Management Of Chronic Cancer Pain Research Articles

Acetaminophen induces mitochondrial apoptosis through proteasome dysfunctions

Acetaminophen is a known antipyretic and non-opioid analgesic for mild pain and fever. Numerous studies uncover their hidden chemotherapeutics applications, including chronic cancer pain management. Acetaminophen also represents an anti-proliferative effect in some cancer cells. Few studies also suggest that the use of Acetaminophen can trigger apoptosis and impede cellular growth. However, Acetaminophen's molecular potential and precise mechanism against improper cellular proliferation and use as an effective anti-proliferative agent still need to be better understood. Here, our current findings show that Acetaminophen induces proteasomal dysfunctions, resulting in aberrant protein accumulation and mitochondrial abnormalities, and consequently induces cell apoptosis. We observed that the Acetaminophen treatment leads to improper aggregation of ubiquitylated expanded polyglutamine proteins, which may be due to the dysfunctions of proteasome activities. Our in-silico analysis suggests the interaction of Acetaminophen and proteasome. Furthermore, we demonstrated the accumulation of proteasome substrates and the depletion of proteasome activities after treating Acetaminophen in cells. Acetaminophen induces proteasome dysfunctions and mitochondrial abnormalities, leading to pro-apoptotic morphological changes and apoptosis successively. These results suggest that Acetaminophen can induce cell death and may retain a promising anti-proliferative effect. These observations can open new possible molecular strategies in the near future for developing and designing specific and effective proteasome inhibitors, which can be helpful in conjugation with other anti-tumor drugs for their better efficiency.

"To prescribe or not to prescribe, that is the question": Perspectives on opioid prescribing for chronic, cancer-related pain from clinicians who treat pain in survivorship.

Opioid pain management in cancer survivorship is a complex and understudied topic. The authors conducted in-depth, qualitative interviews to understand clinician approaches to opioid pain management in chronic cancer pain and to generate ideas for improvement. They used a rigorous, inductive, qualitative, descriptive approach to examine clinician (n=20) perspectives about opioid pain management in survivorship, including oncologists (n=5), palliative care clinicians (n=8), primary care clinicians (n=5), and pain management specialists (n=2). The findings indicated that no consistent medical home exists for chronic pain management in cancer survivors and that there are fundamental differences in how each subspecialty approaches chronic pain management in survivorship (e.g., "Do we think of this as noncancer pain or cancer pain?… This is in this limbo zone-this gray zone-because it's cancer-related pain, right?"). Simultaneously, clinicians are influenced by their peers' perceptions of their opioid prescribing decisions, sparking intraprofessional tension when disagreement occurs. In these instances, clinicians described overthinking and doubting their clinical decision-making as well as a sense of judgment, pressure, and/or shame. Finally, clinicians acknowledged a fear of consequences for opioid prescribing decisions. Specifically, participants cited conflict with patients, sometimes escalating to aggression and threats of violence, as well as potential disciplinary actions and/or legal consequences. Participants suggested that opportunities to improve chronic cancer pain care include developing clear, systematic guidance for chronic cancer pain management, facilitating clinician communication and consultation, creating tailored survivorship care plans in partnership with patients, and developing accessible, evidence-based, complementary pain treatments.

Prevalence of abnormal urine drug tests during COVID-19 pandemic in the cancer patient population: retrospective study.

Background: Opioid misuse is a persistent concern, heightened by the COVID-19 pandemic. This study examines the risk factors contributing to elevated rates of abnormal urine drug tests (UDTs) in the cancer pain patient population during COVID-19. Materials & methods: A retrospective chart review of 500 patient encounters involving UDTs at a comprehensive cancer center. Results: Medication adherence rates increase when UDTs are incorporated into a chronic cancer pain management protocol. Higher positive tests for illicit or nonprescribed substances in patients with specific risk factors: current smokers (tobacco), no active cancer and concurrent benzodiazepine use. Conclusion: This research emphasizes the increased risk of opioid misuse during COVID-19 among cancer pain patients with specific risk factors outlined in the results.

Understand the benefits and risks of intravenous methadone for perioperative and chronic cancer pain management

Understand the benefits and risks of intravenous methadone for perioperative and chronic cancer pain management

Expert recommendations on the formation of pain crisis concept and management plan in cancer pain management

Cancer pain is one of the most common symptoms in cancer patients, which seriously affects their quality of life. Effective cancer pain control can significantly improve the quality of life of cancer patients. There has been mature diagnostic and therapeutic clinical guidelines and consensus on the management of chronic cancer pain at home and abroad. However, the consensus on rapid treatment of severe cancer pain is still lacking worldwide. Therefore, it is necessary to rebuild the concept of pain crisis, clarify the management principles and concepts, and effectively improve the quality of life of patients with cancer pain. Herein, the expert group clarifies the definition, diagnostic criteria and overall monitoring indicators of pain crisis, and forms a relatively complete management plan for cancer patients with pain crisis, thereby exploring a fast, safe and efficient management model of pain crisis that conforms to the clinical practice in China.

Non-pharmacological integrative therapies for chronic cancer pain

Chronic pain is one of the most detrimental symptoms exhibited by cancer patients, being an indication for opioid therapy in up to half of the patients' receiving chemotherapy and in 90% of advanced cases. Various successful non-pharmacological integrative therapy options have been explored and implemented to improve the quality of life in these patients. This review aims to highlight the mechanisms implicated; assessment tools used for cancer pain and summarize current evidence on non-pharmacological approaches in the treatment of chronic cancer pain. A review of the literature was conducted using a combination of MeSH keywords including "Chronic cancer pain," "Assessment," "Non-pharmacological management," and "Integrative therapy." Data on the approach and assessment of chronic cancer pain as well as non-pharmacological integrative options have been displayed with the help of figures and tables. Of note, non-pharmacological integrative management was divided into three subcategories; physical therapy (involving exercise, acupuncture, massage, and transcutaneous electric nerve stimulation), psychosocial therapy (e.g. mindful practices, supportive therapy), and herbal supplementation. The use of non-pharmacological integrative therapy in the management of chronic cancer pain has been grossly underestimated and must be considered before or as an adjuvant of other treatment regimens to ensure appropriate care.

Chronic Pain Treatment for Patients with Vascular Ulcers of the Lower Limbs

Pain is found in 46-84.5% of patients with vascular ulcers of the lower limbs, varying according to the records considered and the etiology of the ulcer. Vascular ulcers associated with arterial insufficiency are generally more painful than vascular ulcers associated with venous insufficiency. An algorithm for the management of chronic cancer pain in patients is provided by the WHO analgesic ladder, which is commonly used by physicians. In clinical practice, the ladder is also applied to chronic non-cancer pain, even though this kind of application is limited by the absence of an evaluation of the pathogenetic mechanisms of pain. The WHO analgesic ladder drives therapy solely depending on the severity and persistence of pain, recommending progressive “step by step” pharmacologic therapy, starting with non-opioid medications (NSAIDs and Paracetamol) for mild pain, followed by mild (e.g. tramadol) and strong opioids (e.g. morphine) for moderate to severe pain. It must be noted that addiction to long-term therapy may occur even with non-opioid drugs. Short-term therapy with opioids has been associated with adverse reactions (nausea, constipation, sleepiness, dizziness and itching) in nearly 50% of the patients. Our revision of the literature on this subject analyzes the issues of analgesic chronic therapy with opioids, providing directions on how to optimize it for patients with chronic pain associated with the presence of vascular ulcers of the legs.

Ketamine Infusion in an Outpatient Surgical Facility

<h3>Background Information</h3> Cancer and the treatment plans associated with its management has the potential to impact a patient physically and physiologically. With the common complication being chronic pain, management can be challenging and at times suboptimal. Ketamine in subanesthetic dose is a widely used phencyclidine derivative for the management of chronic pain when inadequate response to multimodal treatments such as opioid therapy occurs. The Josie Robertson Surgery Center (JRSC) has established a ketamine infusion program to manage chronic pain in our cancer population. <h3>Objectives of Project</h3> To provide ketamine intravenous infusions for the management of chronic cancer pain in conjunction with opioid and/or non-steroidal anti-inflammatory drugs in a controlled setting of a perianesthesia unit; to acquire an extended period of pain relief. <h3>Process of Implementation</h3> A core group of eight nurses were educated in implementing the program within a limited time frame, in partnership with an interdisciplinary team including the office practice pain service. Education included hands-on training of multiple equipment, electronic documentation in a training environment, review of the potential side effects to anticipate and how to navigate effectively the various healthcare technological systems available for monitoring patients during their individualized outpatient visit. Nurses use their perianesthesia clinical judgment in following the titration order of four-hour ketamine infusion in accordance with potential side effects that patients might exhibit. Nursing competency for this program is accomplished by maintaining BLS and ACLS certifications, evaluation of knowledge of moderate sedation through a yearly examination and frequent re-evaluation of workflow created to provide an efficient service. <h3>Statement of Successful Practice</h3> Centered on patient's self-reporting of pain relief as evident by vocalizing improvement in their quality of life through reduction of pain intensity, increase in their ability to perform ADLs and repeat infusions based on long-lasting effect. <h3>Implications for Advancing the Practice of Perianesthesia Nursing</h3> Provides perianesthesia nurses with an autonomous role to translate their perianesthesia skills for an outpatient pain service.

Erector spinae plane block for the management of chronic cancer pain in the era of COVID-19.

Erector spinae plane block for the management of chronic cancer pain in the era of COVID-19.

Opioid Use Disorders among Patients on Long-Term Morphine for Management of Chronic Cancer Pain: A Pilot Study from a Tertiary Palliative Care Facility.

Objectives:Long-term opioid use can be associated with misuse and addiction. In the backdrop of increasing burden of cancer patients in India, it is important to assess the rate of opioid use disorders among those with chronic cancer pain. The objectives were to measure the rate of opioid use disorder in chronic cancer pain patients being managed with morphine and to assess its association with demographic and clinical characteristics.Materials and Methods:A cross-sectional study was conducted on chronic cancer pain patients who were prescribed morphine for ≥12 months, dosage of ≥60 mg/day. They were assessed using MINI version 7.0.0, WHO-ASSIST Hindi questionnaire, Addiction Behavior Checklist, and DSM-5 for opioid use disorder.Results:Forty patients who were treated with morphine for a total of 1479 months participated. The average morphine consumption was 159.50 ± 327.90 mg/day. Six (15%) showed possible inappropriate opioid analgesic use and none of the patients had opioid use disorder.Conclusion:This study reports the absence of opioid use disorder due to vigilant use of morphine in chronic cancer patients.

Patients perceptions of virtual reality therapy in the management of chronic cancer pain

The management of chronic cancer pain remains challenging and complex, with the process often involving a variety of pharmacological and non-pharmacological approaches. Recent studies have shown virtual reality (VR) therapy to be successful in the management of acute pain. However, it remains unclear whether VR-based applications are effective as an adjunctive therapy for cancer patients with chronic pain. Moreover, there exists a gap in the current research landscape that address patient's perceptions of virtual reality therapy. This qualitative study enrolled patients from a larger ongoing randomized controlled clinical trial in two focus groups covering topics including patients experience with and perspectives on using VR for chronic pain control, both generally, and specific to their own circumstances. Five major thematic categories and 23 sub-categories emerged in the analysis process reflecting the participants' narrative. Similar to other research, this study found mixed results in the use of adjunctive VR therapy to manage chronic cancer pain, although a majority of respondents found it to be beneficial. This study confirms that pain management is a highly complex and individualized process. For maximum efficacy, it is recommended that future designs of VR interventions engage pain patients in the design process to ensure maximum efficacy of experiences to with individuals' preferences.

Mind-Body Interventions in the Management of Chronic Cancer Pain.

To describe mind-body interventions used in the management of chronic cancer pain including their mechanisms of action, dosing, and delivery methods based on available evidence to date. Peer-reviewed publications. Further high-quality research is needed to establish the effectiveness and mechanisms of actions for mind-body interventions in chronic cancer pain management. Mind-body interventions for chronic cancer pain management are generally safe and well-accepted by individuals with cancer. Nurses need to be knowledgeable about these interventions to explain their level of effectiveness and any safety issues with patients.

Economic evaluation of the randomised, double-blind, placebo-controlled study of subcutaneous ketamine in the management of chronic cancer pain

Background: Treating chronic, uncontrolled, cancer pain with subcutaneous ketamine in patients unresponsive to opioids and co-analgesics remains controversial, especially in light of recent evidence demonstrating ketamine does not have net clinical benefit in this setting. Aim: To evaluate the cost-effectiveness of subcutaneous ketamine versus placebo in this patient population. Design and setting: A within-trial cost-effectiveness analysis of the Australian Palliative Care Clinical Studies Collaborative’s randomised, double-blind, placebo-controlled trial of ketamine was conducted from a healthcare provider perspective. Mean costs and outcomes were estimated from participant-level data over 5 days including positive response, health-related quality of life (HrQOL) measured with the Functional Assessment of Chronic Illness Therapy–Palliative Care (FACIT-Pal), ketamine costs, medication usage and in-patient stays. Results: There was no statistically significant difference in responder rates, but higher toxicity and worse HrQOL for ketamine participants (mean change −3.10 (standard error (SE) 1.76), ketamine n = 93; 4.53 (SE 1.38), placebo n = 92). Estimated total mean costs were AU$706 higher per ketamine participant (AU$6608) compared with placebo (AU$5902), attributable to the cost of higher in-patient costs as well as costs of ketamine administration. The results were robust to sensitivity analyses accounting for different medication use costing methods and removal of cost outliers. Conclusion: The findings suggest subcutaneous ketamine in conjunction with opioids and standard adjuvant therapy is neither an effective nor cost-effective treatment for refractory pain in advanced cancer patients.

An open-label pilot study of oral vitamin C as an opioid-sparing agent in patients with chronic pain secondary to cancer.

The purpose of this study is to assess the efficacy of oral Vitamin C as an opioid-sparing agent when used in conjunction with opioids and standard adjuvant therapy in the management of chronic cancer pain. An open-label pilot study of patients ≥18years of age with chronic pain secondary to cancer and/or its treatment and a Brief Pain Inventory average pain score of ≥3/10. In addition to opioid analgesia, patients received 1g of vitamin C twice daily over 3days (total daily dose of 2g). Patients' usual medications, including breakthrough medications, were continued throughout the study period. The primary endpoint was total daily opioid use during vitamin C administration compared with that immediately prior to study. Thirty-four patients were enrolled in the study. Seven failed to complete the trial. Across the 17 evaluable patients, the median daily opioid consumption was 360mg oral morphine equivalents (OME) on the days prior to vitamin C and 390mg when administered with vitamin C. This study failed to demonstrate any clinically significant benefit from vitamin C in conjunction with opioids in cancer-related pain and does not provide support for embarking on a larger randomised trial to determine efficacy.

Chronic cancer pain management by the nursing team

BACKGROUND AND OBJECTIVES: patients' pain is related to the tumor, to diagnostic and therapeutic procedures and to the terminality of the disease; however health professionals, especially nursing teams, still have difficulties in evaluating and managing pain. As from experience in hospitals, it was noticed that nursing teams face barriers, which is intensified in case of cancer patients, marked by the incurable cancer pain stigma. This study aimed at identifying in the literature, how nursing teams manage chronic cancer pain. CONTENTS: We have found 710 articles being 194 in LI-LACS and 516 in Scielo, being included 14 articles by means of the descriptors Nursing Care, Nursing, Chronic pain, Pain management, Oncology. In the category Cancer pain management by the nursing team, studies have reinforced the importance of pain evaluation by the nursing team and present resources and strategies to make it effective. In the category Pharmacological methods for pain management, drugs appear as the first method of choice with the three steps stair of the World Health Organization and opiophobia is discussed. In the category Non-pharmacological methods for pain management, there are interventions such as therapeutic massage, spiritual support and comfort measures, such as changing position. CONCLUSION: Assisting painful cancer patients goes beyond performing procedures; it is necessary to think about scientific knowledge acquisition and professional-patient link for a safe assistance when managing cancer pain.

Long- and short-acting opioids in cancer pain management: What is the best ratio?

206 Background: Many cancer patients experience chronic and breakthrough pain necessitating the use of both immediate release (IR) and extended release (ER) opioids. The common strategy in treating chronic cancer pain is using ER opioids with the addition of IR opioids for breakthrough pain. The National Comprehensive Cancer Network recommends IR dosing at 0.1-0.2 times the daily ER dose as needed every 1 hour for breakthrough pain, though data is lacking to validate this recommendation. The aim of this exploratory study was to review the current practice in prescribing IR and ER opioids and the IR/ER ratio used in cancer pain management at one comprehensive cancer center (CCC). Methods: We performed a retrospective chart review of 54 consecutive patients at a CCC over a 6 month period. IR/ER doses, dose adjustments and satisfaction with analgesia were recorded. Adjustments in treatment plans were made based on patients' report of effectiveness and side effects associated with ER and IR opioids. Results: 19 of 54 (35%) patients reported adequate analgesia, with the average daily prescribed IR/ER ratio of 0.6 (range 0 to 3.75). In this group, IR opioids were unchanged during the clinic visit. The ER opioids, on average, were also unchanged, though decreased by 25% and increased by 50% in a few cases over serial clinic visits. Of those patients reporting suboptimal analgesia during the clinic visit (65%), 80% had their ER opioids increased, 6% had IR opioids increased, and 9% had both IR and ER increased. The ER opioids were increased by 40% on average and IR by 11% with the average IR/ER ratio changing from 0.5 (range 0-2) to 0.37 (range 0-1.13). Conclusions: These preliminary data highlight the great variability between patient preferences and clinician decisions in terms of IR/ER opioid ratios. In this retrospective study, analgesia was better in the group using higher IR doses with a higher IR/ER ratio. At the same time, patients with suboptimal analgesia had their ER opioids titrated faster and higher than the IR opioids. More studies are needed to determine best practice in the prescribing of long and short acting opioids for management of chronic cancer pain.

Clinical Pharmacokinetics of Morphine and Its Metabolites During Morphine Dose Titration for Chronic Cancer Pain

Pain is one of the most prevalent and distressing symptoms in patients with cancer. There is evidence from observational studies that many patients do not get adequate relief. Although data in the literature confirm the effectiveness of most opioid drugs for the treatment of chronic pain, there is limited information about opioid titration. The aim of this study was to evaluate the clinical pharmacokinetics of morphine (M) and their correlation with pharmacodynamic results (effective daily dose of M and side effects) during the M titration phase, in the management of chronic cancer pain. Fifty-two consecutive patients were administered Oramorph (Molteni Farmaceutici, Scandicci, Florence, Italy; beginning with 5 mg every 6 hours), to maintain pain intensity at low levels (visual analog scale <4). M, morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G) plasma concentrations were determined by a mass spectrometric assay. Expected pharmacokinetic parameters were based on a pharmacokinetic profile extrapolated from 39 patients: M total clearance varied between 1.5 and 6.42 L·h(-1)·kg(-1); the median apparent volume of M distribution was 25.0 L/kg, and the elimination half-life was 4.4 hours. Over the entire period of treatment, a weak correlation between M and M3G or M6G concentrations was found, but the metabolite ratio (M3G/M6G) remained quite stable for each patient and at different sampling times. At the end of titration, the M6G/M ratio was significantly higher in the patients whose effective M concentration was below the median (5.2 ng/mL), than in patients in whom the concentration was above the median (M6G/M: 13.0 and 9.0, respectively). This article presents the pharmacokinetic profiles of M and its metabolites: their concentration ratio could help clinicians to optimize individual therapies and tailor the dose to individual needs. Our results indicate that the relationship between M6G and M could represent a potentially useful parameter to personalize M dosing.

Implementing practice change in chronic cancer pain management: clinician response to a phase III study of ketamine

An adequately powered, double-blind, multisite, randomised controlled trial has shown no net clinical benefit for subcutaneous ketamine over placebo in the management of cancer pain refractory to combination opioid and co-analgesic therapy. The results of the trial were disseminated widely both nationally and internationally. To determine whether the trial had impacted on clinical practice in Australasia. Members of the Australia and New Zealand Society of Palliative Medicine were sent an online ketamine utilisation survey. A total of 123/392 clinicians responded (31% response rate). The majority of respondents had practised for more than 10 years in a metropolitan hospital setting. Ketamine had been prescribed by 91% of respondents, and 92% were aware of the trial. As a result, 65% of respondents had changed practice (17% no longer prescribed ketamine, 46% used less and 2% more). Thirty-five per cent had not changed practice. Reasons for change included belief in the results of the study, concerns over the toxicity reported or because there were alternatives for pain control. Of those who prescribed less, over 80% were more selective and would now only use the drug in certain clinical situations or pain types, or when all other medications had failed. Although two-thirds of respondents reported practice change as a result of the randomised controlled trial, a minority remained convinced of the benefit of the drug from their own observations and would require additional evidence.

Development and pilot test of a new set of good practice indicators for chronic cancer pain management.

Pain is among the most important symptoms in terms of prevalence and cause of distress for cancer patients and their families. However, there is a lack of clearly defined measures of quality pain management to identify problems and monitor changes in improvement initiatives. We built a comprehensive set of evidence-based indicators following a four-step model: (1) review and systematization of existing guidelines to list evidence-based recommendations; (2) review and systematization of existing indicators matching the recommendations; (3) development of new indicators to complete a set of measures for the identified recommendations; and (4) pilot test (in hospital and primary care settings) for feasibility, reliability (kappa), and usefulness for the identification of quality problems using the lot quality acceptance sampling (LQAS) method and estimates of compliance. Twenty-two indicators were eventually pilot tested. Seventeen were feasible in hospitals and 12 in all settings. Feasibility barriers included difficulties in identifying target patients, deficient clinical records and low prevalence of cases for some indicators. Reliability was mostly very good or excellent (k > 0.8). Four indicators, all of them related to medication and prevention of side effects, had acceptable compliance at 75%/40% LQAS level. Other important medication-related indicators (i.e., adjustment to pain intensity, prescription for breakthrough pain) and indicators concerning patient-centred care (i.e., attention to psychological distress and educational needs) had very low compliance, highlighting specific quality gaps. A set of good practice indicators has been built and pilot tested as a feasible, reliable and useful quality monitoring tool, and underscoring particular and important areas for improvement.

Concomitant use of strong and weak opiods in management of chronic cancer pain

Our aim was to search whether the addition of Tramadol affected treatment when a dose increase was needed before increasing the transdermal fentanyl (TDF) dose in cancer patients using TDF would have any advantages. Patients were divided into two groups: a Control Group (Group K) and a Tramadol Group (Group T). When patients were first admitted to the polyclinic, demographic data, duration of pain and the first VAS values were recorded. Following the first examination, all patients were given TDF containing 25 µg/h of fentanyl as an initial treatment. During the study period, the TDF dose of patients in Group K was increased in a stepwise fashion of 25 µg/h whenever needed. In Group T, 200 mg of tramadol was added to the treatment without increasing the TDF dose when a dose increase was needed. In subsequent dose increase requirements in Group T, the TDF dose was sequentially increased to 25 µg/h when needed without stopping tramadol. Patients VAS score and adverse effects were recorded in each polyclinic examination. Patients were asked to assess pain treatment with the Treatment Assessment Scale (TAS). Each patient's participation in the study and highest TDF dose reached were recorded. The TDS scores measured at 1 month and 2 months after the start of the study were found to be similar. However, TAS scores measured at the end of the 3rd and 4th months were found to be significantly higher in Group T. The mean TDF dose reached at end of the study was found to be significantly higher in Group K compared to Group T. Itching was observed significantly more frequently among patients of Group K. We found in our study that when TDF and tramadol are used together, TDF need is reduced and the pain management protocol is better tolerated by patients. Based on the results of our study, we suggest concomitant use of strong and weak opioids.