls. In secondary analysis we assessed the levels of oxidative DNA damage in peripheral blood lymphocytes of cases and controls using the Comet assay. A significant group*time interaction revealed reduced deactivation in the superior frontal gyrus in the controls at follow-up, in contrast to cases, who exhibited similar magnitude of deactivation at baseline and follow-up. Working memory performance indicated a significant improvement in the controls at follow-up, and no change in performance in cases. In secondary analyses, oxidative DNA damage levels were elevated in the cases at follow-up compared to controls, but no associations were found between the Comet assay variables and functional imaging at either time-point or group. In light of previous reports on task induced deactivations, our findings reflect continuing effortful processing at follow-up in the breast cancer group, with relatively less effortful processing in the control group given the reduced novelty and practice effects from the baseline to follow-up.

Episodic memory for visual scenes suggests compensatory brain activity in breast cancer patients: a prospective longitudinal fMRI study.

It has been hypothesized that breast cancer and its chemotherapy can impart functional neural changes via an overlap with biological mechanisms associated with aging. Here we used fMRI to assess whether changes in neural activity accompanying visual episodic memory encoding and retrieval suggest altered activations according to patterns seen in functional imaging of cognitive aging. In a prospective longitudinal design, breast cancer patients (n = 13) were scanned during memory encoding and retrieval before and after chemotherapy treatment, and compared to healthy-age matched controls (n = 13). Our results indicate that despite equivalent behavioral performance, encoding and retrieval resulted in increased activation of prefrontal regions for the breast cancer group compared to controls for both before and after chemotherapy treatment. This was accompanied by decreased activity in posterior brain regions after chemotherapy, particularly those involved in visual processing, for the breast cancer group compared to controls. These findings are discussed as evidence for a possible anterior shift in neural processing to compensate for deficiencies in posterior brain regions, consistent with an accelerated aging account. Cancer and chemotherapy can impact brain regions underlying episodic memory, leading to additional recruitment of control regions, which may be linked to mechanisms related to aging.

Sleep problems in breast cancer survivors 1-10 years posttreatment.

ABSTRACTObjective:Sleep can affect quality of life (QoL) during cancer survivorship, and symptoms related to poor sleep can be exacerbated. We examined the prevalence, severity, and nature of subjective sleep complaints in women surviving stage I-III breast cancer who were 1-10 years posttreatment. We also examined the demographic, medical, physical, and psychosocial correlates of poor sleep in these women in order to identify the subgroups that may be most in need of intervention. METHOD: A total of 200 patients at a comprehensive cancer center who were 1-10 years posttreatment for primary stage I-III breast cancer with no evidence of disease at the time of enrollment completed a battery of questionnaires on demographics, sleep, physical symptoms, mood, cancer-specific fears, and QoL. RESULTS: The women had a mean age of 57 years (SD = 10.0), with a mean of 63.3 months (SD = 28.8) of post-cancer treatment. Some 38% of these patients were identified as having poor-quality sleep. Women with poor sleep took longer to fall asleep, had more awakenings, and acquired 2 hours less sleep per night than those with good sleep. They also had a lower QoL, greater severity of pain, more concerns about health and recurrence, and increased vasomotor symptoms (p < 0.05). Daytime sleepiness and depression were found to be not significantly correlated with sleep quality. SIGNIFICANCE OF RESULTS: Many breast cancer survivors had severe subjective insomnia, and several breast cancer survivor subgroups were identified as having members who might be most in need of sleep-improvement interventions. Addressing physical symptoms (e.g., vasomotor symptoms and pain) and providing education about the behavioral, social, environmental, and medical factors that affect sleep could result in substantial improvement in the life course of breast cancer survivors.

An Online Survey of Patients' Experiences Since the Rescheduling of Hydrocodone: The First 100 Days.

OBJECTIVE: To conduct an Internet patient survey through the National Fibromyalgia & Chronic Pain Association on reactions to the first 100 days following the rescheduling of hydrocodone. METHODS: Face-valid survey questions were created with expert consensus along with repurposed questions used on previous NFMCPA surveys covering domains such as demographics and symptoms. The questionnaire was designed to be administered over the Internet. RESULTS: 6,420 responders met screening criteria and completed the survey. Most (5,181, or 82.5%) had been prescribed hydrocodone for more than 1 year. 2,296, (39.0%) reported no changes in access to hydrocodone, while the majority experienced some barriers. Of those who could no longer get hydrocodone, 1,067 (18.1%) borrowed pain medications, 1,007 (17.1%) turned to marijuana, 773 (13.1%) used alcohol, and 135 (2.3%) used illicit drugs. Most respondents had to visit their healthcare providers more often (N = 3,699, 64.2%) and 1,735 (30.3%) reported some type of issue interacting with their pharmacy. Most felt that the rescheduling was neither a fair nor appropriate solution to the abuse of hydrocodone (N = 4,938, 88.3%). For those still working, 801 (46.2%) reported that they had missed work because of the stricter regulations. 1,462 (27.2%) reported having thoughts of suicide since the rescheduling. SIGNIFICANCE: The unintended consequences for people with chronic pain that have been caused by the rescheduling effort to impede hydrocodone abuse are negatively impacting thousands. These consequences include suffering from being placed on less effective drugs, increased cost, inconvenience, and negative influence on physician-patient and pharmacist-patient relationships.

Polysomnographic Study of Sleep in Survivors of Breast Cancer.

STUDY OBJECTIVE: Insomnia is a frequent complaint in breast cancer patients during and after treatment. Breast cancer survivors, 1-10 years posttreatment, underwent in-lab polysomnography (PSG) to objectively define the insomnia in those patients with such a complaint. METHODS: Twenty-six breast cancer survivors (aged 39-80, mean 54.0 months posttreatment) spent 2 nights in the sleep laboratory. Sleep on Night 2 was scored for sleep stages, sleep onset latency, REM sleep onset latency, wake time, apneas and hypopneas, periodic limb movements and arousals. Subjects were allocated into 2 groups by their scores on the Pittsburgh Sleep Quality Index (PSQI): no/ mild sleep disturbance (PSQI score ≤ 9, n = 15) or moderate/ severe sleep disturbance (PSQI ≥ 10, n = 11). RESULTS: Standard PSG/EEG parameters failed to differentiate insomniacs from non-insomniacs. The single variable that distinguished the insomnia group was periodic limb movements in sleep (PLMS). PLMS were significantly correlated (r ≅ 0.7, p < 0.02) with subjective report of insomnia on PSQI and insomnia severity index. Log[Number of PLMS] was higher in the moderate/severe insomnia group (p = 0.008). Five of 11 patients in the moderate/severe insomnia group had a PLMS index ≥ 15, compared to only one of 15 patients in the none/mild insomnia group (p = 0.02). Menopausal symptoms and use of caffeine, hypnotics, and antidepressants were unrelated to insomnia severity or PLMS. CONCLUSIONS: PLMS was the sole PSG variable that separated breast cancer survivors with moderate/severe insomnia from those with no/mild sleep disturbance. Further study of the incidence and significance of PLMS in breast cancer survivors with the complaint of insomnia is merited.

A primer on definitive gas and liquid chromatography drug testing: What clinicians need to know.

OBJECTIVE: To describe the differences between mass spectrometry technologies and compare and contrast them with immunoassay techniques of urine drug testing (UDT). Highlight the potential importance of the differences among these technologies for clinicians so as to allow them make decisions in their use in patient care. METHODS: Review of mass spectrometry techniques, including gas chromatography, liquid chromatography, and time-of-flight techniques. RESULTS: The potential clinical implications of these technologies stemming from their scope and accuracy are presented. SIGNIFICANCE: UDT is an important clinical tool, though there are differences in technology and testing processes with important implications for clinical decision making. It is crucial, therefore, that clinicians have an understanding of the technologies behind the tests they order, so that their interpretation and use of results are based on an understanding of the strengths and weaknesses of the technologies used.

Exploring rates of abnormal pharmacogenetic findings in a pain practice.

Pharmacogenetic testing (PGT) is part of increasing efforts to personalize medicine, hopefully leading to better medication selection with more effective, less toxic therapies. Pharmacogenetic testing has relevance for chronic pain treatment, given the frequent comorbidities and polypharmacy. This retrospective study explored the prevalence of polymorphisms in a specialty pain practice in Louisiana. Pharmacogenetic testing was conducted for the cytochrome P450 (CYP) enzymes CYP2B6, CYP2C19, and CYP2D6, or the uridine diphosphate-glucuronosyltransferase 2 family polypeptide B15 (UGT2B15) enzyme utilizing a noninvasive, saliva-based test based on clinical decision-making. The sample consisted of 61 men (58.7%) and 41 women (39.4%), with an average age of 46.7 years (range = 23-83, SD = 11.5 years). Across all tests, 164 (42.3%) were extensive, 99 (25.5%) were intermediate, 28 (7.2%) were ultrarapid, and 27 (7%) were poor metabolizers. Only three patients who had been tested were found to be extensive (normal) for all four genes. These data demonstrate that genetic polymorphisms were frequently encountered. Consideration should be given to obtaining PGT as an aspect of evaluation and treatment planning when working with patients in need of specialty pain consultation and care. Caution is needed, as this brief report encompasses results from a single pain practice in one geographic location with a potentially distinct prevalence of genetic polymorphisms. Further prospective study is needed.

Frequency, characteristics, and correlates of pain in a pilot study of colorectal cancer survivors 1-10 years post-treatment.

OBJECTIVE: The long-term effects of disease and treatment in colorectal cancer (CRC) survivors are poorly understood. This study examined the prevalence and characteristics of pain in a sample of CRC survivors up to 10 years post-treatment. DESIGN: One hundred cancer-free CRC survivors were randomly chosen from an institutional database and completed a telephone survey using the Brief Pain Inventory, Neuropathic Pain Questionnaire-Short Form, Quality of Life Cancer Survivor Summary, Brief Zung Self-Rating Depression Scale, Zung Self-Rating Anxiety Scale, and Fear of Recurrence Questionnaire. RESULTS: Participants were primarily Caucasian (90%) married (69%) males (53.5%) with a mean age of 64.7 years. Chronic pain was reported in 23% of CRC survivors, with a mean moderate intensity rating (mean = 6.05, standard deviation = 2.66) on a 0-10 rating scale. Over one-third (39%) of those with pain attributed it to their cancer or treatment. Chi-square and t-test analyses showed that survivors with pain were more likely to be female, have lower income, be more depressed and more anxious, and show a higher endorsement of suicidal ideation than CRC survivors without chronic pain. On average, pain moderately interfered with daily activity. CONCLUSIONS: Chronic pain is likely a burdensome problem for a small but not inconsequential minority of CRC survivors requiring a biopsychosocial treatment approach to improve recognition and treatment. Open dialogue between clinicians and survivors about physical and emotional symptoms in long-term follow-up is highly recommended.

Transformation of acute cancer pain to chronic cancer pain syndromes.

For many cancer survivors, disease-related long-term morbidities and the application of advanced cancer treatments have resulted in the development of a chronic pain state. This brief review explores the relationship between what is known about the treatment of active cancer pain syndromes-both continuous pain and breakthrough pain-and persisting pain syndromes in cancer survivors. We also posit that because there is evidence to suggest that poorly treated acute pain can lead to protracted pain conditions, acute pain should be recognized and treated promptly, both for short- and long-term gain. In the short term, better acute pain treatment can improve functionality and psychological well-being, whereas in the long term, mounting evidence suggests that it could prevent of future chronic pain.

A comparison of various risk screening methods in predicting discharge from opioid treatment.

OBJECTIVES: Risk assessment and stratification has become an important aspect of the prescribing of opioids to patients with chronic pain. There is little empirical data available on the sensitivity and specificity of commonly used risk assessment tools. This paper describes 2 studies that compare the prediction capabilities of various risk assessment tools. METHODS: The first study presents data on patients at a pain practice whose treatment with opioids was stopped due to their engaging in aberrant drug-related behavior. Patients were assessed with the Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R), the Pain Medication Questionnaire, the Opioid Risk Tool, and a clinical interview. A second study compared the risk assessment measures, SOAPP-R, Pain Medication Questionnaire, Opioid Risk Tool, and a clinical interview. Data were gathered on whether patients had engaged in aberrant drug-related behavior at 6-month follow-up. RESULTS: Significant differences in the measures were found. Accuracy did not appear to be a function of the type of aberrant drug-related behavior that the patient engaged in for any of the measures. The clinical interview showed the best sensitivity of the 4 risk measures in predicting risk. The SOAPP-R showed the best sensitivity of the self-report measures. However, the SOAPP-R appears to overrate risk. DISCUSSION: Overall, these studies indicate that not all risk assessment tools are equal in their ability to accurately predict future aberrant drug-related behavior. It may be that written risk assessment tools that use more subtle items are better suited to certain patient populations.

Screening for abuse risk in pain patients.

As opioid prescribing has dramatically expanded over the past decade, so too has the problem of prescription drug abuse. In response to these now two major public health problems - the problem of poorly treated chronic pain and the problem of opioid abuse - a new paradigm has arisen in pain management, namely risk stratification. Once a prescriber has determined that opioids will be used (a medical decision based on how intense the pain is, what has been tried and failed and, to some extent, what type of pain the patient has), he/she must then decide how opioid therapy is to be delivered. Different models of delivery of opioid therapy can be utilized, beginning the process with a risk assessment that is highly individualized to each patient. Recently, researchers have produced a wide variety of literature regarding assessment tools to be used for this purpose. And while there remains a need for larger prospective studies to examine the ability of each tool to predict aberrant drug-taking behaviors, clinicians can and should utilize one or more of these screening tools and understand their benefits and limitations. This chapter will describe the nature of current screening assessments, their potential for use in the pain population in various settings, past clinical observations and suggestions for moving forward.

Pseudoaddiction revisited: a commentary on clinical and historical considerations.

SUMMARY The term 'pseudoaddiction' has been in the pain management lexicon for two decades. Over this time, pain management has changed significantly - in no small part as a result of a landmark publication by Weissman and Haddox in 1989. The original paper, which describes the experience of a single case study in which a young inpatient with cancer became sullen and difficult when left in uncontrolled pain, is reviewed. It is time for a critical re-examination of the concept, its use and its influence on the pain literature, and finally, how it should be applied today. A commentary is offered along with a brief literature review to determine the presence of pseudoaddiction in published literature. Arriving in the literature at a time when the application of opioid therapy to non-malignant pain was being seriously considered, based on principles borrowed from the cancer pain experience, its impact on the way in which patients' behaviors on opioids are to be interpreted has been profound. The fact that problematic drug-related behavior can be driven by uncontrolled pain and extinguished with adequate pain control became a fundamental rule of opioid therapy. This led to practices such as escalating doses in the face of noncompliance and has been extended to include behaviors unintended by the original authors (e.g., excusing the use of marijuana for pain or symptom control while on opioids for non-malignant pain).

Assessing self-efficacy for coping with cancer: development and psychometric analysis of the brief version of the Cancer Behavior Inventory (CBI-B).

OBJECTIVE: The Cancer Behavior Inventory-Brief Version (CBI-B), a 12-item measure of self-efficacy for coping with cancer derived from the longer 33-item version, was subjected to psychometric analysis. METHOD: Participants consisted of three samples: 735 cancer patients from a multicenter CCOP study, 199 from central Indiana, and 370 from a national sample. Samples were mixed with respect to initial cancer diagnosis. Participants completed the CBI-B and measures of quality of life, optimism, life satisfaction, depression, and sickness impact. RESULTS: Exploratory Factor Analysis with oblique rotation yielded four factors in the first sample: (1) Maintaining Independence and Positive Attitude; (2) Participating in Medical Care; (3) Coping and Stress Management; and (4) Managing Affect, which were confirmed in subsequent samples. Cronbach α coefficient for the 12-item CBI-B ranged from 0.84 to 0.88. Validity of the CBI-B was demonstrated by positive correlations with measures of quality of life and optimism, and negative correlations with measures of depression and sickness impact. CONCLUSION: The CBI-B is a valid brief measure of self-efficacy for coping that could be easily integrated into clinical oncology research and practice, and also used in screening patients.

Substance abuse issues in oral and maxillofacial practice.

Substance abuse has far-reaching consequences for individuals, their families, and the community. Medications with abuse potential play an important role in the management of pain and are widely prescribed by the oral and maxillofacial surgeon. Reducing the likelihood of abuse and providing appropriate pain management for the known abuser are critical aspects of perioperative patient management. Health care providers are not immune to substance abuse and may, in fact, be at an elevated risk. Identification of impaired providers is essential to help them find the appropriate treatment and counseling and to prevent harm to their patients, family, friends, or associates.

Substance abuse in cancer pain.

In the oncology community, opioids recently have become the cornerstone of cancer pain management. This has led to a rapid increase in opioid prescribing in an effort to address the growing public health problem of chronic pain. A new paradigm in noncancer pain management has emerged, that of risk assessment and stratification in opioid therapy. Techniques foreign to cancer pain management have now become commonplace in the noncancer pain setting, such as the use of monitoring compliance via urine drug screens. Amidst these strides in opioid use for pain management, cancer has been changing. The survival rate has increased, and a group of these patients with chronic pain were treated with opioid therapy. With opioid exposure being longer and against the backdrop of prescription drug abuse, the question is how much of the adaptation of the risk management paradigm in chronic pain management is to be imported to cancer pain management?

A comparison of common screening methods for predicting aberrant drug-related behavior among patients receiving opioids for chronic pain management.

OBJECTIVE: The ability to predict risk for violating opioid medication policies, known as aberrant drug-related behavior, is critical for providing optimal treatment. Many pain management centers measure risk using one of several partially validated measures: the Screener and Opioid Assessment for Patients with Pain (SOAPP), the Diagnosis, Intractability, Risk, and Efficacy inventory (DIRE), and/or the Opioid Risk Tool (ORT). However, little is known about how these measures compare with each other in predicting aberrant drug-related behavior and discontinuance of opioid pain medications. The current study aimed to address this research question. PATIENTS: Participants were 48 patients who attended a pain management center in Tennessee but were later discontinued from opioids for aberrant drug-related behavior. Patients referred for opioid medication for pain management participated in a semi-structured clinical interview with the staff psychologist and completed the aforementioned measures. Patients generally returned to the pain clinic on a monthly basis for medication management. Results. Analyses compared the sensitivity of each self-report measure and the clinical interview in predicting discontinuance for aberrant drug-related behavior. RESULTS: showed the highest sensitivity for the clinical interview (0.77) and the SOAPP (0.72), followed by the ORT (0.45) and the DIRE (0.17). Combining the clinical interview with the SOAPP increased sensitivity to 0.90. CONCLUSIONS: Among patients who were discontinued from opioids for aberrant drug-related behaviors, the clinical interview and the SOAPP were most effective at predicting risk at baseline. Implications for future research and clinical practice are discussed.

Current risk assessment and management paradigms: snapshots in the life of the pain specialist.

Opioid analgesics can be a safe and effective treatment option for patients with chronic pain, but issues surrounding their use-including side effects, tolerance, and the potential for misuse and diversion-prompt some clinicians to avoid using these agents, and can lead to the continued undertreatment of pain. This article offers practical advice to clinicians who choose to prescribe opioid analgesics. Through a series of case presentations, it illustrates the steps health care providers can take to prepare their practice for opioid prescribing, assess and select patients for opioid treatment, initiate and manage therapy, and address concerns about aberrant behaviors.

A phase II trial of olanzapine, dexamethasone, and palonosetron for the prevention of chemotherapy-induced nausea and vomiting: a Hoosier oncology group study.

OBJECTIVE: The purpose of this study is to determine the control of acute and delayed chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic chemotherapy (MEC) and highly emetogenic chemotherapy (HEC) with the combined use of palonosetron and olanzapine, and dexamethasone with the dexamethasone given on day 1 only. MATERIALS AND METHODS: Forty chemotherapy-naive patients received on the day of chemotherapy, day 1, an anti-emetic regimen consisting of dexamethasone, palonosetron, and olanzapine. Patients continued olanzapine for days 2-4 after chemotherapy administration. Patients recorded daily episodes of emesis, daily symptoms utilizing the M.D. Anderson Symptom Inventory, and the utilization of rescue therapy. RESULTS: For the first cycle of chemotherapy, the complete response (no emesis, no rescue) for the acute period (24 h post-chemotherapy) was 100%, the delayed period (days 2-5 post-chemotherapy) 75%, and the overall period (0 120 h post-chemotherapy) 75% in 8 patients receiving HEC and was 97, 75, and 72% in 32 patients receiving MEC. Patients with no nausea for the acute period was 100%, the delayed period 50%, and the overall period 50% in 8 patients receiving HEC and was 100, 78, and 78% in 32 patients receiving MEC. DISCUSSION: The complete response and control of nausea in subsequent cycles of chemotherapy were not significantly different from cycle one. CONCLUSION: Olanzapine combined with a single dose of dexamethasone and a single dose of palonosetron was very effective in controlling acute and delayed CINV in patients receiving both HEC and MEC.

Weighing in on the off-label use of Actiq for noncancer-related pain: a recipe for success or a recipe for disaster?

OBJECTIVE: An editorial is provided based in part upon a recent Wall Street Journal article by John Carreyrou, which cast the off-label use of opioids, in this case, Actiq (oral transmucosal fentanyl citrate), in an extremely negative light from the viewpoint of contributing to addiction. As in the past, this article seems to follow a "recipe" used to demonize opioids, the pharmaceutical industry and the physicians who prescribe pain medications. Specifically, the case is made that using oral transmucosal fentanyl citrate in noncancer patients, for whom there is no current indication, is contributing to the prescription drug abuse problem. CONCLUSIONS: We discuss the faulty logic in parsing the use of opioids between malignant and non-malignant pain patients. A call is made to pain professionals to begin discussion of the common use of pharmaceuticals in off-label ways to treat pain issues as well as a discussion of the dangers of not addressing this practice openly.

Distress screening in a multidisciplinary lung cancer clinic: prevalence and predictors of clinically significant distress.

Screening for distress in cancer patients is recommended by the National Comprehensive Cancer Network, and a Distress Thermometer has previously been developed and empirically validated for this purpose. The present study sought to determine the rates and predictors of distress in a sample of patients being seen in a multidisciplinary lung cancer clinic. Consecutive patients (N=333) were recruited from an outpatient multidisciplinary lung cancer clinic to complete the Distress Thermometer, an associated Problem Symptom List, and two questions about interest in receiving help for symptoms. Over half (61.6%) of patients reported distress at a clinically significant level, and 22.5% of patients indicated interest in receiving help with their distress and/or symptoms. Problems in the areas of family relationships, emotional functioning, lack of information about diagnosis/treatment, physical functioning, and cognitive functioning were associated with higher reports of distress. Specific symptoms of depression, anxiety, pain and fatigue were most predictive of distress. Younger age was also associated with higher levels of distress. Distress was not associated with other clinical variables, including stage of illness or medical treatment approach. Similar results were obtained when individuals who had not yet received a definitive diagnosis of lung cancer (n=134) were excluded from analyses; however, family problems and anxiety were no longer predictive of distress. Screening for distress in a multidisciplinary lung cancer clinic is feasible and a significant number of patients can be expected to meet clinical criteria for distress. Results also highlight younger age and specific physical and psychosocial symptoms as predictive of clinically significant distress. Identification of the presence and predictors of distress are the first steps toward appropriate referral and treatment of symptoms and problems that contribute to cancer patients' distress.