Search

Videoconferencing focus groups have emerged as a popular method for collecting qualitative data. However, its use in sexual and reproductive health research is still very much in its infancy. Based on participants’ feedback and researchers’ reflections on using videoconferencing focus groups to collect sexual and reproductive health data with 39 heterosexual and non-heterosexual Chinese im/migrants in Australia, we discuss some of the key lessons learned, and considerations involved in shifting from face-to-face to online focus groups. Overall, videoconferencing focus groups appeared to be a highly feasible and acceptable way to discuss “sensitive” topics with Chinese im/migrants. Importantly, researchers need to be both creative and reflexive during the research process and must not forget that the success of a study lies not only in troubleshooting technical issues but also in cultivating and maintaining a trusting relationship with research participants.

This article describes the rate of suicidal ideation (SI) across three timepoints among treatment-seeking patients recently discharged from psychiatric hospitalization—a group that is at ultrahigh-risk for suicide. Retrospective chart review was used to quantify the rate of SI in 252 consecutive patients discharged to a post-hospital mental health clinic. Data include patients’ lifetime history of SI, SI at the time of hospital intake, and SI at post-hospital outpatient clinic intake, as well as demographics and diagnosis. Overall, 67% of the sample reported a lifetime history of SI, 49% reported SI during hospital intake, and 6% reported SI at post-hospital clinic intake. Age was the only variable associated with history of SI (p = .04), with younger patients more likely (OR = 1.85) to report a history of SI. These results may help inform the development of interventions for the population of ultrahigh-risk patients being discharged from hospital after psychiatric care.

BackgroundSafety planning-type interventions (SPTIs) for patients at risk of suicide are often used in clinical practice, but it is unclear whether these interventions are effective.AimsThis article reports on a meta-analysis of studies that have evaluated the effectiveness of SPTIs in reducing suicidal behaviour and ideation.MethodWe searched Medline, EMBASE, PsycINFO, Web of Science and Scopus from their inception to 9 December 2019, for studies that compared an SPTI with a control condition and had suicidal behaviour or ideation as outcomes. Two researchers independently extracted the data. To assess suicidal behaviour, we used a random-effects model of relative risk based on a pooled measure of suicidal behaviour. For suicidal ideation, we calculated effect sizes with Hedges’ g. The study was registered at PROSPERO (registration number CRD42020129185).ResultsOf 1816 unique abstracts screened, 6 studies with 3536 participants were eligible for analysis. The relative risk of suicidal behaviour among patients who received an SPTI compared with control was 0.570 (95% CI 0.408–0.795, P = 0.001; number needed to treat, 16). No significant effect was found for suicidal ideation.ConclusionsTo our knowledge, this is the first study to report a meta-analysis on SPTIs for suicide prevention. Results support the use of SPTIs to help preventing suicidal behaviour and the inclusion of SPTIs in clinical guidelines for suicide prevention. We found no evidence for an effect of SPTIs on suicidal ideation, and other interventions may be needed for this purpose.

BACKGROUND HIV preexposure prophylaxis (PrEP) with fixed-dose tenofovir disoproxil fumarate (TDF) and emtricitabine has been associated with low rates of renal impairment in clinical trials. Large-scale PrEP implementation may result in higher rates, as the prevalence of associated risk factors may be higher than in trial populations. METHODS A posthoc analysis of EPIC-NSW, a large Australian multicentre PrEP implementation trial for patients at high risk of HIV infection. Participants were eligible for inclusion if they commenced PrEP between 1 March 2016 and 30 April 2018, and had renal function assessed at baseline and at least once more before the censor date. The primary outcome was new-onset renal impairment, defined as an estimated glomerular filtration rate (eGFR)

Introduction:We sought to determine if training program “familiarity” played a role in the successful match of urological surgery residents.Methods:We analyzed information from successful u...

Background National guidelines for the short-term management of self-harm are aimed at healthcare professionals who may be involved in the care of people who have self-harmed. However, evidence from small-scale studies globally suggest there is a lack of awareness of such guidelines among some groups of healthcare professionals. For the first time in a large representative sample of patient-facing healthcare professionals, we aimed to identify: (a) which healthcare professionals are aware of guidelines for the management of self-harm; (b) the perceived availability of training; (c) the use of risk screening tools; and (d) the extent to which healthcare professionals implement guidelines for the management of self-harm. Methods 1020 UK healthcare professionals completed a cross-sectional survey online. Results 85.6% (873/1020) of the sample had heard of the national guidelines, but only 24.3% (248/1020) knew “a fair amount” or more about them. Of the respondents who had previously encountered a patient who had self-harmed or was at risk of repeat self-harm, the guidelines were implemented in fewer than 50% (M = 43.89%, SD = 38.79) of encounters. 31% (312/1020) of the sample had received training in managing self-harm and, contrary to guidelines, 2.25% (23/1020) of the sample had used self-harm risk screening tools. Conclusions Our findings highlight a need to improve knowledge of self-harm management guidelines, and identifies professional groups where awareness and knowledge is currently low. Further work is required to develop interventions to change healthcare professional practice with respect to the implementation of self-harm management guidelines., Highlights • 85.6% of healthcare professionals have heard of the NICE guidelines for self-harm. • 24.3% of healthcare professionals know what is in the guidelines for self-harm. • 2.3% of healthcare professionals breach ‘do not do’ recommendations. • Guidelines for self-harm are implemented in 43.9% of encounters with patients. • Awareness of self-harm guidelines was lowest outside mental health settings.

A rapidly expanding and clinically distinct group of CNS diseases are caused by pathogenic autoantibodies that target neuroglial surface proteins. Despite immunotherapy, patients with these neuroglial surface autoantibody (NSAb)-mediated diseases often experience clinical relapse, high rates of long-term morbidity and adverse effects from the available medications. Fundamentally, the autoantigen-specific B cell lineage leads to production of the pathogenic autoantibodies. These autoantigen-specific B cells have been consistently identified in the circulation of patients with NSAb-mediated diseases, accompanied by high serum levels of autoantigen-specific antibodies. Early evidence suggests that these cells evade well-characterized B cell tolerance checkpoints. Nearer to the site of pathology, cerebrospinal fluid from patients with NSAb-mediated diseases contains high levels of autoantigen-specific B cells that are likely to account for the intrathecal synthesis of these autoantibodies. The characteristics of their immunoglobulin genes offer insights into the underlying immunobiology. In this Review, we summarize the emerging knowledge of B cells across the NSAb-mediated diseases. We review the evidence for the relative contributions of germinal centres and long-lived plasma cells as sources of autoantibodies, discuss data that indicate migration of B cells into the CNS and summarize insights into the underlying B cell pathogenesis that are provided by therapeutic effects.

IntroductionStudies involving Twitter and chronic pain can provide highly valuable patient-generated information. The aim of this paper was to examine pain-related tweets in Ireland over a 2-week period from 22 June 2017 to 5 July 2017 using pain-related keywords. We wished to identify Twitter user gender profile; most common discussion topics; sentiment analysis; and dissemination of tweets.MethodsA third-party data analytics company conducted a Twitter social media analysis over a randomly chosen 14-day period between the dates 22 June and 5 July 2017. All relevant keywords were included in the search. Author group consensus yielded 24 terms. Geographical location was restricted to Ireland. A computational sentiment dictionary was used to provide a rating of the emotional properties of the text on a 9-point scale from −5 to +4 of negative to positive sentiment. Dissemination was calculated by the number of times the tweet was displayed (‘impressions’).ResultsThere were 941 tweets identified during the study from 715 contributors. These generated 2.88 million impressions. The most frequently occurring keywords were headache (n=321); migraine (n=147); back pain (n=123); cannabis (n=114); and chronic pain (n=85). There were 1.94 times as many tweets from females as males. The highest proportion of tweets from female users was in the fibromyalgia (83%) and migraine (60%) categories; and from males in the sciatica (35%), chronic pain (34%) and back pain (32%) categories. Cannabis-related tweets reflected mostly non-personal content (90%), with a highly positive sentiment, and the highest number of impressions per tweet. The largest amount of advice was offered in the back pain category. Reposting of other users’ content (‘retweets’) was more likely to contain a positive sentiment.ConclusionA substantial discussion of pain-related topics took place on Twitter during our study period. This provided real-time, dynamic information from individuals on discussion topics in pain medicine. This can be used to gain a greater understanding of the pain experience. As patients are increasingly acquiring healthcare information through online sources, high-quality information from approved sources should be promoted on such platforms.

The thermal design process for electronic products often minimizes the use of computational fluid dynamics and heat transfer (CFD/HT) software in favor of quick prototyping and testing to determine the thermal characteristics of the product. For large-scale products with many thermal challenges, such a strategy can be impractical due to the high cost of prototyping cycles, time constraints, and inevitable iterations involved. In such cases, thorough CFD/HT models developed early in the design process are valuable for driving the product design. Based on this idea, the study examines thermal performance of 55” outdoor digital displays using CFD/HT tools and a prediction under hazardous outdoor condition is made for two different brightness outputs. The prediction is extrapolated and validated through the outdoor testing and simulation comparisons. It is shown that CFD/HT software can be used as a means of making conservative design choices.

Machine learning (ML) is an increasingly popular approach/technique for analyzing "Big Data" and predicting risk behaviors and psychological problems. However, few published critiques of ML as an approach currently exist. We discuss some fundamental cautions and concerns with ML that are relevant when attempting to predict all clinical and forensic risk behaviors (risk to self, risk to others, risk from others) and mental health problems. We hope to provoke a healthy scientific debate to ensure that ML's potential is realized and to highlight issues and directions for future risk prediction, assessment, management, and prevention research. ML, by definition, does not require the model to be specified by the researcher. This is both its key strength and its key weakness. We argue that it is critical that the ML algorithm (the model or models) and the results are both presented and that ML needs to be become machine-assisted learning like other statistical techniques; otherwise, we run the risk of becoming slaves to our machines. Emerging evidence potentially challenges the superiority of ML over other approaches, and we argue that ML's complexity significantly limits its clinical utility. Based on the available evidence, we believe that researchers and clinicians should emphasize identifying, understanding, and explaining (formulating) individual clinical needs and risks and providing individualized management and treatment plans, rather than trying to predict or putting too much trust in predictions that will inevitably be wrong some of the time (and we do not know when). (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Background and ObjectiveTo determine whether rituximab is safe and potentially beneficial, warranting further investigation in an efficacy trial for acetylcholine receptor antibody-positive generalized myasthenia gravis (AChR-Ab+ gMG).MethodsThe B-Cell Targeted Treatment in MG (BeatMG) study was a randomized, double-blind, placebo-controlled, multicenter phase 2 trial that utilized a futility design. Individuals 21–90 years of age, with AChR-Ab+ gMG (MG Foundation of America Class II–IV) and receiving prednisone ≥15 mg/d were eligible. The primary outcome was a measure of steroid-sparing effect, defined as the proportion achieving ≥75% reduction in mean daily prednisone dose in the 4-weeks prior to week 52 and with clinical improvement or no significant worsening as compared to the 4-week period prior to randomization. The coprimary outcome was safety. Secondary outcomes included MG-specific clinical assessments. Fifty-two individuals were randomized (1:1) to a 2-cycle rituximab/placebo regimen, with follow-up through 52 weeks.ResultsOf the 52 participants included, mean ± SD age at enrollment was 55.1 ± 17.1 years; 23 (44.2%) were women and 31 (59.6%) were Myasthenia Gravis Foundation of America Class II. The mean ± SD baseline prednisone dose was 22.1 ± 9.7 mg/d. The primary steroid-sparing outcome was achieved in 60% of those on rituximab vs 56% on placebo. The study reached its futility endpoint (p = 0.03), suggesting that the predefined clinically meaningful improvement of 30% due to rituximab over placebo was unlikely to be achieved in a subsequent, larger trial. No safety issues were identified.DiscussionAlthough rituximab was safe and well-tolerated, these results suggest that there is a low probability of observing the defined clinically meaningful steroid-sparing effect over a 12-month period in a phase 3 trial of mild to moderately symptomatic AChR-Ab+ gMG.Classification of EvidenceThis study provides Class I evidence that for mild to moderate AChR-Ab+ gMG, compared with placebo, rituximab is safe but unlikely to reduce steroid use by an absolute difference of at least 30% at 1 year.Trial Registration InformationClinicalTrials.gov identifier: NCT02110706.

Proton therapy is increasing in utilization worldwide at a rapid rate. With process improvements in costs, footprints, and continued advances in the delivery of care, including intensity modulation and image guidance, proton therapy may evolve into standard treatment with photon radiation therapy. This chapter reviews process improvements in proton therapy and the application in modern care.

The use of proton therapy in oncology is not a new idea. The unique physical properties of protons and potential advantages in radiation therapy were initially recognized in the 1940s. Since the first patients were treated in the 1950s, technology and clinical applications have evolved as evidenced by the increasing number of proton therapy centers and patients being treated throughout the world. This chapter will review the history of proton therapy providing a detailed overview of the cyclotron and synchrotron techniques used and how they have advanced with time.

Background and ObjectivesThere are limited data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine reactogenicity in persons with multiple sclerosis (PwMS) and how reactogenicity is affected by disease-modifying therapies (DMTs). The objective of this retrospective cross-sectional study was to generate real-world multiple sclerosis–specific vaccine safety information, particularly in the context of specific DMTs, and provide information to mitigate specific concerns in vaccine hesitant PwMS.MethodsBetween 3/2021 and 6/2021, participants in iConquerMS, an online people-powered research network, reported SARS-CoV-2 vaccines, experiences of local (itch, pain, redness, swelling, or warmth at injection site) and systemic (fever, chills, fatigue, headache, joint pain, malaise, muscle ache, nausea, allergic, and other) reactions within 24 hours (none, mild, moderate, and severe), DMT use, and other attributes. Multivariable models characterized associations between clinical factors and reactogenicity.ResultsIn 719 PwMS, 64% reported experiencing a reaction after their first vaccination shot, and 17% reported a severe reaction. The most common reactions were pain at injection site (54%), fatigue (34%), headache (28%), and malaise (21%). Younger age, being female, prior SARS-CoV-2 infection, and receiving the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vs BNT162b2 (Pfizer-BioNTech) vaccine were associated with experiencing a reaction after the first vaccine dose. Similar relationships were observed for a severe reaction, including higher odds of reactions among PwMS with more physical impairment and lower odds of reactions for PwMS on an alpha4-integrin blocker or sphingosine-1-phosphate receptor modulator. In 442 PwMS who received their second vaccination shot, 74% reported experiencing a reaction, whereas 22% reported a severe reaction. Reaction profiles after the second shot were similar to those reported after the first shot. Younger PwMS and those who received the mRNA-1273 (Moderna) vs BNT162b2 vaccine reported higher reactogenicity after the second shot, whereas those on a sphingosine-1-phosphate receptor modulator or fumarate were significantly less likely to report a reaction.DiscussionSARS-CoV-2 vaccine reactogenicity profiles and the associated factors in this convenience sample of PwMS appear similar to those reported in the general population. PwMS on specific DMTs were less likely to report vaccine reactions. Overall, the short-term vaccine reactions experienced in the study population were mostly self-limiting, including pain at the injection site, fatigue, headache, and fever.

Understanding the mechanism(s) by which maternal immune activation (MIA) during gestation may disrupt neurodevelopment and increase the susceptibility for disorders such as autism spectrum disorder (ASD) or schizophrenia is a critical step in the development of better treatments and preventive measures. A large body of literature has investigated the pathophysiology of MIA in rodents. However, a translatability gap plagues pre-clinical research of complex behavioral/developmental diseases and those diseases requiring clinical diagnosis, such as ASD. While ideal for their genetic flexibility, vast reagent toolkit, and practicality, rodent models often lack important elements of ethological validity. Hence, our study aimed to develop and characterize the prenatal MIA model in marmosets. Here, we adapted the well-characterized murine maternal immune activation model. Pregnant dams were administered 5 mg/kg poly-L-lysine stabilized polyinosinic-polycytidylic acid (Poly ICLC) subcutaneously three times during gestation (gestational day 63, 65, and 67). Dams were allowed to deliver naturally with no further experimental treatments. After parturition, offspring were screened for general health and vigor, and individual assessment of communication development and social behavior was measured during neonatal or adolescent periods. Similar to rodent models, offspring subjected to MIA exhibited a disruption in patterns of communication during early development. Assessment of social behavior in a marmoset-modified 3-chamber test at 3 and 9 months of age revealed alterations in social behavior that, in some instances, was sex-dependent. Together, our data indicate that marmosets are an excellent non-human primate model for investigating the neurodevelopmental and behavioral consequences of exposure to prenatal challenges, like MIA. Additional studies are necessary to more completely characterize the effect of prenatal inflammation on marmoset development and explore therapeutic intervention strategies that may be applicable in a clinical setting.

Elevated frequency of afucosylated IgG1 antibodies during dengue virus infection is associated with prior infection and predicts severe disease.

This cross-sectional study assesses somatosensory function in adolescents and compares their somatosensory profiles with community control participants to investigate associations with the incidence and frequency of self-harm., Key Points Question Is pain sensitivity associated with self-harm frequency in children and adolescents aged 12 to 17 years? Findings This cross-sectional study of 64 adolescents systematically examined sensitivity to a range of painful and nonpainful sensory stimuli. Pain hyposensitivity was significantly associated with self-harm frequency, and these findings also extended to nonpainful sensory stimuli; pressure pain threshold was associated with significant specificity and sensitivity for incidence of self-harm. Meaning These findings suggest that pressure pain threshold is a novel biomarker for identifying adolescents at high risk of self-harm., Importance Self-harm is a risk factor for suicide in adolescents, with the prevalence highest in young people in group and residential care programs. Although no established risk factors for self-harm exist, adolescents who self-harm may have decreased pain sensitivity, but this has not been systematically investigated. Objective To assess somatosensory function using quantitative sensory testing (QST) in children and adolescents living in care grouped by the number of episodes of self-harm in the past year and compare their somatosensory profiles with community control participants to investigate associations with the incidence or frequency of self-harm. Design, Setting, and Participants Recruitment for this cross-sectional study began January 2019 and ended March 2020. Exclusion criteria included intellectual disability (intelligence quotient

Background The Pacific Islands have a low HIV prevalence, but high rates of STI’s and large high-risk populations. The UNDP Programme supports 11 Pacific Island Countries (PICs). In-country clinical training are provided as well as HIV/TB diagnostics, treatments, and specialist HIV clinical advice. In 2020, in-country support was not possible because of the COVID19 pandemic. Approach After discussion with UNDP partners and PICs HIV/STI-healthcare workers, we presented the following online education: Monthly webinars. Eight one-hour webinars on Zoom, each repeated 4 hours later as the PICs span 7 time-zones. These case-based educational webinars covered HIV/STI clinical care related topics. Guest speakers were invited for specialist topics. In-country HIV/STI-online education workshops run over one-day for nine PICs and over half-day for Niue and Tuvalu, the two smallest PICs. The workshops ran in late 2020 to build on the webinar knowledge and were tailored to in-country needs. Training was mainly case based, co-facilitated by a worker from the Fijian HIV-positive peoples NGO, FJN+, with guest speakers invited for specialist topics. Outcomes Monthly webinars: 323 individual attendances for the 8 webinars. 114 evaluations were returned; 95% found the HIV webinars very helpful and 92% would recommend them to other clinical staff. As poor internet was a problem, the presentation slides and the recorded webinars were sent to the PIC attendees. In-country online HIV/STI-education workshops: 241 participants across the PICs. A planning meeting was conducted with each PIC. The average scores in questionnaires pre– and post-training doubled from 40% to 80%. Participants found the case-based training useful and requested follow-up training. Innovation/Significance This is first time in the HIV/STI clinical support to the Pacific has been provided on-line and despite internet challenges, it is an economical and efficient way to provide ongoing HIV/STI clinical education in this remote setting.

Background: The current global pandemic has created unprecedented challenges in the blood supply network. Given the recent shortages, there must be a civilian plan for massively bleeding patients when there are no blood products on the shelf. Recognizing that the time to death in bleeding patients is less than 2 h, timely resupply from unaffected locations is not possible. One solution is to transfuse emergency untested whole blood (EUWB), similar to the extensive military experience fine-tuned over the last 19 years. While this concept is anathema in current civilian transfusion practice, it seems prudent to have a vetted plan in place. Methods and Materials: During the early stages of the 2020 global pandemic, a multidisciplinary and international group of clinicians with broad experience in transfusion medicine communicated routinely. The result is a planning document that provides both background information and a high-level guide on how to emergently deliver EUWB for patients who would otherwise die of hemorrhage. Results and Conclusions: Similar plans have been utilized in remote locations, both on the battlefield and in civilian practice. The proposed recommendations are designed to provide high-level guidance for experienced blood bankers, transfusion experts, clinicians, and health authorities. Like with all emergency preparedness, it is always better to have a well-thought-out and trained plan in place, rather than trying to develop a hasty plan in the midst of a disaster. We need to prevent the potential for empty shelves and bleeding patients dying for lack of blood.

Background In recent years, gonorrhea notifications have increased in women in Australia and other countries. We measured trends over time and risk factors among Australian Aboriginal and Torres Strait Islander ("Aboriginal") and non-Aboriginal women. Methods We conducted a cross-sectional analysis of data from 41 sexual health clinics. Gonorrhea positivity at each patient's first visit (first-test positivity) during the period 2009 to 2016 was calculated. Univariate and multivariate analyses assessed risk factors for first-test positivity in Aboriginal and non-Aboriginal women. Results Gonorrhea positivity decreased among Aboriginal women (7.1% in 2009 to 5.2% in 2016, P < 0.001) and increased among non-Aboriginal women (0.6%-2.9%, P < 0.001). Among Aboriginal women, first-test positivity was independently associated with living in a regional or remote area (adjusted odds ratio [aOR], 4.29; 95% confidence interval [CI], 2.52-7.31; P < 0.01) and chlamydia infection (aOR, 4.20; 95% CI,3.22-5.47; P < 0.01). Among non-Aboriginal women, first-test positivity was independently associated with greater socioeconomic disadvantage (second quartile: aOR, 1.68 [95% CI, 1.31-2.16; P < 0.01]; third quartile: aOR, 1.54 [95% CI, 1.25-1.89; P < 0.01]) compared with least disadvantaged quartile: recent sex work (aOR, 1.69; 95% CI, 1.37-2.08; P < 0.01), recent injecting drug use (aOR, 1.85; 95% CI, 1.34-2.57; P < 0.01), and chlamydia infection (aOR, 2.35; 95% CI, 1.90-2.91; P < 0.01). For non-Aboriginal women, being aged 16 to 19 years (aOR, 0.62; 95% CI, 0.49-0.80; P < 0.01) compared with those ≥30 years was a protective factor. Conclusions These findings highlight 2 different epidemics and risk factors for Aboriginal and non-Aboriginal women, which can inform appropriate health promotion and clinical strategies.

BACKGROUND As clinical exome sequencing (CES) becomes more common, understanding which patients are most likely to benefit and in what manner is critical for the general pediatrics community to appreciate. METHODS Five hundred and twenty-three patients referred to the Pediatric Genetics clinic at Michigan Medicine were systematically phenotyped by the presence or absence of abnormalities for 13 body/organ systems by a Clinical Genetics team. All patients then underwent CES. RESULTS Overall, 30% of patients who underwent CES had an identified pathogenic mutation. The most common phenotypes were developmental delay (83%), neuromuscular system abnormalities (81%), and multiple congenital anomalies (42%). In all, 67% of patients had a variant of uncertain significance (VUS) or gene of uncertain significance (GUS); 23% had no variants reported. There was a significant difference in the average number of body systems affected among these groups (pathogenic 5.89, VUS 6.0, GUS 6.12, and no variant 4.6; P

Introduction: Atherosclerotic coronary artery disease, in particular acute myocardial infarction (AMI), is a leading cause of morbidity and mortality globally. Percutaneous coronary intervention (PCI) is the mainstay of treatment for obstructive coronary artery disease and AMI through the restoration of TIMI III flow. Despite good macrovascular flow, the myocardium can remain hypoperfusion due to poor microvascular perfusion, and this is referred to as 'no-reflow'. Various treatments have been studied with variable success in both prevention and treatment of no-reflow. Areas covered: This review outlines the cutting-edge diagnostic investigations which have been explored in no-reflow, allowing a deeper understanding of mechanism and microvascular pathological processes involved in its genesis. These include utility of novel MRI techniques and perfusion echo in conjunction with traditional approaches. Detailed review has been undertaken of both pharmacological and non-pharmacological techniques to prevent and manage microvascular dysfunction associated with no-reflow. Particular attention was paid to the evolution and successes of various mechanical protection devices. Expert opinion: Most promising innovations in the diagnosis and management of no-reflow are evaluated, and future outlook is explored. Emerging advances in acute coronary syndrome have their findings applied a role in modifying the pathophysiology of no-reflow.

Background Infective endocarditis (IE) is a potentially life-threatening infection of the heart’s endocardial surface. Despite advances in the diagnosis and management of IE, morbidity and mortality remain high. Aim To characterize the demographics, bacteriology and outcomes of IE cases presenting to an Irish tertiary referral centre. Design Retrospective cohort study. Methods Patients were identified using Hospital Inpatient Enquiry and Clinical Microbiology inpatient consult data, from January 2005 to January 2014. Patients were diagnosed with IE using Modified Duke Criteria. Standard Bayesian statistics were employed for analysis and cases were compared to contemporary international registries. Results Two hundred and two patients were diagnosed with IE during this period. Mean age 54 years. Of these, 136 (67%) were native valve endocarditis (NVE), 50 (25%) were prosthetic valve endocarditis (PVE) and 22 (11%) were cardiovascular implantable electronic device-associated endocarditis. Culprit organism was identified in 176 (87.1%) cases and Staphylococcal species were the most common (57.5%). Fifty-nine per cent of NVE required surgery compared to 66% of PVE. Mean mortality rate was 17.3%, with NVE being the lowest (12.5%) and PVE the highest (32%). Increasing age was also associated with increased mortality. Fifty-three (26.2%) patients had embolic complications. Conclusions This Irish cohort exhibited first-world demographic patterns comparable to those published in contemporary international literature. PVE required surgery more often and was associated with higher rates of mortality than NVE. Embolic complications were relatively common and represent important sequelae, especially in the intravenous drug user population. It is also pertinent to aggressively treat older cohorts as they were associated with increased mortality.

Aims: To estimate the prevalence of lameness in sheep transported to meat processing plants in New Zealand, and to identify factors associated with the prevalence of lameness.Methods: The survey wa...

Background Autoimmune disease prevention requires tools to assess an individual's risk of developing a specific disease. One tool is disease-associated autoantibodies, which accumulate in an asymptomatic preclinical period. However, patients sometimes exhibit autoantibodies associated with a different disease classification. When and how these alternative autoantibodies first appear remain unknown. This cross-sectional study characterizes alternative autoimmunity, and associated genetic and environmental factors, in unaffected first-degree relatives (FDRs) of patients, who exhibit increased future risk for the same disease. Methods Samples (n = 1321) from disease-specific autoantibody-positive (aAb+) systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and type 1 diabetes (T1D) patients; and unaffected aAb+ and autoantibody-negative (aAb–) SLE and RA FDRs were tested for SLE, RA, and T1D aAbs, as well as anti-tissue transglutaminase, anti-cardiolipin and anti-thyroperoxidase. FDR SLE and RA genetic risk scores (GRS) were calculated. Findings Alternative autoimmunity occurred in SLE patients (56%) and FDRs (57·4%), RA patients (32·6%) and FDRs (34·8%), and T1D patients (43%). Expanded autoimmunity, defined as autoantibodies spanning at least two other diseases, occurred in 18·5% of SLE patients, 16·4% of SLE FDRs, 7·8% of RA patients, 5·3% of RA FDRs, and 10·8% of T1D patients. SLE FDRs were more likely to have alternative (odds ratio [OR] 2·44) and expanded (OR 3·27) autoimmunity than RA FDRs. Alternative and expanded autoimmunity were associated with several environmental exposures. Alternative autoimmunity was associated with a higher RA GRS in RA FDRs (OR 1·41), and a higher SLE GRS in aAb+ RA FDRs (OR 1·87), but not in SLE FDRs. Interpretation Autoimmunity commonly crosses disease-specific boundaries in systemic (RA, SLE) and organ-specific (T1D) autoimmune diseases. Alternative autoimmunity is more common in SLE FDRs than RA FDRs, and is influenced by genetic and environmental factors. These findings have substantial implications for preclinical disease pathogenesis and autoimmune disease prevention studies. Fund NIH U01AI101981, R01AR051394, U19AI082714, P30AR053483, P30GM103510, U54GM104938, U01AI101934, R01AI024717, U01AI130830, I01BX001834, & U01HG008666.

This publication summarizes discussions that were held during an international expert hearing organized by the German Federal Institute for Risk Assessment (BfR) in Berlin, Germany, in October 2017. The expert hearing was dedicated to providing practical guidance for the measurement of circulating hormones in regulatory toxicology studies. Adequate measurements of circulating hormones have become more important given the regulatory requirement to assess the potential for endocrine disrupting properties for all substances covered by the plant protection products and biocidal products regulations in the European Union (EU). The main focus was the hypothalamus–pituitary–thyroid axis (HPT) and the hypothalamus–pituitary–gonadal axis (HPG). Insulin, insulin-like growth factor 1 (IGF-1), parathyroid hormone (PTH) and vitamins A and D were also discussed. During the hearing, the experts agreed on specific recommendations for design, conduct and evaluation of acceptability of studies measuring thyroid hormones, thyroid stimulating hormone and reproductive hormones as well as provided some recommendations for insulin and IGF-1. Experts concluded that hormonal measurements as part of the test guidelines (TGs) of the Organisation for Economic Co-operation and Development (OECD) were necessary on the condition that quality criteria to guarantee reliability and reproducibility of measurements are adhered to. Inclusion of the female reproductive hormones in OECD TGs was not recommended unless the design of the study was modified to appropriately measure hormone concentrations. The current report aims at promoting standardization of the experimental designs of hormonal assays to allow their integration in OECD TGs and highlights research needs for better identification of endocrine disruptors using hormone measurements.

Diseases of the central nervous system (CNS) remain a significant health, social and economic problem around the globe. The development of therapeutic strategies for CNS conditions has suffered due to a poor understanding of the underlying pathologies that manifest them. Understanding common etiological origins at the cellular and molecular level is essential to enhance the development of efficacious and targeted treatment options. Over the years, neuroinflammation has been posited as a common link between multiple neurological, neurodegenerative and neuropsychiatric disorders. Processes that precipitate neuroinflammatory conditions including genetics, infections, physical injury and psychosocial factors, like stress and trauma, closely link dysregulation in kynurenine pathway (KP) of tryptophan metabolism as a possible pathophysiological factor that ‘fuel the fire’ in CNS diseases. In this study, we aim to review emerging evidence that provide mechanistic insights between different CNS disorders, neuroinflammation and the KP. We provide a thorough overview of the different branches of the KP pertinent to CNS disease pathology that have therapeutic implications for the development of selected and efficacious treatment strategies.

T cells are critical effectors of cancer immunotherapies, but little is known about their gene expression programs in diffuse gliomas. Here, we leverage single-cell RNA-seq to chart the gene expression and clonal landscape of tumor-infiltrating T cells across 31 patients with IDH-wildtype glioblastoma and IDH-mutant glioma. We identify potential effectors of anti-tumor immunity in subsets of T cells that co-express cytotoxic programs and several NK cell genes. Analysis of clonally expanded tumor-infiltrating T cells further identifies the NK gene KLRB1 (encoding CD161) as a candidate inhibitory receptor. Accordingly, genetic inactivation of KLRB1 or antibody-mediated CD161 blockade enhances T cell-mediated killing of glioma cells in vitro and their anti-tumor function in vivo. KLRB1 and its associated transcriptional program are also expressed by substantial T cell populations in other human cancers. Our work provides an atlas of T cells in gliomas and highlights CD161 and other NK cell receptors as immunotherapy targets.

Type 2 diabetes mellitus (T2D) and associated comorbid medical conditions are leading causes of strain on the American health care system. There has been a synchronous rise of obesity to epidemic proportions. If poorly treated, T2D is a scourge for patients, leading to end-organ damage and early mortality. Although T2D is considered best managed with lifestyle modification, medical management, and pharmacotherapy, recent studies have confirmed the superiority of metabolic surgery to conventional treatment algorithms as a path to remission. Increasing access to metabolic surgery will continue to yield benefits to patient health and improve the macroeconomic health of the world.

Introduction During the COVID-19 pandemic, most medical services were shut down and resources were redistributed. Closures included pain management departments where many staff were redeployed. The aim of this study was to assess the impact of COVID-19 on chronic pain services in the Republic of Ireland. Methods An online survey was sent to pain consultants working in public hospitals in the Republic of Ireland between the 22nd and 28th September 2020. Results We received responses from 18 consultants from all 15 public hospitals in the Republic of Ireland with chronic pain services. Procedural volume during lockdown fell to 26% of pre-COVID levels. This had recovered somewhat by the time of the survey to 71%. Similarly, in-person outpatient clinic volume fell to 10% of per-COVID numbers and recovered to 50%. On average, 39% of public hospital activity was made up for by the availability of private hospitals. This varied significantly across the country. The use of telemedicine increased significantly during the pandemic. Before COVID, on average, 13% of outpatient clinic volume was composed of telephone or video consultations. This increased to 46% at the time of the survey. Conclusion This survey of consultant pain physicians in the Republic of Ireland has revealed how chronic pain services have been affected during the pandemic and how they have evolved.

Neuropathic pain is triggered by injury to the somatosensory system, and is one of the most important types of chronic pain. Nevertheless, critical pathophysiological mechanisms that maintain neuropathic pain are poorly understood. Here, we show that neuropathic pain is abrogated when the kynurenine metabolic pathway (KYNPATH) initiated by the enzyme indoleamine 2,3-dioxygenase (IDO) is ablated pharmacologically or genetically. Mechanistically, it was found that IDO upregulation in dendritic cells that accumulate in the dorsal root leptomeninges led to increased levels of kynurenine (Kyn) in the spinal cord, where Kyn is metabolized by astrocytes-expressed kynurenine-3-monooxygenase into a pro-nociceptive metabolite 3-hydroxykynurenine. In conclusion, these data reveal a novel role for KYNPATH as an important factor maintaining neuropathic pain during neuroimmune-glia cells interactions. This novel paradigm offers potential new targets for drug development against this type of chronic pain.

Constrictive pericarditis is a relatively uncommon form of cardiac failure and presents due to scarring and consequent loss of the normal elasticity of the pericardial sac. This results in abnormal/limited ventricular filling and symptoms of heart failure. The aetiology is varied, from infective causes to idiopathic causes, or can manifest after cardiothoracic surgery. This case involves a 46-year-old man presenting with acute group A beta haemolytic streptococcus infection, and over the subsequent 6 months develops constrictive pericarditis due to what is believed to be a rheumatic aetiology. The patient subsequently underwent pericardiectomy and had restoration of normal filling dynamics confirmed on follow-up echocardiography. This case provides a subject matter for the review of the features of constrictive pericarditis and its investigation and management. This case is that it highlights the fact that pericarditis is not a benign condition. Emerging evidence suggests that pericarditis is due to a failure in inflammatory regulatory mechanisms, and patients suffering this condition have a preponderance to ‘autoinflammation’. Pericarditis should be recognised early and treated fully with anti-inflammatory agents.

Acetylcholine receptor (AChR) autoantibodies, found in patients with autoimmune myasthenia gravis (MG), can directly contribute to disease pathology through activation of the classical complement pathway. Accordingly, complement inhibitors are used as a therapeutic strategy, but the response can be heterogeneous even though AChR autoantibodies are present. The mechanisms underlying the variable response are not defined. Yet there is a need for further understanding so that responses can be better predicted. There is a broad spectrum of circulating complement activity levels activity among MG patients. It is not clear whether this activity associates with disease burden or the circulating levels of autoantibodies. We measured complement activity and investigated these associations in MG patients as a means to explore candidate biomarkers. Most study subjects had complement activity within the range defined by healthy controls and no association between this activity and disease burden or AChR autoantibody titer was observed. Assays measuring the complement activating properties of AChR autoantibodies are needed to identifying patients expected to respond to complement inhibitor-based treatments.

BackgroundThe COVID-19 pandemic has had an impact on the mental health of healthcare and social care workers, and its potential effect on suicidal thoughts and behaviour is of particular concern.MethodsThis systematic review identified and appraised the published literature that has reported on the impact of COVID-19 on suicidal thoughts and behaviour and self-harm amongst healthcare and social care workers worldwide up to May 31, 2021.ResultsOut of 37 potentially relevant papers identified, ten met our eligibility criteria. Our review has highlighted that the impact of COVID-19 has varied as a function of setting, working relationships, occupational roles, and psychiatric comorbidities.LimitationsThere have been no completed cohort studies comparing pre- and post-pandemic suicidal thoughts and behaviours. It is possible some papers may have been missed in the search.ConclusionsThe current quality of evidence pertaining to suicidal behaviour in healthcare workers is poor, and evidence is entirely absent for those working in social care. The clinical relevance of this work is to bring attention to what evidence exists, and to encourage, in practice, proactive approaches to interventions for improving healthcare and social care worker mental health.

Background: The COVID-19 pandemic has caused considerable morbidity, mortality and disruption to people’s lives around the world. There are concerns that rates of suicide and suicidal behaviour may rise during and in its aftermath. Our living systematic review synthesises findings from emerging literature on incidence and prevalence of suicidal behaviour as well as suicide prevention efforts in relation to COVID-19, with this iteration synthesising relevant evidence up to 19th October 2020. Method: Automated daily searches feed into a web-based database with screening and data extraction functionalities. Eligibility criteria include incidence/prevalence of suicidal behaviour, exposure-outcome relationships and effects of interventions in relation to the COVID-19 pandemic. Outcomes of interest are suicide, self-harm or attempted suicide and suicidal thoughts. No restrictions are placed on language or study type, except for single-person case reports. We exclude one-off cross-sectional studies without either pre-pandemic measures or comparisons of COVID-19 positive vs. unaffected individuals. Results: Searches identified 6,226 articles. Seventy-eight articles met our inclusion criteria. We identified a further 64 relevant cross-sectional studies that did not meet our revised inclusion criteria. Thirty-four articles were not peer-reviewed (e.g. research letters, pre-prints). All articles were based on observational studies. There was no consistent evidence of a rise in suicide but many studies noted adverse economic effects were evolving. There was evidence of a rise in community distress, fall in hospital presentation for suicidal behaviour and early evidence of an increased frequency of suicidal thoughts in those who had become infected with COVID-19. Conclusions: Research evidence of the impact of COVID-19 on suicidal behaviour is accumulating rapidly. This living review provides a regular synthesis of the most up-to-date research evidence to guide public health and clinical policy to mitigate the impact of COVID-19 on suicide risk as the longer term impacts of the pandemic on suicide risk are researched.

BackgroundOver the past two decades non-communicable diseases (NCDs) have steadily increased as a cause of worldwide disability and mortality with a concomitant decrease in disease burden from communicable, maternal, neonatal and nutritional conditions. Congenital anomalies, the most common NCD affecting children, have recently become the fifth leading cause of under-five mortality worldwide, ahead of other conditions such as malaria, neonatal sepsis and malnutrition. Genetic counseling has been shown to be an effective method to decrease the impact of congenital anomalies and genetic conditions but is absent in almost all sub-Saharan Africa countries. To address this need for counseling services we designed and implemented the first broad-based genetic counseling curriculum in Ethiopia, launching it at St. Paul’s Millennium Medical College (SPHMMC) in Addis Ababa, Ethiopia.MethodsThe curriculum, created by Michigan Medicine and SPHMMC specialists, consisted of medical knowledge and genetic counseling content and was delivered to two cohorts of nurses. Curriculum evaluation consisted of satisfaction surveys and pre- and post-assessments covering medical knowledge and genetic counseling content. Following Cohort 1 training, the curriculum was modified to increase the medical knowledge material and decrease Western genetic counseling principles material.ResultsBoth cohorts reported high levels of satisfaction but felt the workshop was too short. No significant improvements in assessment scores were seen for Cohort 1 in terms of total scores and medical knowledge and genetic counseling-specific questions. Following curriculum modification, improvements were seen in Cohort 2 with an increase in total assessment scores from 63% to 73% (p = 0.043), with medical knowledge-specific questions increasing from 57% to 79% (p = 0.01) with no significant change in genetic counseling-specific scores. Multiple logistic, financial, cultural and systems-specific barriers were identified with recommendations for their consideration presented.ConclusionGenetics medical knowledge of Ethiopian nurses increased significantly following curriculum delivery though difficulty was encountered with Western genetic counseling material.

Contains fulltext : 237675.pdf (Publisher’s version ) (Open Access) In the face of the COVID-19 pandemic, the swift response of mental health research funders and institutions, service providers, and academics enabled progress toward understanding the mental health consequences. Nevertheless, there remains an urgent need to understand the true extent of the short- and long-term effects of the COVID-19 pandemic on mental health, necessitating ongoing research. Although the speed with which mental health researchers have mobilized to respond to the pandemic so far is to be commended, there are valid concerns as to whether speed may have compromised the quality of our work. As the pandemic continues to evolve, we must take time to reflect on our initial research response and collectively consider how we can use this to strengthen ensuing COVID-19 mental health research and our response to future crises. Here, we offer our reflections as members of the UK mental health research community to discuss the continuing progress and persisting challenges of our COVID-19 response, which we hope can encourage reflection and discussion among the wider research community. We conclude that (1) Fragmentation in our infrastructure has challenged the efficient, effective and equitable deployment of resources, (2) In responding quickly, we may have overlooked the role of experts by experience, (3) Robust and open methods may have been compromised by speedy responses, and (4) This pandemic may exacerbate existing issues of inequality in our workforce.

The discovery of radiation has led to many advances. Guidelines have been created to minimize radiation exposure and treatment management following both unintentional and intentional exposure. The effects of radiation exposure on specific tissues varies. Tragic consequences can result, ranging from severe, acute injury to long- lasting effects that present years after the initial exposure. In this chapter we provide observations that demonstrate the importance of understanding guidelines to minimize radioactive exposure and the expectations and treatment management following exposure. For the safety and well-being of patients, health care professionals need to remain well-informed to minimize the risks of this tool.

Self-harm is a major public health concern. In order to respond to self-harm effectively, it is important to understand the factors associated with self-harm with and without suicidal intent. To this end, we investigated psychological factors selected from the Integrated Motivational-Volitional (IMV) model of suicidal behaviour in individuals who had recently been admitted to hospital for self-harm, with the aim of examining the characteristics of those who expressed intent to die versus those without suicidal intent. Individuals (n = 500, 60.6% female) admitted to two hospitals in central Scotland following self-harm with (suicide attempt [SA] group, n = 336) or without (non-suicidal self-harm [NSSH] group, n = 164) suicidal intent completed a range of psychological measures. Over half of the participants reported previous episodes of self-harm (SA, n = 239, 71.1%; NSSH, n = 91, 55.5%). Univariate analyses revealed that the SA and NSSH groups differed on some of the psychological measures with higher depressive symptoms, defeat, entrapment, acquired capability and impulsivity in the SA compared to the NSSH group. In the multivariate model, suicidal ideation, defeat, internal entrapment and perceived burdensomeness independently differentiated between the groups. These findings highlight the complex profiles of individuals presenting at hospital with self-harm and emphasise the need to investigate differences between subtypes of self-harm in order to support individuals optimally. Applying frameworks such as the IMV model to further understanding of self-harm might assist in the development of targeted psychological interventions to reduce risk of repeat self-harm or suicide.

Substance abuse is an established precursor to violent and non-violent crimes. Typical violent crimes are usually related to narcotics and alcohol sale, while non-violent crimes are related to the purchase. This study investigates correlations between substance abuse and crime rate in the United States. Data from the Federal Bureau of Investigation’s Uniform Crime Reports (UCR) Program was used in the study to compare drug usage, alcohol consumption, and crime rate. The researchers used Tableau (Visualization Application) to analyze the data and visual the comparison between the three entities. The main goal of the study was to seek a correlation that could provide insight to the increase in crime rate when people abuse substances.

BackgroundThe effects of coronavirus disease 2019 (COVID-19) on the population's mental health and well-being are likely to be profound and long lasting.AimsTo investigate the trajectory of mental health and well-being during the first 6 weeks of lockdown in adults in the UK.MethodA quota survey design and a sampling frame that permitted recruitment of a national sample was employed. Findings for waves 1 (31 March to 9 April 2020), 2 (10 April to 27 April 2020) and 3 (28 April to 11 May 2020) are reported here. A range of mental health factors was assessed: pre-existing mental health problems, suicide attempts and self-harm, suicidal ideation, depression, anxiety, defeat, entrapment, mental well-being and loneliness.ResultsA total of 3077 adults in the UK completed the survey at wave 1. Suicidal ideation increased over time. Symptoms of anxiety, and levels of defeat and entrapment decreased across waves whereas levels of depressive symptoms did not change significantly. Positive well-being also increased. Levels of loneliness did not change significantly over waves. Subgroup analyses showed that women, young people (18–29 years), those from more socially disadvantaged backgrounds and those with pre-existing mental health problems have worse mental health outcomes during the pandemic across most factors.ConclusionsThe mental health and well-being of the UK adult population appears to have been affected in the initial phase of the COVID-19 pandemic. The increasing rates of suicidal thoughts across waves, especially among young adults, are concerning.

Abstract. Background: Infectious disease-related public health emergencies (epidemics) may increase suicide risk, and high-quality evidence is needed to guide an international response. Aims: We investigated the potential impacts of epidemics on suicide-related outcomes. Method: We searched MEDLINE, EMBASE, PsycInfo, CINAHL, Scopus, Web of Science, PsyArXiv, medRxiv, and bioRxiv from inception to May 13–16, 2020. Inclusion criteria: primary studies, reviews, and meta-analyses; reporting the impact of epidemics; with a primary outcome of suicide, suicidal behavior, suicidal ideation, and/or self-harm. Exclusion criteria: not concerned with suicide-related outcomes; not suitable for data extraction. PROSPERO registration: #CRD42020187013. Results: Eight primary papers were included, examining the effects of five epidemics on suicide-related outcomes. There was evidence of increased suicide rates among older adults during SARS and in the year following the epidemic (possibly motivated by social disconnectedness, fears of virus infection, and concern about burdening others) and associations between SARS/Ebola exposure and increased suicide attempts. A preprint study reported associations between COVID-19 distress and past-month suicidal ideation. Limitations: Few studies have investigated the topic; these are of relatively low methodological quality. Conclusion: Findings support an association between previous epidemics and increased risk of suicide-related outcomes. Research is needed to investigate the impact of COVID-19 on suicide outcomes.

Introduction In 2019, the national center for pharmacoeconomics (NCPE) released a managed access protocol (MAP) for the prescribing of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) in Ireland. To be eligible for a PCSK9i, patients must have had a myocardial infarction or coronary artery bypass grafting, LDL of >4.0 mmol/L, treated with high dose statin and ezetimibe. In contrast, the 2019 ESC/EAS guidelines on the management of dyslipidemias recommend that patients at ‘very high risk’ with an LDL-C of >1.4 mmol/L on a maximally tolerated dose of a statin and ezetimibe, be considered for PCSK9i. We aimed to define the proportion of patients who are suitable for a PCSK9i following completion of cardiac rehabilitation based on these criteria. Method We retrospectively analysed data on patients undergoing cardiac rehabilitation in our center from January 2018 to December 2019. We then applied the NCPE MAP and the ESC/EAS criteria to assess eligibility for a PCSK9i in the cohort. ‘Very high risk’ was defined as documented atherosclerotic coronary artery disease as per ESC dyslipidaemias guidelines. Results The analysis includes 299 patients, who had complete lipid profiles at baseline and 6 months of follow-up, and who have a history of coronary artery disease. Baseline characteristics, mean age 62.5 years, 76% male. 202 (67.6%) patients had a history of MI or CABG making them eligible for a PCSK9i based on NCPE clinical criteria. Only 1 patient (0.5%) in this group was on a high dose statin, ezetimibe and had a 6 month LDL-C of >4.0 mmol/L making them eligible for a PCSK9i as per NCPE MAP criteria. In contrast to the NCPE MAP criteria all 299 patients were deemed eligible for a PCSK9i based on ESC/EAS clinical criteria of ‘very high risk’. 160 patients (53.5%) had an LDL-C level >1.4 mmol/L at 6 months despite maximally tolerated statin therapy, mean LDL-C 2.29 mmol/L. Only a minority of patients in this cohort were on ezetimibe, 30/160 (18.7%), however previous studies have shown that on average ezetimibe reduces LDL-C by 25% in combination with statins. Based on this, we sought to define the cohort who would potentially be eligible if they had been on ezetimbe and experienced a 25% reduction in LDL-C. 81/160 patients had a 6-monthly LDL-C >1.8 mmol/L and were on high dose statin therapy, we included these patients in our final analysis, resulting in 37.1% (111/299) patients in our cohort being eligible for a PCSK9i based on current ESC guidelines, results are summarized in figure 1. Discussion Our results highlight the discrepancy between current ESC/EAS guidelines and the reimbursement criteria for PCSK9i in Ireland. This discrepancy results in minimal patients with coronary artery disease being eligible for a PCSK9i in Ireland. The results also highlight that a significant proportion of patients in clinical practice do not meet LDL-C goals post cardiac rehabilitation, these targets should be met in order to reduce future cardiovascular risk and improve outcomes for patients.

Stress and Hypothalamic–Pituitary–Adrenal (HPA) axis dysregulation play a major role in various pathophysiological processes associated with both mood disorders and suicidal behavior. We conducted a systematic review with the primary aim of clarifying the nature and extent of HPA axis activity and suicidal behavior. The second aim of this review was to investigate whether potential biomarkers related to HPA axis abnormalities act as individual susceptibility factors for suicide. The PRISMA statement for reporting systematic reviews was used. Only articles published in English peer-reviewed journals were considered for possible inclusion; we excluded case reports, meta-analyses, and systematic reviews, and studies that did not clearly report statistical analysis, diagnostic criteria, or the number of patients included. Overall, 36 articles on HPA axis and suicide risk met inclusion criteria and were reviewed. Studies that investigated tests detecting biomarkers and the role of early life stressors in suicide risk were also included. We found that HPA axis activity is involved in suicide risk, regardless of the presence or absence of psychiatric conditions. The HPA axis abnormalities, mainly characterized by hyperactivity of the HPA axis, may exert an important modulatory influence on suicide risk. Impaired stress response mechanisms contribute to suicide risk. Targeting HPA axis dysregulation might represent a fruitful strategy for identifying new treatment targets and improving suicide risk prediction.

ObjectiveTo identify candidate biomarkers associated with neuromyelitis optica spectrum disorder (NMOSD) using high-throughput technologies that broadly assay the concentrations of serum analytes and frequencies of immune cell subsets.MethodsSera, peripheral blood mononuclear cells (PBMCs), and matched clinical data from participants with NMOSD and healthy controls (HCs) were obtained from the Collaborative International Research in Clinical and Longitudinal Experience Study NMOSD biorepository. Flow cytometry panels were used to measure the frequencies of 39 T-cell, B-cell, regulatory T-cell, monocyte, natural killer (NK) cell, and dendritic cell subsets in unstimulated PBMCs. In parallel, multiplex proteomics assays were used to measure 46 serum cytokines and chemokines in 2 independent NMOSD and HC cohorts. Multivariable regression models were used to assess molecular and cellular profiles in NMOSD compared with HC.ResultsNMOSD samples had a lower frequency of CD16+CD56+ NK cells. Both serum cohorts and multivariable logistic regression revealed increased levels of B-cell activating factor associated with NMOSD. Interleukin 6, CCL22, and CCL3 were also elevated in 1 NMOSD cohort of the 2 analyzed. Multivariable linear regression of serum analyte levels revealed a correlation between CX3CL1 (fractalkine) levels and the number of days since most recent disease relapse.ConclusionsIntegrative analyses of cytokines, chemokines, and immune cells in participants with NMOSD and HCs provide congruence with previously identified biomarkers of NMOSD and highlight CD16+CD56+ NK cells and CX3CL1 as potential novel biomarker candidates.