Initiation of opioid agonist therapy after hospital visits for opioid poisonings in Ontario.

BACKGROUND: Emergency department visits and hospital admissions for opioid toxicity are opportunities to initiate opioid agonist therapy (OAT), which reduces morbidity and mortality in patients with opioid use disorder (OUD). The study objectives were to evaluate OAT initiation rates after a hospital encounter for opioid toxicity in Ontario, Canada, and determine whether publication of a 2018 Canadian OUD management guideline was associated with increased initiation. METHODS: We conducted a retrospective, population-based serial cross-sectional study of hospital encounters for opioid toxicity among patients with OUD between Jan. 1, 2013, and Mar. 31, 2020, in Ontario, Canada. The primary outcome was OAT initiation (methadone, buprenorphine-naloxone, or slow-release oral morphine) within 7 days of discharge, measured quarterly. We examined the impact of the release of the OUD management guideline on OAT initiation rates using Autoregressive Integrated Moving Average models. RESULTS: Among 20 702 hospital visits for opioid toxicity among patients with OUD, the median age was 35 years, and 65.1% were male. Over the study period, the percentage of visits leading to OAT initiation within 7 days rose from 1.7% or less (Q1 2013) to 5.6% (Q1 2020); however, the publication of the Canadian OUD management guideline was not associated with a significant increase in these rates (0.14% slope change, 95% confidence interval -0.11% to 0.38%; p = 0.3). INTERPRETATION: Among hospital encounters for opioid toxicity, despite rising prevalence over time, only 1 in 18 patients were dispensed OAT within a week of discharge in early 2020. These findings highlight missed opportunities to initiate therapies proven to reduce mortality in patients with OUD.

Chronic running-wheel exercise from adolescence leads to increased anxiety and depression-like phenotypes in adulthood in rats: Effects on stress markers and interaction with BDNF Val66Met genotype.

Exercise has been shown to be beneficial in reducing symptoms of affective disorders and to increase the expression of brain-derived neurotrophic factor (BDNF). The BDNF Val66Met polymorphism is associated with reduced activity-dependent BDNF release and increased risk for anxiety and depression. Male and female Val66Met rats were given access to running wheels from 3 weeks of age and compared to sedentary controls. Anxiety- and depression-like behaviors were measured in adulthood using the elevated plus maze (EPM), open field (OF), and forced swim test (FST). Expression of BDNF and a number of stress-related genes, the glucocorticoid receptor (Nr3c1), serum/glucocorticoid-regulated kinase 1 (Sgk1), and FK506 binding protein 51 (Fkbp5) in the hippocampus were also measured. Rats given access to running wheels developed high levels of voluntary exercise, decreased open-arm time on the EPM and center-field time in the OF, reduced overall exploratory activity in the open field, and increased immobility time in the FST with no differences between genotypes. Chronic exercise induced a significant increase in Bdnf mRNA and BDNF protein levels in the hippocampus with some of these effects being genotype specific. Exercise decreased the expression of Nr3c1 and Sgk1, but increased the expression of Fkbp5. These results suggest that chronic running-wheel exercise from adolescence increased anxiety and depression-like phenotypes in adulthood, independent of BDNF Val66Met genotype. Further studies are required to confirm that increased indices of anxiety-like behavior are independent from reduced overall locomotor activity.

A visually striking case of primary acrocyanosis: A rare cause of the blue digit.

Cold environments can trigger a variety of conditions, which, in their acute phase often present to the Emergency Department. Primary acrocyanosis is a distinct, rare condition which may be missed resulting in misdiagnosis and mismanagement. Primary acrocyanosis is a peripheral vascular disorder defined by painless, symmetrical discoloration of the distal appendages and uniquely characterized by persistence of the skin color changes after cold exposure. We present a case of a 24-year-old female who presented to the Emergency Department with peripheral cyanosis after cold exposure and was eventually diagnosed with primary acrocyanosis by Rheumatology. The prognosis for primary acrocyanosis is quite good in comparison to other acrosyndromes and once secondary causes of acrocyanosis have been ruled, out can be managed conservatively with lifestyle modifications and potential follow-up with Rheumatology.

Influence of two bulge loops on the stability of RNA duplexes.

Fifty-three RNA duplexes containing two single nucleotide bulge loops were optically melted in 1 M NaCl in order to determine the thermodynamic parameters ΔH°, ΔS°, ΔG°37, and TM for each duplex. Because of the large number of possible combinations and lack of sequence effects observed previously, we limited our initial investigation to adenosine bulges, the most common naturally occurring bulge. For example, the following duplexes were investigated: 5'GGCAXYAGGC/3'CCG YX CCG, 5'GGCAXY GCC/3'CCG YXACGG, and 5'GGC XYAGCC/3'CCGAYX CGG. The identity of XY (where XY are Watson-Crick base pairs) and the total number of base pairs in the terminal and central stems were varied. As observed for duplexes with a single bulge loop, the effect of the two bulge loops on duplex stability is primarily influenced by non-nearest neighbor interactions. In particular, the stability of the stems influences the destabilization of the duplex by the inserted bulge loops. The model proposed to predict the influence of multiple bulge loops on duplex stability suggests that the destabilization of each bulge is related to the stability of the adjacent stems. A database of RNA secondary structures was examined to determine the naturally occurring abundance of duplexes containing multiple bulge loops. Of the 2000 examples found in the database, over 65% of the two bulge loops occur within 3 base pairs of each other. A database of RNA three-dimensional structures was examined to determine the structure of duplexes containing two single nucleotide bulge loops. The structures of the bulge loops are described.

Non-nearest-neighbor dependence of stability for group III RNA single nucleotide bulge loops.

Thirty-five RNA duplexes containing single nucleotide bulge loops were optically melted and the thermodynamic parameters for each duplex determined. The bulge loops were of the group III variety, where the bulged nucleotide is either a AG/U or CU/G, leading to ambiguity to the exact position and identity of the bulge. All possible group III bulge loops with Watson-Crick nearest-neighbors were examined. The data were used to develop a model to predict the free energy of an RNA duplex containing a group III single nucleotide bulge loop. The destabilization of the duplex by the group III bulge could be modeled so that the bulge nucleotide leads to the formation of the Watson-Crick base pair rather than the wobble base pair. The destabilization of an RNA duplex caused by the insertion of a group III bulge is primarily dependent upon non-nearest-neighbor interactions and was shown to be dependent upon the stability of second least stable stem of the duplex. In-line structure probing of group III bulge loops embedded in a hairpin indicated that the bulged nucleotide is the one positioned further from the hairpin loop irrespective of whether the resulting stem formed a Watson-Crick or wobble base pair. Fourteen RNA hairpins containing group III bulge loops, either 3' or 5' of the hairpin loop, were optically melted and the thermodynamic parameters determined. The model developed to predict the influence of group III bulge loops on the stability of duplex formation was extended to predict the influence of bulge loops on hairpin stability.

An Autopsy Checklist: A Monitor of Safety and Risk Management.

Any autopsy has safety and risk management issues, which can arise in the preautopsy, autopsy, and postautopsy phases. The London Health Sciences Department of Pathology and Laboratory Medicine Autopsy Checklist was developed to address these issues. The current study assessed 1 measure of autopsy safety: the effectiveness of the checklist in documenting pathologists' communication of the actual or potential risk of blood-borne infections to support staff. Autopsy checklists for cases done in 2012 and 2013 were reviewed. The frequency of communication, as recorded in checklists, by pathologists to staff of previously diagnosed blood-borne infections (hepatitis B/C and human immunodeficiency virus) or the risk of infection based on lifestyle (eg, intravenous drug abuse) was tabulated. These data were compared with medical histories of the deceased and circumstances of their deaths described in the final autopsy reports. Information about blood-borne infections was recorded less frequently in the checklists compared with the final reports. Of 4 known human immunodeficiency virus cases, there was no checklist documentation in 3. All 11 hand injuries were documented. None of these cases had known infectious risks. The Autopsy Checklist is a standardized means of documenting safety and risk issues arising during the autopsy process, but its effectiveness relies on accurate completion.

Barriers and facilitators to the implementation of rapid HIV testing in Canadian Emergency Departments: a mixed methods study.

OBJECTIVES: 1 in 7 Canadians with Human Immunodeficiency Virus (HIV) do not know their status. Patients at increased risk of HIV routinely access the emergency department (ED), yet few are tested, representing a missed opportunity for diagnosis and linkage-to-care. Rapid HIV testing provides reliable results within the same ED encounter but is not routinely implemented. The objective of this study was to identify barriers and facilitators to rapid HIV testing in Ontario EDs. METHODS: We employed a mixed-methods, convergent, parallel design study including online surveys and semi-structured interviews of physicians, nurses, and allied health across four hospitals in Toronto and Thunder Bay, Ontario. Data were analyzed in equal priority using descriptive statistics for quantitative data and thematic analysis for qualitative data guided by the Theoretical Domains framework and Capability, Opportunity, Motivation Behaviour change model. RESULTS: Among 187 survey respondents, 150 (80%) felt implementing rapid HIV testing would be helpful in the ED. Facilitators included availability of resources to link patients to care after testing (71%), testing early in patient encounters (41%), and having dedicated staff with lived experience support testing (34%). Motivation to offer testing included opportunities to support an underserved population (66%). Challenges to implementation included limited time during ED patient encounters (51%) and a lack of knowledge around HIV testing (42%) including stigma. Interview themes confirmed education, and integration of people with lived experience being essential to provide rapid HIV testing and linkage-to-care in the ED. CONCLUSIONS: Implementation of rapid HIV testing in the ED is perceived to be important irrespective of practice location or profession. Intrinsic motivations to support underserved populations and providing linkage-to-care are novel insights to facilitate testing in the ED. Streamlined implementation, including clear testing guidelines and improved access to follow-up care, is felt to be necessary for implementation.

ABSTRAIT: OBJECTIFS: 1 Canadien sur 7 atteint du virus de l'immunodéficience humaine (VIH) ne connaît pas son statut. Les patients présentant un risque accru de contracter le VIH ont régulièrement accès au service des urgences (SU), mais peu d'entre eux sont testés, ce qui représente une occasion manquée de diagnostic et de lien avec les soins. Le dépistage rapide du VIH fournit des résultats fiables dans la même situation d'urgence, mais n'est pas systématiquement mis en œuvre. L'objectif de cette étude était d'identifier les obstacles et les facilitateurs au dépistage rapide du VIH dans les urgences de l'Ontario. MéTHODES: Nous avons utilisé une étude de conception mixte, convergente et parallèle, y compris des sondages en ligne et des entrevues semi-structurées auprès de médecins, d'infirmières et d'auxiliaires de la santé dans quatre hôpitaux de Toronto et de Thunder Bay, en Ontario. Les données ont été analysées en priorité égale à l'aide de statistiques descriptives pour les données quantitatives et d'analyses thématiques pour les données qualitatives guidées par le cadre des domaines théoriques et le modèle de changement de capacité, d'opportunité et de motivation. RéSULTATS: Parmi 187 répondants au sondage, 150 (80 %) étaient d'avis que la mise en œuvre d'un dépistage rapide du VIH serait utile à l'urgence. Les facilitateurs comprenaient la disponibilité de ressources pour lier les patients aux soins après le test (71 %), le dépistage précoce lors des rencontres avec les patients (41 %) et la présence d'un personnel dévoué avec des tests de soutien de l'expérience vécue (34 %). La motivation à offrir des tests comprenait des occasions de soutenir une population mal desservie (66 %). Les difficultés de mise en œuvre comprenaient un temps limité pendant les rencontres avec les patients aux urgences (51 %) et un manque de connaissances sur le dépistage du VIH (42 %), y compris la stigmatisation. Les thèmes des entrevues ont confirmé que l'éducation et l'intégration des personnes ayant une expérience vécue sont essentielles pour fournir un dépistage rapide du VIH et un lien avec les soins aux urgences. CONCLUSIONS: La mise en œuvre du dépistage rapide du VIH aux urgences est perçue comme importante, quel que soit le lieu de pratique ou la profession. Les motivations intrinsèques à soutenir les populations mal desservies et à fournir un lien avec les soins sont de nouvelles idées pour faciliter les tests à l'urgence. Une mise en œuvre simplifiée, y compris des lignes directrices claires sur les tests et un meilleur accès aux soins de suivi, est jugée nécessaire pour la mise en œuvre.

Predictors of psychological distress during self-isolation.

OBJECTIVES: Global pandemics, such as the current COVID-19 pandemic, are predicted to increase in prevalence in the future. Transmission suppression techniques such as social distancing and stay-at-home restrictions have introduced an abundance of additional stressors while simultaneously reducing our capacity to cope with stress, thus increasing the collective burden of the pandemic. Numerous psychosocial factors have been identified to protect against distress in difficult circumstances. However, it is unknown whether these factors will continue to be protective in the pandemic context. DESIGN: The aim of the current study was to determine whether locus of control (LOC), coping style or self-compassion were debilitating or protective factors towards psychological well-being (depression, anxiety, stress and positive and negative affect) during the COVID-19 pandemic. METHODS: In the current study, Australian adults (N = 176) completed a longitudinal online survey (two time points, 2 weeks apart) incorporating measures of demographics, locus of control, coping, self-compassion (measured at T1), depression, anxiety, stress and positive and negative affect (measured at T1 and T2) throughout June-August 2020, during the height of lockdown in Australia. RESULTS: Multiple regression analyses suggested that avoidant coping was predictive of increases in stress and negative affect across time points. Additionally, self-compassion was predictive of increased positive affect across time points. CONCLUSIONS: These results suggest that the pandemic context represents a unique stressor, demanding a distinctive set of strategies and psychosocial characteristics to cope. Interventions targeted at reducing avoidant coping behaviours and promoting self-compassion may contribute to improvements in psychological well-being during the COVID-19 pandemic as well as future pandemics.

Treatment Outcomes for Rheumatoid Arthritis-Associated Interstitial Lung Disease: A Real-World, Multisite Study of the Impact of Immunosuppression on Pulmonary Function Trajectory.

BACKGROUND: Rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) is common in patients with RA and leads to significant morbidity and mortality. No randomized, placebo-controlled data are available that support the role of immunosuppression to treat RA-associated ILD, despite being widely used in clinical practice. RESEARCH QUESTION: How does immunosuppression impact pulmonary function trajectory in a multisite retrospective cohort of patients with RA-associated ILD? STUDY DESIGN AND METHODS: Patients with RA who started treatment for ILD with mycophenolate, azathioprine, or rituximab were identified retrospectively from five ILD centers. Change in lung function before and after treatment was analyzed using a linear spline mixed-effect model with random intercept. Prespecified secondary analyses examined the impact of radiologic pattern of ILD (ie, usual interstitial pneumonia [UIP] vs non-UIP) on treatment trajectory. RESULTS: Two hundred twelve patients were included in the analysis: 92 patients (43.4%) were treated with azathioprine, 77 patients (36.3%) were treated with mycophenolate mofetil, and 43 patients (20.3%) were treated with rituximab. In the combined analysis of all three agents, an improvement in FVC % predicted was found after 12 months of treatment compared with the potential 12-month response without treatment (+3.90%; P ≤ .001; 95% CI, 1.95-5.84). Diffusing capacity of the lungs for carbon monoxide (Dlco) % predicted also improved at 12 months (+4.53%; P ≤ .001; 95% CI, 2.12-6.94). Neither the UIP pattern of ILD nor choice of immunosuppressive agent significantly impacted the pulmonary function trajectory on immunosuppression. INTERPRETATION: Immunosuppression was associated with an improved trajectory in FVC and Dlco compared with the pretreatment pulmonary function trajectory. Prospective, randomized trials are required to validate these findings.

Behavioral phenotyping of a rat model of the BDNF Val66Met polymorphism reveals selective impairment of fear memory.

The common brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is associated with reduced activity-dependent BDNF release and increased risk for anxiety disorders and PTSD. Here we behaviorally phenotyped a novel Val66Met rat model with an equivalent valine to methionine substitution in the rat Bdnf gene (Val68Met). In a three-day fear conditioning protocol of fear learning and extinction, adult rats with the Met/Met genotype demonstrated impaired fear memory compared to Val/Met rats and Val/Val controls, with no genotype differences in fear learning or extinction. This deficit in fear memory occurred irrespective of the sex of the animals and was not seen in adolescence (4 weeks of age). There were no changes in open-field locomotor activity or anxiety measured in the elevated plus maze (EPM) nor in other types of memory measured using the novel-object recognition test or Y-maze. BDNF exon VI expression in the dorsal hippocampus was higher and BDNF protein level in the ventral hippocampus was lower in female Val/Met rats than female Val/Val rats, with no other genotype differences, including in total BDNF, BDNF long, or BDNF IV mRNA. These data suggest a specific role for the BDNF Met/Met genotype in fear memory in rats. Further studies are required to investigate gene-environment interactions in this novel animal model.

Clinical characteristics and choices regarding risk-reducing surgery in BRCA mutation carriers.

BACKGROUND/AIMS: BRCA mutation carriers have a high lifetime risk of developing breast and ovarian malignancies. As genetic testing becomes widely available, preventative measures are a choice. We evaluated the characteristics of BRCA mutation carriers who chose prophylactic surgery (PS) compared to those who opted for surveillance. METHODS: A retrospective chart review of patients with a mutation in the BRCA1 or BRCA2 genes was performed. RESULTS: Ninety women were included, of whom 46 (51%) underwent PS. They were more likely to be a BRCA2 mutation carrier, parous, married, employed, and had a prior history of breast cancer. PS included 39 bilateral salpingo-oophorectomies and 13 mastectomies. Pathology was typically benign; however, 15% showed ductal carcinoma in situ of the breast, 8% reported infiltrating ductal carcinoma of the breast, 3% was adenocarcinoma of the fallopian tube, and 3% was adenocarcinoma of the ovary. CONCLUSION: It is notable that BRCA1 mutation carriers were less inclined to elect for PS. Evaluating the reasons for pursuing PS among women with a BRCA mutation is necessary and will require a larger data set. Long-term follow-up is required to describe the potential side effects of PS on quality of life.

Sleep-dependent enhancement of emotional memory in early childhood.

Naps in early childhood support declarative memory consolidation. However, emotional memories are unique in the neural basis of encoding as well as the sleep physiology underlying consolidation. Specifically, while consolidation of declarative memories has been associated with slow wave sleep, a prevailing theory suggests that REM sleep is necessary for consolidation of memories with emotional valence. Thus, we presented children (34-64 months) with faces paired with mean or nice descriptions. There were no significant main effects of emotional valence on recognition memory. Change in memory accuracy also did not differ when probed after a nap compared to the change in memory accuracy after an interval awake. However, when memory was probed again following overnight sleep, the change in memory accuracy was greater if the child napped the previous day. Greater nap slow wave activity was associated with greater memory decay during the nap. Yet nap slow wave activity also predicted greater overnight improvement in memory. These results suggest that sleep bouts can interact to benefit memory in early childhood.

Seasonal influenza vaccination coverage among local health department personnel in North Carolina, 2007-2008.

BACKGROUND: National estimates indicate that a low proportion of institutional and hospital-based healthcare workers obtain influenza vaccine. Information on seasonal influenza vaccination coverage in county-level public healthcare workers is lacking, including knowledge, attitudes, and perceptions regarding seasonal influenza vaccination. PURPOSE: The purpose of this study was to investigate the percentage of employees receiving seasonal influenza vaccination, including perceptions and attitudes of employees of 17 health agencies in a 25-county region in eastern, rural North Carolina. METHODS: Prior to the H1N1 pandemic, an 18-item voluntary, self-administered survey (pen-and-paper or web-based) was provided to 1653 employees of 15 local health departments and two health jurisdictions in 25 counties of eastern North Carolina in May 2008, obtaining vaccination information for 2007-2008 influenza season. Analysis was conducted in summer 2008 and October 2009. RESULTS: A total of 1209 respondents completed the survey (73% response proportion). Seventy-two percent of valid survey respondents voluntarily received free influenza vaccine for the 2007-2008 season. Gender, ethnicity, and >or=10 years working in public health were significantly associated with obtaining vaccine. Using logistic regression, positive significant predictors were having a vaccination last year and perceived importance of vaccine. Cost to obtain vaccination was a deterrent. The most common reason stated was to protect people (66%), while the most common reason for not receiving the vaccine was belief that the vaccine can cause illness (19%). Almost 60% of employees reported support for a mandatory seasonal influenza vaccination program at their health department. CONCLUSIONS: The percentage of county public health workers obtaining seasonal influenza vaccination is almost twice that of healthcare workers in other settings. This study provides evidence that efforts may be successful in increasing influenza vaccination coverage of healthcare workers.