Visitation policies at NCI-designated comprehensive cancer centers during the COVID-19 pandemic.

PURPOSE: Family/caregiver visitation provides critical support for patients confronting cancer and is associated with positive outcomes. However, the COVID-19 pandemic brought historic disruptions including widespread visitation restrictions. Here, we characterize in-depth the visitor policies of NCI-designated comprehensive cancer centers (CCCs) and analyze geographic/temporal patterns across CCCs. METHODS: The public-facing CCC websites, including archived webpages, were reviewed to abstract initial visitation policies and revisions, including end-of-life (EoL) exceptions and timing of visitation restrictions relative to regional lockdowns. Chi-squared and Fisher's exact tests were employed to analyze associations between geographic region, timing, and severity of restrictions. RESULTS: Most CCCs (n=43, 86%) enacted visitation restrictions between March 15 and April 15, 2020. About half barred all visitors for COVID-negative inpatients (n=24, 48%) or outpatients (n=26, 52%). Most (n=36, 72%) prohibited visitors for patients with confirmed/suspected COVID-19. Most (n=40, 80%) published EoL exceptions but the specifics were highly variable. The median time from initial restrictions to government-mandated lockdowns was 1 day, with a wide range (25 days before to 26 days after). There was no association between timing of initial restrictions and geographic location (p=0.14) or severity of inpatient policies (p=1.0), even among centers in the same city. Outpatient policies published reactively (after lockdown) were more restrictive than those published proactively (p=0.04). CONCLUSION: CCCs enacted strict but strikingly variable COVID-19 visitation restrictions, with important implications for patients/families seeking cancer care. A unified, evidence-based approach to visitation policies is needed to balance proven infection control measures with the needs of patients and families.

Palliative Pharmacotherapy: State-of-the-Art Management of Symptoms in Patients With Cancer.

BACKGROUND: Advanced cancer produces multiple symptoms as patients progress through their disease trajectory. Identifying, measuring, and providing therapy for uncontrolled symptoms becomes important because disease-altering therapies may be no longer possible. Symptoms other than pain that cause distress in patients with cancer include delirium, dyspnea, anorexia, nausea, and fatigue. Precise management of these symptoms can lead to the best possible quality of life and lessen distress. This article reviews current management strategies of these symptoms. METHODS: The epidemiology, mechanisms, assessment, and therapies of common symptoms in the advanced cancer population are reviewed. RESULTS: Identifiable approaches facilitate symptom management in advanced illness. CONCLUSIONS: Using a systematic approach to symptoms in advanced illness can improve the quality of life and lessen distress among patients with cancer and their families, friends, and caregivers.

Pharmacological Management of Cancer-Related Pain.

BACKGROUND: Pain occurs in 50% of patients with cancer at the time of diagnosis, and nearly 80% of patients with advanced stage cancer have moderate to severe pain. Assessment of pain requires the health care professional to measure pain intensity, delineate opioid responsiveness, and clarify the impact of pain on a patient's psychological, social, spiritual, and existential domains. To this end, the World Health Organization (WHO) has developed a 3-step pain ladder to help the health care professional effectively manage pain, classifying pain intensity according to severity and recommending analgesic agents based on their strength. METHODS: Health care professionals should follow the WHO guidelines to manage cancer-related pain in their patients. With regard to opioids, dosing, equianalgesic conversions, the management of adverse events, and the identification of new agents are discussed. Integrating adjuvant analgesics and interventional pain techniques into the management of cancer-related pain is also discussed. RESULTS: The WHO analgesic ladder is an effective tool for managing cancer-related pain. Successful pain management in patients with cancer relies upon the health care professional to pay attention to detail, especially during the introduction of new drugs and in identifying potential adverse events. Health care professionals must assess opioid responsiveness to determine whether adjuvant analgesics should also play a role in a patient's treatment plan. CONCLUSION: Adherence to the WHO pain ladder and understanding proper use of interventional pain techniques complement the pharmacological management of cancer-related pain.

Safety and Utility of Chloroquine/ Hydroxychloroquine in Palliative Care Patients.

The coronavirus disease 2019 (COVID-19) pandemic represents a significant healthcare challenge for the world. Many drugs have therapeutic potential. The aminoquinolones, hydroxychloroquine, and chloroquine are undergoing evaluation as a potential therapy against COVID -19. In vitro and in vivo studies suggest that these drugs affect viral adherence and modify inflammatory responses, which may provide some impact on the symptoms associated with COVID. As palliative care specialists encounter more COVID positive patients, palliative care specialists need to know how these drugs work, and importantly how they interact with palliative care drugs used for symptom control. At the same time, there is a need to reduce polypharmacy in any seriously ill patient population. The goals of this paper are to identify whether or not hydroxychloroquine/chloroquine improves symptoms in palliative care patients and whether or not these drugs are safe to use in the advanced illness population who have COVID.

Healthcare Disparities and the COVID-19 Pandemic: Analysis of Primary Language and Translations of Visitor Policies at NCI-Designated Comprehensive Cancer Centers.

CONTEXT: Coronavirus Disease 2019 (COVID-19) has caused unprecedented disruptions to cancer care, including through strict hospital visitation policies. Since a substantial proportion of the U.S. population report a non-English language as their primary language, it is critical that information is disseminated in multiple languages. OBJECTIVES: To examine the availability of language translations of visitation restrictions on adult National Cancer Institute-designated comprehensive cancer centers (CCCs) Web sites. METHODS: Cross-sectional analysis of visitation policies abstracted from public-facing Web sites of CCCs in June 2020. Using U.S. Census data, CCC's city and state proportions of self-identifying Hispanic/Latinx population were categorized into three cohorts: low (<10%), moderate (10%-20%), and high (>20%). RESULTS: As of June 2020, all 50 CCCs published a COVID-19 visitation policy on their Web site. Of these, 33 (66%) posted policies only in English, whereas 17 (34%) included one or more non-English translations. A minority of CCCs published Spanish language resources, which did not differ based on state or city demographics: for example, only 42% (8 of 19), 10% (1 of 10), and 38% (8 of 21) of CCCs published Spanish language resources in cities with low, moderate, and high Hispanic/Latinx populations, respectively. CONCLUSION: `Most CCC's did not publish non-English language translations of their visitor policies. Even in cities and states with larger Hispanic/Latinx populations, most CCCs did not publish resources in Spanish. This study highlights a key opportunity to mitigate communication barriers and deliver culturally competent, patient-centered care.

Using the values-based history to fine-tune advance care planning for oncology patients.

There is no standardized approach to the discussion of advanced care planning. One approach to discussing advanced care planning involves the use of a values history. The values history focuses on questions related to overall health, personal relationships, and independence, as well as symptoms. The values history facilitates communication with the patient and allows the patient to express their view. This approach to patient communication is less threatening to patients and does not force the patient into thinking that they need the right answer. Values-based directives are less intrusive on a doctor's skill in making appropriate clinical decisions. They ask questions that require no technical skill and are easily done by other members of the health-care team. Values histories are useful in a wide range of situations where the doctor needs to understand the patient as a person. Compared to traditional, medicalized advance directives, values histories are less subject to the objections of not being clearly established at the time of their writing, or applicable in the circumstances that subsequently arise as in this case. They can help to validate preferences about treatment and also indicate appropriate courses of action that were not, or could not, be covered by traditional advance directives alone. This article illustrates the use of a values-based history in a patient with advanced head and neck cancer.

Midazolam: an essential palliative care drug.

Midazolam is a commonly used benzodiazepine in palliative care and is considered one of the four essential drugs needed for the promotion of quality care in dying patients. Acting on the benzodiazepine receptor, it promotes the action of gamma-aminobutyric acid. Gamma-aminobutyric acid action promotes sedative, anxiolytic, and anticonvulsant properties. Midazolam has a faster onset and shorter duration of action than other benzodiazepines such as diazepam and lorazepam lending itself to greater flexibility in dosing than other benzodiazepines. The kidneys excrete midazolam and its active metabolite. Metabolism occurs in the liver by the P450 system. This article examines the pharmacology, pharmacodynamics, and clinical uses of midazolam in palliative care.

Pharmacologic Management of Malignant Bowel Obstruction: When Surgery Is Not an Option.

Malignant bowel obstruction (MBO) complicates 3%-15% of cancers and often necessitates inpatient admission. Hospitalists are increasingly involved in treating patients with MBO and coordinating their care across multiple subspecialties. Direct resolution of the obstruction via surgical or interventional means is always preferable. When such options are not possible, pharmacological treatments are the mainstay of therapy. Medications such as somatostatin analogs, steroids, H2-blockers, and other modalities can be effective in palliation and possible resolution of obstruction. Awareness of these pharmacologic therapies can aid hospitalists in treating patients who are confronted with this devastating condition.

Oncology Update: Anamorelin.

BACKGROUND: Cancer cachexia is a catabolic syndrome associated with uncontrolled muscle breakdown. There may be associated fat loss. Occurring in high frequency in advanced cancer, it is an indicator of poor prognosis. Besides weight loss, patients experience a cluster of symptoms including anorexia, early satiety, and weakness. The 3 stages of cachexia include stages of precachexia, cachexia, and refractory cachexia. Refractory cachexia is associated with active catabolism or the presence of factors that make active management of weight loss no longer possible. Patients with refractory cachexia often receive glucocorticoids or megasterol acetate. Glucocorticoid effect is short and responses to megasterol are variable. Anamorelin is a new agent for cancer anorexia-cachexia, with trials completed in advanced lung cancer. Acting as an oral mimetic of ghrelin, it improves appetite and muscle mass. This article reviews the pharmacology, pharmacodynamics, and effect on cancer cachexia. METHODS: A PubMed search was done using the Medical Subject Headings term anamorelin. Articles were selected to provide a pharmacologic characterization of anamorelin. RESULTS: Anamorelin increases muscle mass in patients with advanced cancer in 2-phase 3 trials. CONCLUSIONS: Anamorelin improves anorexia-cachexia symptoms in patients with advanced non-small-cell lung cancer.

Aripiprazole.

Delirium is a palliative care emergency where patients experience changes in perception, awareness, and behavior. Common features include changes in the sleep-wake cycle, emotional lability, delusional thinking, and language and thought disorders. Delirium results from neurotransmitter imbalances involving several neurotransmitters such as dopamine, glutamate, norepinephrine, acetylcholine, gamma-aminobutyric acid, and serotonin. Untreated delirium causes significant morbidity and mortality. Nonpharmacologic and pharmacologic approaches treat delirium. Current pharmacologic management of delirium involves using agents such as haloperidol or second-generation antipsychotics. Third-generation atypical antipsychotic drugs have emerged as a potential choice for delirium management. Aripiprazole is a third-generation antipsychotic with a dopamine receptor-binding profile distinct from other second-generation antipsychotics. Aripiprazole acts as partial agonist at dopamine D2 and 5-hydroxytryptamine (5-HT)1A receptors, stabilizing the dopamine receptor leading to improvement in symptoms. The article reviews the pharmacology, pharmacodynamics, metabolism, and evidence of clinical efficacy for this new antipsychotic agent. This article explores possible roles in palliative care.

Naloxegol: A Novel Therapy in the Management of Opioid-Induced Constipation.

Opioid-related bowel dysfunction is a common and potentially severe adverse effect from treatment with opioid analgesics. Its development is not dose related, nor do patients develop tolerance. Opioid-induced constipation (OIC) can lead to fecal impaction, bowel obstruction, and bowel perforation as well as noncompliance with opioid analgesics and poor quality of life. Routine administration of laxatives is necessary to maintain bowel function, and, in refractory cases, other modalities must be pursued. Available options are limited but include peripherally acting µ-opioid receptor antagonists (PAMORAs), including methylnaltrexone. Naloxegol is a newly developed PAMORA that is available through the oral route. At the therapeutic dose of 25 mg daily, naloxegol is effective and safe, with a limited side effect profile and is associated with preservation of centrally mediated analgesia. In this article, we discuss the pharmacokinetics, pharmacodynamics, adverse effects, clinical trials, and cost considerations of naloxegol. Finally, we discuss its potential role as a novel key treatment for OIC in palliative medicine patients.

Ziconotide: can we use it in palliative care?

Ziconotide (PRIALT) is a new nonopioid treatment for chronic pain. It is a peptide that is the synthetic analog of the omega-conotoxin, derived from the marine snail, Conus magus. The therapeutic benefit of ziconotide derives from its potent and selective blockade of neuronal N-type voltage-sensitive calcium channels. Interference with these channels inhibits input from pain-sensing primary nociceptors. A recent clinical trial demonstrated that ziconotide has a significant analgesic effect compared to placebo in patients considered intolerant or refractory to other treatment such as systemic analgesics, adjunctive therapies, or intrathecal (IT) morphine. Thus, ziconotide is the first of a new class of agents--N-type calcium channel blockers, or NCCBs. Ziconotide may represent another option for patients with refractory pain.

Aprepitant (EMEND): the role of substance P in nausea and vomiting.

Aprepitant (EMEND) is the first commercially available drug from a new class of agents, the Substance P/neurokinin NK-1 receptor antagonists. Aprepitant is indicated for prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) associated with highly emetogenic chemotherapy in adults. Its ability to antagonize the effects of Substance P has lead to greater understanding of the pathophysiology of nausea and vomiting. Its broad range of activity against a wide variety of central and peripheral emetogenic stimuli make it potentially useful in non-chemotherapy related nausea and vomiting.

Buprenorphine for cancer pain: is it ready for prime time?

Buprenorphine (BUP) is a semisynthetic derivative of the opium alkaloid thebaine found in the poppy Papaver somniferum. Its chemical structure contains the morphine structure but differs by having a cyclopropylmethyl group. Buprenorphine is a potent µ opioid agonist. Buprenorphine undergoes extensive first-pass metabolism in the liver and gut. The development of a transdermal BUP formulation in 2001 led to its evaluation in cancer pain. This article provides the practitioner with an update on the current role of BUP in cancer care. It highlights data suggesting effectiveness in various types of cancer pain. The article reviews pharmacology, routes of administration, adverse effects, drug interactions, and cost considerations.

Palliative Oncology: Denosumab.

Bone metastases cause devastating clinical complications leading patients to have pain, poor quality of life, loss of mobility, and autonomy. Complications from osseous metastases cause a big economic burden reflected by repeated admissions for uncontrolled symptoms. Management of symptoms associated with bone metastasis includes systemic analgesics, glucocorticoids, radiation (external beam radiation and radiopharmaceuticals), ablative techniques (radiofrequency ablation and cryoablation), chemotherapeutic agents, hormonal therapies, interventional techniques (eg, kyphoplasty), and surgical approaches. Bisphosphonates have become a standard therapy for bony metastasis. They bind to bone eventually inhibiting osteoclast action. Bisphosphonates decrease fractures when given routinely. Adverse effects of bisphosphonates include osteonecrosis of the jaw and renal insufficiency. Late last year, the Food and Drug Administration approved denosumab to prevent skeletal-related events (SREs) associated with metastatic solid tumors. This drug is a monoclonal antibody that inhibits the receptor activator of nuclear factor κB (RANK)-RANK ligand interaction. Clinical trials have shown superiority over bisphosphonates for the prevention of SREs. This article reviews the mechanism of action, pharmacology, adverse effects, and clinical trial evidence for this new drug.

Gefitinib: a new agent in palliative care.

In 2003, gefitinib (Iressa, AstraZeneca, London, UK) in 250 mg tablet form received accelerated approval by the US Food and Drug Administration. Gefitinib targets the cancer cell at the molecular level and has the ability to palliate lung cancer symptoms. Gefitinib's ability to control symptoms with minimal toxicity provides physicians with a new option to complement current symptom control methods. It is nonmarrow suppressive and seems to have an ability to control symptoms quickly, even in the absence of obvious tumor reduction. However, further studies are needed to compare gefitinib's ability to control symptoms with intensive palliative modalities for lung cancer, such as opioids, oxygen, and radiation therapy.

Organ donation and palliative care: can palliative care make a difference?

Donation after cardiac death (DCD) is technique of organ donation that has increased the number of available organs for transplant. This process allows organ donation after declaring death using cardiopulmonary criteria. Concerns exist with quality of symptom control and family support during this process. The case presented illustrates a specific example of how palliative care integrates with organ donation at Mayo Clinic Hospital in Phoenix, Arizona. This hospital has a DCD protocol established. The article reviews basic concepts of DCD. It reviews how a palliative care team interacts with other hospital teams to provide expert symptom control and emotional support for families during the DCD process.

Levorphanol: revisiting an underutilized analgesic.

Levorphanol (levo-3-hydroxy-N-methylmorphinan) is a step 3 opioid first developed in the 1940s as an alternative to morphine. Levorphanol belongs to the morphinan opioid series. Levorphanol has greater potency than morphine and is a potent N-methyl-d aspartate (NMDA) antagonist. Levorphanol interferes with the uptake of norepinephrine and serotonin, which makes it potentially useful for neuropathic pain. Glucuronidation changes Levorphanol to Levorphanol-3-glucuronide with excretion by the kidney. Levorphanol has a long half-life and may accumulate with repeated dosing. Levorphanol can be administered orally, intravenously, and subcutaneously. This article provides an update regarding the pharmacodynamics, pharmacology, and clinical efficacy of this often overlooked step 3 opioid.

Anticholinergics in palliative medicine: an update.

Anticholinergics, or antimuscarinic drugs, are drugs that competitively inhibit the action of acetylcholine at muscarinic receptors, leading to a blockade of the actions of the parasympathetic nervous system at sites where overactivity can lead to increased symptom burden. Successful blockade of the parasympathetic nervous system ultimately leads to decreased production of secretions in the salivary, bronchial, and gastrointestinal tracts. These effects are often used for several symptoms that originate due to parasympathetic nervous system overactivity, such as the "death rattle" and malignant bowel obstruction. Anticholinergic agents are divided into either tertiary amines or quaternary ammonium compounds, which differ in their ability to cross into the central nervous system. Quaternary compounds do not cross into the central nervous system and have a different adverse effect profile than the tertiary amines. The purpose of this review is to highlight anticholinergic agents, their pharmacology, and an evidence-based assessment of their role in palliative care.