Trajectories of health-related quality of life and symptom burden in patients with advanced cancer towards the end of life: Longitudinal results from the eQuiPe study.

BACKGROUND: Support for health-related quality of life (HRQOL) is an essential part of cancer care in the final stages of life, yet empirical guidance regarding HRQOL and symptom trajectories is lacking. AIM: To assess the change in HRQOL and symptom burden in the last year of life in patients with advanced cancer and its association with health care-related factors, cancer-specific treatment, and comorbidity. METHODS: A prospective, multicenter, observational study in patients with advanced cancer (eQuiPe). Three monthly questionnaires included European Organization for Research and Treatment of Cancer Quality of Life-C30 and reported continuity of care. Multivariable mixed-effects analysis was used to assess the association between HRQOL and health care-related factors. RESULTS: A total of 762 deceased patients were included with a mean age of 66 (SD, 10) years and 52% were male. The most common primary tumors were lung (29%), colorectal (20%), and breast cancer (13%). Mean overall HRQOL decreased in the last 9 months of life, with the greatest decrease in the last 3 months (ß -16.2). Fatigue, pain, appetite loss, dyspnea, constipation, and nausea worsened significantly in the last year of life. Multimorbidity (ß -7.5) and a better reported continuity of care (ß 0.7) were both significantly associated with the trajectory of HRQOL. CONCLUSION: Mean overall HRQOL begins to decline 9 months before death, highlighting the need for early identification and (re)assessment of different symptoms as aspects of HRQOL follow different trajectories. Multimorbidity and reported continuity of care may be associated with the trajectory of HRQOL.

Reduction in potentially inappropriate end-of-life hospital care for cancer patients during the COVID-19 pandemic: A retrospective population-based study.

BACKGROUND: The COVID-19 pandemic impacted cancer diagnosis and treatment. However, little is known about end-of-life cancer care during the pandemic. AIM: To investigate potentially inappropriate end-of-life hospital care for cancer patients before and during the COVID-19 pandemic. DESIGN: Retrospective population-based cohort study using data from the Netherlands Cancer Registry and the Dutch National Hospital Care Registration. Potentially inappropriate care in the last month of life (chemotherapy administration, >1 emergency room contact, >1 hospitalization, hospitalization >14 days, intensive care unit admission or hospital death) was compared between four COVID-19 periods and corresponding periods in 2018/2019. PARTICIPANTS: A total of 112,919 cancer patients (⩾18 years) who died between January 2018 and May 2021 were included. RESULTS: Fewer patients received potentially inappropriate end-of-life care during the COVID-19 pandemic compared to previous years, especially during the first COVID-19 peak (22.4% vs 26.0%). Regression analysis showed lower odds of potentially inappropriate end-of-life care during all COVID-19 periods (between OR 0.81; 95% CI 0.74-0.88 and OR 0.92; 95% CI 0.87-0.97) after adjustment for age, sex and cancer type. For the individual indicators, fewer patients experienced multiple or long hospitalizations, intensive care unit admission or hospital death during the pandemic. CONCLUSIONS: Cancer patients received less potentially inappropriate end-of-life care during the COVID-19 pandemic. Because several factors may have contributed, it is unclear whether this reflects better quality care. However, these findings raise important questions about what pandemic-induced changes in care practices can help provide appropriate end-of-life care for future patients in the context of increasing patient numbers and limited resources.

Educational level and gender are associated with emotional well-being in a cohort of Dutch dialysis patients.

BACKGROUND: Patients undergoing dialysis have an impaired health-related quality of life (HRQOL). There are conflicting data from small series on whether patient-related factors such as educational level have an impact on experienced HRQOL. The aim of this study was to investigate the association between educational level and HRQOL in dialysis patients. METHODS: In a single-center retrospective cross-sectional study HRQOL was measured using the Kidney Disease Quality of Life Short Form-36 (KDQOL-SF36) in prevalent chronic dialysis patients. Educational level was categorized into low, intermediate and high subgroups. Univariate and multivariate regression analyses were performed to assess the effects of age, gender, ethnicity, and dialysis vintage on the association between HRQOL and educational level. RESULTS: One hundred twenty-nine chronic dialysis patients were included. Patients with an intermediate educational level had significantly higher odds of a higher emotional well-being than patients with a low educational level 4.37 (1.-89-10.13). A similar trend was found for a high educational level (OR 4.13 (1.04-16.42), p = 0.044) The odds for women compared to men were 2.83 (1.32-6.06) for better general health and 2.59 (1.15-5,84) for emotional well-being. There was no interaction between gender and educational level for both subdomains. Each year of increasing age significantly decreased physical functioning (OR 0.94 (0.91-0.97)). CONCLUSIONS: Educational level and sex were associated with emotional well-being, since patients with intermediate and high educational level and females had better emotional well-being in comparison to patients with low educational level and males. Physical functioning decreased with increasing age.

Development of the conversation tool "I-HARP for COPD" for early identification of palliative care needs in patients with chronic obstructive pulmonary disease.

OBJECTIVES: This study aimed to develop the conversation tool "I-HARP for COPD" for timely identification of palliative care needs in Dutch patients with chronic obstructive pulmonary disease (COPD). METHODS: An iterative and participatory research design was used to develop "I-HARP for COPD". There were 2 phases to the development of "I-HARP for COPD": content development and testing. A review of current literature, parallel focus groups, and a questionnaire among experts were used to develop the content of "I-HARP for COPD". "I-HARP for COPD" was then assessed by health-care professionals (HCPs) in clinical practice for understanding, difficulty, and relevance. RESULTS: A total of 46 HCPs, 6 patients, 1 informal caregiver, and 1 bereaved informal caregiver participated in this study. "I-HARP for COPD" included 14 screening questions, additional in-depth questions, and recommendations to address identified needs. The content of "I-HARP for COPD" was accepted by 86.2% of the HCPs. SIGNIFICANCE OF RESULTS: "I-HARP for COPD" was successfully developed for providing guidance in the palliative care of Dutch patients with COPD and their informal caregivers. By supporting HCPs with "I-HARP for COPD", they are better able to timely identify and direct palliative care needs.

Finding predictors for successful opioid response in cancer patients: An analysis of data from four randomized controlled trials.

CONTEXT: There is no consensus on which "strong" (or step 3 WHO analgesic ladder) opioid to prescribe to a particular patient with cancer-related pain. A better understanding of opioid and patient characteristics on treatment response will contribute to a more personalized opioid treatment. OBJECTIVES: Assessment of potential predictors for successful opioid treatment response in patients with cancer pain. METHODS: An international partnership between four cancer pain research groups resulted in a combined individual-level database from four relevant randomized controlled trials (RCTs; n = 881). Together, these RCTs investigated the short-term (1 week) and medium-term (4 or 5 weeks) treatment responses for morphine, buprenorphine, methadone, oxycodone, and fentanyl. Candidate predictors for treatment response were sex, age, pain type, pain duration, depression, anxiety, Karnofsky performance score, opioid type, and use of anti-neuropathic drug. RESULTS: Opioid type and pain type were found statistically significant predictors of short-term treatment success. Sex, age, pain type, anxiety, and opioid type were statistically, significantly associated with medium-term treatment success. However, these models showed low discriminative power. CONCLUSION: Fentanyl and methadone, and mixed pain were found to be statistically significant predictors of treatment success in patients with cancer-related pain. With the predictors currently assessed our data did not allow for the creation of a clinical prediction model with good discriminative power. Additional - unrevealed - predictors are necessary to develop a future prediction model.

End-of-life care and advance care planning for outpatients with inoperable aortic aneurysms.

OBJECTIVE: A significant proportion of patients with abdominal and thoracic aortic aneurysms (AA) do not proceed to intervention after reaching treatment threshold diameter due to a combination of poor cardiovascular reserve, frailty, and aortic morphology. This patient cohort has a high mortality; however, until this study, there exist no studies on the end-of-life care conservatively managed patients receive. METHODS: This is a retrospective multicenter cohort study of 220 conservatively managed patients with AA referred to Leeds Vascular Institute (UK) and Maastricht University Medical Centre (the Netherlands) for intervention between 2017 and 2021. Demographic details, mortality, cause of death, advance care planning and palliative care outcomes were analysed to examine predictors of palliative care referral and efficacy of palliative care consultation. RESULTS: A total of 1506 patients with AA were seen over this time period, giving a nonintervention rate of 15%. There was a 3-year mortality rate of 55%, a median survival of 364 days, and rupture was the reported cause of death in 18% of the decedents. Median follow-up was 34 months. Only 8% of all patients and 16% of decedents received a palliative care consultation, which took place a median of 3.5 days before death. Patients >81 years of age were more likely to have advance care planning. Only 5% and 23% of conservatively managed patients had documentation of preferred place of death and care priorities respectively. Patients with a palliative care consultation were more likely to have these services in place. CONCLUSIONS: Only a small proportion of conservatively treated patients had advance care planning and this was far below international guidelines on end-of-life care for adults, which recommends it for each of these patients. Pathways and guidance should be implemented to ensure patients not offered AA intervention receive end-of-life care and advance care planning.

Trajectories of emotional functioning and experienced care of relatives in the last year of life of patients with advanced cancer: A longitudinal analysis of the eQuiPe study.

OBJECTIVE: Advanced cancer has a major impact on both patients and their relatives. To allow for personalized support, it is important to recognize which relatives will experience a decline in emotional functioning during the patient's last year of life, when this decline will occur, and what factors are associated with it. This study aimed to examine the trajectory of emotional functioning of relatives during that time and the characteristics associated with changes in this trajectory. METHODS: A prospective, longitudinal, multicenter, observational study in patients with advanced cancer and their relatives was conducted (eQuiPe). We analyzed relatives' changes in emotional functioning in the patient's last year using the EORTC QLQ-C30 and assessed associations with sociodemographic and care characteristics using multivariable mixed-effects analysis. RESULTS: 409 relatives completed ≥1 questionnaires during the patient's last year of life. Mean age was 64 years, 61% were female and 75% were the patient's partner. During this year, mean emotional functioning declined significantly over time from 73.9 to 64.6 (p = 0.023, effect size = 0.43). The type of relationship between relatives and patients (p = 0.002), patient' sleep problems (p = 0.033), and continuity of care (p = 0.002) were significantly associated with changes in emotional functioning. CONCLUSIONS: Relatives' emotional functioning declined during the patient's last year of life. Support for them, especially partners and relatives of patients with sleep problems, is important. Relatives who experienced more continuity of care had a less steep decline in emotional functioning.

Are gastrointestinal problems, nutritional care, and nutritional care needs associated with quality of life in patients with advanced cancer? Results of the observational eQuiPe study.

PURPOSE: To assess the association of gastrointestinal problems, received nutritional care, and nutritional care needs with quality of life (QoL) in patients with advanced cancer. METHODS: A cross-sectional analysis within the observational prospective eQuiPe cohort study on experienced quality of care and QoL in patients with advanced cancer was performed. QoL and gastrointestinal problems were measured using the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30. Received nutritional care (yes/no) and nutritional care needs (yes/a little bit/no) were measured by two questions. Gastrointestinal problems were categorized as clinically important based on the Giesinger thresholds. Univariable and multivariable linear regression analyses adjusted for age, gender, and treatment were used to analyze the association of gastrointestinal problems, received nutritional care, and nutritional care needs with QoL. RESULTS: Half of the 1080 patients with advanced cancer had clinically important gastrointestinal problems, 17% experienced nutritional care needs, and 14% received nutritional care. Multivariable analyses revealed that the presence of clinically important gastrointestinal problems (ß (95% CI): -13.0 (-15.6; -10.4)), received nutritional care (ß (95% CI): -5.1 (-8.5; -1.7)), and nutritional care needs (ß (95% CI): -8.7 (-11.9; -5.5)) were associated with a low QoL. CONCLUSION: Many patients with advanced cancer experience gastrointestinal problems, while only few patients receive nutritional care. These gastrointestinal problems, nutritional care needs, and nutritional care are associated with lower QoL, probably due to reversed causality or the irreversible nature of these problems in the palliative phase. More research on the relation of nutritional care, gastrointestinal problems, and QoL is needed to optimize nutritional support in end-of-life care.

Dry mouth in patients with a life-limiting condition or frailty: a study protocol for two intervention studies and a nested qualitative sub-study (the Dry mOuth Project, DROP).

BACKGROUND: Despite its prevalent and impactful nature, dry mouth remains an underexposed and undertreated symptom in patients with a life-limiting condition or frailty. The main contributing factors are a lack of awareness and knowledge amongst both healthcare professionals and patients, and a scarcity of effective, evidence-based interventions. In the DRy mOuth Project (DROP), we address these factors by investigating both a non-pharmacological and a pharmacological intervention: a nurse-led patient education program and locally applied pilocarpine. METHODS: This intervention-based research project consists of two parallel studies. The non-pharmacological study is a cluster non-randomized controlled trial in 228 palliative nursing home and hospital patients, investigating the effect of structured use of guidelines and of patient education on dry mouth symptoms. This intervention, a nurse-led patient education program (the Mouth Education Program, MEP), will be compared to care as usual, the control. The pharmacological study is a double-blind placebo-controlled randomized trial that examines the effect of locally applied pilocarpine drops in 120 patients with dry mouth symptoms. Both studies use the same mixed-methods study design, in which the primary outcome is the clinical response to the intervention at 4 weeks, as measured by a dry mouth severity score (numeric rating scale from 0 to 10). Other outcomes, as measured by questionnaires over a 12-week follow-up period, include durability of the effect, impact on quality of life and, adherence and acceptability of the intervention. In addition, the feasibility and cost-effectiveness are evaluated by means of questionnaires and focus groups with healthcare professionals, and interviews with patients. DISCUSSION: This study investigates the effectiveness and feasibility of two interventions for dry mouth symptoms in patients with life-limiting conditions or frailty. Due to the large-scale and mixed-method nature of the study, this study will also improve our understanding of dry mouth and its relating factors and of the patients' and healthcare professionals' experiences with symptoms, care and guidelines of dry mouth, including any perceived barriers and facilitators. TRIAL REGISTRATION: NCT05964959 & NCT05506137.

Unacceptable pain in oncology: The patients' perspective on reasons for absence of pain interventions.

OBJECTIVE: Around 40% of oncology patients receive inadequate pain treatment. A previous study reported pain interventions for only 70% of patients who reported unacceptable pain at the self-service registration desk. The aim of this study is to gain insight in reasons for the absence of pain intervention among oncology patients who reported unacceptable pain. METHODS: In this mixed methods study, 20 patients visiting the oncology outpatient clinic were selected via patient record assessment and interviewed about their perceived reasons for absence of pain intervention. RESULTS: The reasons mentioned by the patients for absence of pain intervention included reluctance of the patient to discuss pain, no treatment preferred by the patient, focus of the physician on treatment of the disease, pain treatment difficult or impossible, and the perception that pain is an inevitable consequence of the cancer treatment. Almost 50% of the patients considered the physician responsible for the absence of pain intervention. CONCLUSION: In conclusion, a variety of reasons for absence of pain intervention are reported by patients, including patient-related and health professional-related reasons. Improvements can be made by promoting regular discussion of pain during hospital visits and empowerment of patients.

What to consider when implementing a tool for timely recognition of palliative care needs in heart failure: a context-based qualitative study.

BACKGROUND: Needs assessment tools can facilitate healthcare professionals in timely recognition of palliative care needs. Despite the increased attention for implementation of such tools, most studies provide little or no attention to the context of implementation. The aim of this study was to explore factors that contribute positively and negatively to timely screening of palliative care needs in advanced chronic heart failure. METHODS: Qualitative study using individual interviews and focus groups with healthcare professionals. The data were analysed using a deductive approach. The Consolidated Framework for Implementation Research was used to conceptualise the contextual factors. RESULTS: Twenty nine healthcare professionals with different backgrounds and working in heart failure care in the Southern and Eastern parts of the Netherlands participated. Several factors were perceived to play a role, such as perception and knowledge about palliative care, awareness of palliative care needs in advanced chronic heart failure, perceived difficulty when and how to start palliative care, limited acceptance to treatment boundaries in cardiology, limited communication and collaboration between healthcare professionals, and need for education and increased attention for palliative care in advanced chronic heart failure guidelines. CONCLUSIONS: This study clarified critical factors targeting patients, healthcare professionals, organisations to implement a needs assessment tool for timely recognition of palliative care needs in the context of advanced chronic heart failure. A multifaceted implementation strategy is needed which has attention for education, patient empowerment, interdisciplinary collaboration, identification of local champions, chronic heart failure specific guidelines and culture.

Design and evaluation of a learning assignment in the undergraduate medical curricula on the four dimensions of care: a mixed method study.

BACKGROUND: Chronic and palliative care are rapidly gaining importance within the physician's range of duties. In this context, it is important to address the four dimensions of care: physical, psychological, social, and spiritual. Medical students, however, feel inadequately equipped to discuss these dimensions with the patient. To bridge this gap, a new assignment was developed and implemented, in which students talked to a chronic or palliative patient about the four dimensions of care during an internship. This study, reports the evaluation of this assignment by students and teachers using a design-based approach. METHODS: Mixed methods were used, including a) student questionnaires, b) student focus groups, c) teacher interviews, and d) student's written reflections. Two researchers performed analyses of the qualitative data from the focus groups, interviews, and written reflections using qualitative research software (ALTLAS.TI). Descriptive statistics were computed for the quantitative data using SPSS 21.0. RESULTS: Students and teachers valued talking to an actual patient about the four dimensions of care. Reading and providing peer feedback on each other's reports was considered valuable, especially when it came to the diversity of illnesses, the way that patients cope and communication techniques. The students considered reflection useful, especially in the group and provided it was not too frequent. All the dimensions were addressed in the interviews, however the spiritual dimension was found to be the most difficult to discuss. The analysis of the written reflections revealed an overlap between the social and spiritual dimensions. Students pay a lot of attention to the relationship between the illness and the patient's daily life, but the reflections do often not show insight in the potential relationship between the four dimensions and decisions in patient care. CONCLUSIONS: During internships, medical students can practice talking about four dimensions of care with a chronically ill or palliative patient. Due to the format, it can be implemented across existing internships with relatively little extra time and effort. Reflection, peer feedback, and group discussion under the guidance of a teacher are important additions.

Healthcare and Societal Costs in Patients with COPD and Breathlessness after Completion of a Comprehensive Rehabilitation Program.

Breathlessness is one of the most frequent symptoms in chronic obstructive pulmonary disease (COPD). COPD may result in disability, decreased productivity and increased healthcare costs. The presence of comorbidities increases healthcare utilization. However, the impact of breathlessness burden on healthcare utilization and daily activities is unclear. This study's goal was to analyze the impact of breathlessness burden on healthcare and societal costs. In this observational single-center study, patients with COPD were followed-up for 24 months after completion of a comprehensive pulmonary rehabilitation program. Every three months participants completed a cost questionnaire, covering healthcare utilization and impact on daily activities. The results were compared between participants with low (modified Medical Research Council (mMRC) grade <2; LBB) and high baseline breathlessness burden (mMRC grade ≥2; HBB). Healthcare costs in year 1 were €7302 (95% confidence interval €6476-€8258) for participants with LBB and €10,738 (€9141-€12,708) for participants with HBB. In year 2, costs were €8830 (€7372-€10,562) and €14,933 (€12,041-€18,520), respectively. Main cost drivers were hospitalizations, contact with other healthcare professionals and rehabilitation. Costs outside the healthcare sector in year 1 were €682 (€520-€900) for participants with LBB and €1520 (€1210-€1947) for participants with HBB. In year 2, costs were €829 (€662-€1046) and €1457 (€1126-€1821) respectively. HBB in patients with COPD is associated with higher healthcare and societal costs, which increases over time. This study highlights the relevance of reducing costs with adequate breathlessness relief. When conventional approaches fail to improve breathlessness, a personalized holistic approach is warranted.

Measuring pain in oncology outpatients: Numeric Rating Scale versus acceptable/non acceptable pain. A prospective single center study.

OBJECTIVES: During all stages of oncologic diseases, pain is still a major problem. The Numeric Rating Scale (NRS) is one of the most frequently used tools for pain assessment, although interpretation is difficult. The main objective of this study is to compare two types of pain evaluation scales: NRS versus (non) acceptable pain evaluation scale. The secondary aim is to analyze a 10% sample of patients indicating non acceptable pain more in-depth. METHODS: To assess the pain evaluation scales, a prospective observational study, with a nested retrospective in-depth exploration, was conducted. One-year data of patients visiting the outpatient clinic of the oncology center of a university hospital were used. Besides the pain scores of all patients, a 10% sample of patients indicating non acceptable pain was analyzed more in-depth. RESULTS: During 1 year, a total of 37,580 patients registered at the outpatient clinic, of whom approximately 10% indicated non acceptable pain. The mean NRS of patients indicating non acceptable pain was 6.5 (n = 2153). For patients indicating acceptable pain, the mean NRS was 1.6 (n = 21,010). Although the presence of pain recorded in the patient record increased substantially over the year, the percentage of reported interventions only slightly increased. CONCLUSION: The (non) acceptable pain evaluation seems a valuable addition to the NRS for assessing pain among patients with cancer. As interpretation of the NRS appears to be difficult, using the (non) acceptable pain evaluation is recommended. Moreover, creating awareness among specialists to discuss pain has a positive effect on the amount of pain discussed during consultation.

Palliative care education in the undergraduate medical curricula: students' views on the importance of, their confidence in, and knowledge of palliative care.

BACKGROUND: The need for palliative care is increasing. Since almost every junior doctor will come across palliative care patients, it is important to include palliative care in the undergraduate curriculum. The objective of this research is to gather undergraduate students' views on palliative care in terms of its importance, their confidence in and knowledge of the domain. METHODS: Final-year medical students at four Dutch medical faculties were surveyed. The questionnaire measured their views on the education they had received, their self-reported confidence in dealing with palliative care patients and their knowledge of palliative care. RESULTS: Two hundred twenty-two medical students participated in this study. Students considered palliative care education relevant, especially training in patient-oriented care and communication with the patient. Students felt that several topics were inadequately covered in the curriculum. Overall, the students did not feel confident in providing palliative care (59.6%), especially in dealing with the spiritual aspect of palliative care (77%). The knowledge test shows that only 48% of the students answered more than half of the questions correctly. CONCLUSION: The students in this study are nearly junior doctors who will soon have to care for palliative patients. Although they think that palliative care is important, in their opinion the curriculum did not cover many important aspects, a perception that is also in line with their lack of confidence and knowledge in this domain. Therefore, it is important to improve palliative care education in the medical curriculum.

Methadone versus Fentanyl in Patients with Radiation-Induced Nociceptive Pain with Head and Neck Cancer: A Randomized Controlled Noninferiority Trial.

BACKGROUND: Pain is still a burden for many patients with cancer. A recent trial showed the superiority of methadone over fentanyl in neuropathic pain, and we expect that this finding could influence the number of patients treated with methadone. METHODS: We performed a randomized controlled noninferiority trial in patients with nociceptive pain. Eighty-two strong-opioid-naïve patients with head and neck cancer with substantial pain (pain numeric rating scale [NRS] score ≥ 4) due to radiation therapy were included. Forty-two patients were treated with methadone, and 40 with fentanyl. Patients were evaluated at 1, 3, and 5 weeks. The primary outcomes were reduction in average pain and clinical success (50% pain decrease). We set the predefined noninferiority margin at 1 on the NRS and 10% clinical success. Secondary outcomes were pain interference, global perceived effect (GPE), side effects, and opioid escalation index. RESULTS: Noninferiority was shown for decrease in NRS for maximum and mean pain scores at 1 and 3 weeks. Noninferiority was shown for clinical success at 1 week only. The opioid escalation index was lower in the methadone group at 3 and 5 weeks as compared to fentanyl (1.44 vs. 1.99, P = 0.004; and 1.50 vs. 2.32, P = 0.013). The pain interference in the methadone group was significantly decreased at 3 weeks only. GPE and side effects were not different. CONCLUSION: This is the first study to show noninferiority of methadone compared to fentanyl at 1 and 3 weeks in the treatment of radiation-induced nociceptive pain in patients with head and neck cancer.

Respiratory adverse effects of opioids for breathlessness: a systematic review and meta-analysis.

Previous studies have shown that opioids can reduce chronic breathlessness in advanced disease. However, physicians remain reluctant to prescribe opioids for these patients, commonly due to fear of respiratory adverse effects. The aim of this study was to systematically review reported respiratory adverse effects of opioids in patients with advanced disease and chronic breathlessness.PubMed, Embase, the Cochrane Central Register of Controlled Trials, CINAHL, ClinicalTrials.gov and the reference lists of relevant systematic reviews were searched. Two independent researchers screened against predefined inclusion criteria and extracted data. Meta-analysis was conducted where possible.We included 63 out of 1990 articles, describing 67 studies. Meta-analysis showed an increase in carbon dioxide tension (0.27 kPa, 95% CI 0.08-0.45 kPa,) and no significant change in oxygen tension and oxygen saturation (both p>0.05). Nonserious respiratory depression (definition variable/not stated) was described in four out of 1064 patients. One cancer patient pretreated with morphine for pain needed temporary respiratory support following nebulised morphine for breathlessness (single case study).We found no evidence of significant or clinically relevant respiratory adverse effects of opioids for chronic breathlessness. Heterogeneity of design and study population, and low study quality are limitations. Larger studies designed to detect respiratory adverse effects are needed.

Pharmacological Treatment of Pain in Cancer Patients: The Role of Adjuvant Analgesics, a Systematic Review.

CONTEXT: In patients with cancer, pain is one of the most feared and burdensome symptoms. Adjuvant analgesics are an important cornerstone on which treatment of pain in patients with cancer is based. OBJECTIVES: To update our guidelines for the treatment of pain in patients with cancer, we performed a systematic review on the use of adjuvant analgesics in pain in cancer. METHODS: A systematic search of the literature was performed searching for articles that studied the effect of (1) antidepressants, (2) anti-epileptics, (3) N-methyl-d-aspartate (NMDA) receptor antagonists, and (4) other adjuvant analgesics in patients with cancer pain and described their effects on pain intensity and/or side effects. RESULTS: Based on the keywords and after reading the full papers, we could include 12 papers on anticonvulsants, 10 papers on antidepressants, four on NMDA receptor antagonists, and 10 papers on other adjuvant analgesics. The methodological quality of the included papers was graded as low to very low. Overall, there was a low quality of evidence that gabapentin, pregabalin, amitriptyline, and venlafaxine were effective in reducing pain intensity in patients with cancer pain. There was insufficient evidence on the effectiveness of lamotrigine, levetiracetam, NMDA antagonists, cannabinoids, corticosteroids, and local anesthetics on reducing pain intensity in patients with cancer pain. CONCLUSION: The quality of currently available evidence on the effectiveness of adjuvant analgesics in the treatment of cancer pain is low. The treatment of pain associated with cancer should be tailored to the patient's personal preferences.

Shifting Views on Cancer Pain Management: A Systematic Review and Network Meta-Analysis.

CONTEXT: Strong opioids are the cornerstone in the treatment of cancer-related pain. OBJECTIVES: This study aims to compare analgesic effectiveness of different strong opioids for the treatment of cancer-related pain. METHODS: PubMed and Embase were searched for RCTs that compared strong opioids for treatment of cancer-related pain against one another. A network meta-analysis was conducted and the related Surface Under the Cumulative RAnking (SUCRA)-based treatment ranks were calculated. Primary outcome was pain intensity (numerical rating scale (NRS)) and/or the percentage of patients with ≥50% pain reduction, after 1 and 2-4 weeks. RESULTS: Sixteen RCTs (1813 patients) were included. Methadone showed, with a high certainty of evidence, increased ORs for treatment success at 1 week, compared with morphine, buprenorphine, fentanyl, and oxycodone, range 3.230-36.833. Methadone had the highest likelihood to be the treatment of preference (ToP) (SUCRA 0.9720). For fentanyl, ORs were lower, however significant and with high certainty. After 2-4 weeks, methadone again showed the highest likelihood for ToP, however, with moderate certainty and nonsignificant ORs. The combination of morphine/methadone, compared with morphine, buprenorphine, fentanyl, hydromorphone, methadone, and oxycodone achieved a treatment effect of mean NRS difference after 2-4 weeks between -1.100 and -1.528 and had the highest likelihood for ToP. CONCLUSION: The results suggest that methadone possibly deserves further promotion as first-line treatment for the treatment of cancer-related pain.