A comparison of health-related quality of life in chronic intestinal failure and end-stage kidney disease: A cross-sectional study.

BACKGROUND: There is inequal access to treatment and scarce evidence on how the disease burden in chronic intestinal failure (CIF) compares to other chronic nonmalignant types of organ failure. Therefore, we compared the health-related quality of life (HRQOL) of people with CIF with that of people with end-stage kidney disease (ESKD) receiving hemodialysis (HD). These groups were selected for comparison as they have similar treatment characteristics. We hypothesized that people treated with HD and people with CIF had similarly poor HRQOL. METHODS: HRQOL was evaluated and compared in a cross-sectional study of adult people with CIF and people with ESKD HD at a tertiary hospital in Denmark, using the Short-Form 36 (SF-36). RESULTS: One hundred forty-one people with CIF and 131 people with ESKD receiving HD were included in the analysis. Both groups reported low scores (<50) for HRQOL on general health, vitality, and role limitation-physical. People with ESKD receiving HD had significantly lower scores than people with CIF regarding physical functioning, general health, and vitality when adjusted for sex and age. No significant difference was found for any other SF-36 domain. CONCLUSION: HRQOL was similarly and significantly reduced in people with CIF and in people with ESKD receiving HD. People with ESKD receiving HD had significantly poorer HRQOL than people with CIF in some aspects of physical and mental health. Access to home parenteral support treatment varies among countries that typically provide HD, suggesting an inequality in healthcare based on the type of organ failure.

Co-Occurrence of Prevalent Symptoms in Patients Receiving Hemodialysis - A Cross-Sectional Survey.

Patients with chronic kidney disease undergoing hemodialysis generally have a significant symptom burden, which may interfere with their quality of life. The aim of this study was to identify the prevalence of fatigue, pain, anxiety, and depression in patients on hemodialysis and analyze their co-occurrence. A cross-sectional study used self-reported measures. A total of 242 patients aged 18 years or older were initially screened; 141 were included in the study; 129 answered the questionnaires (response rate 91%). Preva lences were 24.8% had moderate to severe fatigue, 38.0% had pain, 32.6% had anxiety, and 29.5% had depression. The prevalence of coexistent moderate to severe symptoms ranged from 15.5% to 25.6%. Further research is needed to better understand the symptom burden and their co-occurrence in patients receiving hemodialysis.

Long-term opioid treatment and endocrine measures in chronic non-cancer pain patients.

BACKGROUND: The prevalence of chronic non-cancer pain (CNCP) has increased dramatically the past decades, which combined with indiscriminate use of prescribed opioids has become a public health problem. Endocrine dysfunction may be a complication of long-term opioid treatment (L-TOT), but the evidence is limited. This study aimed at investigating the associations between L-TOT and endocrine measures in CNCP patients. METHODS: Cortisol (spot and after stimulation), thyrotropin (TSH), thyroxin (T4), insulin-like growth factor 1 (IGF-1), prolactin (PRL), 17-hydroxyprogesterone, androstenedione, dehydroepiandrosterone (DHEAS), sex hormone-binding globulin (SHBG), total testosterone (TT) and free testosterone (fT) were measured. Group comparisons were done between CNCP patients in L-TOT and controls as well as between patients on high- or low-dose morphine equivalents. RESULTS: Eighty-two CNCP patients (38 in L-TOT and 44 controls not receiving opioids) were included. Low TT (p = 0.004) and fT concentrations (p < 0.001), high SHBG (p = 0.042), low DEAS (p = 0.017) and low IGF-1 (p = 0.003) in men were found when comparing those in L-TOT to controls and high PRL (p = 0.018), low IGF-1 standard deviation score (SDS) (p = 0.006) along with a lesser, but normal cortisol response to stimulation (p = 0.016; p = 0.012) were found when comparing L-TOT to controls. Finally, a correlation between low IGF-1 levels and high opioid dose was observed (p < 0.001). CONCLUSIONS: Our study not only supports previous findings but even more interestingly disclosed new associations. We recommend future studies to investigate endocrine effects of opioids in larger, longitudinal studies. In the meanwhile, we recommend monitoring endocrine function in CNCP patients when prescribing L-TOT. SIGNIFICANCE: This clinical study found associations between L-TOT, androgens, growth hormone and prolactin in patients with CNCP compared to controls. The results support previous studies as well as add new knowledge to the field, including an association between high opioid dose and low growth hormone levels. Compared to existing research this study has strict inclusion/exclusion criteria, a fixed time period for blood sample collection, and adjustments for potential confounders, which has not been done before.

Use of Opioids for Adults With Pain From Cancer or Cancer Treatment: ASCO Guideline.

PURPOSE: To provide guidance on the use of opioids to manage pain from cancer or cancer treatment in adults. METHODS: A systematic review of the literature identified systematic reviews and randomized controlled trials of the efficacy and safety of opioid analgesics in people with cancer, approaches to opioid initiation and titration, and the prevention and management of opioid adverse events. PubMed and the Cochrane Library were searched from January 1, 2010, to February 17, 2022. American Society of Clinical Oncology convened an Expert Panel to review the evidence and formulate recommendations. RESULTS: The evidence base consisted of 31 systematic reviews and 16 randomized controlled trials. Opioids have primarily been evaluated in patients with moderate-to-severe cancer pain, and they effectively reduce pain in this population, with well-characterized adverse effects. Evidence was limited for several of the questions of interest, and the Expert Panel relied on consensus for these recommendations or noted that no recommendation could be made at this time. RECOMMENDATIONS: Opioids should be offered to patients with moderate-to-severe pain related to cancer or active cancer treatment unless contraindicated. Opioids should be initiated PRN (as needed) at the lowest possible dose to achieve acceptable analgesia and patient goals, with early assessment and frequent titration. For patients with a substance use disorder, clinicians should collaborate with a palliative care, pain, and/or substance use disorder specialist to determine the optimal approach to pain management. Opioid adverse effects should be monitored, and strategies are provided for prevention and management.Additional information is available at www.asco.org/supportive-care-guidelines.

Long-term opioid treatment and endocrine measures in patients with cancer-related pain: a systematic review.

OBJECTIVES: Opioid analgesics are the main stay for cancer pain management; however, long-term opioid treatment (L-TOT) may suppress the endocrine system. This systemic review aimed at investigating effects of L-TOT on the endocrine system in patients with cancer-related pain. METHODS: A search on MEDLINE, EMBASE and Web of Science databases was performed. Inclusion criteria were clinical studies investigating endocrine measures in adult patients with cancer-related pain in L-TOT (≥4 weeks). Outcomes and quality of evidence were assessed. RESULTS: A total of 252 abstracts were identified; out of which 247 were excluded and five cross-sectional studies were included and analyzed. L-TOT was associated with lower serum concentration levels of total- and free testosterone in males, follicular stimulating hormone in females, and luteinizing hormone in both sexes. Moreover, higher morphine equivalent daily doses (MEDDs) were correlated with higher levels of cortisol and lower levels of LH in both sexes, and lower levels of total- and free testosterone in males. Sexual dysfunction was associated with low sex hormone levels. Level of evidence was low/very low. CONCLUSIONS: The studies identified demonstrated that patients with cancer-related pain in L-TOT may have gonadal hypofunction causing sexual dysfunction, which may be correlated with opioid dose level. In addition, high serum concentrations of cortisol were positively correlated with high opioid dose levels. However, the evidence was weak and further research is necessary. PROSPERO, ID-number: CRD42020213059.

Management of cancer pain: challenging the evidence of the recent guidelines for opioid use in palliative care.

Opioid therapy is indisputably the mainstay of cancer pain management. However, important issues such as the worldwide variability in the availability and accessibility of opioids, myths and misconceptions about opioid use, and lack of knowledge about prescribing opioids among health care professionals have been pointed out by researchers, clinicians, and several health organizations. In an attempt to improve cancer pain management, guidelines for opioid use were elaborated to assist practitioners in prescribing opioids for the management of cancer-related pain. Recent opioid guidelines were developed based on a systematic assessment of evidence and they are considered one of the best resources to improve knowledge and clinical practice. However, most of the recommendations for cancer pain management included in these guidelines are based on low levels of evidence, which demonstrates that more studies on the use of opioids in pain management are necessary. Moreover, the increased frequency of prescribing opioids for chronic noncancer pain has raised other issues, such as iatrogenic adverse effects, which may also occur in patients with cancer pain on long-term opioid therapy (L-TOT). In this narrative review, we discussed the role of opioid guidelines and recent knowledge regarding the consequences of L-TOT, in particular opioid addiction and deficiencies of the immune and endocrine systems. Finally, we addressed new strategies to strengthen the L-TOT in the management of cancer-related pain among patients in palliative care.

Long-term opioid treatment and endocrine measures in chronic non-cancer pain patients: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Long-term opioid treatment (L-TOT) of chronic non-cancer pain (CNCP) patients has been suspected to alter the endocrine system. This systematic review and meta-analysis aimed at investigating the published evidence of L-TOT effects on the endocrine system in adult CNCP patients. DATABASES AND DATA TREATMENT: A systematic search of the literature in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and the CINAHL was performed. Studies examining measures of endocrine function of the hypothalamic-pituitary-gonadal, -adrenal, -thyroid, -somatotropic and -prolactin axis in adult CNCP patients in L-TOT (≥4 weeks of use) were included. Outcomes and the level of evidence were analyzed (The Cochrane Collaboration Tool, modified version of the Newcastle-Ottawa Scale and Rating of Recommendations Assessment, Development and Evaluation working group). RESULTS: A total of 2,660 studies were identified; 1981 excluded and finally thirteen studies (one randomized controlled trial (RCT), three longitudinal- and nine cross-sectional studies) were analyzed. L-TOT was associated with low insulin, suppression of the hypothalamic-pituitary-gonadal axis and alterations of the hypothalamic-pituitary-adrenal axis in both men and women with CNCP compared to different control groups (CNCP or healthy pain-free). No other significant differences were reported. The studies had a high risk of bias and the overall quality of evidence was low. CONCLUSION: There seems to be an impact of L-TOT in CNCP patients on several components of the endocrine system, but the level of evidence is weak. Given the high prevalence of L-TOT use systematic studies of larger patient populations are urgently needed. SIGNIFICANCE: This systematic review and meta-analysis suggested that long-term opioid treatment may suppress the hypothalamic-pituitary-gonadal axis, and result in lower insulin levels and alter the glucocorticoid adrenal axis in adult chronic non-cancer pain patients. This adds to the need of more research of both clinical and paraclinical outcomes and their association when initiating and maintaining long-term opioid treatment.

Mild to Moderate Cognitive Impairment Does Not Affect the Ability to Self-Report Important Symptoms in Patients With Cancer: A Prospective Longitudinal Multinational Study (EPCCS).

CONTEXT: Patients with advanced cancer commonly suffer from both distressing symptoms and cognitive impairment, but the effect of cognitive impairment on the reliability and validity of symptom self-report is unknown. OBJECTIVES: To evaluate the reliability and validity of symptom self-report in cancer outpatients with and without mild to moderate cognitive impairment. METHODS: This was an analysis of the longitudinal European Palliative Care Cancer Symptom study of adults with incurable cancer in specialized palliative care (30 centers across 12 countries). Patients who could not comply with the study because of severe cognitive impairment were excluded. Cognitive status on the Mini-Mental State Examination short version and nine symptoms (pain, tiredness, drowsiness, nausea, appetite, breathlessness, depression, anxiety, and well-being) using the revised Edmonton Symptom Assessment System were self-reported at baseline and one-month follow-up. Reliability was analyzed using intraclass correlation coefficients and validity using regression of each symptom with health-related quality of life (HrQoL) measured with European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 for Palliative Care. RESULTS: A total of 1047 patients were included: mean age of 62.9 years; 54.4% women; main cancer types were of digestive organs (26.6%), breast (21.6%), and lungs (21.2%). Cognitive impairment was present in 181 (17.3%) at baseline and associated with worse self-reported tiredness, drowsiness, appetite, and depression. Reliability (intraclass correlation coefficient) and validity (associations with HrQoL) were similar between people with/without cognitive impairment across the nine symptoms, except breathlessness, which showed a weaker relation to HrQoL in patients with cognitive impairment. Findings were robust in sensitivity analyses and after controlling for potential confounders. CONCLUSION: In advanced cancer, self-report of nine major symptoms was reliable and valid also in people with mild-to-moderate cognitive impairment. TRIAL REGISTRATION: ClinicalTrials.gov database (NCT01362816).

Validation of a Battery of Neuropsychological Tests for Patients With Metastatic Cancer.

This study aimed to investigate the psychometric properties of Trail Making Test (TMT), Continuous Reaction Time (CRT), Finger Tapping Test (FTT), Digit Span Test (DST), and Mini-Mental State Examination (MMSE) in Brazilian patients with metastatic cancer. Cognitive performance of 178 patients with metastatic cancer and 79 controls was assessed using the TMT, CRT, FTT, DST, and MMSE. Discriminant validity, concurrent validity, and reliability (39 patients were retested after 3-7 days) were investigated. Discriminant validity between groups was observed in TMT, DST, and MMSE. Measures of concurrent validity and cognitive performance were positively correlated with physical performance, education level, and better performance on MMSE. Negative correlations were observed between cognitive function, pain, anxiety, and depression. All tests but FTT demonstrated very good reliability. Thus, all neuropsychological tests but FTT showed psychometric properties that permit their use in clinical and research purposes in patients with metastatic cancer.

The effects of long-term opioid treatment on the immune system in chronic non-cancer pain patients: A systematic review.

BACKGROUND AND OBJECTIVE: Opioids have been increasingly prescribed for chronic non-cancer pain (CNCP). An association between long-term opioid treatment (L-TOT) of CNCP patients and suppression of both the innate and the adaptive immune system has been proposed. This systematic review aims at investigating the effects of L-TOT on the immune system in CNCP patients. DATABASES AND DATA TREATMENT: A systematic search of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and the CINAHL for relevant articles was performed. Studies examining measures of both the innate and the adaptive immune system in adult CNCP patients in L-TOT (≥4 weeks of intake) were included. Outcomes and the level of evidence were analysed. RESULTS: A total of 382 studies were identified; however, 376 were excluded (352 inappropriate methodology, 21 duplicates, three full-text could not be obtained) and one randomized controlled trial (RCT) and five cross-sectional studies were included and analysed. L-TOT compared with no treatment was associated with a lower percentage of natural killer (NK) cells, a lower absolute number of CD56bright NK cells, a higher absolute number of IL-2-activated NK cells and a higher concentration of IL-1ß as a response to toll-like receptor (TLR) agonists stimulation (Pam3CSK4, LPS, Imiquimod). No other significant differences were reported. Generalizability of the results was limited due to inconsistency of outcomes and an overall low quality of the studies. CONCLUSIONS: L-TOT may alter the immune system in CNCP patients, but the level of evidence is still weak. More studies are needed to clarify the impact of L-TOT on immune system function. SIGNIFICANCE: This systematic review found indication that long-term opioid treatment alters the immune system in chronic non-cancer pain patients. These alterations involved the NK cells and IL-1ß production. However, the level of evidence is weak.

Patient reported outcomes and neuropsychological testing in patients with chronic non-cancer pain in long-term opioid therapy: a pilot study.

Background and aims Opioid consumption has increased dramatically in patients with chronic non-cancer pain (CNCP), but long-term consequences are still unclear. The aim of this study is to investigate the effects of long-term opioid treatment on pain, cognition, mood, sleep and quality of life in CNCP patients. Methods In this cross-sectional pilot study, two groups of patients with CNCP treated in a multidisciplinary pain center were selected: (1) opioid group: ≥30 mg morphine equivalent/day for >4 weeks, and (2) control group: no opioid consumption for >4 weeks. Socio-demographic data, alcohol consumption, smoking habits and body mass index (BMI) were registered and pain (brief pain inventory), mood (Hospital Anxiety and Depression Scale), sleep (Pittsburgh Sleep Quality Index) and quality of life (RAND 36-Item Health Survey) were assessed. Continuous Reaction Time and the Digit Span Test were used to evaluate cognitive function. Data was analyzed with a Fisher's exact test and Wilcoxon two-sample test. Results Forty-two patients with CNCP were included (21 in each group). No differences regarding socio-demographics, smoking/alcohol habits and duration, type, or intensity of pain were found. More patients in the opioid group had significantly higher BMI (62% above BMI 25 vs. 33.3%, p = 0.042). Consequently, the subsequent data analyses were controlled for BMI. The two groups did not differ in pain, cognition, anxiety, depression, sleep or quality of life but both showed lower values than the normal standards. Further, the opioid group presented a tendency to lower ratings regarding pain and social function and performed below the normal cut off in the continuous reaction time. Conclusions No significant differences between the two groups were found regarding any of the above-mentioned variables. Interestingly, the patients assessed, regardless of taking opioids or not, could be classified with moderate pain intensity, anxiety and low quality of sleep and life compared to norm standards. Implications The findings of this pilot study suggested that long-term opioid treatment may influence pain and quality of life among CNCP patients. A larger cohort is needed to verify these findings.

Integration of oncology and palliative care: a Lancet Oncology Commission.

Full integration of oncology and palliative care relies on the specific knowledge and skills of two modes of care: the tumour-directed approach, the main focus of which is on treating the disease; and the host-directed approach, which focuses on the patient with the disease. This Commission addresses how to combine these two paradigms to achieve the best outcome of patient care. Randomised clinical trials on integration of oncology and palliative care point to health gains: improved survival and symptom control, less anxiety and depression, reduced use of futile chemotherapy at the end of life, improved family satisfaction and quality of life, and improved use of health-care resources. Early delivery of patient-directed care by specialist palliative care teams alongside tumour-directed treatment promotes patient-centred care. Systematic assessment and use of patient-reported outcomes and active patient involvement in the decisions about cancer care result in better symptom control, improved physical and mental health, and better use of health-care resources. The absence of international agreements on the content and standards of the organisation, education, and research of palliative care in oncology are major barriers to successful integration. Other barriers include the common misconception that palliative care is end-of-life care only, stigmatisation of death and dying, and insufficient infrastructure and funding. The absence of established priorities might also hinder integration more widely. This Commission proposes the use of standardised care pathways and multidisciplinary teams to promote integration of oncology and palliative care, and calls for changes at the system level to coordinate the activities of professionals, and for the development and implementation of new and improved education programmes, with the overall goal of improving patient care. Integration raises new research questions, all of which contribute to improved clinical care. When and how should palliative care be delivered? What is the optimal model for integrated care? What is the biological and clinical effect of living with advanced cancer for years after diagnosis? Successful integration must challenge the dualistic perspective of either the tumour or the host, and instead focus on a merged approach that places the patient's perspective at the centre. To succeed, integration must be anchored by management and policy makers at all levels of health care, followed by adequate resource allocation, a willingness to prioritise goals and needs, and sustained enthusiasm to help generate support for better integration. This integrated model must be reflected in international and national cancer plans, and be followed by developments of new care models, education and research programmes, all of which should be adapted to the specific cultural contexts within which they are situated. Patient-centred care should be an integrated part of oncology care independent of patient prognosis and treatment intention. To achieve this goal it must be based on changes in professional cultures and priorities in health care.

A cortical source localization analysis of resting EEG data after remifentanil infusion.

OBJECTIVE: To explore changes in current source density locations after remifentanil infusion in healthy volunteers using source localization of the electroencephalography (EEG). METHODS: EEG data was collected from 21 males using a 62-electrode system. Additionally, cognitive performance was evaluated by a continuous reaction time paradigm, and pain scores were obtained for experimental bone and heat stimuli. Data were recorded before and during treatment with remifentanil and placebo. Source localization was performed by sLORETA at delta (1-3.9 Hz), theta (4-7.9 Hz), alpha (8-12 Hz), beta1 (12.1-18 Hz), and beta2 (18.1-30 Hz) frequency bands. RESULTS: Pre-treatment recordings demonstrated reproducible source characteristics. The alterations (i.e., pre- versus post-treatment) due to remifentanil were significantly and robustly different from placebo infusions. The results indicated that neurons in several brain areas including inferior frontal gyrus and insula at frontal lobe oscillated more strongly after remifentanil infusion compared to placebo. Furthermore, the source activity at delta band was correlated with continuous reaction time index. CONCLUSIONS: These results indicate that alterations in brain oscillations during remifentanil are mostly localized to frontal, fronto-temporal and fronto-central lobes and related to cognitive function. SIGNIFICANCE: The approach offers the potential to be used for understanding the underlying mechanism of action of remifentanil on brain activity.

Disruption of cortical connectivity during remifentanil administration is associated with cognitive impairment but not with analgesia.

BACKGROUND: The authors investigated the effect of remifentanil administration on resting electroencephalography functional connectivity and its relationship to cognitive function and analgesia in healthy volunteers. METHODS: Twenty-one healthy male adult subjects were enrolled in this placebo-controlled double-blind cross-over study. For each subject, 2.5 min of multichannel electroencephalography recording, a cognitive test of sustained attention (continuous reaction time), and experimental pain scores to bone-pressure and heat stimuli were collected before and after infusion of remifentanil or placebo. A coherence matrix was calculated from the electroencephalogram, and three graph-theoretical measures (characteristic path-length, mean clustering coefficient, and relative small-worldness) were extracted to characterize the overall cortical network properties. RESULTS: Compared to placebo, most graph-theoretical measures were significantly altered by remifentanil at the alpha and low beta range (8 to 18 Hz; all P < 0.001). Taken together, these alterations were characterized by an increase in the characteristic path-length (alpha 17% and low beta range 24%) and corresponding decrements in mean clustering coefficient (low beta range -25%) and relative small-worldness (alpha -17% and low beta range -42%). Changes in characteristic path-lengths after remifentanil infusion were correlated to the continuous reaction time index (r = -0.57; P = 0.009), while no significant correlations between graph-theoretical measures and experimental pain tests were seen. CONCLUSIONS: Remifentanil disrupts the functional connectivity network properties of the electroencephalogram. The findings give new insight into how opioids interfere with the normal brain functions and have the potential to be biomarkers for the sedative effects of opioids in different clinical settings.

Altered frequency distribution in the electroencephalogram is correlated to the analgesic effect of remifentanil.

Opioids alter resting state brain oscillations by multiple and complex factors, which are still to be elucidated. To increase our knowledge, multi-channel electroencephalography (EEG) was subjected to multivariate pattern analysis (MVPA), to identify the most descriptive frequency bands and scalp locations altered by remifentanil in healthy volunteers. Sixty-two channels of resting EEG followed by independent measures of pain scores to heat and bone pain were recorded in 21 healthy males before and during remifentanil infusion in a placebo-controlled, double-blind crossover study. EEG frequency distributions were extracted by a continuous wavelet transform and normalized into delta, theta, alpha, beta and gamma bands. Alterations relative to pre-treatment responses were calculated for all channels and used as input to the MVPA. Compared to placebo, remifentanil increased the delta band and decreased the theta and alpha band oscillations as a mean over all channels (all p ≤ 0.007). The most discriminative channels in these frequency bands were F1 in delta (83.33%, p = 0.0023) and theta bands (95.24%, p < 0.0001), and C6 in the alpha band (80.95%, p = 0.0054). These alterations were correlated to individual changes in heat pain in the delta (p = 0.045), theta (p = 0.038) and alpha (p = 0.039) bands and to bone pain in the alpha band (p = 0.0092). Hence, MVPA of multi-channel EEG was able to identify frequency bands and corresponding channels most sensitive to altered brain activity during remifentanil treatment. As the EEG alterations were correlated to the analgesic effect, the approach may prove to be a novel methodology for monitoring individual efficacy to opioids.

Altered cortical causality after remifentanil administration in healthy volunteers: a novel approach for pharmaco-EEG.

Alterations in cortical causality information flow induced by remifentanil infusion in healthy volunteers was investigated in a placebo-controlled double-blind cross-over study. For each of the 21 enrolled male subjects, 2.5 minutes of resting electroencephalography (EEG) data were collected before and after infusion of remifentanil and placebo. Additionally, to assess cognitive function and analgesic effect, continuous reaction time (CRT) and bone pressure and heat pain were assessed, respectively. The causality information was extracted from the EEG by phase slope index (PSI). Among the features being reproducible between the two baseline recordings, several PSI features were altered by remifentanil administration in comparison to placebo. Furthermore, several of the PSI features altered by remifentanil were correlated to changes in both CRT and pain scores. The results indicate that remifentanil administration influence the information flow between several brain areas. Hence, the EEG causality approach offers the potential to assist in deciphering the cortical effects of remifentanil administration.

Prevalence and predictors of cognitive dysfunction in opioid-treated patients with cancer: a multinational study.

PURPOSE: To identify prevalence and associated factors of cognitive dysfunction in opioid-treated patients with cancer. PATIENTS AND METHODS: EPOS (European Pharmacogenetic Opioid Study) is a prospective cross-sectional multicenter study in which adult patients with cancer who received treatment with opioids for moderate or severe pain for at least 3 days were included. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). MMSE scores were categorized into definite cognitive dysfunction (scores < 24), possible cognitive dysfunction (scores 24-26), and no cognitive dysfunction (scores > 26). Factors potentially associated with cognitive dysfunction were assessed. Associations between MMSE and explanatory variables were analyzed by ordinal logistic regression models. RESULTS: We included 1,915 patients with cancer from 17 centers. MMSE scores less than 27 were observed in 32.9% of patients. Patients with lung cancer had higher odds (adjusted odds ratio, 1.46; 95% CI, 1.09 to 1.95) for having lower MMSE scores compared with patients with other cancer diagnoses. Patients receiving daily opioid doses of 400 mg or more (oral morphine equivalents) had 1.75 (95% CI, 1.25 to 2.46) times higher odds of having lower MMSE scores compared with those receiving daily doses less than 80 mg. Other risk factors for cognitive dysfunction were older age, low Karnofsky performance status (KPS), time since diagnosis (< 15 months), and absence of breakthrough pain (BTP). CONCLUSION: One third of opioid-treated patients with cancer had possible or definite cognitive dysfunction. Lung cancer, daily opioid doses of 400 mg or more (oral morphine equivalents), older age, low KPS, shorter time since cancer diagnosis, and absence of BTP were predictors for cognitive dysfunction.