Comparison of numerical and verbal rating scales to measure pain exacerbations in patients with chronic cancer pain

<p>Abstract</p> <p>Background</p> <p>Numerical rating scales (NRS), and verbal rating scales (VRS) showed to be reliable and valid tools for subjective cancer pain measurement, but no one of them consistently proved to be superior to the other. Aim of the present study is to compare NRS and VRS performance in assessing breakthrough or episodic pain (BP-EP) exacerbations.</p> <p>Methods</p> <p>In a cross sectional multicentre study carried out on a sample of 240 advanced cancer patients with pain, background pain and BP-EP intensity in the last 24 hours were measured using both a 6-point VRS and a 0-10 NRS. In order to evaluate the reproducibility of the two scales, a subsample of 60 patients was randomly selected and the questionnaire was administered for a second time three to four hours later. The proportion of "inconsistent" (background pain intensity higher than or equal to peak pain intensity) evaluations was calculated to compare the two scales capability in discriminating between background and peak pain intensity and Cohen's K was calculated to compare their reproducibility.</p> <p>Results</p> <p>NRS revealed higher discriminatory capability than VRS in distinguishing between background and peak pain intensity with a lower proportion of patients giving inconsistent evaluations (14% vs. 25%). NRS also showed higher reproducibility when measuring pain exacerbations (Cohen's K of 0.86 for NRS vs. 0.53 for VRS) while the reproducibility of the two scales in evaluating background pain was similar (Cohen's K of 0.80 vs. 0.77).</p> <p>Conclusions</p> <p>Our results suggest that, in the measurement of cancer pain exacerbations, patients use NRS more appropriately than VRS and as such NRS should be preferred to VRS in this patient's population.</p

Analysis of shared common genetic risk between amyotrophic lateral sclerosis and epilepsy

Because hyper-excitability has been shown to be a shared pathophysiological mechanism, we used the latest and largest genome-wide studies in amyotrophic lateral sclerosis (n = 36,052) and epilepsy (n = 38,349) to determine genetic overlap between these conditions. First, we showed no significant genetic correlation, also when binned on minor allele frequency. Second, we confirmed the absence of polygenic overlap using genomic risk score analysis. Finally, we did not identify pleiotropic variants in meta-analyses of the 2 diseases. Our findings indicate that amyotrophic lateral sclerosis and epilepsy do not share common genetic risk, showing that hyper-excitability in both disorders has distinct origins

Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

A. Palotie on työryhmän Schizophrenia Working Grp Psychiat jäsen.We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P = 1 x 10(-4)) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P = 8.4 x 10(-7)). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.Peer reviewe

Development of the palliative care referral system: proposal of a tool for the referral of cancer patients to specialized palliative care

Abstract Background Early palliative care (PC) has shown beneficial effects for advanced cancer patients. However, it is still debated what criteria to use to identify patients for PC referral. Aim To document the initial steps of the development of the Palliative Care Referral System (PCRS), a tool to be used by oncologists in clinical practice. Methods A multiprofessional working group developed the PCRS based on the results of a scoping literature review on PC referral criteria. PCRS criteria were evaluated by experts via a nominal group technique (NGT). Descriptive statistics were used to summarize expert scores on relevance, appropriateness and perceived feasibility of the criteria proposed. Quotations of participants during the discussion were also reported. Results Sixteen studies, including PC referral criteria/tools, emerged from the scoping review. Severe symptoms, poor performance status, comorbidities and prognosis were the most commonly used criteria. The PCRS included nine major criteria and nine assessment methods; a scoring procedure was also proposed. Answers to the questionnaire during the NGT showed that five criteria reached full agreement on all items, while four did not, and were then discussed within the group. Participants agreed on the relevance of all criteria and on the appropriateness of methods proposed to assess most of them, while issues were raised about potential feasibility of the overall assessment of the PCRS in clinical practice. Conclusion The PCRS has been developed as an help for oncologists to timely identify patients for specialized PC referral. Since feasibility emerged as the main concern, implementation strategies have to be tested in subsequent studies

The neurobiology of human aggressive behavior: Neuroimaging, genetic, and neurochemical aspects.

In modern societies, there is a strive to improve the quality of life related to risk of crimes which inevitably requires a better understanding of brain determinants and mediators of aggression. Neurobiology provides powerful tools to achieve this end. Pre-clinical and clinical studies show that changes in regional volumes, metabolism-function and connectivity within specific neural networks are related to aggression. Subregions of prefrontal cortex, insula, amygdala, basal ganglia and hippocampus play a major role within these circuits and have been consistently implicated in biology of aggression. Genetic variations in proteins regulating the synthesis, degradation, and transport of serotonin and dopamine as well as their signal transduction have been found to mediate behavioral variability observed in aggression. Gene-gene and gene-environment interactions represent additional important risk factors for aggressiveness. Considering the social burden of pathological forms of aggression, more basic and translational studies should be conducted to accelerate applications to clinical practice, justice courts, and policy making

FNDC5/Irisin System in Neuroinflammation and Neurodegenerative Diseases: Update and Novel Perspective

Irisin, the circulating peptide originating from fibronectin type III domain-containing protein 5 (FNDC5), is mainly expressed by muscle fibers under peroxisome proliferator-activated receptor gamma coactivator 1-alpha PGC1α control during exercise. In addition to several beneficial effects on health, physical activity positively affects nervous system functioning, particularly the hippocampus, resulting in amelioration of cognition impairments. Recently, FNDC5/irisin detection in hippocampal neurons and the presence of irisin in the cerebrospinal fluid opened a new intriguing chapter in irisin history. Interestingly, in the hippocampus of mice, exercise increases FNDC5 levels and upregulates brain-derived neurotrophic factor (BDNF) expression. BDNF, displaying neuroprotection and anti-inflammatory effects, is mainly produced by microglia and astrocytes. In this review, we discuss how these glial cells can morphologically and functionally switch during neuroinflammation by modulating the expression of a plethora of neuroprotective or neurotoxic factors. We also focus on studies investigating the irisin role in neurodegenerative diseases (ND). The emerging involvement of irisin as a mediator of the multiple positive effects of exercise on the brain needs further studies to better deepen this issue and the potential use in therapeutic approaches for neuroinflammation and ND

Neuropathic pain: clinical classification and assessment in patients with pain due to cancer

Neuropathic cancer pain (NcP) is associated with worse treatment responses and specific therapy indications, but a standardized clinical diagnosis of NcP is still lacking. This is a prospective observational study on outpatients with cancer, comparing different clinical approaches with NcP evaluation. A three-step assessment of NcP was performed using DN4 (cutoff of 4), palliative care physician Clinical Impression, including etiology and pain syndrome identification, and Retrospective Clinical Classification by a board of specialists with the IASP Neuropathic Pain Special Interest Group criteria. Neuropathic cancer pain classification was specifically referred to pain directly due to cancer. Three hundred fifty patients were assessed, and NcP prevalence was 20% (95% confidence interval [CI] 15.9%-24.6%), 36.9%, (95% CI 31.6%-42.1%), and 28.6% (95% CI 23.8%-33.9%) according to DN4, Clinical Impression, and Retrospective Clinical Classification, respectively. Cohen's kappa concordance coefficient between DN4 and Retrospective Clinical Classification was 0.57 (95% CI 0.47-0.67), indicating moderate concordance. Higher percentages of discordance were found for specific pain syndromes such as pain due to deep soft tissue infiltration and pain associated with tenesmus. Disagreement among clinicians accounted also for different NcP diagnoses and highlighted lack of homogeneous clinical criteria. Rigorous application of etiological and syndrome diagnosis to explain pain cause, associated with standardized diagnostic criteria and assessment of pain characteristics, that is also specific for the cancer pain condition could improve clinical classification of NcP

A real‐world study on the prevalence and risk factors of medication related osteonecrosis of the jaw in cancer patients with bone metastases treated with Denosumab

Abstract Aim Assessing the incidence of Medication Related Osteonecrosis of the Jaw (MRONJ) in cancer patients with bone metastases receiving Denosumab (Dmab) and identifying potential risk factors. Methods A retrospective observational study on consecutive cancer patients with bone metastases, who received at least one dose of Dmab and one follow‐up visit. MRONJ crude cumulative incidence (CCI) was estimated considering death without MRONJ as competing event. Multiple regression models were used to study the association between MRONJ incidence and potential risk factors: age, cancer diagnosis, previous bisphosphonates, dental treatments before starting Dmab, extraction or other dental treatment during Dmab, chemotherapy, hormone therapy, and antiangiogenic (AA) agents concurrent use. Results On 780 patients included (median follow‐up 17 months), 54% and 18% had, respectively, breast and prostate cancer. The mean number of Dmab administration was 12. Fifty‐six patients developed MRONJ with a 24‐ and a 48‐month crude cumulative incidence of 5.7% (95% Cl: 4.2%–7.8%) and 9.8% (95% CI: 7.6%–12.7%), respectively. Higher MRONJ incidence was significantly associated with middle aged group (>56 and ≤73), both at univariate and multivariate analysis (p = 0.029 and 0.0106). Dental treatments (Hazard Ratio [HR] = 3.67; p = 0.0001), dental extractions (HR = 23.40; p < 0.0001), and previous BP administration (HR = 2.62; p = 0.0024) were significantly associated with higher MRONJ incidence at multivariate Cox analysis. Although not statistically significant, MRONJ incidence was lower for patients receiving chemotherapy or hormone therapy and higher for those receiving AAs. Conclusions The results confirm a clinically relevant incidence of Dmab‐induced MRONJ. Dental treatments, especially extraction, during and before Dmab, constitute a serious risk factor. The role of AA concurrent administration deserves further investigations

A Transgenic Mouse Model for the Detection of Cellular Stress Induced by Toxic Inorganic Compounds.

In the last few years plasmid-based transgenic mice which can be used for genotoxicitytesting have been devised, though no such models have yet been produced for the evaluation of toxic, non-genotoxic chemical compounds. We present here a novel approach to this problem based on transgenic mice.We engineered a mouse lineage with the human growth hormone(hGH) gene under the control of the human hsp-70 promoter, in which a plasma-detectable hGH response can be elicited by exposure to heat shock.JRC.(EI)-Environment Institut