Non-suicidal self-injury (NSSI) in adult psychiatric outpatients – A nationwide study

Background: Non-suicidal self-injury (NSSI) is a highly prevalent behavioural problem among people with mental illness, yet many fundamental aspects of NSSI remain unknown. We studied the prevalence of NSSI, and its relationship with suicide ideation (SI) and suicide attempts (SA) among adult psychiatric outpatients, with a special focus on patients with personality disorders compared with patients with other disorders. Method: During a 14-day period, data were collected on all available patients in all outpatient psychiatric clinics in Norway. This national clinical unselected cross-sectional dataset from 23,124 outpatients was used to generate proportional Venn diagrams of the prevalence of NSSI, SI and SA and their co-occurrence over the last four weeks. Differences in the risk for these behaviours across diagnoses were tested, both with and without adjustments for demographic and socio-demographic characteristics. Results: Over the previous four-week period, 8.1% of the patients had experienced at least one episode of NSSI, 17.3% had SI and 0.6% had made at least one SA. Among patients with NSSI, 27.8% had co-occurring SI, and among patients with SI, 13% had co-occurring NSSI. The prevalence of SA was more than seven times higher among patients with NSSI behaviour than among patients without NSSI behaviour. Patients with a diagnosis of personality disorder had a significantly higher prevalence of SI, NSSI, and NSSI with co-occurring SI, than all other diagnostic groups; however, they were not systematically different from patients with other diagnoses in their prevalence of NSSI without co-occurring SI. These findings remained statistically significant even when controlling for socio-demographic variables. Conclusions: The prevalence of recent NSSI is high in patients receiving outpatient psychiatric treatment in Norway. NSSI is significantly more prevalent in patients with personality disorders than in patients with other diagnoses, mainly due to the significantly higher prevalence of NSSI with co-occurring SI in patients with personality disorders. The co-occurrence of NSSI and SI is also prevalent in all diagnostic groups, but both NSSI and SI appear alone more often than together. The strong association between NSSI and SA calls for a more proactive focus on NSSI behaviour in mental health clinical settings as an important suicide preventive measure.publishedVersio

Interleukin-6 and C-reactive protein as prognostic biomarkers in metastatic colorectal cancer

OBJECTIVES: The aim was to explore the prognostic significance of IL-6 and markers of systemic inflammatory response (SIR), in particular C-reactive protein (CRP), in metastatic colorectal cancer (mCRC) patients, in the total study population and according to RAS and BRAF mutation status. RESULTS: High levels of pretreatment serum IL-6 or CRP were associated with impaired outcome, in terms of reduced PFS and OS. Patients with low versus high serum IL-6 levels had median OS of 26.0 versus 16.6 months, respectively (P < 0.001). Stratified according to increasing CRP levels, median OS varied from 24.3 months to 12.3 months, (P < 0.001). IL-6 and CRP levels affected overall prognosis also in adjusted analyses. The effect of IL-6 was particularly pronounced in patients with BRAF mutation (interaction P = 0.004). MATERIALS AND METHODS: IL-6 and CRP were determined in pre-treatment serum samples from 393 patients included in the NORDIC-VII trial, in which patients with mCRC received first line treatment. The effect of serum IL-6 and CRP on progression-free survival (PFS) and overall survival (OS) was estimated. CONCLUSIONS: High baseline serum consentrations of IL-6 or CRP were associated with impaired prognosis in mCRC. IL-6 and CRP give independent prognostic information in addition to RAS and BRAF mutation status

Survival-associated heterogeneity of marker-defined perivascular cells in colorectal cancer

Perivascular cells (PC) were recently implied as regulators of metastasis and immune cell activity. Perivascular heterogeneity in clinical samples, and associations with other tumor features and outcome, remain largely unknown. Here we report a novel method for digital quantitative analyses of vessel characteristics and PC, which was applied to two collections of human metastatic colorectal cancer (mCRC). Initial analyses identified marker-defined subsets of PC, including cells expressing PDGFR-beta or alpha-SMA or both markers. PC subsets were largely independently expressed in a manner unrelated to vessel density and size. Association studies implied specific oncogenic mutations in malignant cells as determinants of PC status. Semi-quantitative and digital-image-analyses-based scoring of the NORDIC-VII cohort identified significant associations between low expression of perivascular PDGFR-alpha and -beta and shorter overall survival. Analyses of the SPCRC cohort confirmed these findings. Perivascular PDGFR-alpha and -beta remained independent factors for survival in multivariate analyses. Overall, our study identified host vasculature and oncogenic status as determinants of tumor perivascular features. Perivascular PDGFR-alpha and -beta were identified as novel independent markers predicting survival in mCRC. The novel methodology should be suitable for similar analyses in other tumor collections

Expression of NDRG2 is down-regulated in high-risk adenomas and colorectal carcinoma

<p>Abstract</p> <p>Background</p> <p>It has recently been shown that <it>NDRG2 </it>mRNA is down-regulated or undetectable in several human cancers and cancer cell-lines. Although the function of NDRG2 is unknown, high <it>NDRG2 </it>expression correlates with improved prognosis in high-grade gliomas. The aim of this study has been to examine <it>NDRG2 </it>mRNA expression in colon cancer. By examining affected and normal tissue from individuals with colorectal adenomas and carcinomas, as well as in healthy individuals, we aim to determine whether and at which stages <it>NDRG2 </it>down-regulation occurs during colonic carcinogenesis.</p> <p>Methods</p> <p>Using quantitative RT-PCR, we have determined the mRNA levels for <it>NDRG2 </it>in low-risk (n = 15) and high-risk adenomas (n = 57), colorectal carcinomas (n = 50) and corresponding normal tissue, as well as control tissue from healthy individuals (n = 15). <it>NDRG2 </it>levels were normalised to <it>β-actin</it>.</p> <p>Results</p> <p><it>NDRG2 </it>mRNA levels were lower in colorectal carcinomas compared to normal tissue from the control group (p < 0.001). When comparing adenomas/carcinomas with adjacent normal tissue from the same individual, <it>NDRG2 </it>expression levels were significantly reduced in both high-risk adenoma (p < 0.001) and in colorectal carcinoma (p < 0.001). There was a trend for <it>NDRG2 </it>levels to decrease with increasing Dukes' stage (p < 0.05).</p> <p>Conclusion</p> <p>Our results demonstrate that expression of <it>NDRG2 </it>is down-regulated at a late stage during colorectal carcinogensis. Future studies are needed to address whether <it>NDRG2 </it>down-regulation is a cause or consequence of the progression of colorectal adenomas to carcinoma.</p

The level of claudin-7 is reduced as an early event in colorectal carcinogenesis

<p>Abstract</p> <p>Background</p> <p>Compromised epithelial barriers are found in dysplastic tissue of the gastrointestinal tract. Claudins are transmembrane proteins important for tight junctions. Claudins regulate the paracellular transport and are crucial for maintaining a functional epithelial barrier. Down-regulation of the oncogenic serine protease, matriptase, induces leakiness in epithelial barriers both <it>in vivo </it>and <it>in vitro</it>. We found in an <it>in-silico </it>search tight co-regulation between <it>matriptase </it>and <it>claudin-7 </it>expression. We have previously shown that the <it>matriptase </it>expression level decreases during colorectal carcinogenesis. In the present study we investigated whether <it>claudin-7 </it>expression is likewise decreased during colorectal carcinogenesis, thereby causing or contributing to the compromised epithelial leakiness of dysplastic tissue.</p> <p>Methods</p> <p>The mRNA level of <it>claudin-7 </it>(CLDN7) was determined in samples from 18 healthy individuals, 100 individuals with dysplasia and 121 colorectal cancer patients using quantitative real time RT-PCR. In addition, immunohistochemical stainings were performed on colorectal adenomas and carcinomas, to confirm the mRNA findings.</p> <p>Results</p> <p>A 2.7-fold reduction in the <it>claudin-7 </it>mRNA level was found when comparing the biopsies from healthy individuals with the biopsies of carcinomas (p < 0.001). Reductions in the <it>claudin-7 </it>mRNA levels were also detected in mild/moderate dysplasia (p < 0.001), severe dysplasia (p < 0.01) and carcinomas (p < 0.01), compared to a control sample from the same individual. The decrease at mRNA level was confirmed at the protein level by immunohistochemical stainings.</p> <p>Conclusions</p> <p>Our results show that the <it>claudin-7 </it>mRNA level is decreased already as an early event in colorectal carcinogenesis, probably contributing to the compromised epithelial barrier in adenomas.</p

Differential Expression of miRNAs in Colorectal Cancer: Comparison of Paired Tumor Tissue and Adjacent Normal Mucosa Using High-Throughput Sequencing

We present the results of a global study of dysregulated miRNAs in paired samples of normal mucosa and tumor from eight patients with colorectal cancer. Although there is existing data of miRNA contribution to colorectal tumorigenesis, these studies are typically small to medium scale studies of cell lines or non-paired tumor samples. The present study is to our knowledge unique in two respects. Firstly, the normal and adjacent tumor tissue samples are paired, thus taking into account the baseline differences between individuals when testing for differential expression. Secondly, we use high-throughput sequencing, thus enabling a comprehensive survey of all miRNAs expressed in the tissues. We use Illumina sequencing technology to perform sequencing and two different tools to statistically test for differences in read counts per gene between samples: edgeR when using the pair information and DESeq when ignoring this information, i.e., treating tumor and normal samples as independent groups. We identify 37 miRNAs that are significantly dysregulated in both statistical approaches, 19 down-regulated and 18 up-regulated. Some of these miRNAs are previously published as potential regulators in colorectal adenocarcinomas such as miR-1, miR-96 and miR-145. Our comprehensive survey of differentially expressed miRNAs thus confirms some existing findings. We have also discovered 16 dysregulated miRNAs, which to our knowledge have not previously been associated with colorectal carcinogenesis: the following significantly down-regulated miR-490-3p, -628-3p/-5p, -1297, -3151, -3163, -3622a-5p, -3656 and the up-regulated miR-105, -549, -1269, -1827, -3144-3p, -3177, -3180-3p, -4326. Although the study is preliminary with only eight patients included, we believe the results add to the present knowledge on miRNA dysregulation in colorectal carcinogenesis. As such the results would serve as a robust training set for validation of potential biomarkers in a larger cohort study. Finally, we also present data supporting the hypothesis that there are differences in miRNA expression between adenocarcinomas and neuroendocrine tumors of the colon

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Suksess i redusert ventetid og målrettet behandling i psykisk helsevern kan gi utilsiktede vanskeligheter med behandling for pasientgrupper med store behov

Non-suicidal self-injury (NSSI) in adult psychiatric outpatients – A nationwide study

Background Non-suicidal self-injury (NSSI) is a highly prevalent behavioural problem among people with mental illness, yet many fundamental aspects of NSSI remain unknown. We studied the prevalence of NSSI, and its relationship with suicide ideation (SI) and suicide attempts (SA) among adult psychiatric outpatients, with a special focus on patients with personality disorders compared with patients with other disorders. Method During a 14-day period, data were collected on all available patients in all outpatient psychiatric clinics in Norway. This national clinical unselected cross-sectional dataset from 23,124 outpatients was used to generate proportional Venn diagrams of the prevalence of NSSI, SI and SA and their co-occurrence over the last four weeks. Differences in the risk for these behaviours across diagnoses were tested, both with and without adjustments for demographic and socio-demographic characteristics. Results Over the previous four-week period, 8.1% of the patients had experienced at least one episode of NSSI, 17.3% had SI and 0.6% had made at least one SA. Among patients with NSSI, 27.8% had co-occurring SI, and among patients with SI, 13% had co-occurring NSSI. The prevalence of SA was more than seven times higher among patients with NSSI behaviour than among patients without NSSI behaviour. Patients with a diagnosis of personality disorder had a significantly higher prevalence of SI, NSSI, and NSSI with co-occurring SI, than all other diagnostic groups; however, they were not systematically different from patients with other diagnoses in their prevalence of NSSI without co-occurring SI. These findings remained statistically significant even when controlling for socio-demographic variables. Conclusions The prevalence of recent NSSI is high in patients receiving outpatient psychiatric treatment in Norway. NSSI is significantly more prevalent in patients with personality disorders than in patients with other diagnoses, mainly due to the significantly higher prevalence of NSSI with co-occurring SI in patients with personality disorders. The co-occurrence of NSSI and SI is also prevalent in all diagnostic groups, but both NSSI and SI appear alone more often than together. The strong association between NSSI and SA calls for a more proactive focus on NSSI behaviour in mental health clinical settings as an important suicide preventive measure

FCGR2A and FCGR3A polymorphisms and clinical outcome in metastatic colorectal cancer patients treated with first-line 5-fluorouracil/folinic acid and oxaliplatin +/- cetuximab

Background Polymorphisms of genes encoding the Fcy receptors (Fc fragment of IgG receptor 2A (FCGR2A) and 3A (FCGR3A)), which influence their affinity for the Fc fragment, have been linked to the pharmacodynamics of monoclonal antibodies. Most studies have been limited by small samples sizes and have reported inconsistent associations between the FCGR2A and the FCGR3A polymorphisms and clinical outcome in metastatic colorectal cancer (mCRC) patients treated with cetuximab. We investigated the association of these polymorphisms and clinical outcome in a large cohort of mCRC patients treated with first-line 5-fluorouracil/folinic acid and oxaliplatin (Nordic FLOX) +/- cetuximab in the NORDIC-VII study (NCT00145314). Methods 504 and 497 mCRC patients were evaluable for the FCGR2A and FCGR3A genotyping, respectively. Genotyping was performed on TaqMan ABI HT 7900 (Applied Biosystems, Foster City, CA, USA) with pre-designed SNP genotyping assays for FCGR2A (rs1801274) and FCGR3A (rs396991). Results The response rate for patients with the FCGR2A R/R genotype was significantly increased when cetuximab was added to Nordic FLOX (31% versus 53%, interaction P?=?0.03), but was not significantly different compared to the response rate of patients with the FCGR2A H/H or H/R genotypes given the same treatment. A larger increase in response rate with the addition of cetuximab to Nordic FLOX in patients with KRAS mutated tumors and the FCGR2A R/R genotype was observed (19% versus 50%, interaction P?=?0.04). None of the FCGR3A polymorphisms were associated with altered response when cetuximab was added to Nordic FLOX (interaction P?=?0.63). Neither of the FCGR polymorphisms showed any significant associations with progression-free survival or overall survival. Conclusion Patients with KRAS mutated tumors and the FCGR2A R/R polymorphism responded poorly when treated with chemotherapy only, and experienced the most benefit of the addition of cetuximab in terms of response rate

Unplanned Admissions to Inpatient Psychiatric Treatment and Services Received Prior to Admission

Background Inpatient bed numbers are continually being reduced but are not being replaced with adequate alternatives in primary health care. There is a considerable risk that eventually all inpatient treatment will be unplanned, because planned or elective treatments are superseded by urgent needs when capacity is reduced. Aims of the study To estimate the rate of unplanned admissions to inpatient psychiatric treatment facilities in Norway and analyse the difference between patients with unplanned and planned admissions regarding services received during the three months prior to admission as well as clinical, demographical and socioeconomic characteristics of patients. Method Unplanned admissions were defined as all urgent and involuntary admissions including unplanned readmissions. National mapping of inpatients was conducted in all inpatient treatment psychiatric wards in Norway on a specific date in 2012. Binary logit regressions were performed to compare patients who had unplanned admissions with patients who had planned admissions (i.e., the analyses were conditioned on admission to inpatient psychiatric treatment). Results Patients with high risk of unplanned admission are suffering from severe mental illness, have low functional level indicated by the need for housing services, high risk for suicide attempt and of being violent, low education and born outside Norway. Conclusion Specialist mental health services should support the local services in their efforts to prevent unplanned admissions by providing counselling, short inpatient stays, outpatient treatment and ambulatory outpatient psychiatry services. Implications for health policies This paper suggests the rate of unplanned admissions as a quality indicator and considers the introduction of economic incentives in the income models at both service levels.publishedVersio