"Don't Look Up": Eco-anxiety presenting in a Community Mental Health Service.

This case report discusses a 25-year-old male who was referred to community mental health services from primary care with symptoms of anxiety and depression related to climate change, which the referring clinician believed were of delusional intensity. This case report gives the history of his interaction with the service. A literature review is performed noting the dearth of case reports in this area and a subsequent discussion charts the emerging literature on mental health issues related to climate change. Finally the paper makes some broad recommendations for mental health practitioners on how to approach these issues.

Systemic sclerosis associated myopathy: how to treat.

Purpose of review: Systemic sclerosis (SSc) and myositis are two different entities that may coexist as an overlap syndrome. Immunological biomarkers such as anti-PM/Scl or anti-Ku reinforce the syndrome. This review is focused on the treatment of different and characteristic manifestations of this syndrome. Recent findings: Among the different phenotypes of muscle involvement in patients with SSc, the fibrotic pattern and the sporadic inclusion body myositis must be identified early to avoid a futile immunosuppressive treatment. Other forms such as dermatomyositis, non-specific myositis and immune-mediated necrotizing myopathy need to receive conventional immunosuppressive therapy considering that high dose of glucocorticoids may induce a scleroderma renal crisis in patients with SSc. Physicians must be aware of the existence of a "double trouble" association of hereditary myopathy with an autoimmune phenomenon. Several autoantibodies, mainly anti-PM/Scl and anti-Ku may help to define specific phenotypes with characteristic clinical manifestations that need a more specific therapy. Vasculopathy is one of the underlying mechanisms that link SSc and myositis. Recent advances in this topic are reviewed. Summary: Current treatment of SSc associated myopathy must be tailored to specific organs involved. Identifying the specific clinical, pathological, and immunological phenotypes may help to take the correct therapeutic decisions.

A cross-sectional, face-to-face, community survey of mental health and deprivation in post-recession Ireland: a rising tide lifts all boats?

OBJECTIVE: To assess community mental health in suburban Dublin in 2018, 5 years after Ireland's economic recession ended. METHODS: A cross-sectional, face-to-face, household survey was conducted in a random cluster sample of 351 households in Tallaght, a deprived suburb of Dublin. RESULTS: A majority of respondents (61.3%) reported stress over the previous 12 months, with a higher rate in areas of high (66.9%) compared to lower deprivation (55.5%). Deprivation was not related to rates of loneliness (20.2%), feeling depressed (20.2%), loss of interest (19.7%) or anxiety (22.5%). Mean score for positive mental health (59.3/100, with a higher score indicating better mental health) was lower than that reported in a national sample in 2007 (68/100); positive mental health was associated with not living with a person with chronic illness, self-identifying as 'non-Irish' and greater age. Mean score for psychological distress (76.7/100, with a higher score indicating less distress) was also lower than that in 2007 (82/100); less psychological distress was associated with not living with a person with chronic illness or disability, greater age and identifying as non-Irish. The rate of 'probable mental illness' over the previous 4 weeks (13.1%) was higher than in 2007 (7%). CONCLUSIONS: Our findings emphasise the high prevalence of stress, especially in deprived suburban areas; the centrality of carer burden in determining mental wellbeing; and associations between positive mental health on the one hand and greater age and identifying as non-Irish on the other.

Dignity, coercion and involuntary psychiatric care: a study of involuntary and voluntary psychiatry inpatients in Dublin.

OBJECTIVES: There is a paucity of research about psychiatric inpatients' experience of dignity. Most of the limited literature on this topic is qualitative. Our study provides quantitative data about self-rated dignity among involuntary and voluntary psychiatry inpatients. We explore relationships between perceived dignity and legal status, coercion, level of insight, diagnosis, and therapeutic alliance, among other parameters. METHODS: We recruited 107 participants aged 18 years or over from two inpatient psychiatric units in Dublin, Ireland over a 30-month period. Interviews consisted of structured, validated assessment tools. Demographic and clinical data were obtained from patient charts. RESULTS: Patient Dignity Inventory (PDI) score was non-normally distributed (skewed to the right), with a median score of 63.0 out of 125 (inter-quartile range: 40.0-80.0). On multi-variable testing, lower self-rated dignity was associated with higher perceived coercion, better insight and more negative symptoms. There was no association between dignity and gender, employment status, marital status, ethnicity, age, admission status, diagnosis, working alliance, positive symptoms or cognition. CONCLUSIONS: Lack of dignity is linked with perceived coercion and negative symptoms, and is seen in patients with better insight. These links merit further study if we are to understand patient dignity in a more nuanced and useful way.KEYPOINTSWe interviewed psychiatric inpatients using the Patient Dignity Inventory and other structured assessment tools.There was no significant difference between voluntary and involuntary patient groups' self-rated dignity.Less self-rated dignity was seen in patients with higher levels of perceived coercion.Patients with better insight reported lower dignity.Dignity scores were not significantly associated with age, gender, ethnicity, diagnosis or length of stay in hospital.

Pharmacologic Treatment of Anti-MDA5 Rapidly Progressive Interstitial Lung Disease.

Purpose of the Review: Idiopathic inflammatory myopathies are a heterogeneous group of autoimmune disorders. The presence of different autoantibodies allows clinicians to define distinct phenotypes. Antibodies against the melanoma differentiation-associated protein 5 gene, also called anti-MDA5 antibodies, are associated with a characteristic phenotype, the clinically amyopathic dermatomyositis with rapidly progressive interstitial lung disease. This review aims to analyze the different pharmacological options for the treatment of rapidly progressive interstitial lung disease in patients with anti-MDA5 antibodies. Recent Findings: Evidence-based therapeutic recommendations suggest that the best initial approach to treat these patients is an early combination of immunosuppressive drugs including either glucocorticoids and calcineurin inhibitors or a triple therapy adding intravenous cyclophosphamide. Tofacitinib, a Janus kinase inhibitor, could be useful according to recent reports. High ferritin plasma levels, generalized worsening of pulmonary infiltrates, and ground-glass opacities should be considered predictive factors of a bad outcome. In this scenario, clinicians should consider rescue therapies such as therapeutic plasma exchange, polymyxin-B hemoperfusion, veno-venous extracorporeal membrane oxygenation, or even lung transplantation. Summary: Combined immunosuppressive treatment should be considered the first-line therapy for patients with anti-MDA5 rapidly progressive interstitial lung disease. Aggressive rescue therapies may be useful in refractory patients.

Functioning in adult patients with idiopathic inflammatory myopathy: Exploring the role of environmental factors using focus groups.

OBJECTIVE: Health-related quality of life is impaired in idiopathic inflammatory myopathies. This study aimed to identify the main areas of the health-related quality of life environment domain that are affected in patients with myositis. METHODS: A qualitative study was performed using focus groups and applying the International Classification of Functioning, Disability, and Health. Participants were recruited from a cohort of 323 adult inflammatory myopathy patients consulting at a reference center for idiopathic inflammatory myopathy in Spain, selected by the maximum variation strategy, and placed in focus groups with 5 to 7 patients per group. The number of focus groups required was determined by data saturation. RESULTS: Twenty-five patients distributed in 4 focus groups were interviewed. The verbatim provided 54 categories directly related with environmental factors. Those associated with products or substances for personal consumption (e110), health professionals (e355), health services, systems and policies (e580), products and technology for personal use in daily living (e115), and immediate family (e310) were the ones most frequently reported. CONCLUSION: The results of this study led to identification of several environmental factors that affect the health-related quality of life of patients with myositis. Remedial interventions should be designed to address some of these factors.

Recommendations for the treatment of anti-melanoma differentiation-associated gene 5-positive dermatomyositis-associated rapidly progressive interstitial lung disease.

OBJECTIVES: The study aimed to develop evidence-based recommendations for the treatment of rapidly progressive interstitial lung disease (RPILD) associated with the anti-Melanoma Differentiation-Associated Gene 5-positive dermatomyositis (DM) syndrome. METHODS: The task force comprised an expert panel of specialists in rheumatology, intensive care medicine, pulmonology, immunology, and internal medicine. The study was carried out in two phases: identifying key areas in the management of DM-RPILD syndrome and developing a set of recommendations based on a review of the available scientific evidence. Four specific questions focused on different treatment options were identified. Relevant publications in English, Spanish or French up to April 2018 were searched systematically for each topic using PubMed (MEDLINE), EMBASE, and Cochrane Library (Wiley Online). The experts used evidence obtained from these studies to develop recommendations. RESULTS: A total of 134 studies met eligibility criteria and formed the evidentiary basis for the recommendations regarding immunosuppressive therapy and complementary treatments. Overall, there was general agreement on the initial use of combined immunosuppressive therapy. Combination of high-dose glucocorticoids and calcineurin antagonists with or without cyclophosphamide is the first choice. In the case of calcineurin antagonist contraindication or treatment failure, switching or adding other immunosuppressants may be individualized. Plasmapheresis, polymyxin B hemoperfusion and/or intravenous immunoglobulins may be used as rescue options. ECMO should be considered in life-threatening situations while waiting for a clinical response or as a bridge to lung transplant. CONCLUSIONS: Thirteen recommendations regarding the treatment of the anti-MDA5 positive DM-RPILD were developed using research-based evidence and expert opinion.

Emergency endovascular management of acute thoracic aortic pathology A safe and feasible option.

Endovascular repair has revolutionised the emergency treatment of thoracic aortic disease. We report our 10 year experience using this treatment in emergency cases. A prospectively maintained vascular database was analysed. Patients' medical records and CT images stored on the hospital PACS system were also reviewed. Statistical analysis was done using IBM SPSS V21. There were a total of 59 thoracic aortic stenting procedures of which 33 (60% males with a mean age of 58 yrs) were performed for emergency thoracic pathologies: traumatic transection (n = 10), ruptured aneurysm (n = 6), non-traumatic dissection (n = 8) and penetrating aortic ulcer (n = 9). All patients had self-expanding endografts implanted. Two patients required debranching procedures before the endovascular treatment. Thirty-day mortality was 12.1% (4/33). 70% of patients received a single device. There were 7 procedure related complications, 6 requiring re-intervention: thoracotomy and drainage in 2 patients, proximal graft extension in 2, open drainage of groin haematoma in 1 and open repair of a common femoral artery pseudo-aneurysm in one patient. In total 23 patients were transferred from 11 centres nationwide. There were no mortalities or other complications related to patient transfer from peripheral centres. Although acute thoracic aortic pathology is life threatening, appropriate blood pressure management and treatment of associated injuries can result in favourable outcomes. Endovascular repair is a safe and effective treatment option which enables patients to be treated with reduced morbidity and mortality. Transfer of patients with acute pathology to a tertiary centre can safely be performed.

Statin-associated autoimmune myopathy: A distinct new IFL pattern can increase the rate of HMGCR antibody detection by clinical laboratories.

BACKGROUND AND OBJECTIVE: Statin-associated autoimmune myopathy (SAAM) with anti-HMGCR antibodies has recently been described. Several specific immunoassays are in use to detect HMGCR antibodies. In the course of systematic autoantibody screening we recognized a new distinct IFL staining pattern on rat liver sections that regularly coincided with anti-HMGCR antibodies. In this study we investigated whether this new IFL pattern is specifically associated to statin-associated autoimmune myopathy and corresponds to anti-HMGCR antibodies. PATIENTS AND METHODS: Twenty-three patients positive for anti-HMGCR antibodies (14 diagnosed with SAAM) were investigated for anti-HMGCR antibodies by two ELISA assays and confirmed by immmunoblot. HMGCR associated liver IFL pattern (HALIP) was detected by indirect IFL and the reactivity against HMGCR was confirmed by immunoabsorption using purified human HMGCR antigen. 90 patients with other autoimmune diseases and 45 non-autoimmune statin treated patients were studied as controls. RESULTS: 21 out of 23 (91%) anti-HMGCR positive patients were HALIP positive. The staining was completely and specifically removed by immunoabsorption with human purified HMGCR. None of the control sera from autoimmune patients or non-autoimmune statin treated subjects was positive for HALIP. Statistical concordance between HALIP and anti-HMGCR antibody specific tests was 98.7%, kappa 0.95. CONCLUSIONS: A new and distinct IFL staining pattern (HALIP) is associated to HMGCR associated myopathy. Absorption and concordance studies indicate that the antigen recognized in the liver by HALIP is HMGCR or a closely related protein. Awareness of this new pattern can help to detect HMGCR autoantibodies in statin treated patients tested for autoimmune serology.

The effect of carotid stenting on endarterectomy practice--A single institution experience.

OBJECTIVES: The number of operations performed per surgeon is thought to determine the quality of carotid endarterectomy (CEA) surgery. The advent of carotid artery stenting (CAS) threatens to reduce the volume of CEA. This paper assesses CEA and the effects of the introduction of CAS service on outcomes. DESIGN: Retrospective cohort study. METHODS: Clinical data and results of CEA were reviewed retrospectively for the treatment of carotid stenosis, between January 1988 and December 2010. CEA patients were grouped into those treated before and after the introduction of CAS to our hospital in 2001. RESULTS: 757 patients underwent a CEA between 1988 and 2010. The perioperative stroke rate prior to the introduction of CAS was 4.9%, and 3.3% after stent introduction in 2001. In this latter period, 85.5% had symptomatic stenosis which suggests that the patients were not low risk. The major adverse event rate (inclusive of death and myocardial infarction) post introduction of CAS from 2001 to 2010 was 4.1%. There was no correlation between post-operative stroke/MAE and procedure volume, despite the trend of decreasing CEA numbers over time. CONCLUSION: The introduction of carotid artery stenting has led to a decrease in carotid endarterectomy volume. However, outcomes in our high risk patient population are acceptable. Therefore, CEA remains the procedure of choice for carotid artery revascularization.

Sequence analysis of TMEM173 exon 5 in patients with systemic autoimmune diseases.

BACKGROUND: Overactivation of the interferon pathways has been demonstrated in patients suffering from different systemic autoimmune diseases (SADs). Genetic associations have been described for many genes involved in these pathways. Gain-of-function mutations in the TMEM173 gene have recently been reported in patients with autoinflammatory diseases that share some clinical features with SADs. METHODS: We aimed at detecting the reported three mutations of transmembrane protein 173 (TMEM173) exon 5 in 100 patients suffering from: systemic lupus erythematosus (SLE) (n = 22), primary antiphospholipid syndrome (PAPS) (n = 20), systemic sclerosis (SSc) (n = 20), dermatomyositis (DM) (n = 20), and vasculitis (n = 18). Samples from 19 healthy controls were also included. Sequence analyses were performed from the derived TMEM173 exon 5 PCR fragment amplified from DNA obtained from whole blood. RESULTS: Neither mutations nor single nucleotide polymorphisms (SNPs) in the exon 5 of the TMEM173 gene were detected. Just the rs7380272 SNP, located in the intronic region upstream exon 5, was detected in some patients and controls. The allele frequency of this SNP, though, was not statistically different between the patients groups and the control group. CONCLUSIONS: Our study demonstrates the lack of association between the presence of SADs and mutations in exon 5 of the TMEM173 gene. SADs are complex multifactorial diseases in which not just one but probably many different genetic alterations may coexist. Although we cannot rule out the possibility that other variations may exist in other regions of this gene, we think that studies must be directed towards the analysis of other genes which, as TMEM173, also code for nucleic acid sensors that activate the nucleic-acid induced type I IFN pathway.

Pangenome analysis of Bifidobacterium longum and site-directed mutagenesis through by-pass of restriction-modification systems.

BACKGROUND: Bifidobacterial genome analysis has provided insights as to how these gut commensals adapt to and persist in the human GIT, while also revealing genetic diversity among members of a given bifidobacterial (sub)species. Bifidobacteria are notoriously recalcitrant to genetic modification, which prevents exploration of their genomic functions, including those that convey (human) health benefits. METHODS: PacBio SMRT sequencing was used to determine the whole genome seqeunces of two B. longum subsp. longum strains. The B. longum pan-genome was computed using PGAP v1.2 and the core B. longum phylogenetic tree was constructed using a maximum-likelihood based approach in PhyML v3.0. M.blmNCII was cloned in E. coli and an internal fragment if arfBarfB was cloned into pORI19 for insertion mutagenesis. RESULTS: In this study we present the complete genome sequences of two Bifidobacterium longum subsp. longum strains. Comparative analysis with thirty one publicly available B. longum genomes allowed the definition of the B. longum core and dispensable genomes. This analysis also highlighted differences in particular metabolic abilities between members of the B. longum subspecies infantis, longum and suis. Furthermore, phylogenetic analysis of the B. longum core genome indicated the existence of a novel subspecies. Methylome data, coupled to the analysis of restriction-modification systems, allowed us to substantially increase the genetic accessibility of B. longum subsp. longum NCIMB 8809 to a level that was shown to permit site-directed mutagenesis. CONCLUSIONS: Comparative genomic analysis of thirty three B. longum representatives revealed a closed pan-genome for this bifidobacterial species. Phylogenetic analysis of the B. longum core genome also provides evidence for a novel fifth B. longum subspecies. Finally, we improved genetic accessibility for the strain B. longum subsp. longum NCIMB 8809, which allowed the generation of a mutant of this strain.

Genome-wide association study identifies HLA 8.1 ancestral haplotype alleles as major genetic risk factors for myositis phenotypes.

Autoimmune muscle diseases (myositis) comprise a group of complex phenotypes influenced by genetic and environmental factors. To identify genetic risk factors in patients of European ancestry, we conducted a genome-wide association study (GWAS) of the major myositis phenotypes in a total of 1710 cases, which included 705 adult dermatomyositis, 473 juvenile dermatomyositis, 532 polymyositis and 202 adult dermatomyositis, juvenile dermatomyositis or polymyositis patients with anti-histidyl-tRNA synthetase (anti-Jo-1) autoantibodies, and compared them with 4724 controls. Single-nucleotide polymorphisms showing strong associations (P<5×10(-8)) in GWAS were identified in the major histocompatibility complex (MHC) region for all myositis phenotypes together, as well as for the four clinical and autoantibody phenotypes studied separately. Imputation and regression analyses found that alleles comprising the human leukocyte antigen (HLA) 8.1 ancestral haplotype (AH8.1) defined essentially all the genetic risk in the phenotypes studied. Although the HLA DRB1*03:01 allele showed slightly stronger associations with adult and juvenile dermatomyositis, and HLA B*08:01 with polymyositis and anti-Jo-1 autoantibody-positive myositis, multiple alleles of AH8.1 were required for the full risk effects. Our findings establish that alleles of the AH8.1 comprise the primary genetic risk factors associated with the major myositis phenotypes in geographically diverse Caucasian populations.

Prevalence of HHV-8 in systemic autoimmune diseases.

BACKGROUND: Epidemiological data suggest that some viruses may be linked to the development of autoimmunity. OBJECTIVES: The objective of this work was to determine the presence of HHV-8 viral DNA in whole blood from patients suffering from different systemic autoimmune diseases (SAD). We also aimed at testing the prevalence of patients showing antibodies against an HHV-8 orfK8.1 peptide. STUDY DESIGN: Two hundred and eighty SAD patients and 50 healthy blood donor controls were included. Molecular analyses were performed by nested PCR from DNA obtained from whole blood and an enzyme immunoassay was developed in order to test for the presence of antibodies directed against a synthetic peptide derived from the HHV-8 orfK8.1 protein. RESULTS: Only 2 out of the 280 samples analyzed yielded the specific HHV-8 PCR product. Antibodies against orfK8.1 were detected in 2 SLE patients, 1 patient suffering from Sjögren's syndrome and 2 patients with vasculitis. CONCLUSIONS: We conclude that HHV-8 is usually not present in blood neither from autoimmune patients nor from healthy controls. Furthermore, HHV-8 antibodies against the HHV-8 orfK8.1 peptide were rarely detected. It leads us to infer that HHV-8 is not involved on the development of these disorders. It does not rule out the possibility that other environmental and microbiological triggers may account for their etiopathogenesis.

Correlation of ultrasound B-lines with high-resolution computed tomography in antisynthetase syndrome.

OBJECTIVES: Interstitial lung disease is a common finding in patients with the antisynthetase syndrome. High-resolution computed tomography is the reference test for diagnosis and follow-up of this condition, but it involves considerable radiation exposure. Our aim was to describe chest ultrasound features and its correlation with high-resolution computed tomography findings in a series of patients with the antisynthetase syndrome. METHODS: The study included patients from our antisynthetase syndrome cohort with varying degrees of interstitial lung disease, consulting in our outpatient clinic over a 1-year period. Chest high-resolution computed tomography and chest sonography were prospectively performed within a 1-week period. High-resolution computed tomography Warrick score was calculated and chest sonography findings (B-lines) at several sonographic points along the anterior and posterior intercostal spaces were semi-quantitatively analyzed. Rho Spearman statistics were applied for possible correlations. RESULTS: Twenty-one consecutive patients were studied. A median of 59 thoracic points was studied per patient (IQR 6); 44.1% (95% CI 29.9-60.7) of them showed at least one B-line. A correlation coefficient of 0.135 (p=0.5) was found between the percentage of ultrasound points with B-lines and the Warrick's score. Only the number of bronchopulmonary segments showing ground glass findings was associated with the percentage of sonographic points with B-lines (Rho=0.5, p=0.02). CONCLUSIONS: A good correlation between the percentage of sonographic points with B-lines and high-resolution computed tomography ground glass opacities was observed in patients with the antisynthetase syndrome.