Do We Have Structure, Process and Outcomes to Support Cannabis as Supportive Therapy in Cancer?

Cannabis is becoming more popular and more available in the United States. It has been approved for use by multiple states for various conditions and several states now allow recreational cannabis. We explore the structure of cannabis distribution, the process of acquisition, outcomes, and the safety of cannabis in the United States.

Broad Needs Assessment of Pain Education in Graduate Medical Education.

This article describes a survey-based study of graduate medical residents and fellows in an integrated health system. The study explores pain curricula, learner perspectives about pain education, and learner knowledge, attitudes, and confidence. Results indicate that pain education in the graduate medical setting is inadequate to meet learner needs.

The Management of Nausea and Vomiting Not Related to Anticancer Therapy in Patients with Cancer.

OPINION STATEMENT: In cancer patients, the management of nausea and vomiting that is not directly related to treatment is challenging. Much current practice is based on expert opinion and anecdote. Fortunately, over recent years, a number of quality trials have been undertaken to strengthen the evidence base that guides the care of our patients with these distressing symptoms. Much is still unknown however. In this article, we present the latest literature that addresses some of the outstanding issues.

Ginseng: A Qualitative Review of Benefits for Palliative Clinicians.

Ginseng has been used for centuries to treat various diseases and has been commercially developed and cultivated in the past 300 years. Ginseng products may be fresh, dried (white), or dried and steamed (red). Extracts may be made using water or alcohol. There are over 50 different ginsenosides identified by chromatography. We did an informal systematic qualitative review that centered on fatigue, cancer, dementia, respiratory diseases, and heart failure, and we review 113 studies in 6 tables. There are multiple potential benefits to ginseng in cancer. Ginseng, in certain circumstances, has been shown to improve dementia, chronic obstructive pulmonary disease, and heart failure through randomized trials. Most trials had biases or unknown biases and so most evidence is of low quality. We review the gaps in the evidence and make some recommendations regarding future studies.

Sarcopenia associated with chemotherapy and targeted agents for cancer therapy.

Clinicians often believe that cachexia is caused by cancer and anorexia as a toxicity of chemotherapy or targeted anti-cancer agents. It is now recognized that chemotherapy and certain targeted agents cause sarcopenia which reduce physical function and quality of life. Pre-treatment sarcopenia predicts chemotherapy toxicity, reduced response, increased disability, poor anti-tumor response and survival. Though bioelectrical impedance and dual energy X-ray absorptiometry (DEXA) scans have been used in the past for body composition measurements, CT scan cuts at the level of the 3rd lumbar vertebral body with measurement of skeletal muscle and visceral and subcutaneous fat areas has become standard. Nonpharmacological approaches to reducing sarcopenia during chemotherapy includes resistance training and dietary counselling. Pharmacologic therapies include vitamin D replacement if depleted, omega-3 fatty acids, testosterone and selective androgen receptor modulators (SARMS) and ghrelin. A comprehensive multimodal and multiple drug approach is likely to be better than single modalities. However, this is yet to be proven. Finally, it is not known if intervening to prevent or reverse sarcopenia will have a clinical benefit in terms of better tolerance to cancer therapy, physical function, well-being, tumor response and survival. Reversing sarcopenia and improving objective outcomes should be the goal of therapy.

Cannabinoids for Symptom Management and Cancer Therapy: The Evidence.

Cannabinoids bind not only to classical receptors (CB1 and CB2) but also to certain orphan receptors (GPR55 and GPR119), ion channels (transient receptor potential vanilloid), and peroxisome proliferator-activated receptors. Cannabinoids are known to modulate a multitude of monoamine receptors. Structurally, there are 3 groups of cannabinoids. Multiple studies, most of which are of moderate to low quality, demonstrate that tetrahydrocannabinol (THC) and oromucosal cannabinoid combinations of THC and cannabidiol (CBD) modestly reduce cancer pain. Dronabinol and nabilone are better antiemetics for chemotherapy-induced nausea and vomiting (CINV) than certain neuroleptics, but are not better than serotonin receptor antagonists in reducing delayed emesis, and cannabinoids have largely been superseded by neurokinin-1 receptor antagonists and olanzapine; both cannabinoids have been recommended for breakthrough nausea and vomiting among other antiemetics. Dronabinol is ineffective in ameliorating cancer anorexia but does improve associated cancer-related dysgeusia. Multiple cancers express cannabinoid receptors directly related to the degree of anaplasia and grade of tumor. Preclinical in vitro and in vivo studies suggest that cannabinoids may have anticancer activity. Paradoxically, cannabinoid receptor antagonists also have antitumor activity. There are few randomized smoked or vaporized cannabis trials in cancer on which to judge the benefits of these forms of cannabinoids on symptoms and the clinical course of cancer. Smoked cannabis has been found to contain Aspergillosis. Immunosuppressed patients should be advised of the risks of using "medical marijuana" in this regard.

Pharmacokinetic and pharmacodynamic evaluation of oxycodone and naltrexone for the treatment of chronic lower back pain.

INTRODUCTION: Chronic low back pain (CLBP) is a common and difficult illness to manage. Some individuals with CLBP have pain processing disorders and are also at risk for opioid abuse, misuse; addiction and diversion. Guidelines have been published to guide management; neuromodulation, exercise, mindfulness-based stress reduction and cognitive behavior therapies among other non-pharmacological reduce the pain of CLBP with minimal toxicity. Pharmacological management includes acetaminophen, NSAIDs and antidepressants, mainly duloxetine. Abuse-deterrent opioids have been developed which have been shown to reduce pain and opioid abuse risk. ALO-02 is a tamper-resistant sustained release opioid consisting of extended release oxycodone and sequestered naltrexone. Pivotal studies of ALO-02 have centered on patients with CLBP. AREAS COVERED: This manuscript will review CLBP, the pivotal analgesic and clinical abuse potential studies of ALO-02. The opinion will cover whether opioids should be used for CLBP, when they should be used and opioid choices. EXPERT OPINION: ALO-02 is one of several opioids which can be considered in the management of CLBP. The outcome to a trial of opioids should be function rather than analgesia. Most analgesic trials for CLBP have had analgesia as the primary outcome and function has not been vigorously studied as an outcome. Opioids should be considered as a trial only when other non-opioid analgesics have failed to improve analgesia and function. Universal precautions should be routinely part of phase III analgesic trial particularly for chronic non-malignant pain.

New therapies for antiemetic prophylaxis for chemotherapy.

A number of new advances have occurred over the past 2 years in the management of chemotherapy-related nausea and vomiting (CINV). A new neurokinin-1 receptor antagonist (NK1RA), netupitant, has been combined with palonosetron in a single oral tablet for treating the effects of moderately emetogenic chemotherapy (MEC) and highly emetogenic chemotherapy (HEC). Rolapitant, another NK1RA, unlike aprepitant, has a long half-life and does not block CYP-3A4 and therefore has fewer drug interactions. Olanzapine reduces nausea more effectively than aprepitant in patients who are receiving HEC and is a better rescue antiemetic than is metoclopramide. Ginger lacks efficacy as an antiemetic agent for CINV. Although there was some evidence in a pilot study of gabapentin as an antiemetic, it was no better in reducing CINV than was placebo. Compliance to guidelines in multiple settings ranges from 50%-60% but is improved by computerized order entry of antiemetics and recommendations displayed with chemotherapy.

Use of non-opioid analgesics as adjuvants to opioid analgesia for cancer pain management in an inpatient palliative unit: does this improve pain control and reduce opioid requirements?

BACKGROUND: Cancer pain is complex, and despite the introduction of the WHO cancer pain ladder, few studies have looked at the prevalence of adjuvant medication use in an inpatient palliative medicine unit. In this study, we evaluate the use of adjuvant pain medications in patients admitted to an inpatient palliative care unit and whether their use affects pain scores or opiate dosing. METHODS: In this retrospective observational study, patients admitted to the inpatient palliative care unit over a 3-month period with a diagnosis of cancer on opioid therapy were selected. Data pertaining to demographics, diagnosis, oral morphine dose equivalent of the opioid at the time of discharge, adjuvant analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), and pain scores as reported by nurses and physicians were collected. RESULTS: Seventy-seven patients were eligible over a 3-month period, out of which 65 (84 %) were taking an adjuvant medication. The most commonly prescribed adjuvant was gabapentin (70 %). Fifty-seven percent were taking more than one adjuvant. There were more women in the group receiving adjuvants (57 vs. 17%, p = 0.010). Those without adjuvants compared with those on adjuvants did not have worse pain scores on discharge as reported by physicians (0.8 ± 0.8 vs. 1.0 ± 0.7, p = 0.58) or nurses (2.0 ± 2.7 vs. 2.1 ± 2.6, p = 0.86). There was no difference in morphine equivalent doses of the opioid in both groups (median (min, max); 112 (58, 504) vs. 200 (30, 5,040)) at the time of discharge; 75-80 % of patients had improvement in pain scores as measured by a two-point reduction in numerical rating scale (NRS). DISCUSSION: This study shows that adjuvant medications are commonly used for treating pain in patients with cancer. More than half of study population were on two adjuvants or an adjuvant plus NSAID along with an opioid. We did not demonstrate any benefit in terms of improved pain scores or opioid doses with adjuvants, but this could reflect confounding variables and physician choice. Larger prospective studies are needed to define the opioid-sparing effects of adjuvants. CONCLUSION: Adjuvant agents are used in over 80 % of those treated for cancer pain.

Long-term and short-term effects of insomnia in cancer and effective interventions.

Sleep disorders and insomnia are more prevalent in patients with cancer than in the normal population. Sleep disorders consist of delayed sleep latency, waking episodes after sleep onset, unrefreshing sleep, reduced quality of sleep, and reduced sleep efficiency. Sleep disorders cluster with pain, fatigue, depression, anxiety, and vasomotor symptoms, depending on stage of disease, treatment, and comorbidities. Premorbid sleep problems and shift work have been associated with a higher prevalence of cancer; in fact, shift work has been labeled a carcinogen. Treatment for insomnia includes cognitive behavioral therapy with sleep hygiene, bright-light therapy, exercise, yoga, melatonin, and hypnotic medications. Unfortunately, there are few randomized trials in cancer-related sleep disorders such that most recommendations particularly for hypnotics are based on treatment for primary insomnia. In this article, insomnia is reviewed as a predisposing factor to cancer, prior to and during treatment, in cancer survivorship and in advanced cancer. Recommendations for treatment are based on low-quality evidence but are also reviewed.

Fighting insomnia and battling lethargy: the yin and yang of palliative care.

There is an interdependent relationship between insomnia and fatigue in the medical literature, but both remain distinct entities. Insomnia entails problematic sleep initiation, maintenance, or restoration with an accompanying decrease in perceived daytime function. Lethargy is a symptom that has a wide differential diagnosis that heavily overlaps with cancer-related fatigue; however, insomnia may contribute to worsened fatigue and lethargy in cancer patients. Insomnia is a major risk factor for mood disturbances such as depression, which may also contribute to lethargy in this at-risk population. The pathophysiology of fatigue and insomnia is discussed in this review, including their differential diagnoses as well as the emerging understanding of the roles of neurotransmitters, branched-chain amino acids, and inflammatory cytokines. Treatment approaches for insomnia and fatigue are also discussed and reviewed, including the role of hypnotics, psychotropics, hormonal agents, and alternative therapies.

The care of the actively dying in an academic medical center: a survey of registered nurses' professional capability and comfort.

BACKGROUND: Care of the dying is a significant component of nursing practice particularly in hospitals. Nurses who work in certain areas like oncology, intensive care unit (ICU) face the care of the dying, more so than other units. OBJECTIVES: The survey was conducted to assess nurses' self-perception of their professional capability and comfort in the care of the actively dying. Determine if professional capability and comfort was associated with any of the six demographics characteristics (age, gender, clinical experience, education level, nursing unit, continuing education). Identify areas of clinical challenge to promote educational initiatives to stimulate best nursing practice in the actively dying. DESIGN: The survey comprised of two parts: Part I with demographic characteristics and a single open-ended question, Part II with twenty questions on the domains recommended by the NCP. RESULTS: Older age and greater clinical experience were associated with greater levels of capability/comfort. Most nurses felt professionally capable and comfortable in domains such as knowledge, physical and psychosocial care but bioethics, communication, cultural, spiritual and bereavement issues challenged ≥ 40%. CONCLUSIONS: Nurses self-perceived professional capability and comfort levels in caring for the dying were positively influenced by older age, greater clinical experience and extensive continuing education. Bioethics, communication and grief impacted nurses personally and emotionally. Continuing education, organized debriefing, grief-counseling, and preceptors support should be routine for nurses who work in units with predictable high mortality.

Music interventions for psychological and physical outcomes in cancer: a systematic review and meta-analysis.

PURPOSE: A systematic review and meta-analysis to examine the effect of music interventions on psychological and physical outcome measures in cancer patients. METHODS: We searched six English-language databases and three major Chinese-language databases in March 2011. Nine databases were reviewed from 1966 or the start of the database to March 2011. All randomized controlled trials comparing music intervention with standard care, other interventions, or placebo for psychological and physical outcomes in cancer were included. Study quality was evaluated by the Grading of Recommendations Assessment, Development, and Evaluation Working Group. We then performed a meta-analysis of music interventions for psychological and physical outcomes in cancer. RESULTS: Of 322 total studies found, 32 randomized trials (3181 participants) met the inclusion criteria. Seven high-quality studies indicated music had positive effects on coping anxiety assessed by the Self-Rating Anxiety Scale. Two moderate-quality studies suggested music reduced anxiety assessed by the Hamilton Anxiety Scale. Eight moderate-quality studies revealed music lowered anxiety assessed by the Spielberger State-Trait Anxiety Inventory. Seven moderate-quality studies demonstrated that music improved depression. Seven moderate-quality studies observed that music had positive effects on pain management. Two moderate-quality studies suggested music worsened fatigue. Four moderate-quality studies indicated music lowered heart rate. Three low-quality studies suggested music could reduce respiratory rate. Two moderate-quality studies indicated that music improved quality of life. CONCLUSIONS: Individual randomized trials suggest that music intervention is accepted by patients and associated with improved psychological outcomes. The effects of music on vital signs especially blood pressure are small. High-quality trials are needed to further determine the effects of music intervention.

The business of palliative medicine - part 5: service utilization in a comprehensive integrated program.

The aim of palliative medicine is to provide multidisciplinary comprehensive care in advanced illness. Patient and family utilization of various product service lines offered by the Harry R Horvitz Center for Palliative Medicine at the Cleveland Clinic Foundation was studied. Newly referred patients were followed up prospectively until 85% had either died or been lost to follow-up. Demographic, clinical, and referral data were recorded; subsequent product service line utilization was updated daily. The total study period was 171 days, and 238 patients entered. Acute care inpatient unit, outpatient clinic visits, and 24-hour phone contacts were the most frequently used product service lines. Patients had a median of 3 contacts (range, 1 to 27) with individual service lines. Multiple palliative medicine product service lines were utilized often, with repeated use of the individual service lines. A comprehensive integrated palliative medicine program is necessary to fully meet the complex needs of those with advanced disease.

Acute inpatient palliative medicine in a cancer center: clinical problems and medical interventions--a prospective study.

The clinical characteristics and medical interventions of the 100 consecutive cancer admissions to the acute care inpatient palliative medicine unit at the Cleveland Clinic for 2 months are described. Median age was 62 years (range, 31 to 92 years). The male-female ratio was 1:1. Most admissions were referred by hematology-oncology and had prior antineoplastic therapy. Reasons for admission were symptom control and cancer-related complications. Patients underwent invasive diagnostic and therapeutic procedures, hydration, transfusions, radiation, or chemotherapy, or a combination, during their admission. Most were discharged home with hospice care or had outpatient clinic follow-up. The mortality rate was 20%. Aggressive multidisciplinary management of symptoms, disease complications, comorbid conditions, and psychosocial problems were provided. Palliative medicine physicians provided continuity of care in the outpatient clinic and at home. An acute inpatient palliative medicine unit within a tertiary level medical center has a definable and important role in comprehensive cancer care.

The clinical effects of music therapy in palliative medicine.

GOAL: This study was to objectively assess the effect of music therapy on patients with advanced disease. PATIENTS AND METHODS: Two hundred patients with chronic and/or advanced illnesses were prospectively evaluated. The effects of music therapy on these patients are reported. Visual analog scales, the Happy/Sad Faces Assessment Tool, and a behavior scale recorded pre- and post-music therapy scores on standardized data collection forms. A computerized database was used to collect and analyze the data. RESULTS: Utilizing the Wilcoxon signed rank test and a paired t test, music therapy improved anxiety, body movement, facial expression, mood, pain, shortness of breath, and verbalizations. Sessions with family members were also evaluated, and music therapy improved families' facial expressions, mood, and verbalizations. All improvements were statistically significant (P<0.001). Most patients and families had a positive subjective and objective response to music therapy. Objective data were obtained for a large number of patients with advanced disease. CONCLUSIONS: This is a significant addition to the quantitative literature on music therapy in this unique patient population. Our results suggest that music therapy is invaluable in palliative medicine.

A syllabus for fellowship education in palliative medicine.

Recent years have seen significant growth in palliative medicine training programs and positions. There are plans to pursue palliative medicine specialty status with the American Board of Medical Specialties and accreditation of fellowship programs with the American College of Graduate Medical Education. A work group of program directors, supported initially by the Cleveland Clinic and then by the American Board of Hospice and Palliative Medicine, has recently published standards for fellowship training. Despite this, fundamental questions remain about defining the field and delineating the knowledge and skills expected following completion of specialty training. In this article, we describe the first fellowship program in palliative medicine (PMP) in the United States, developed and supported by the Cleveland Clinic Foundation. The program has been implemented as part of the Harry R. Horvitz Center for Palliative Medicine, founded in 1987 as the first comprehensive integrated US program in this field. This training program, in existence since 1989, features a traditional rotational structure with an inpatient primary care service, inpatient consult services, and an outpatient consult/hospice service. This article outlines the syllabus developed for this fellowship, given what we believe to be the essential knowledge base for the field of palliative medicine.

Demographics, assessment and management of pain in the elderly.

The prevalence of pain increases with each decade of life. Pain in the elderly is distinctly different from pain experienced by younger individuals. Cancer is a leading cause of pain; however, other conditions that cause pain such as facet joint arthritis (causing low back pain), polymyalgia rheumatica, Paget's disease, neuropathies, peripheral vascular disease and coronary disease most commonly occur in patients over the age of 50 years. Poorly controlled pain in the elderly leads to cognitive failure, depression and mood disturbance and reduces activities of daily living. Barriers to pain management include a sense of fatalism, denial, the desire to be 'the good patient', geographical barriers and financial limitations. Aging causes physiological changes that alter the pharmacokinetics and pharmacodynamics of analgesics, narrowing their therapeutic index and increasing the risk of toxicity and drug-drug interactions. CNS changes lead to an increased risk of delirium. Assessment among the verbal but cognitively impaired elderly is satisfactorily accomplished with the help of unidimensional and multidimensional pain scales. A comprehensive physical examination and pain history is essential, as well as a review of cognitive function and activities of daily living. The goal of pain management among the elderly is improvement in pain and optimisation of activities of daily living, not complete eradication of pain nor the lowest possible drug dosages. Most successful management strategies combine pharmacological and nonpharmacological (home remedies, massage, topical agents, heat and cold packs and informal cognitive strategies) therapies. A basic principle of the pharmacological approach in the elderly is to start analgesics at low dosages and titrate slowly. The WHO's three-step guideline to pain management should guide prescribing. Opioid choices necessitate an understanding of pharmacology to ensure safe administration in end-organ failure and avoidance of drug interactions. Adjuvant analgesics are used to reduce opioid adverse effects or improve poorly controlled pain. Adjuvant analgesics (NSAIDs, tricyclic antidepressants and antiepileptic drugs) are initiated prior to opioids for nociceptive and neuropathic pain. Preferred adjuvants for nociceptive pain are short-acting paracetamol (acetaminophen), NSAIDs, cyclo-oxygenase-2 inhibitors and corticosteroids (short-term). Preferred drugs for neuropathic pain include desipramine, nortriptyline, gabapentin and valproic acid. Drugs to avoid are pentazocine, pethidine (meperidine), dextropropoxyphene and opioids that are both an agonist and antagonist, ketorolac, indomethacin, piroxicam, mefenamic acid, amitriptyline and doxepin. The type of pain, and renal and hepatic function, alter the preferred adjuvant and opioid choices. Selection of the appropriate analgesics is also influenced by versatility, polypharmacy, severity and type of pain, drug availability, associated symptoms and cost.