Toll-like receptor 4 and CD14 polymorphisms in ankylosing spondylitis: Evidence of a weak association in finns

Objective To investigate the association of CD14 and Toll-like receptor (TLR4) with ankylosing spondylitis (AS). Methods A promoter variant in CD14 and 2 coding polymorphisms in TLR4 were investigated in UK and Finnish families with AS and in a UK case-control study. A metaanalysis of published TLR4 and CD14 studies was performed. Results In the Finnish study the CD74-260bp T variant showed an association (p = 0.006), and the common 2-marker TLR4 haplotype showed a weak association (global p = 0.03), with AS. No associations were seen in the UK based studies or in the metaanalyses. Conclusion CD14 and TLR4 showed an association with AS in the Finns only.

Association between CASP8-652 6N Del Polymorphism (rs3834129) and Colorectal Cancer Risk: Results from a Multi-Centric Study

The common 2652 6N del variant in the CASP8 promoter (rs3834129) has been described as a putative low-penetrance risk factor for different cancer types. In particular, some studies suggested that the deleted allele (del) was inversely associated with CRC risk while other analyses failed to confirm this. Hence, to better understand the role of this variant in the risk of developing CRC, we performed a multi-centric case-control study. In the study, the variant 2652 6N del was genotyped in a total of 6,733 CRC cases and 7,576 controls recruited by six different centers located in Spain, Italy, USA, England, Czech Republic and the Netherlands collaborating to the international consortium COGENT (COlorectal cancer GENeTics). Our analysis indicated that rs3834129 was not associated with CRC risk in the full data set. However, the del allele was under-represented in one set of cases with a family history of CRC (per allele model OR = 0.79, 95% CI = 0.69-0.90) suggesting this allele might be a protective factor versus familial CRC. Since this multi-centric case-control study was performed on a very large sample size, it provided robust clarification of the effect of rs3834129 on the risk of developing CRC in Caucasians.

Religious Coping, Social Support and Subjective Severity as Predictors of Posttraumatic Growth in People Affected by the Earthquake in Chile on 27/2/2010

The aim of this research is to study the impact of religious coping, social support and subjective severity on Posttraumatic Growth (PTG) in people who lost their homes after the earthquake in Chile in 2010 and who now live in transitional shelters. One hundred sixteen adult men and women were evaluated using a subjective severity scale, the Posttraumatic Growth Inventory (PTGI), the Multidimensional Scale of Perceived Social Support (MSPSS) scale of social support and the Brief RCOPE scale of religious coping. The multiple linear regression analysis shows that social support and positive religious coping have an impact on PTG. On using a bootstrap estimate, it was found that positive religious coping fully mediates the relationship between subjective severity and PTG.

Dispositivos suprágloticos: una aproximación a su uso en el ámbito extrahospitalario

[Es]Introducción: El manejo óptimo de la vía aérea extrahospitalaria es todavía incierto. Los dispositivos supraglóticos y la intubación endotraqueal han sido utilizados en los últimos años por los servicios de emergencia, pero no se conoce aún si el uso de los nuevos dispositivos supraglóticos mejora la supervivencia. Objetivo: Determinar la supervivencia a corto plazo (igual o menor a 1 mes) entre los dispositivos supraglóticos y la intubación endotraqueal en la parada cardíaca extrahospitalaria. Metodología: Se realizó una revisión bibliográfica en las bases de datos de Cochrane, Pubmed, MEDES, Scopus, CINAHL, Science Direct e IBECS y una búsqueda manual en las revistas Emergencias, Prehospital Emergency Care y Annals Emergency Medicine de estudios comprendidos entre los años 2004- 2014 que comparasen la supervivencia en la parada cardíaca extrahospitalaria del adulto entre los dispositivos supraglóticos y la intubación endotraqueal. Resultados: Se identificaron 9 estudios elegibles: 2 revisiones sistemáticas (una con metaanálisis), 1 ensayo clínico aleatorizado y 6 estudios de cohortes. 6 de los estudios mostraron mejores resultados en la intubación endotraqueal, 2 en los que no hubo diferencias y uno de ellos mostró mejores resultados en los dispositivos supraglóticos. Conclusiones: La intubación endotraqueal proporciona mayor supervivencia que los dispositivos supraglóticos en la parada cardíaca extrahospitalaria en adultos. Los dispositivos supraglóticos deberían utilizarse por parte de personal con poca experiencia en el uso de la intubación endotraqueal o como alternativa a la intubación fallida o con dificultad.

Cytokine pathway disruption in a mouse model of schizophrenia induced by Munc18-1a overexpression in the brain

Background: An accumulating body of evidence points to the significance of neuroinflammation and immunogenetics in schizophrenia, and an imbalance of cytokines in the central nervous system (CNS) has been suggested to be associated with the disorder. Munc18-overexpressing mice (Munc18-OE) have provided a model for the study of the alterations that may underlie the symptoms of subjects with schizophrenia. The aim of the present study was to elucidate the involvement of neuroinflammation and cytokine imbalance in this model. Methods: Cytokines were evaluated in the cortex and the striatum of Munc18-OE and wild-type (WT) mice by enzyme-linked immunosorbent assay (ELISA). Protein levels of specific microglia and macrophage, astrocytic and neuroinflammation markers were quantified by western blot in the cortex and the striatum of Munc18-OE and WT mice. Results: Each cytokine evaluated (Interferon-gamma (IFN-gamma), Tumor Necrosis Factor-alpha (TNF-alpha), Interleukin-2 (IL-2) and CCL2 chemokine) was present at higher levels in the striatum of Munc18-OE mice than WT. Cortical TNF-alpha and IL-2 levels were significantly lower in Munc18-OE mice than WT mice. The microglia and macrophage marker CD11b was lower in the cortexes of Munc18-OE mice than WT, but no differences were observed in the striatum. Glial Fibrillary Acidic Protein (GFAP) and Nuclear Factor-kappaB (NF-kappa B)p65 levels were not different between the groups. Interleukin-1beta (IL-1 beta) and IL-6 levels were beneath detection limits. Conclusions: The disrupted levels of cytokines detected in the brain of Munc18-OE mice was found to be similar to clinical reports and endorses study of this type for analysis of this aspect of the disorder. The lower CD11b expression in the cortex but not in the striatum of the Munc18-OE mice may reflect differences in physiological activity. The cytokine expression pattern observed in Munc18-OE mice is similar to a previously published model of schizophrenia caused by maternal immune activation. Together, these data suggest a possible role for an immune imbalance in this disorder.

Predictive score for mortality in patients with COPD exacerbations attending hospital emergency departments

Background: Limited information is available about predictors of short-term outcomes in patients with exacerbation of chronic obstructive pulmonary disease (eCOPD) attending an emergency department (ED). Such information could help stratify these patients and guide medical decision-making. The aim of this study was to develop a clinical prediction rule for short-term mortality during hospital admission or within a week after the index ED visit. Methods: This was a prospective cohort study of patients with eCOPD attending the EDs of 16 participating hospitals. Recruitment started in June 2008 and ended in September 2010. Information on possible predictor variables was recorded during the time the patient was evaluated in the ED, at the time a decision was made to admit the patient to the hospital or discharge home, and during follow-up. Main short-term outcomes were death during hospital admission or within 1 week of discharge to home from the ED, as well as at death within 1 month of the index ED visit. Multivariate logistic regression models were developed in a derivation sample and validated in a validation sample. The score was compared with other published prediction rules for patients with stable COPD. Results: In total, 2,487 patients were included in the study. Predictors of death during hospital admission, or within 1 week of discharge to home from the ED were patient age, baseline dyspnea, previous need for long-term home oxygen therapy or non-invasive mechanical ventilation, altered mental status, and use of inspiratory accessory muscles or paradoxical breathing upon ED arrival (area under the curve (AUC) = 0.85). Addition of arterial blood gas parameters (oxygen and carbon dioxide partial pressures (PO2 and PCO2)) and pH) did not improve the model. The same variables were predictors of death at 1 month (AUC = 0.85). Compared with other commonly used tools for predicting the severity of COPD in stable patients, our rule was significantly better. Conclusions: Five clinical predictors easily available in the ED, and also in the primary care setting, can be used to create a simple and easily obtained score that allows clinicians to stratify patients with eCOPD upon ED arrival and guide the medical decision-making process.

The MLH1 c.1852_1853delinsGC (p.K618A) Variant in Colorectal Cancer: Genetic Association Study in 18,723 Individuals

Colorectal cancer is one of the most frequent neoplasms and an important cause of mortality in the developed world. Mendelian syndromes account for about 5% of the total burden of CRC, being Lynch syndrome and familial adenomatous polyposis the most common forms. Lynch syndrome tumors develop mainly as a consequence of defective DNA mismatch repair associated with germline mutations in MLH1, MSH2, MSH6 and PMS2. A significant proportion of variants identified by screening these genes correspond to missense or noncoding changes without a clear pathogenic consequence, and they are designated as "variants of uncertain significance'', being the c.1852_1853delinsGC (p.K618A) variant in the MLH1 gene a clear example. The implication of this variant as a low-penetrance risk variant for CRC was assessed in the present study by performing a case-control study within a large cohort from the COGENT consortium-COST Action BM1206 including 18,723 individuals (8,055 colorectal cancer cases and 10,668 controls) and a case-only genotype-phenotype correlation with several clinical and pathological characteristics restricted to the Epicolon cohort. Our results showed no involvement of this variant as a low-penetrance variant for colorectal cancer genetic susceptibility and no association with any clinical and pathological characteristics including family history for this neoplasm or Lynch syndrome.

Association between CASP8-652 6N Del Polymorphism (rs3834129) and Colorectal Cancer Risk: Results from a Multi-Centric Study

The common 2652 6N del variant in the CASP8 promoter (rs3834129) has been described as a putative low-penetrance risk factor for different cancer types. In particular, some studies suggested that the deleted allele (del) was inversely associated with CRC risk while other analyses failed to confirm this. Hence, to better understand the role of this variant in the risk of developing CRC, we performed a multi-centric case-control study. In the study, the variant 2652 6N del was genotyped in a total of 6,733 CRC cases and 7,576 controls recruited by six different centers located in Spain, Italy, USA, England, Czech Republic and the Netherlands collaborating to the international consortium COGENT (COlorectal cancer GENeTics). Our analysis indicated that rs3834129 was not associated with CRC risk in the full data set. However, the del allele was under-represented in one set of cases with a family history of CRC (per allele model OR = 0.79, 95% CI = 0.69-0.90) suggesting this allele might be a protective factor versus familial CRC. Since this multi-centric case-control study was performed on a very large sample size, it provided robust clarification of the effect of rs3834129 on the risk of developing CRC in Caucasians.

At what price? A cost-effectiveness analysis comparing trial of labour after previous caesarean versus elective repeat caesarean delivery

Background: Elective repeat caesarean delivery (ERCD) rates have been increasing worldwide, thus prompting obstetric discourse on the risks and benefits for the mother and infant. Yet, these increasing rates also have major economic implications for the health care system. Given the dearth of information on the cost-effectiveness related to mode of delivery, the aim of this paper was to perform an economic evaluation on the costs and short-term maternal health consequences associated with a trial of labour after one previous caesarean delivery compared with ERCD for low risk women in Ireland.Methods: Using a decision analytic model, a cost-effectiveness analysis (CEA) was performed where the measure of health gain was quality-adjusted life years (QALYs) over a six-week time horizon. A review of international literature was conducted to derive representative estimates of adverse maternal health outcomes following a trial of labour after caesarean (TOLAC) and ERCD. Delivery/procedure costs derived from primary data collection and combined both "bottom-up" and "top-down" costing estimations.Results: Maternal morbidities emerged in twice as many cases in the TOLAC group than the ERCD group. However, a TOLAC was found to be the most-effective method of delivery because it was substantially less expensive than ERCD ((sic)1,835.06 versus (sic)4,039.87 per women, respectively), and QALYs were modestly higher (0.84 versus 0.70). Our findings were supported by probabilistic sensitivity analysis.Conclusions: Clinicians need to be well informed of the benefits and risks of TOLAC among low risk women. Ideally, clinician-patient discourse would address differences in length of hospital stay and postpartum recovery time. While it is premature advocate a policy of TOLAC across maternity units, the results of the study prompt further analysis and repeat iterations, encouraging future studies to synthesis previous research and new and relevant evidence under a single comprehensive decision model.

A meta-analysis of the association between Caesarean section and childhood asthma

Background: Children born by Caesarean section have modified intestinal bacterial colonization and consequently may have an increased risk of developing asthma under the hygiene hypothesis. The results of previous studies that have investigated the association between Caesarean section and asthma have been conflicting.

Objective: To review published literature and perform a meta-analysis summarizing the evidence in support of an association between children born by Caesarean section and asthma.

Methods: MEDLINE, Web Science, Google Scholar and PubMed were searched to identify relevant studies. Odds ratio (OR) and 95% confidence interval (CI) were calculated for each study from the reported prevalence of asthma in children born by Caesarean section and in control children. Meta-analysis was then used to derive a combined OR and test for heterogeneity in the findings between studies.

Results: Twenty-three studies were identified. The overall meta-analysis revealed an increase in the risk of asthma in children delivered by Caesarean section (OR=1.22, 95% CI 1.14, 1.29). However, in this analysis, there was evidence of heterogeneity (I2=46%) that was statistically significant (P<0.001). Restricting the analysis to childhood studies, this heterogeneity was markedly decreased (I2=32%) and no longer attained statistical significance (P=0.08). In these studies, there was also evidence of an increase (P<0.001) in the risk of asthma after Caesarean section (OR=1.20, 95% CI 1.14, 12.6).

Conclusion: In this meta-analysis, we found a 20% increase in the subsequent risk of asthma in children who had been delivered by Caesarean section.

Dietary glycaemic index, glycaemic load and endometrial and ovarian cancer risk: a systematic review and meta-analysis.

Long-term consumption of a high glycaemic index (GI) or glycaemic load (GL) diet may lead to chronic hyperinsulinaemia, which is a potential risk factor for cancer. To date, many studies have examined the association between GI, GL and cancer risk, although results have been inconsistent, therefore our objective was to conduct a systematic review of the literature. Medline and Embase were systematically searched using terms for GI, GL and cancer to identify studies published before December 2007. Random effects meta-analyses were performed for endometrial cancer, combining maximally adjusted results that compared risk for those in the highest versus the lowest category of intake. Separate analysis examined risk by body mass index categories. Five studies examining GI and/or GL intake and endometrial cancer risk were identified. Pooled effect estimates for endometrial cancer showed an increased risk for high GL consumers (RR 1.20; 95% CI: 1.06-1.37), further elevated in obese women (RR 1.54; 95% CI: 1.18-2.03). No significant associations were observed for GI. Only two studies examined ovarian cancer and therefore no meta-analysis was performed, but results indicate positive associations for GL also. A high GL, but not a high GI, diet is positively associated with the risk of endometrial cancer, particularly among obese women. © 2008 Cancer Research UK All rights reserved.