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Smoking and hazardous drinking are common and important risk factors for an increased rate of complications after surgery. The underlying pathophysiological mechanisms include organic dysfunctions that can recover with abstinence. Abstinence starting 3-8 weeks before surgery will significantly reduce the incidence of several serious postoperative complications, such as wound and cardiopulmonary complications and infections. However, this intervention must be intensive to obtain sufficient effect on surgical complications. All patients presenting for surgery should be questioned regarding smoking and hazardous drinking, and interventions appropriate for the surgical setting applied. [ABSTRACT FROM AUTHOR]

The oncogene PIM2 is upregulated in several malignancies but has never been investigated in mycosis fungoides (MF), the most common type of cutaneous T-cell lymphoma (CTCL). PIM2 is a well-known oncogene and is regulated by cell signaling pathways like the JAK/STAT- and NF-kB-pathway, key regulators in the pathogenesis of CTCL. The aim of this study was to examine the role of PIM2 in MF. PIM2 gene expression was measured in 81 formalin-fixed paraffin-embedded skin biopsies from patients with MF and 46 control biopsies from healthy skin (HS) and benign inflammatory skin disease (BID). Validation of PIM2 protein expression was performed on selected biopsies with immunohistochemical staining. We found a significant difference in gene expression levels between both early stage MF and HS (p < 0.0001), and BID (p < 0.0001). In addition, the PIM2 gene expression was higher in advanced-stage MF compared to early stage disease (p = 0.0001). No significant difference in gene expression levels was found between patients with and without disease progression. In conclusion, we found PIM2 expression is significantly increased in MF compared to controls, and in advanced-stage MF compared to early stage MF. These findings could potentially have diagnostic value in discriminating early stage MF from BID., (© 2024 Scandinavian Societies for Pathology, Medical Microbiology and Immunology.)

Mycosis fungoides is the most frequent subtype of primary cutaneous T-cell lymphomas. The diagnosis is based on a thorough clinic-pathologic correlation, which can, especially in early-stage disease, be challenging due to similarities with several benign skin disorders such as psoriasis and atopic dermatitis. Here, we present a case of an 81-year-old man with a 20-year-long medical history of skin problems treated as psoriasis with limited effect. Since December 2021, the patient experienced worsening of his skin symptoms with rapidly growing tumors and widespread patches and plaques. Positron emission tomography/computed tomography evaluation revealed markedly metabolic activity related to the skin tumors and increased FDG uptake in several retroperitoneal lymph nodes. Histological assessment of skin biopsies demonstrated a highly proliferative T-cell lymphoma with a γ/δ+ and CD8+ cytotoxic phenotype. The morphology of the tumor cells appeared blastic with an abnormal immunephenotype CD3+, CD2-, CD5 dim , CD4-, CD8+, CD56-, and CD30-. Next-generation sequencing detected a likely pathogenic SOCS1 mutation with an allele frequency of 72% as well as a STAT3 variant of unknown significance. This case highlights the diagnostic complexity of an indolent skin lymphoma evolving into an aggressive cytotoxic lymphoma., Competing Interests: Conflict of interest: Authors state no conflict of interest., (© 2024 the author(s), published by De Gruyter.)

Cutaneous T cell lymphoma (CTCL) is a group of non-Hodgkin's primary cutaneous T cell lymphomas, with Mycosis Fungoides and Sézary syndrome (SS) being the two most common subtypes. Fatty acid synthase (FASN) is a crucial enzyme that catalyses the biosynthesis of fatty acids, which has been reported to play an oncogenic role in various malignancies but not in CTCL so far. Herein, we show that FASN is highly expressed in CTCL cell lines and in peripheral blood mononuclear cells (PBMCs) from CTCL patients, while it is not in PBMCs from healthy individuals. The inhibition of FASN in CTCL cell lines impairs cell viability, survival, and proliferation, but, interestingly, it also increases FASN expression. However, inhibiting sterol regulatory element binding protein (SREBP), a transcription factor that promotes the expression of FASN, partially reversed the upregulation of FASN induced by FASN inhibitors. Thus, the combination of FASN and SREBP inhibitors enhanced the effects on both CTCL cell lines and PBMCs from SS patients, where a valid inhibition on cell proliferation could be verified. Importantly, compared to non-malignant cells, primary malignant cells are more sensitive to the inhibition of FASN and SREBP, making the combination of FASN and SREBP inhibitors a promising novel therapeutic strategy in CTCL.

Mycosis fungoides is the most common type of cutaneous T-cell lymphoma. The inflammatory micro-environment in mycosis fungoides is complex. There is accumulating evidence that the neoplastic T-cells take control of the microenvironment and thereby promote their own expansion by suppressing cellular immunity. B-cells have proved to be upregulated in large-cell transformed mycosis fungoides, and could potentially play a role in disease progression. To investigate the presence of B-cells in mycosis fungoides compared with controls, this study analysed 85 formalin-fixed and paraffin-embedded mycosis fungoides biopsies. MS4A1 gene expression was significantly upregulated in mycosis fungoides compared with controls (p < 0.0001) and further upregulated in disease progression, (p = 0.001). Digital quantification of PAX5+/CD20+ cells confirmed the increased presence of B-cells in mycosis fungoides compared with controls. No co-labelling of CD3/CD20 was observed in the neoplastic T-cells. This study found a significantly increased presence of B-cells in the tumour-associated microenvironment in mycosis fungoides. These findings could potentially lead to new treatment strategies for mycosis fungoides.

Neuroinflammation is an essential part of neurodegeneration. Yet, the current understanding of neuroinflammation-associated molecular events in distinct brain regions of prion disease patients is insufficient to lay the ground for effective treatment strategies targeting this complex neuropathological process. To address this problem, we analyzed the expression of 800 neuroinflammation-associated genes to create a profile of biological processes taking place in the frontal cortex and cerebellum of patients who suffered from sporadic Creutzfeldt-Jakob disease. The analysis was performed using NanoString nCounter technology with human neuroinflammation panel+. The observed gene expression patterns were regionally and sub-regionally distinct, suggesting a variable neuroinflammatory response. Interestingly, the observed differences could not be explained by the molecular subtypes of sporadic Creutzfeldt-Jakob disease. Furthermore, analyses of canonical pathways and upstream regulators based on differentially expressed genes indicated an overlap between biological processes taking place in different brain regions. This suggests that even smaller-scale spatial data reflecting subtle changes in brain cells' functional heterogeneity and their immediate pathologic microenvironments are needed to explain the observed differential gene expression in a greater detail.

Background: The voltage-gated potassium channel Kv1.3 (KCNA3) is expressed by effector memory T cells (TEM) and plays an important role in their activation and proliferation. Mycosis fungoides (MF), the most common subtype of cutaneous T-cell lymphoma (CTCL), was recently proposed to be a malignancy of skin-resident TEM. However, the expression of Kv1.3 in CTCL has not been investigated., Objectives: This study aims to examine the expression of Kv1.3 in situ and in vitro in CTCL., Methods: The expression of Kv1.3 was examined by immunohistochemistry in skin lesions from 38 patients with MF, 4 patients with Sézary syndrome (SS), and 27 patients with benign dermatosis. In 4 malignant T-cell lines of CTCL (Myla2059, PB2B, SeAx, and Mac2a) and a non-malignant T-cell line (MyLa1850), the expression of Kv1.3 was determined by flow cytometry. The proliferation of those cell lines treated with various concentrations of Kv1.3 inhibitor ShK was measured by 3H-thymdine incorporation., Results: Half of the MF patients (19/38) displayed partial Kv1.3 expression including 1 patient with moderate Kv1.3 positivity, while the other half (19/38) exhibited Kv1.3 negativity. An almost identical distribution was observed in patients with benign conditions, that is, 44.4% (12/27) were partially positive for Kv1.3 including 1 patient with moderate Kv1.3 positivity, while 55.6% (15/27) were Kv1.3 negative. In contrast, 3 in 4 SS patients displayed partial Kv1.3 positivity including 2 patients with weak staining and 1 with moderate staining, while 1 in 4 SS patients was Kv1.3 negative. In addition, all malignant T-cell lines, and a non-malignant T-cell line, displayed low Kv1.3 surface expression with a similar pattern. Whereas 2 cell lines (PB2B and Mac2a) were sensitive to Kv1.3 blockade, the other 2 (Myla2059 and SeAx) were completely resistant., Conclusions: We provide the first evidence of a heterogeneous Kv1.3 expression in situ in CTCL lesions., (© 2019 S. Karger AG, Basel.)

Diagnosis of mycosis fungoides and Sézary syndrome can be very challenging. Clinical and histopathological data for patients with mycosis fungoides and Sézary syndrome in Denmark are limited. A retrospective study was performed in Region Zealand, Denmark from 1990 to 2016. A total of 43 patients with mycosis fungoides or Sézary syndrome were identified during the period. At the time of diagnosis the patients' mean age was 64.3 years and 74.5% had early-stage (≤IIA) disease. The mean time from onset of skin disease to diagnosis was 4.4 years. Surprisingly, 43% progressed to a higher disease stage, and risk of disease progression was higher for stage IB than IA (p = 0.01). All cases displayed some degree of epidermotropism and the infiltrates consisted of pleomorphic lymphocytes with a T-helper (CD4+/CD8-) phenotype. This study describes, for the first time, all aspects of clinical and histopathological findings in patients with mycosis fungoides and Sézary syndrome in a well-characterized Danish cohort.

It has been proposed that CD4 T-cell responses to Staphylococcus aureus (SA) can inadvertently enhance neoplastic progression in models of skin cancer and cutaneous T-cell lymphoma (CTCL). In this prospective study, we explored the effect of transient antibiotic treatment on tumor cells and disease activity in 8 patients with advanced-stage CTCL. All patients experienced significant decrease in clinical symptoms in response to aggressive, transient antibiotic treatment. In some patients, clinical improvements lasted for more than 8 months. In 6 of 8 patients, a malignant T-cell clone could be identified in lesional skin, and a significant decrease in the fraction of malignant T cells was observed following antibiotics but an otherwise unchanged treatment regimen. Immunohistochemistry, global messenger RNA expression, and cell-signaling pathway analysis indicated that transient aggressive antibiotic therapy was associated with decreased expression of interleukin-2 high-affinity receptors (CD25), STAT3 signaling, and cell proliferation in lesional skin. In conclusion, this study provides novel evidence suggesting that aggressive antibiotic treatment inhibits malignant T cells in lesional skin. Thus, we provide a novel rationale for treatment of SA in advanced CTCL.

Octapeptide repeat insertions (OPRI) found in the prion protein gene (PRNP) constitute a subgroup of pathogenic mutations linked to inherited prion diseases, a hallmark of which is a misfolded prion protein. The number of repeats in OPRI has been associated with different disease phenotypes. However, due to the rarity of the cases and heterogenous disease manifestations, the recognition and classification of these variants has been difficult. Here, we report the first Danish family, the fifth worldwide, carrying a novel 8-OPRI with a unique sequence of the additional 8 inserts: R1-R2-R2-R3-R2-R2-R2a-R2-R3g-R2-R2-R3-R4. The mutation was found on the allele coding for methionine at codon 129 in the PRNP gene. The clinical exome sequencing revealed that no other dementia-associated genes harbored pathogenic alterations. Mutation carriers had onset of symptoms in their early thirties, but disease duration varied from 5 to 11 years. Progressive dementia with psychiatric and motor symptoms were the most prominent clinical features. Clinical, pathological, and genetic characteristics of other 4 reported families with 8-OPRI were reviewed and compared with the findings in the Danish family., (© 2019 American Association of Neuropathologists, Inc. All rights reserved.)

Background: Staphylococcus aureus is the most frequent and fatal cause of left-sided infective endocarditis (IE). New treatment strategies are needed to improve the outcome. S. aureus coagulase promotes clot and fibrin formation. We hypothesized that dabigatran, could reduce valve vegetations and inflammation in S. aureus IE., Methods: We used a rat model of severe aortic valve S. aureus IE. All infected animals were randomized to receive adjunctive dabigatran (10 mg/kg b.i.d., n = 12) or saline (controls, n = 11) in combination with gentamicin. Valve vegetation size, bacterial load, cytokine, cell integrins expression and peripheral platelets and neutrophils were assessed 3 days post-infection., Results: Adjunctive dabigatran treatment significantly reduced valve vegetation size compared to controls (p< 0.0001). A significant reduction of the bacterial load in aortic valves was seen in dabigatran group compared to controls (p = 0.02), as well as expression of key pro-inflammatory markers keratinocyte-derived chemokine, IL-6, ICAM-1, TIMP-1, L-selectin (p< 0.04). Moreover, the dabigatran group had a 2.5-fold increase of circulating platelets compared to controls and a higher expression of functional and activated platelets (CD62p+) unbound to neutrophils., Conclusion: Adjunctive dabigatran reduced the vegetation size, bacterial load, and inflammation in experimental S. aureus IE., Competing Interests: The authors have declared that no competing interests exist.

Lipocalin-2 is a constituent of the neutrophil secondary granules and is expressed de novo by macrophages and epithelium in response to inflammation. Lipocalin-2 acts in a bacteriostatic fashion by binding iron-loaded siderophores required for bacterial growth. Mycobacterium tuberculosis (M.tb) produces siderophores that can be bound by lipocalin-2. The impact of lipocalin-2 in the innate immune response toward extracellular bacteria has been established whereas the effect on intracellular bacteria, such as M.tb, is less well-described. Here we show that lipocalin-2 surprisingly confers a growth advantage on M.tb in the early stages of infection (3 weeks post-challenge). Using mixed bone marrow chimeras, we demonstrate that lipocalin-2 derived from granulocytes, but not from epithelia and macrophages, leads to increased susceptibility to M.tb infection. In contrast, lipocalin-2 is not observed to promote mycobacterial growth at later stages of M.tb infection. We demonstrate co-localization of granulocytes and mycobacteria within the nascent granulomas at week 3 post-challenge, but not in the consolidated granulomas at week 5. We hypothesize that neutrophil-derived lipocalin-2 acts to supply a source of iron to M.tb in infected macrophages within the immature granuloma, thereby facilitating mycobacterial growth.

There is a limited understanding about the impact of rare protein-truncating variants across multiple phenotypes. We explore the impact of this class of variants on 13 quantitative traits and 10 diseases using whole-exome sequencing data from 100,296 individuals. Protein-truncating variants in genes intolerant to this class of mutations increased risk of autism, schizophrenia, bipolar disorder, intellectual disability, and ADHD. In individuals without these disorders, there was an association with shorter height, lower education, increased hospitalization, and reduced age at enrollment. Gene sets implicated from GWASs did not show a significant protein-truncating variants burden beyond what was captured by established Mendelian genes. In conclusion, we provide a thorough investigation of the impact of rare deleterious coding variants on complex traits, suggesting widespread pleiotropic risk., (Copyright © 2018 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Background: The postpartum period is well-known risk period for the first onset of autoimmune thyroid disorders (AITDs) as well as first onset of psychiatric disorders. These two disorders are some of the most prevalent medical conditions postpartum, often misdiagnosed and disabling if left untreated. Our study was designed to explore the possible bidirectional association between AITDs and psychiatric disorders during the postpartum period., Methods: A population-based cohort study through linkage of Danish national registers, which comprised 312 779 women who gave birth to their first child during 1997-2010. We conducted Poisson regression analysis to estimate the incidence rate ratio (IRR) of psychiatric disorders among women with first-onset AITDs, the IRR of AITDs among women with first-onset psychiatric disorders as well as the overlap between these disorders using a comorbidity index., Results: Women with first-onset AITDs postpartum were more likely to have first-onset psychiatric disorders than women who did not have postpartum AITDs (IRR = 1.88, 95% confidence interval (CI): 1.25-2.81). Women with first-onset postpartum psychiatric disorders had a higher risk of AITDs than women with no psychiatric disorders (IRR = 2.16, 95% CI: 1.45-3.20). The comorbidity index 2 years after delivery was 2.26 (95% CI: 1.61-2.90), indicating a comorbidity between first-onset AITDs and psychiatric disorders., Conclusions: First-onset AITDs and psychiatric disorders co-occur in the postpartum period, which has relevance to further studies on the etiologies of these disorders and why childbirth in particular triggers the onset.

This study outlines a new method of automatically estimating weed species and growth stages (from cotyledon until eight leaves are visible) of in situ images covering 18 weed species or families. Images of weeds growing within a variety of crops were gathered across variable environmental conditions with regards to soil types, resolution and light settings. Then, 9649 of these images were used for training the computer, which automatically divided the weeds into nine growth classes. The performance of this proposed convolutional neural network approach was evaluated on a further set of 2516 images, which also varied in term of crop, soil type, image resolution and light conditions. The overall performance of this approach achieved a maximum accuracy of 78% for identifying Polygonum spp. and a minimum accuracy of 46% for blackgrass. In addition, it achieved an average 70% accuracy rate in estimating the number of leaves and 96% accuracy when accepting a deviation of two leaves. These results show that this new method of using deep convolutional neural networks has a relatively high ability to estimate early growth stages across a wide variety of weed species.

Background Disagreement among healthcare professionals on the clinical relevance of drug-related problems can lead to suboptimal treatment and increased healthcare costs. Elderly patients with chronic non-cancer pain and comorbidity are at increased risk of drug related problems compared to other patient groups due to complex medication regimes and transition of care. Objective To investigate the agreement among healthcare professionals on their classification of clinical relevance of drug-related problems in elderly patients with chronic non-cancer pain and comorbidity. Setting Multidisciplinary Pain Centre, Rigshospitalet, Copenhagen, Denmark. Method A pharmacist performed medication review on elderly patients with chronic non-cancer pain and comorbidity, identified their drug-related problems and classified these problems in accordance with an existing categorization system. A five-member clinical panel rated the drug-related problems' clinical relevance in accordance with a five-level rating scale, and their agreement was compared using Fleiss' κ. Main outcome measure Healthcare professionals' agreement on clinical relevance of drug related problems, using Fleiss' κ. Results Thirty patients were included in the study. A total of 162 drug related problems were identified, out of which 54% were of lower clinical relevance (level 0-2) and 46% of higher clinical relevance (level 3-4). Only slight agreement (κ = 0.12) was found between the panellists' classifications of clinical relevance using a five-level rating scale. Conclusion The clinical pharmacist identified drug related problems of lower and higher clinical relevance. Poor overall agreement on the severity of the drug related problems was found among the panelists.

Staphylococcus aureus infective endocarditis (IE) is a serious disease with an in-hospital mortality of up to 40%. Improvements in the effects of antibiotics and host responses could potentially benefit outcomes. Hyperbaric oxygen therapy (HBOT) represents an adjunctive therapeutic option. In this study, the efficacy of HBOT in combination with tobramycin in S. aureus IE was evaluated. A rat model of S. aureus IE mimicking the bacterial load in humans was used. Infected rats treated subcutaneously with tobramycin were randomised into two groups: (i) HBOT twice daily (n = 13); or (ii) normobaric air breathing (non-HBOT) (n = 17). Quantitative bacteriology, cytokine expression, valve vegetation size and clinical status were assessed 4 days post-infection. Adjunctive HBOT reduced the bacterial load in the aortic valves, myocardium and spleen compared with the non-HBOT group (P = 0.004, <0.001 and 0.01, respectively) and improved the clinical score (P <0.0001). Photoplanimetric analysis and weight of valve vegetations showed significantly reduced vegetations in the HBOT group (P <0.001). Key pro-inflammatory cytokines [IL-1β, IL-6, keratinocyte-derived chemokine (KC) and vascular endothelial growth factor (VEGF)] were significantly reduced in valves from the HBOT group compared with the non-HBOT group. In conclusion, HBOT augmented tobramycin efficacy as assessed by several parameters. These findings suggest the potential use of adjunctive therapy in severe S. aureus IE., (Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

Objective: Recent studies have suggested that autoimmune diseases and immune activation play a part in the pathogenesis of different neurodevelopmental disorders. This study investigated the association between a personal history and a family history of autoimmune disease and the risk of developing attention-deficit/hyperactivity disorder (ADHD)., Method: A cohort was formed of all singletons born in Denmark from 1990 to 2007, resulting in a study population of 983,680 individuals followed from 1995 to 2012. Information on autoimmune diseases was obtained from the Danish National Hospital Register. Individuals with ADHD were identified through the Danish National Hospital Register and the Danish Psychiatric Central Register., Results: In total, 23,645 children were diagnosed with ADHD during the study period. Autoimmune disease in the individual was associated with an increased risk of ADHD by an incidence rate ratio of 1.24 (95% CI 1.10-1.40). The primary analyses associated maternal autoimmune disease with ADHD in the offspring (incidence rate ratio 1.12, 95% CI 1.06-1.19), whereas a paternal history of autoimmune diseases was not significantly associated with ADHD in the offspring. In exploratory analyses, an increased risk of ADHD was observed for children with a family history of thyrotoxicosis, type 1 diabetes, autoimmune hepatitis, psoriasis, and ankylosing spondylitis., Conclusion: A personal history and a maternal history of autoimmune disease were associated with an increased risk of ADHD. The previously reported association between type 1 diabetes and ADHD was confirmed. In addition, specific parental autoimmune diseases were associated with ADHD in offspring., (Copyright © 2016 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Increased prevalence of lifestyle risk factors or shared etiology may underlie the association between schizophrenia and the subsequent risk of dementia. We explored the association between having a spouse with schizophrenia and the risk of dementia. We found a positive relationship between having a spouse with schizophrenia and vascular dementia in individuals without a mental disorder themselves but no association between having a spouse with schizophrenia and Alzheimer's dementia. As spouses share environmental risk factors and lifestyle, this might suggest that the excess risk of dementia in probands with schizophrenia could be ascribed to the unhealthy living environment among individuals with schizophrenia.

Purpose: In this paper, we investigate the hypothesis that there is an overlap between infection and schizophrenia. Infections have been identified as a risk factor for schizophrenia, but the possible overlap between schizophrenia and infections remains unidentified so far. Here, we describe the use of the comorbidity index, a method for objectively integrating associations into a single measure estimating overlap., Methods: Data were drawn from three population-based registers, the Civil Registration Register, the Danish Psychiatric Central Research Register, and the Danish National Hospital Register. We selected a cohort of 1,403,183 persons born in Denmark 1977-2002., Results: Our results indicate that persons who have had a hospital contact with an infection (IRR 1.53, CI 1.46-1.61) are more likely to develop schizophrenia than persons who have not had such a contact. Persons who have had a diagnosis with schizophrenia are more likely to have had a hospital contact with an infection (IRR 1.73, 95 % CI 1.57-1.91) than persons who have had no schizophrenia diagnosis. A comorbidity index of 1.40 (95 % CI 1.34-1.46) was found, indicating an overlap between schizophrenia and infection., Conclusion: Our findings indicate that schizophrenia and infections overlap and that they share risk factors. The comorbidity index showed that the co-occurrence of schizophrenia and infection was 40 % higher than if the two disorders had occurred independently. Although the incidence of schizophrenia and infection was associated with each factor, the overlap could not be explained by urbanicity, parental history of psychiatric admission and infection.

Viruses, bacteria and other infectious pathogens are the major postulated environmental triggers of autoimmunity. In the present nation-wide study we describe the association between infections and 29 autoimmune diseases. We used the Danish Civil Registration System to identify 4.5 million persons born between 1945 and 2000. Information on infections and autoimmune diseases was obtained from the Danish Hospital Register. The cohort was followed from 1977 to 2012. Incidence rate ratios for developing an autoimmune disease were estimated using poisson regression. We found an association between hospital admission for an infection and 29 autoimmune diseases. This study shows that infections are risk factors for a broad spectrum of autoimmune diseases in a dose-response and temporal manner, in agreement with the hypothesis that infections are an environmental risk factor contributing to the etiology of autoimmune diseases together with genetic factors., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background/aims: Prior studies have consistently found a higher risk of dementia in individuals with schizophrenia, but whether this is due to a common etiology between the disorders remains obscure. We wanted to elucidate this association by investigating whether schizophrenia in offspring increases the risk of Alzheimer's dementia., Methods: All individuals born between 1930 and 1953 were identified through national registers and followed from their 50th birthday until the date of Alzheimer's dementia, death or end of the study. Regressions were performed to evaluate the association between offspring with schizophrenia and Alzheimer's dementia., Results: Individuals with offspring with schizophrenia did not have an increased risk of Alzheimer's dementia [incidence rate ratio (IRR), 0.97; 95% CI, 0.88-1.07] compared to individuals with offspring without psychiatric contact. This finding remained stable when evaluating early-onset (IRR, 1.10; 95% CI, 0.91-1.31) and late-onset Alzheimer's dementia (IRR, 0.92; 95% CI, 0.88-1.07). Similar findings were made for vascular and unspecified dementia., Conclusion: The finding of no familial coaggregation between schizophrenia and Alzheimer's dementia may suggest that no common etiology between the disorders exists. This may indicate that the excess risk of dementia in individuals with schizophrenia is a by-product of the higher rates of somatic comorbidity and adverse health risk factors among these individuals.

Background: Maternal iron deficiency and infection during pregnancy have individually been associated with increased risk of schizophrenia in the offspring, but possible interactions between the two remain unidentified thus far. Therefore, we determined the individual and combined effects of maternal infection during pregnancy and prepartum anemia on schizophrenia risk in the offspring., Methods: We conducted a population-based study with individual record linkage of the Danish Civil Registration System, the Danish Hospital Register, and the Central Danish Psychiatric Register. In a cohort of Danish singleton births 1,403,183 born between 1977 and 2002, 6729 developed schizophrenia between 1987 and 2012. Cohort members were considered as having a maternal history of anemia if the mother had received a diagnosis of anemia at any time during the pregnancy. Maternal infection was defined based on infections requiring hospital admission during pregnancy., Results: Maternal anemia and infection were both associated with increased risk of schizophrenia in unadjusted analyses (1.45-fold increase for anemia, 95% CI: 1.14-1.82; 1.32-fold increase for infection, 95% CI: 1.17-1.48). The effect of maternal infection remained significant (1.16-fold increase, 95% CI: 1.03-1.31) after adjustment for possible confounding factors. Combined exposure to anemia and an infection increased the effect size to a 2.49-fold increased schizophrenia risk (95% CI: 1.29-4.27). The interaction analysis, however, failed to provide evidence for multiplicative interactions between the two factors., Conclusion: Our findings indicate that maternal anemia and infection have additive but not interactive effects, and therefore, they may represent two independent risk factors of schizophrenia., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Complex regional pain syndrome (CRPS) is a complex, painful, debilitating disease which occurs after trauma or surgery mainly in the wrists with a variation of 5.5-26.2 at 100,000 inhabitants in international studies. In Denmark the prevalence is unknown, and it is perceived that many patients with CRPS are diagnosed late in their illness. There is international consensus on diagnostic criteria and early identification. Evidence for treatment is weak, but there are good experiences with highly specialized multidisciplinary treatment. A national clinical guideline is required.

Background: Pain and mental health concerns are prevalent among veterans. While the majority of research has focused on chronic pain as an entity, there has been little work directed towards investigating the role of neuropathic pain in relation to psychological comorbidity. As such, we hypothesised that participants with signs of neuropathic pain would report higher levels of psychological distress and diminished self-rated health compared to those without a neuropathic component., Methods: A retrospective review of standardised questionnaires (PainDETECT Questionnaire, Post-traumatic Stress Disorder Checklist-Civilian, the Hospital Anxiety and Depression Scale, and EuroQOL Visual Analogue Scale) administered to injured soldiers. The participants were classified into three groups according to the PainDETECT questionnaire: non-neuropathic pain, possible neuropathic pain and definite neuropathic pain., Results: Fifty-three participants were included. The Post-traumatic Stress Disorder Checklist-Civilian score was in median (interquartile range) 26 (22-31), the Hospital Anxiety and Depression Scale score was 4 (2-6.5) and 2 (1-5) for anxiety and depression respectively. Evidence of neuropathic pain correlated positively with the Post-traumatic Stress Disorder Checklist-Civilian score (rho = 0.469, P < 0.001) and Hospital Anxiety and Depression Scale subscale for anxiety score (rho = 0.357, P = 0.009), and inversely with the EuroQOL Visual Analogue Scale score (rho = -0.361, P = 0.008). In multivariate regression analyses, the associations remained when adjusting for socio-demographics and clinical characteristics., Conclusions: The results from the present study suggest that neuropathic pain is related to increased psychological distress and deterioration in self-rated health in injured soldiers., (© 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: Infections and activated immune responses can affect the brain through several pathways that might also affect cognition. However, no large-scale study has previously investigated the effect of infections on the general cognitive ability in the general population., Methods: Danish nationwide registers were linked to establish a cohort of all 161,696 male conscripts during the years 2006-2012 who were tested for cognitive ability, which was based on logical, verbal, numerical and spatial reasoning at a mean age of 19.4 years. Test scores were converted to a mean of 100.00 and with a standard deviation (SD) of 15. Data were analyzed as a cohort study with severe infections requiring hospitalization as exposure using linear regression., Results: Adjusted effect sizes were calculated with non-exposure to severe infections as reference, ranging from 0.12 SD to 0.63 SD on general cognitive ability. A prior infection was associated with significantly lower cognitive ability by a mean of 1.76 (95%CI: -1.92 to -1.61; corresponding to 0.12 SD). The cognitive ability was affected the most by the temporal proximity of the last infection (P<0.001) and by the severity of infection measured by days of admission (P<0.001). The number of infections were associated with decreased cognitive ability in a dose-response relationship, and highest mean differences were found for ≥10 hospital contacts for infections (Mean: -5.54; 95%CI: -7.20 to -3.89; corresponding to 0.37 SD), and for ≥5 different types of infections (Mean: -9.44; 95%CI: -13.2 to -5.69; corresponding to 0.63 SD). Hospital contacts with infections had occurred in 35% of the individuals prior to conscription., Conclusions: Independent of a wide range of possible confounders, significant associations between infections and cognitive ability were observed. Infections or related immune responses might directly affect the cognitive ability; however, associated heritable and environmental factors might also account for the lowered cognitive ability.

Background: There is a long-standing interest in investigating the impact of early-life immune abnormalities on later onset of psychosis. The aim of this study was to assess inflammatory marker levels in neonatal dried blood spots and their association with later risk of schizophrenia., Methods: This nested case-control study included 995 cases and 980 control subjects. Cases were identified using the Danish Psychiatric Central Register. Control subjects of same age and sex were identified using the Danish Civil Registration System. Samples for the identified individuals were retrieved from the Danish Neonatal Screening Biobank. Concentrations of 17 inflammatory markers were measured in eluates from dried blood spots using a bead-based multiplex assay. Incidence rate ratios were calculated using conditional logistic regression. Principal component analysis was used to capture the overall variation in the inflammatory markers' concentrations., Results: No significant differences were found for any of the analyzed interleukins. We did not find any association with schizophrenia for any of the other examined inflammatory markers., Conclusions: Our results suggest that persons who develop schizophrenia do not have higher or lower levels of the examined inflammatory markers at the time of birth. Our findings differ from the studies of maternal inflammatory changes during the antenatal period for which associations with schizophrenia have previously been demonstrated., (Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: Schizophrenia is associated with excess physical comorbidity. Yet, to our knowledge, large studies are lacking on the associations with somatic diseases before the onset of schizophrenia. The authors conducted a nationwide study of the full spectrum of treated somatic diseases before the first diagnosis of schizophrenia., Method: Nationwide sample of the Danish population consisting of singletons (n = 954351) born 1977-1993 and followed from birth to 2009, during which period 4371 developed schizophrenia. Somatic diagnoses at all general hospital contacts (admitted or outpatient care at a somatic hospital) from 1977 to 2009 were used as exposures. The incidence rate ratio (IRR) of schizophrenia was calculated using Poisson regression adjusted for confounders., Results: Among the 4371 persons who developed schizophrenia from 1992 to 2009, a total of 4180 (95.6%) persons had a previous somatic hospital contact. A history of any somatic hospital contact was associated with an elevated risk of schizophrenia (IRR = 2.04, 95% CI = 1.77-2.37). A wide range of somatic diseases and conditions were associated with an increased risk of schizophrenia, including epilepsy (IRR = 2.26, 95% CI = 1.93-2.62), nutritional or metabolic disorders (IRR = 1.57, 95% CI = 1.39-1.77), circulatory system diseases (IRR = 1.63, 95% CI= 1.38-1.92), and brain injury (IRR = 1.58, 95% CI = 1.45-1.72)., Conclusions: A wide range of potential etiological factors could have contributed to the observed associations, including genetic or physiological overlaps between conditions, and interacting immunological, behavioral, and neurodevelopmental factors., (© The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Infections and immune responses have been suggested to play an important role in the etiology of schizophrenia. Several studies have reported associations between maternal infections during pregnancy and the child's risk of schizophrenia; however, infection during childhood and adolescence unrelated to maternal infection during pregnancy has not been studied to nearly the same extent and the results are far from conclusive. Data were drawn from 2 population-based registers, the Danish Psychiatric Central Register and the Danish National Hospital Register. We used a historical population-based cohort design and selected all individuals born in Denmark between 1981 and 1996 (n = 843 390). We identified all individuals with a first-time hospital contact with schizophrenia from 1991 through 2010. Out of the 3409 individuals diagnosed with schizophrenia, a total of 1549 individuals had had a hospital contact with infection before their schizophrenia diagnosis (45%). Our results indicate that individuals who have had a hospital contact with infection are more likely to develop schizophrenia (relative risk [RR] = 1.41; 95% CI: 1.32-1.51) than individuals who had not had such a hospital contact. Bacterial infection was the type of infection that was associated with the highest risk of schizophrenia (RR = 1.63; 95% CI: 1.47-1.82). Our study does not exclude that a certain type of infection may have a specific effect; yet, it does suggest that schizophrenia is associated with a wide range of infections. This association may be due to inflammatory responses affecting the brain or genetic and environmental risk factors aggregating in families., (© The Author 2013. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Importance: Despite a remarkable co-occurrence of obsessive-compulsive disorder (OCD) and schizophrenia, little is known about the clinical and etiological relationship of these 2 disorders. Exploring the degree to which these disorders share etiological factors might provide useful implications for clinicians, researchers, and those with the disorders., Objectives: To assess whether patients with OCD experience an enhanced risk of developing schizophrenia and schizophrenia spectrum disorders and to determine whether a family history of OCD constitutes a risk factor for schizophrenia and schizophrenia spectrum disorders., Design, Setting, and Participants: Using individual data from longitudinal nationwide Danish registers, we conducted a prospective cohort study with 45 million person-years of follow-up. All survival analyses were adjusted for sex, age, calendar year, parental age, and place of residence at the time of birth. A total of 3 million people born between January 1, 1955, and November 30, 2006, were followed up from January 1, 1995, through December 31, 2012. During this period, 30 556 people developed schizophrenia or schizophrenia spectrum disorders., Main Outcomes and Measures: The presence of a prior diagnosis of OCD and the risk of a first lifetime diagnosis of schizophrenia and a schizophrenia spectrum disorder assigned by a psychiatrist in a hospital, outpatient clinic, or emergency department setting. Incidence rate ratios (IRRs) and accompanying 95% confidence intervals are used as measures of relative risk., Results: The presence of prior diagnosis of OCD was associated with an increased risk of developing schizophrenia (IRR = 6.90; 95% CI, 6.25-7.60) and schizophrenia spectrum disorders (IRR = 5.77; 95% CI, 5.33-6.22) later in life. Similarly, offspring of parents diagnosed as having OCD had an increased risk of schizophrenia (IRR = 4.31; 95% CI, 2.72-6.43) and schizophrenia spectrum disorders (IRR = 3.10; 95% CI, 2.17-4.27). The results remained significant after adjusting for family history of psychiatric disorders and the patient's psychiatric history., Conclusions and Relevance: A diagnosis of OCD was associated with higher rates of schizophrenia and schizophrenia spectrum disorders. The observed increase in risk suggests that OCD, schizophrenia, and schizophrenia spectrum disorders probably lay on a common etiological pathway.

Carbon monoxide (CO) inhalation is a well-known method of committing suicide. There has been a drastic increase in suicide by inhalation of CO, produced from burning charcoal, in some parts of Asia, and a few studies have reported an increased number of these deaths in Europe. CO-related deaths caused by charcoal burning have, to our knowledge, not been recorded in the Danish population before. In this retrospective study we present all autopsied cases of CO poisoning caused by charcoal burning in the period 2008-2012. 19 autopsied cases were identified, comprising 11 suicides, 4 accidents, and 2 cases of maternal/paternal filicide-suicide. The mean age of decedents was 38.2 years and the majority of the decedents were men. In 16 cases carboxyhemoglobin levels were above 50 % and in 14 cases we found distinctive cherry red livor mortis. Various concentrations of ethanol and drugs were found in 9 cases. Data suggest that this method of death has increased significantly in Denmark. Therefore, it is highly relevant to draw attention to the subject, to increase awareness as well as prevent future escalation.

Although several studies have examined the relative contributions of familial and environmental risk factors for schizophrenia, few have additionally examined the predictive power on the individual level and simultaneously examined the population impact associated with a wide range of familial and environmental risk factors. The authors present rate ratios (IRR), population-attributable risks (PAR) and sex-specific cumulative incidences of the following risk factors: parental history of mental illness, urban place of birth, advanced paternal age, parental loss and immigration status. We established a population-based cohort of 2,486,646million persons born in Denmark between 1 January 1955 and 31 December 1993 using Danish registers. We found that PAR associated with urban birth was 11.73%; PAR associated with one, respectively 2, parent(s) with schizophrenia was 2.67% and 0.12%. PAR associated with second-generation immigration was 0.70%. Highest cumulative incidence (CI=20.23%; 95% CI=18.10-22.62) was found in male offspring of 2 parents with schizophrenia. Cumulative incidences for male offspring or female offspring of a parent with schizophrenia were 9.53% (95% CI=7.71-11.79), and 4.89%, (95% CI 4.50-5.31). The study showed that risk factors with highest predictive power on the individual level have a relatively low population impact. The challenge in future studies with direct genetic data is to examine gene-environmental interactions that can move research beyond current approaches and seek to achieve higher predictive power on the individual level and higher population impact., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The association between low birth weight and schizophrenia has been suggested by many studies. Small for gestational age (SGA) is a measure used as a proxy for intrauterine growth restriction. We aim to examine if children who are born SGA are at increased risk of developing schizophrenia and whether an association may be explained by factors shared among siblings. We linked 3 population-based registers: the Danish National Medical Birth Register, the Danish Psychiatric Central Register, and the Danish Civil Registration register to identify all persons born between 1978 and 2000. A nested case-control study and a case-sibling study design were used. There were 4650 cases of schizophrenia. Incidence rate ratios (IRRs) were estimated using conditional logistic regression. SGA was defined as the lowest 10th birth weight percentile for a given sex and gestational age. SGA was associated with an IRR of 1.23 (95% CI: 1.11-1.37) for schizophrenia in the case-control study. An IRR of 1.28 (95% CI: 0.97-1.68) was found in the case-sibling study. There is a modest association between SGA and schizophrenia. Our results indicate that this association is due to an independent effect of factors associated with low birth weight for gestational age per se, rather than other factors shared by siblings.

Background: Several myths on buprenorphine's pharmacology exist: possible analgesic ceiling effect, feasibility of combination with other opioid agonists, and the reversibility of side effects. Aim to evaluate: 1) if cancer patients receiving high doses of pure agonists could obtain adequate pain relief after switching to transdermal (TD) buprenorphine and 2) whether the numbers of breakthrough pain episodes after switching increased and whether they could be treated with the same doses of pure agonist as before switching., Design: The prospective open multicenter study included outpatients with moderate-to-severe cancer pain satisfactorily controlled., Setting: Patients were switched from the usual pure agonist to TD buprenorphine and were titrated to a stable dose. The assessments were: 1) daily self-assessment of pain intensity, numbers of rescue medications, and pain interference with sleep; 2) brief pain inventory; 3) pain relief and pain intensity; 4) quality of life; and 5) adverse events and symptoms., Results: Eighteen patients receiving 150-516 mg of morphine/day were included. The buprenorphine dose at the end of the study varied between 52.5 and 140 μg/h. No difference in pain before and after switching was shown. The level of rescue doses was maintained. The patches were well tolerated. A significant decrease in fatigue and an increase in global health status were seen after the switch., Conclusion: It is feasible to switch cancer patients from high doses of pure μ-opioid agonists to TD buprenorphine without eliciting any antagonist effects, but the dose conversion factor is individual and the switching process should be tailored for the individual patient.

It has been suggested that infection during perinatal life may lie at the etiological root of schizophrenia. It has thus been hypothesized that the origin of schizophrenia may lie either in direct fetal infection and/or in a generally increased familial susceptibility to infections, some of which may occur during pregnancy. We explored these 2 hypotheses by assessing maternal infection during pregnancy and maternal as well as paternal infection in general as predictors of schizophrenia in their offspring. We found a slightly increased risk to be associated with prenatal infection exposure. However, the effect of prenatal infection exposure was not statistically significantly different from the effect of infection exposure in general. Parental infection appeared to be associated with development of schizophrenia in adolescence and early adulthood. Our study does not exclude a specific effect of infection during fetal life; yet, it does suggest that schizophrenia is associated with an increased familial liability to develop severe infection.

Background: There is a well-established association between psychotic disorders and subsequent offending but the extent to which those who develop psychosis might have a prior history of offending is less clear. Little is known about whether the association between illness and offending exists in non-psychotic disorders. The aim of this study was to determine whether the association between mental disorder and offending is present prior to illness onset in psychotic and non-psychotic disorders., Method: In a nested case-control study, cases (n=101,890) with a first psychiatric contact during the period 1995 to 2006 were identified and matched by age and gender to population-based controls (n=2,236,195). Exposure was defined as prior criminal and violent offending., Results: Males with one offence had an incidence rate ratio (IRR) of 2.32 [95% confidence interval (CI) 2.26-2.40] for psychiatric admission whereas two or more convictions yielded an IRR of 4.97 (95% CI 4.83-5.11). For violent offending the associations were stronger and IRRs of 3.97 (95% CI 3.81-4.12) and 6.18 (95% CI 5.85-6.52) were found for one and several offences respectively. Estimates for females were of a similar magnitude. The pattern was consistent across most diagnostic subgroups, although some variability in effect sizes was seen, and persisted after adjustment for substance misuse and socio-economic status (SES)., Conclusions: A prior history of offending is present in almost one in five patients presenting to mental health services, which makes it an important issue for clinicians to consider when assessing current and future risks and vulnerabilities.

Background: The paucity of studies regarding cognitive function in patients with chronic pain, and growing evidence regarding the cognitive effects of pain and opioids on cognitive function prompted us to assess cognition via neuropsychological measurement in patients with chronic non-cancer pain treated with opioids., Methods: In this cross-sectional study, 49 patients were assessed by Continuous Reaction Time, Finger Tapping, Digit Span, Trail Making Test-B and Mini-mental State Examination tests. Linear regressions were applied., Results: Patients scored poorly in the Trail Making Test-B (mean = 107.6 s, SD = 61.0, cut-off = 91 s); and adequately on all other tests. Several associations among independent variables and cognitive tests were observed. In the multiple regression analyses, the variables associated with statistically significant poor cognitive performance were female sex, higher age, lower annual income, lower schooling, anxiety, depression, tiredness, lower opioid dose, and more than 5 h of sleep the night before assessment (P < 0.05)., Conclusions: Patients with chronic pain may have cognitive dysfunction related to some reversible factors, which can be optimized by therapeutic interventions., (© 2012 The Authors. Acta Anaesthesiologica Scandinavica © 2012 The Acta Anaesthesiologica Scandinavica Foundation.)

Background: In Denmark, the first acute pain service (APS) was introduced in 1993. An important objective became to facilitate implementation of accelerated post-operative rehabilitation programmes (ACC) in selected procedures in abdominal, gynaecological and orthopaedic surgery. Therefore, it is of considerable interest to study the association between the developments of post-operative pain management and the ACC by sequential analyses from 2000 to 2009., Methods: In 2000, 2003, 2006 and 2009, a questionnaire was mailed to all Danish anaesthesiology departments. The headings of the questionnaire were demographics of responder departments, resources allocated to pain management methods, quality assessment methods, research activities and implementation of ACC., Results: The responder rates varied between 80% and 94% (mean 88%) representing a mean number of anaesthetics of 340.000 per year. The number of APSs in the study period varied in university hospitals between 52% and 71% (P = 0.01), regional hospitals between 8% and 40% (P < 0.01), and local hospitals between 0% and 47% (P < 0.01). The prevalences of departments actively engaged in ACC were 40% in 2000, 54% in 2003, 73% in 2006 and 80% in 2009 (P < 0.01)., Conclusions: The study, spanning nearly a decade, illustrates that following an increase in number of APSs from 2000 to 2006, followed by a significant decline, a steadily increasing number of departments implemented ACC., (© 2012 The Authors. Acta Anaesthesiologica Scandinavica © 2012 The Acta Anaesthesiologica Scandinavica Foundation.)

Objective: Autoimmune diseases have been associated with an increased risk of schizophrenia. It has been suggested that brain-reactive autoantibodies are part of the mechanisms behind this association. Furthermore, an increased permeability of the blood-brain barrier has been observed during periods of infection and inflammation. The authors therefore investigated whether autoimmune diseases combined with exposures to severe infections may increase the risk of schizophrenia, Method: Nationwide population-based registers in Denmark were linked, and the data were analyzed in a cohort study using survival analysis. All analyses were adjusted for calendar year, age, and sex. Incidence rate ratios and accompanying 95% confidence intervals (CIs) as measures of relative risk were used., Results: A prior autoimmune disease increased the risk of schizophrenia by 29% (incidence rate ratio=1.29; 95% CI=1.18-1.41). Any history of hospitalization with infection increased the risk of schizophrenia by 60% (incidence rate ratio=1.60; 95% CI=1.56-1.64). When the two risk factors were combined, the risk of schizophrenia was increased even further (incidence rate ratio=2.25; 95% CI=2.04-2.46). The risk of schizophrenia was increased in a dose-response relationship, where three or more infections and an autoimmune disease were associated with an incidence rate ratio of 3.40 (95% CI=2.91-3.94). The results remained significant after adjusting for substance use disorders and family history of psychiatric disorders. Hospital contact with infection occurred in nearly 24% of individuals prior to a schizophrenia diagnosis., Conclusions: Autoimmune disease and the number of infections requiring hospitalization are risk factors for schizophrenia. The increased risk is compatible with an immunological hypothesis in subgroups of schizophrenia patients.

Background: Addiction is a feared complication of long-term opioid therapy for chronic pain patients. A screening tool to assess the potential risk of addiction may be helpful., Methods: The Pain Medication Questionnaire (PMQ) was translated into Danish by a 'forward' and 'backward' translation procedure. Patients with chronic non-cancer pain and cancer pain treated at a tertiary pain center were screened for addiction using Portenoy's criteria and invited to answer the Danish version of the PMQ., Results: Two hundred nine patients participated in the study. PMQ was able to discriminate between addicted and non-addicted patients. Patients with high PMQ scores indicating a risk of addiction drank more alcohol, smoked more tobacco, used higher doses of morphine, had a higher anxiety and depression score, and had poorer mental health. Using a cut-off score of 22, the PMQ had a sensitivity of 82%, but the specificity at this cut-point was 56%, indicating a risk of false positive cases. Convergent and discriminant validity were confirmed by correlation with opioid doses, alcohol and tobacco use, anxiety and depression scores, and inverse correlation with mental health and social role. Test-retest showed a very strong correlation. Cronbach's alpha for internal consistency was 0.61. Ten components were found to have eigenvalues above 1.0, confirming the multidimensional structure of the questionnaire., Conclusions: The PMQ may assist physicians in addiction risk assessment and stratification when treating chronic pain patients with opioids. PMQ is not a diagnostic tool and should only be used as an indicator for possible addiction problems., (© 2011 The Authors. Acta Anaesthesiologica Scandinavica © 2011 The Acta Anaesthesiologica Scandinavica Foundation.)

Recent findings suggest that maternal iron deficiency may increase the risk of schizophrenia-spectrum disorder in offspring. We initiated this study to determine whether maternal prepartum anemia influences offspring risk of schizophrenia. We conducted a population-based study with individual record linkage of the Danish Civil Registration System, the Danish Psychiatric Central Register, and the Danish National Hospital Register. In a cohort of 1,115,752 Danish singleton births from 1978 to 1998, cohort members were considered as having a maternal history of anemia if the mother had received a diagnosis of anemia at any time during the pregnancy. Cohort members were followed from their 10th birthday until onset of schizophrenia, death, or December 31, 2008, whichever came first. Adjusted for relevant confounders, cohort members whose mothers had received a diagnosis of anemia during pregnancy had a 1.60-fold (95% confidence interval = 1.16-2.15) increased risk of schizophrenia. Although the underlying mechanisms are unknown and independent replication is needed, our findings suggest that maternal iron deficiency increases offspring risk of schizophrenia.

Hypovitaminosis D is highly prevalent in adult kidney-transplanted patients. The knowledge of vitamin D status in kidney-transplanted children and adolescents is sparse. The present study investigated the vitamin D status of a cohort of kidney-transplanted children and adolescents, and the association between vitamin D status and plasma concentrations of PTH, ionized calcium, and phosphate. The study included 35 patients with a functioning graft. Their mean age was 12.0 yr, and the mean graft age was 2.8 yr. Forty percent of the patients were vitamin D insufficient (P-25-hydroxyvitamin D 40-75 nm), and 14% were deficient (P-25-hydroxyvitamin D < 40 nm). S-25-hydroxyvitamin D was inversely associated with PTH (p = 0.02) and positively associated with S-1,25-dihydroxyvitamin D (p = 0.02). There was no significant association between S-1,25-dihydroxyvitamin D and PTH. In conclusion, we found hypovitaminosis D in 54% of the study population despite the fact that samples were collected in spring and summer months. Hypovitaminosis D was associated with adverse effects on PTH and 1,25-dihydroxyvitamin D. Our data suggest that it is warranted to monitor vitamin D status of kidney-transplanted children and adolescents and indicate that correction of hypovitaminosis D might have favorable effects on calcium-phosphate metabolism., (© 2011 John Wiley & Sons A/S.)

Addiction is a feared consequence of long-term opioid treatment of chronic pain patients. The ICD-10 and DSM-IV diagnostic addiction criteria may not be appropriate in these patients. Therefore Portenoy's criteria (PC) were launched. The aim was to estimate the prevalence of addiction, to investigate whether PC were applicable and to compare these criteria with the ICD-10 criteria. The study was cross-sectional and included 253 patients with chronic pain at a tertiary pain centre. Patients were screened for addiction by a physician and a nurse. The addiction prevalence was 14.4% according to ICD-10 and 19.3% according to PC. A significant difference between the prevalence of addiction according to ICD-10 and to PC was found. The inter-rater reliability was 0.95 for ICD-10 and 0.93 for PC. The sensitivity of PC was 0.85 and the specificity was 0.96. According to PC patients classified as addicted were treated with significantly higher opioid doses, drank more alcohol, smoked more tobacco, used benzodiazepines and had higher levels of depression. According to ICD-10 patients classified as addicted used higher doses of opioids, drank more alcohol and had higher scores of anxiety and depression. High opioid doses, concomitant use of alcohol and younger age were risk factors. The risk profile for PC was different to ICD-10 by adding risk factors as concomitant use of benzodiazepines, having depression and low educational level. PC seems to be appropriate for diagnosing addiction in opioid treated pain patients and seems to be more sensitive and specific than ICD-10 criteria., (Copyright © 2010 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.)

Objective: Clinic-based studies of immune function, as well as comorbidity of autoimmune diseases, bipolar disorder, and schizophrenia, suggest a possible autoimmune etiology. Studies of non-affective psychosis and schizophrenia suggest common etiologies. The objective was to determine the degree to which 30 different autoimmune diseases are antecedent risk factors for bipolar disorder, schizophrenia, and non-affective psychosis., Methods: A cohort of 3.57 million births in Denmark was linked to the Psychiatric Case Register and the National Hospital Register. There were 20,317 cases of schizophrenia, 39,076 cases of non-affective psychosis, and 9,920 cases of bipolar disorder., Results: As in prior studies, there was a range of autoimmune diseases which predicted raised risk of schizophrenia in individuals who had a history of autoimmune diseases, and also raised risk in persons whose first-degree relatives had an onset of autoimmune disease prior to onset of schizophrenia in the case. These relationships also existed for the broader category of non-affective psychosis. Only pernicious anemia in the family was associated with raised risk for bipolar disorder (relative risk: 1.7), suggesting a small role for genetic linkage. A history of Guillain-Barré syndrome, Crohn's disease, and autoimmune hepatitis in the individual was associated with raised risk of bipolar disorder., Conclusions: The familial relationship of schizophrenia to a range of autoimmune diseases extends to non-affective psychosis, but not to bipolar disorder. The data suggest that autoimmune processes precede onset of schizophrenia, but also non-affective psychosis and bipolar disorder., (© 2010 John Wiley and Sons A/S.)

Objective: To evaluate the outcome after spinal surgery when adding prehabilitation to the early rehabilitation., Design: A randomized clinical study., Setting: Orthopaedic surgery department., Subject: Sixty patients scheduled for surgery followed by inpatient rehabilitation for degenerative lumbar disease., Interventions: The patients were computer randomized to prehabilitation and early rehabilitation (28 patients) or to standard care exclusively (32 patients). The intervention began two months prior to the operation. The prehabilitation included an intensive exercise programme and optimization of the analgesic treatment. Protein drinks were given the day before surgery. The early postoperative rehabilitation included balanced pain therapy with self-administered epidural analgesia, doubled intensified mobilization and protein supplements., Main Measures: The outcome measurements were postoperative stay, complications, functionality, pain and satisfaction., Results: At operation the intervention group had improved function, assessed by Roland Morris Questionnaire (P = 0.001). After surgery the intervention group reached the recovery milestones faster than the control group (1-6 days versus 3-13, P =0.001), and left hospital earlier (5 (3-9) versus 7 (5-15) days, P =0.007). There was no difference in postoperative complications, adverse events, low back pain and radiating pain, timed up and go, sit-to-stand or in life quality. Patient satisfaction was significantly higher in the intervention group compared with the control group., Conclusion: The integrated programme of prehabilitation and early rehabilitation improved the outcome and shortened the hospital stay - without more complications, pain or dissatisfaction.

The structural stability of a peroxidase, a dimeric protein from royal palm tree (Roystonea regia) leaves, has been characterized by high-sensitivity differential scanning calorimetry, circular dichroism, steady-state tryptophan fluorescence and analytical ultracentifugation under different solvent conditions. It is shown that the thermal and chemical (using guanidine hydrochloride (Gdn-HCl)) folding/unfolding of royal palm tree peroxidase (RPTP) at pH 7 is a reversible process involving a highly cooperative transition between the folded dimer and unfolded monomers, with a free stabilization energy of about 23 kcal per mol of monomer at 25 degrees C. The structural stability of RPTP is pH-dependent. At pH 3, where ion pairs have disappeared due to protonation, the thermally induced denaturation of RPTP is irreversible and strongly dependent upon the scan rate, suggesting that this process is under kinetic control. Moreover, thermally induced transitions at this pH value are dependent on the protein concentration, allowing it to be concluded that in solution RPTP behaves as dimer, which undergoes thermal denaturation coupled with dissociation. Analysis of the kinetic parameters of RPTP denaturation at pH 3 was accomplished on the basis of the simple kinetic scheme N-->kD, where k is a first-order kinetic constant that changes with temperature, as given by the Arrhenius equation; N is the native state, and D is the denatured state, and thermodynamic information was obtained by extrapolation of the kinetic transition parameters to an infinite heating rate. Obtained in this way, the value of RPTP stability at 25 degrees C is ca. 8 kcal per mole of monomer lower than at pH 7. In all probability, this quantity reflects the contribution of ion pair interactions to the structural stability of RPTP. From a comparison of the stability of RPTP with other plant peroxidases it is proposed that one of the main factors responsible for the unusually high stability of RPTP which enhances its potential use for biotechnological purposes, is its dimerization.