Tetrahydrocannabinol and Cannabidiol for Pain Treatment-An Update on the Evidence.

In light of the current International Association for the Study of Pain (IASP) clinical practice guidelines (CPGs) and the European Society for Medical Oncology (ESMO) guidelines, the topic of cannabinoids in relation to pain remains controversial, with insufficient research presently available. Cannabinoids are an attractive pain management option due to their synergistic effects when administered with opioids, thereby also limiting the extent of respiratory depression. On their own, however, cannabinoids have been shown to have the potential to relieve specific subtypes of chronic pain in adults, although controversies remain. Among these subtypes are neuropathic, musculoskeletal, cancer, and geriatric pain. Another interesting feature is their effectiveness in chemotherapy-induced peripheral neuropathy (CIPN). Analgesic benefits are hypothesized to extend to HIV-associated neuropathic pain, as well as to lower back pain in the elderly. The aim of this article is to provide an up-to-date review of the existing preclinical as well as clinical studies, along with relevant systematic reviews addressing the roles of various types of cannabinoids in neuropathic pain settings. The impact of cannabinoids in chronic cancer pain and in non-cancer conditions, such as multiple sclerosis and headaches, are all discussed, as well as novel techniques of administration and relevant mechanisms of action.

The Degree of Acceptance of Cocoon Strategy of Vaccination against Influenza and COVID-19 in Palliative Home Care Professionals and Caregivers.

Palliative care patients are an immunocompromised population, so the cocooning strategy of vaccinating those around them is a suitable protective strategy against infections. This is especially significant for infectious diseases such as influenza and COVID-19, which pose a challenge to the healthcare system. In order to improve the patient's quality of life, it is necessary to develop research-based, defined strategies. This questionnaire-based study was conducted to determine the level of knowledge about influenza and SARS-CoV-2 coronavirus vaccination among the factual caregivers and medical staff in the palliative care setting. The survey revealed that the sources of knowledge about vaccination varied and depended on one's role. Doctors and nurses used professional literature, while other medical professionals relied on the Internet, mass media, and information from family and friends. The study also showed that adherence to vaccination guidelines was not associated with COVID-19 incidence. The overall opinion on vaccination was positive, but the degree of acceptance varied by the role. Palliative care nurses and caregivers were the groups that were the least accepting of vaccination. To improve the acceptance of vaccinations, a remedial program based on professional education should be implemented using the sources declared by the respondents. It may help improve the quality of life for palliative care patients and prevent the spread of infectious diseases.

Practices to overcome the inexistence of Advance Care Planning in Poland.

Although the first Advance Care Planning (ACP) models were developed decades ago, Poland is still a country where ACP has not yet been implemented, despite its apparent benefits for both patients and the health care system. This article presents the legal and cultural context, main impediments, and opportunities for implementing ACP in Poland. Legal regulations are mandatory to ensure respect for the patient's will. Raising public awareness seems to be a cornerstone of the shift of paradigm. We strongly believe that the support of experienced countries is indispensable.

Personal fear of their own death and determination of philosophy of life affects the breaking of bad news by internal medicine and palliative care clinicians.

Introduction: Patients with life-threatening disease should be informed about the diagnosis and prognosis of life-expectancy. Breaking bad news (BBN) by a clinician may be affected not only by their lack of communication skills but also their philosophy of life, beliefs, fear of their own death, their length of tenure, and their exposure to dying and death. Material and methods: This questionnaire-based study aimed to investigate the impact of these factors on BBN in internal medicine practitioners (INT) versus palliative care physicians (PCP), and to detect the possible impediments to the proper communication process and the clinicians' needs regarding their preparation for such a conversation. Results: Thirty-eight PCPs and 64 INTs responded. Determination of philosophy of life, but not religiousness, positively correlated with the number of working years in palliative care. Two-thirds of the respondents declared fear of death, and it diminishes along with working years, especially in palliative care. For most physicians, BBN appeared difficult; however, less so for PCPs, persons with a high level of determination of philosophy of life, and men. The most frequent impediment was insufficient communication skills. Consistently, the respondents expressed the need for closing the gap in communication skills, especially by mentoring or training on communication. Conclusions: Fear of death may restrain inexperienced medical professionals from BBN to patients and makes it difficult. Working in palliative care augments the determination of philosophy of life and diminishes fear of death. The higher the determination of philosophy of life, the more likely BBN is to be performed. Philosophy of life, spirituality, and communication skills should be addressed in postgraduate education.

Itopride increases the effectiveness of the management of opioid-induced constipation in palliative care patients: an observational non-interventional study.

Introduction: It is strongly recommended that laxatives be routinely prescribed for the prevention of opioid-induced constipation (OIC). The evidence supporting the effectiveness of prokinetics for this indication is sparse. This study aims to verify if itopride, added to preventive OIC therapy, increases the effectiveness of the prevention of opioid-induced constipation in adult palliative care patients. Material and methods: In a questionnaire-based observational study, all patients received regular laxatives plus one of the following: oxycodone/naloxone (OXN); itopride (ITP); or oxycodone/naloxone + itopride (OXN + ITP). The primary measure was the decrease in the necessity of laxative use in a 0-4 scale assessed after 7 days of treatment. Results: Ninety-two patients met the inclusion criteria in the four groups: OXN (n = 12), ITP (11), OXN + ITP (9), and the control group (laxatives only if needed) (60). The necessity of laxatives decreased in groups where itopride was used, with a statistically significant difference versus control, oxycodone/naloxone (p = 0.009), or in combination. The OXN did not decrease laxative use (p = 0.22). Conclusions: All interventions appeared similarly effective in the prevention of OIC. However, adding itopride, but not oxycodone/naloxone, resulted in a decrease in the necessity of laxative use in OIC patients, and it seems to be valuable in this often refractory condition. Randomised, controlled trials would be valuable to obtain good quality evidence without systematic bias.

Opioid-Induced Sexual Dysfunction in Cancer Patients.

Sexual dysfunction is common in patients with advanced cancer, although it is frequently belittled, and thus consistently underdiagnosed and untreated. Opioid analgesics remain fundamental and are widely used in cancer pain treatment. However, they affect sexual functions primarily due to their action on the hypothalamus-pituitary-gonadal axis. Other mechanisms such as the impact on the central and peripheral nervous systems are also possible. The opioid-induced sexual dysfunction includes erectile dysfunction, lack of desire and arousal, orgasmic disorder, and lowered overall sexual satisfaction. Around half of the individuals taking opioids chronically may be affected by sexual dysfunction. The relative risk of sexual dysfunction in patients on chronic opioid therapy and opioid addicts increased two-fold in a large meta-analysis. Opioids differ in their potential to induce sexual dysfunctions. Partial agonists and short-acting opioids may likely cause sexual dysfunction to a lesser extent. Few pharmaceutical therapies proved effective: testosterone replacement therapy, PDE5 inhibitors, bupropion, trazodone, opioid antagonists, and plant-derived medicines such as Rosa damascena and ginseng. Non-pharmacological options, such as psychosexual or physical therapies, should also be considered. However, the evidence is scarce and projected primarily from non-cancer populations, including opioid addicts. Further research is necessary to explore the problem of sexuality in cancer patients and the role of opioids in inducing sexual dysfunction.

Constipation in Cancer Patients - an Update of Clinical Evidence.

OPINION STATEMENT: Constipation is one of the most frequent problems in cancer patients, and its etiology is multifactorial. It leads to decreased quality of life and impedes optimal pain treatment. Despite the high prevalence, constipation is frequently underdiagnosed mainly because of lack of validated diagnostic criteria or widely accepted definition of constipation in cancer patients. All cancer patients should be evaluated regularly for constipation, and concomitant causes and risk factors were assessed. Opioids are responsible for a much of the secondary constipation in cancer patients. The management of constipation in cancer patients should be multifaceted, addressing dietary and behavioral issues and optimizing pharmacological interventions. Prevention of opioid-induced constipation (OIC) is pivotal, as treatment is often unsatisfactory or inefficient. Dietary and behavioral interventions should be considered. Non-pharmacological measures include hydration and nutrition, ensuring privacy during defecation, using a commode or footstool, and the availability of a caregiver. Abdominal massage may be of value. Traditional laxatives are recommended in prevention but not in the treatment of OIC. Peripherally acting mu-opioid receptor antagonists (PAMORA) appear the first choice in the treatment and an alternative to laxatives in some recent clinical practice guidelines in preventing OIC. Naldemedine, naloxegol, and methylnaltrexone are supported by quality evidence for OIC management. Naloxone or naltrexone, taken orally in combined formulations with opioids, may be valuable in preventing or reducing OIC symptoms.

Orthostatic hypotonia as a probably late sequela of SARS-CoV-2 infection in a patient provided with palliative home care: a case report.

BACKGROUND: The SARS-CoV-2 pandemic has become a challenge for the entire healthcare system. Treatment for COVID-19 includes casual and symptomatic management in the acute phase of the disease and focuses on the treating early complications of the disease. Long-term health consequences of the infection have not yet been fully identified. A special group of patients with comorbidities, including neoplastic disease for whom the interpretation and management of symptoms is a major challenge. CASE PRESENTATION: In this case report, we present a 73-year-old woman with recently diagnosed gastric adenocarcinoma in whom we diagnosed orthostatic hypotonia in the aftermath of SARS-CoV-2 infection. We administered thiethylperazine maleate 6.5 mg daily. Additionally, we advised the patient to slowly lift from the recumbent position, raise the headboard, take meals in small portions, and increase fluid intake. These pharmacological and nonpharmacological measures resulted in sustained relief of dizziness and nausea. CONCLUSIONS: The occurrence of orthostatic hypotonia seems a possible late sequela of SARS-CoV-2 infection, and simple measures appeared sufficient to achieve sustained symptom control.

MASCC multidisciplinary evidence-based recommendations for the management of malignant bowel obstruction in advanced cancer.

PURPOSE: To provide evidence-based recommendations on the management of malignant bowel obstruction (MBO) for patients with advanced cancer. METHODS: The Multinational Association for Supportive Care in Cancer (MASCC) MBO study group conducted a systematic review of databases (inception to March 2021) to identify studies about patients with advanced cancer and MBO that reported on the following outcomes: symptom management, bowel obstruction resolution, prognosis, overall survival, and quality of life. The review was restricted to studies published in English, but no restrictions were placed on publication year, country, and study type. As per the MASCC Guidelines Policy, the findings were synthesized to determine the levels of evidence to support each MBO intervention and, ultimately, the graded recommendations and suggestions. RESULTS: The systematic review identified 17,656 published studies and 397 selected for the guidelines. The MASCC study group developed a total of 25 evidence-based suggestions and recommendations about the management of MBO-related nausea and vomiting, bowel movements, pain, inflammation, bowel decompression, and nutrition. Expert consensus-based guidance about advanced care planning and psychosocial support is also provided. CONCLUSION: This MASCC Guideline provides comprehensive, evidence-based recommendations about MBO management for patients with advanced cancer.

Opioid prescribing attitudes of palliative care physicians versus other specialists: a questionnaire-based survey.

PURPOSE OF THE STUDY: While opioid overuse is a public health crisis in the USA, opioid analgesics are used suboptimally in Central and Eastern Europe, causing many pain cases to remain untreated or undertreated. STUDY DESIGN: This questionnaire study aimed to identify the prevalent prescribing patterns and attitudes and the possible internal impediments to optimal opioid use among palliative care physicians and other specialists in Poland. RESULTS: Tramadol was the most commonly preferred opioid. While palliative care physicians (n=81) used various strong opioids, other physicians (n=87) prescribed mostly buprenorphine, accessible with standard prescription forms. Neither internal prejudices and beliefs nor administrative regulations impede prescribing opioids by palliative care physicians, unlike specialists other than palliative medicine. Special prescription forms for psychoactive medications, fear of drug addiction of their patients and penalties for possible errors on prescriptions affect the latter's optimal prescribing. They also revealed significant gaps in the knowledge of prescribing opioids and would take part in additional training. Palliative care physicians appeared optimally prepared for cancer pain management and report fewer internal barriers than other specialists. CONCLUSIONS: Continuous medical education on cancer pain treatment should be provided to all specialists to ensure optimal opioid pharmacotherapy and avoid overprescribing or underprescribing opioids. Administrative restrictions are the main barrier to optimal pain treatment.

The Therapeutic Potential of Cannabis in Counteracting Oxidative Stress and Inflammation.

Significant growth of interest in cannabis (Cannabis sativa L.), especially its natural anti-inflammatory and antioxidative properties, has been observed recently. This narrative review aimed to present the state of the art of research concerning the anti-inflammatory activity of all classes of cannabinoids published in the last five years. Multimodal properties of cannabinoids include their involvement in immunological processes, anti-inflammatory, and antioxidative effects. Cannabinoids and non-cannabinoid compounds of cannabis proved their anti-inflammatory effects in numerous animal models. The research in humans is missing, and the results are unconvincing. Although preclinical evidence suggests cannabinoids are of value in treating chronic inflammatory diseases, the clinical evidence is scarce, and further well-designed clinical trials are essential to determine the prospects for using cannabinoids in inflammatory conditions.

Targeting Inflammation by Anthocyanins as the Novel Therapeutic Potential for Chronic Diseases: An Update.

Low-grade chronic inflammation (LGCI) and oxidative stress act as cooperative and synergistic partners in the pathogenesis of a wide variety of diseases. Polyphenols, including anthocyanins, are involved in regulating the inflammatory state and activating the endogenous antioxidant defenses. Anthocyanins' effects on inflammatory markers are promising and may have the potential to exert an anti-inflammatory effect in vitro and in vivo. Therefore, translating these research findings into clinical practice would effectively contribute to the prevention and treatment of chronic disease. The present narrative review summarizes the results of clinical studies from the last 5 years in the context of the anti-inflammatory and anti-oxidative role of anthocyanins in both health and disease. There is evidence to indicate that anthocyanins supplementation in the regulation of pro-inflammatory markers among the healthy and chronic disease population. Although the inconsistencies between the result of randomized control trials (RCTs) and meta-analyses were also observed. Regarding anthocyanins' effects on inflammatory markers, there is a need for long-term clinical trials allowing for the quantifiable progression of inflammation. The present review can help clinicians and other health care professionals understand the importance of anthocyanins use in patients with chronic diseases.

Survival of Patients with Multi-Level Malignant Bowel Obstruction on Total Parenteral Nutrition at Home.

Home parenteral nutrition (HPN) may improve the survival in selected patients with malignant bowel obstruction. This retrospective, medical registry-based study aimed to identify clinical and laboratory markers predicting short survival, which would allow a more accurate selection of patients that would benefit from HPN in inoperative bowel obstruction. In a retrospective analysis of 114 patients receiving HPN, the median survival was 89 days after discharge home, and the three and six-month survival probability was 48% and 26%, respectively. Parenteral nutrition was provided during 98% of overall survival time and ended on a median of one day before the patient's death. Discontinuing chemotherapy, anemia, severe hypoalbuminemia, and water retention appeared correlated with survival shorter than three months. In these cases, routine initiation of HPN should be discouraged, as it may not bring any benefits to the patient. The decision on the initiation of HPN should be made along with continuing or initiating chemotherapy.

Prospects for the Use of Cannabinoids in Psychiatric Disorders.

Increasing evidence suggests an essential role of the endocannabinoid system in modulating cognitive abilities, mood, stress, and sleep. The psychoactive effects of cannabis are described as euphoric, calming, anxiolytic, and sleep-inducing and positively affect the mood, but can also adversely affect therapy. The responses to cannabinoid medications depend on the patient's endocannabinoid system activity, the proportion of phytocannabinoids, the terpenoid composition, and the dose used. There is some evidence for a therapeutic use of phytocannabinoids in psychiatric conditions. THC and CBD may have opposing effects on anxiety. Current guidelines recommend caution in using THC in patients with anxiety or mood disorders. In a small number of clinical trials, cannabinoids used to treat cancer, HIV, multiple sclerosis, hepatitis C, Crohn's disease, and chronic neuropathic pain report decreases in anxiety or depression symptoms and presented sedative and anxiolytic effects. Several studies have investigated the influence of potential genetic factors on psychosis and schizophrenia development after cannabis use. THC may increase the risk of psychosis, especially in young patients with an immature central nervous system. There is limited evidence from clinical trials that cannabinoids are effective therapy for sleep disorders associated with concomitant conditions. There is evidence for a possible role of cannabis as a substitute for alcohol and drugs, also in the context of the risks of opioid use (e.g., opioid-related mortality). In this narrative review of the recent evidence, we discuss the prospects of using the psychoactive effects of cannabinoids in treating mental and psychiatric disorders. However, this evidence is weak for some clinical conditions and well-designed randomized controlled trials are currently lacking. Furthermore, some disorders may be worsened by cannabis use.

Proposed Criteria for Constipation in Palliative Care Patients. A Multicenter Cohort Study.

Although constipation is one of the most frequently reported symptoms in palliative care, there is no widely accepted definition of constipation and none suitable for patients unable to self-report or express symptoms. This study aimed to verify the objective and subjective symptoms of constipation to develop a diagnostic algorithm for constipation, which is also feasible in unconscious patients. In a pooled analysis of two observational studies, 369 out of 547 adult end-stage cancer patients met the inclusion criteria. The patient-reported difficulty of defecation correlated with observable measures, such as days since last bowel movement, and frequency of bowel movements. Difficulty became at least moderate when there were no bowel movements for ≥2 days, or the frequency of bowel movements was ≤3 per week. The diagnostic algorithm, comprising these three symptoms offers a simple, rapid, and comprehensive tool for palliative care, independent of the patient's state of consciousness. A clinical trial is necessary to confirm its validity and usefulness.

Palliative Performance Scale: cross cultural adaptation and psychometric validation for Polish hospice setting.

BACKGROUND: Measuring functional status in palliative care may help clinicians to assess a patient's prognosis, recommend adequate therapy, avoid futile or aggressive medical care, consider hospice referral, and evaluate provided rehabilitation outcomes. An optimized, widely used, and validated tool is preferable. The Palliative Performance Scale Version 2 (PPSv2) is currently one of the most commonly used performance scales in palliative settings. The aim of this study is the psychometric validation process of a Polish translation of this tool (PPSv2-Polish). METHODS: Two hundred patients admitted to a free-standing hospice were evaluated twice, on the first and third day, for test-retest reliability. In the first evaluation, two different care providers independently evaluated the same patient to establish inter-rater reliability values. PPSv2-Polish was evaluated simultaneously with the Karnofsky Performance Score (KPS), Eastern Cooperative Oncology Group (ECOG) Performance Status (ECOG PS), and Barthel Activities of Daily Living (ADL) Index, to determine its construct validity. RESULTS: A high level of full agreement between test and retest was seen (63%), and a good intra-class correlation coefficient of 0.85 (P < 0.0001) was achieved. Excellent agreement between raters was observed when using PPSv2-Polish (Cohen's kappa 0.91; P < 0.0001). Satisfactory correlations with the KPS and good correlations with ECOG PS and Barthel ADL were noticed. Persons who had shorter prognoses and were predominantly bedridden also had lower scores measured by the PPSv2-Polish, KPS and Barthel ADL. A strong correlation of 0.77 between PPSv2-Polish scores and survival time was noted (P < 0.0001). Moderate survival correlations were seen between KPS, ECOG PS, and Barthel ADL of 0.41; - 0.62; and 0.58, respectively (P < 0.0001). CONCLUSION: PPSv2-Polish is a valid and reliable tool measuring performance status in a hospice population and can be used in daily clinical practice in palliative care and research.

Topical morphine for treatment of cancer-related painful mucosal and cutaneous lesions: a double-blind, placebo-controlled cross-over clinical trial.

INTRODUCTION: Painful mucosal and cutaneous lesions are often less responsive or even refractory to systemic opioid analgesics. There is evidence suggesting that the effectiveness of topical morphine be restricted to inflammatory pain. The studied groups were small and the observation period relatively short. The aim of this study was to assess the effectiveness and safety of topical morphine for pain related to mucosal lesions and skin ulcers. MATERIAL AND METHODS: The study was a 14-day randomized placebo-controlled cross-over trial (RCT) with a 28-day follow-up open phase (OP). The trial was conducted in adult patients with localized cancer-related pain and treated with systemic opioids in an oncology center or home hospice. The patients administered 0.2% gel on the mucosal lesion or 0.2% ointment on the skin lesion by themselves, without restrictions regarding the number of doses per day. The primary measurements were mean pain intensity (MPI) and mean pain relief (MPR) on the numeric rating scale (NRS 0-10), and ITT analysis was performed. RESULTS: Thirty-five patients were randomized to the RCT, and all of them completed 14-day observation. The MPI before the treatment was NRS 5.9 and decreased to 2.5 after morphine (p < 0.0001 vs. placebo). The MPR was 57% after morphine, and 77% of the patients using topical morphine obtained clinically significant (at least 50% of the starting value) pain relief, statistically different from placebo. The analgesic effect was sustained over the 28-day OP period (p = 0.00001). There were only 2 cases of moderate pruritus, and no other side effects were reported. CONCLUSIONS: Topical morphine was found to be a fast acting, highly effective, and safe medication for mucosal and skin lesions in palliative patients, with a sustainable pain relief effect over the 28-day observation period.

Prospects for the Use of Cannabinoids in Oncology and Palliative Care Practice: A Review of the Evidence.

There is an increased interest in the use of cannabinoids in the treatment of symptoms in cancer and palliative care patients. Their multimodal action, in spite of limited efficacy, may make them an attractive alternative, particularly in patients with multiple concomitant symptoms of mild and moderate intensity. There is evidence to indicate cannabis in the treatment of pain, spasticity, seizures, sleep disorders, nausea and vomiting, and Tourette syndrome. Although the effectiveness of cannabinoids is limited, it was confirmed in neuropathic pain management and combination with opioids. A relatively favorable adverse effects profile, including no depressive effect on the respiratory system, may make cannabis complement a rather narrow armamentarium that is in the disposition of a palliative care professional.