Care management of the agitation or aggressiveness crisis in patients with TBI. Systematic review of the literature and practice recommendations

AbstractThe agitation crisis in the awakening phase after traumatic brain injury (TBI) is one of the most difficult behavioral disorders to alleviate. Current treatment options are heterogeneous and may involve excessive sedation. Practice guidelines are required by professionals in charge of TBI patients. Few reviews were published but those are old and based on expert opinions. The purpose of this work is to propose evidence-based guidelines to treat the agitation crisis.MethodsThe elaboration of these guidelines followed the procedure validated by the French health authority for good practice recommendations, close to the Prisma statement. Guidelines were elaborated on the basis of a systematic and critical review of the literature.ResultsTwenty-eight articles concerning 376 patients were analyzed. Recommendations are: when faced with an agitation crisis, the management strategy implies to search for an underlying factor that should be treated such as pain, acute sepsis, and drug adverse effect (expert opinion). Physical restraints should be discarded when possible (expert opinion). Neuroleptic agent with a marketing authorization can be used in order to obtain a quick sedation so as to protect the patient from himself, closed ones or the healthcare team but the duration should be as short as possible (expert opinion). The efficacy of beta-blockers and antiepileptics with mood regulation effects like carbamazepine and valproate yield the most compelling evidence and should be preferably used when a background regimen is envisioned (grade B for beta-blocker and C for antiepileptics). Neuroleptics, antidepressants, benzodiazepines, buspirone may be prescribed but are considered second-line treatments (expert opinion).ConclusionThis study provides a strategy for treating the agitation crisis based on scientific data and expert opinion. The level of evidence remains low and published data are often old. New studies are essential to validate results from previous studies and test new drugs and non-pharmaceutical therapies

Sleep-Deprivation Regulates α-2 Adrenergic Responses of Rat Hypocretin/Orexin Neurons

We recently demonstrated, in rat brain slices, that the usual excitation by noradrenaline (NA) of hypocretin/orexin (hcrt/orx) neurons was changed to an inhibition following sleep deprivation (SD). Here we describe that in control condition (CC), i.e. following 2 hours of natural sleep in the morning, the α2-adrenergic receptor (α2-AR) agonist, clonidine, had no effect on hcrt/orx neurons, whereas following 2 hours of SD (SDC), it hyperpolarized the neurons by activating G-protein-gated inwardly rectifying potassium (GIRK) channels. Since concentrations of clonidine up to a thousand times (100 µM) higher than those effective in SDC (100 nM), were completely ineffective in CC, a change in the availability of G-proteins is unlikely to explain the difference between the two conditions. To test whether the absence of effect of clonidine in CC could be due to a down-regulation of GIRK channels, we applied baclofen, a GABAB agonist known to also activate GIRK channels, and found that it hyperpolarized hcrt/orx neurons in that condition. Moreover, baclofen occluded the response to clonidine in SDC, indicating that absence of effect of clonidine in CC could not be attributed to down-regulation of GIRK channels. We finally tested whether α2-ARs were still available at the membrane in CC and found that clonidine could reduce calcium currents, indicating that α2-ARs associated with calcium channels remain available in that condition. Taken together, these results suggest that a pool of α2-ARs associated with GIRK channels is normally down-regulated (or desensitized) in hcrt/orx neurons to only become available for their inhibition following sleep deprivation

Particulate matter exposure during pregnancy is associated with birth weight, but not gestational age, 1962-1992: a cohort study

<p>Abstract</p> <p>Background</p> <p>Exposure to air pollutants is suggested to adversely affect fetal growth, but the evidence remains inconsistent in relation to specific outcomes and exposure windows.</p> <p>Methods</p> <p>Using birth records from the two major maternity hospitals in Newcastle upon Tyne in northern England between 1961 and 1992, we constructed a database of all births to mothers resident within the city. Weekly black smoke exposure levels from routine data recorded at 20 air pollution monitoring stations were obtained and individual exposures were estimated via a two-stage modeling strategy, incorporating temporally and spatially varying covariates. Regression analyses, including 88,679 births, assessed potential associations between exposure to black smoke and birth weight, gestational age and birth weight standardized for gestational age and sex.</p> <p>Results</p> <p>Significant associations were seen between black smoke and both standardized and unstandardized birth weight, but not for gestational age when adjusted for potential confounders. Not all associations were linear. For an increase in whole pregnancy black smoke exposure, from the 1^st(7.4 μg/m³) to the 25^th(17.2 μg/m³), 50^th(33.8 μg/m³), 75^th(108.3 μg/m³), and 90^th(180.8 μg/m³) percentiles, the adjusted estimated decreases in birth weight were 33 g (SE 1.05), 62 g (1.63), 98 g (2.26) and 109 g (2.44) respectively. A significant interaction was observed between socio-economic deprivation and black smoke on both standardized and unstandardized birth weight with increasing effects of black smoke in reducing birth weight seen with increasing socio-economic disadvantage.</p> <p>Conclusions</p> <p>The findings of this study progress the hypothesis that the association between black smoke and birth weight may be mediated through intrauterine growth restriction. The associations between black smoke and birth weight were of the same order of magnitude as those reported for passive smoking. These findings add to the growing evidence of the harmful effects of air pollution on birth outcomes.</p

EVOLUTION ET FACTEURS PRONOSTIQUES DU COMA ANOXIQUE (A PROPOS DE 14 CAS)

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Associations between omega-3 fatty acids and 25(OH)D and psychological distress among Inuit in Canada

Background: Inuit in Canada have experienced dietary changes over recent generations, but how this relates to psychological distress has not been investigated. Objective: To evaluate how nutritional biomarkers are related to psychological distress. Design: A total of 36 communities in northern Canada participated in the International Polar Year Inuit Health Survey (2007–2008). Of 2796 households, 1901 (68%) participated; 1699 Inuit adults gave blood samples for biomarker analysis and answered the Kessler 6-item psychological distress questionnaire (K6). Biomarkers included n-3 fatty acids and 25-hydroxyvitamin D (25(OH)D). The K6 screens for psychological distress over the last 30 days with six items scored on a 4-point scale. A total score of 13 or more indicates serious psychological distress (SPD). Logistic regression models were used to investigate any associations between SPD and biomarkers while controlling for age, gender, marital status, days spent out on the land, feeling of being alone, income and smoking. Results: The 30-day SPD prevalence was 11.2%, with women below 30 years having the highest and men 50 years and more having the lowest SPD prevalence at 16.1% and 2.6%, respectively. SPD was associated with being female, younger age, not being married or with a common-law partner, spending few days out on the land, feelings of being alone, smoking and low income. Low levels of both 25(OH)D and long-chain n-3 FAs were associated with higher odds for SPD in both unadjusted and adjusted logistic regression models. Conclusion: In this cross-sectional analysis, low levels of 25(OH)D and long-chain n-3 FAs were associated with higher odds ratios for SPD, which highlights the potential impact of traditional foods on mental health and wellbeing. Cultural practices are also important for mental health and it may be that the biomarkers serve as proxies for cultural activities related to food collection, sharing and consumption that increase both biomarker levels and psychological well-being

Common colorectal cancer risk alleles contribute to the multiple colorectal adenoma phenotype, but do not influence colonic polyposis in FAP

The presence of multiple (5-100) colorectal adenomas suggests an inherited predisposition, but the genetic aetiology of this phenotype is undetermined if patients test negative for Mendelian polyposis syndromes such as familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP). We investigated whether 18 common colorectal cancer (CRC) predisposition single-nucleotide polymorphisms (SNPs) could help to explain some cases with multiple adenomas who phenocopied FAP or MAP, but had no pathogenic APC or MUTYH variant. No multiple adenoma case had an outlying number of CRC SNP risk alleles, but multiple adenoma patients did have a significantly higher number of risk alleles than population controls (P=5.7 × 10(-7)). The association was stronger in those with ≥10 adenomas. The CRC SNPs accounted for 4.3% of the variation in multiple adenoma risk, with three SNPs (rs6983267, rs10795668, rs3802842) explaining 3.0% of the variation. In FAP patients, the CRC risk score did not differ significantly from the controls, as we expected given the overwhelming effect of pathogenic germline APC variants on the phenotype of these cases. More unexpectedly, we found no evidence that the CRC SNPs act as modifier genes for the number of colorectal adenomas in FAP patients. In conclusion, common colorectal tumour risk alleles contribute to the development of multiple adenomas in patients without pathogenic germline APC or MUTYH variants. This phenotype may have 'polygenic' or monogenic origins. The risk of CRC in relatives of multiple adenoma cases is probably much lower for cases with polygenic disease, and this should be taken into account when counselling such patients