Validation of the NELA risk prediction model in emergency abdominal surgery.

Risk prediction models are frequently used to identify high-risk patients undergoing emergency laparotomy. The National Emergency Laparotomy Audit (NELA) developed a risk prediction model specifically for emergency laparotomy patients, which was recently updated. In this study, we validated the updated NELA model in an external population. Furthermore, we compared it with three other risk prediction models: the original NELA model, the Portsmouth Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (P-POSSUM) model, and the American Society of Anesthesiologists Physical Status (ASA-PS). We included adult patients undergoing emergency laparotomy at Zealand University Hospital, from March 2017 to January 2019, and Herlev Hospital, from November 2017 to January 2020. Variables included in the risk prediction models were collected retrospectively from the electronic patient records. Discrimination of the risk prediction models was evaluated with area under the curve (AUC) statistics, and calibration was assessed with Cox calibration regression. The primary outcome was 30-day mortality. Out of 1226 included patients, 146 patients (11.9%) died within 30 days. AUC (95% confidence interval) for 30-day mortality was 0.85 (0.82-0.88) for the updated NELA model, 0.84 (0.81-0.87) for the original NELA model, 0.81 (0.77-0.84) for the P-POSSUM model, and 0.76 (0.72-0.79) for the ASA-PS model. Calibration showed underestimation of mortality risk for both the updated NELA, original NELA and P-POSSUM models. The updated NELA risk prediction model performs well in this external validation study and may be used in similar settings. However, the model should only be used to discriminate between low- and high-risk patients, and not for prediction of individual risk due to underestimation of mortality.

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.

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.

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.

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.