Outcomes Following Pedestal Cup Reconstruction of (Impending) Pathological Fractures of the Acetabulum due to Metastatic Bone Disease.

Management of periacetabular metastatic bone disease (MBD) is challenging, specifically if associated with bone loss or fracture. The aim of this study was to evaluate the complications and outcomes after undergoing peri-acetabular reconstruction using an 'ice-cream cone' pedestal cup endoprostheses for the most severe cases of (impending) pathological acetabular fractures. Fifty cases with severe periacetabular disease were identified. Acetabular defects were classified using the Metastatic Acetabular Classification (MAC). Pre- and post-operative mobility was assessed using the Eastern Cooperative Oncology Group (ECOG) Performance Status. Pain levels were assessed using a verbal rating scale. Surgical complications and patient survival were analysed; the Prognostic Immune Nutritional Index (PINI) was applied retrospectively to survival. There were 32 females and 18 males with a median age of 65 (41-88). Median post-operative follow-up was 16 months (IQR 5.5-28.5 months). Thirty-nine had complete, and 11, impending pathological fractures. The observed five-year survival was 19%, with a median survival of 16 months (IQR 5.8-42.5 months). Significantly worse survival was observed with PINI scores < 3.0 (p = 0.003). Excluding three perioperative deaths, 13 complications occurred in 12 patients: Implant failure in six patients (four aseptic loosening, one dislocation and one infection). At the final follow-up, mobility and pain levels were improved in 85% and 100%, respectively. Reconstruction of significant pelvic MBD with the 'ice-cream cone' reduces pain and improves mobility. Whilst the mortality rate is high, it remains a reasonable option for bed-bound, immobile patients. We advocate the use of an 'ice-cream cone' prosthesis for selected patients balancing the reported risks with the observed benefits. Supplementary Information: The online version contains supplementary material available at 10.1007/s13193-024-01917-x.

Management of chemotherapy hypersensitivity reactions and desensitization: An SGO clinical practice statement.

OBJECTIVE: The goal of this practice statement is to help members and their multidisciplinary teams recognize infusion reactions and hypersensitivity reactions in the clinical setting. It will provide recommendations to help guide response to reactions and desensitization when appropriate, to promote safe use of chemotherapeutic agents among all providers in the delivery process. METHODS: A multi-disciplinary team of healthcare professionals from the Society of Gynecologic Oncology Education Committee collaborated to review peer reviewed literature and guidelines to develop a practice statement on the management of chemotherapy hypersensitivity reactions and desensitization regimens. RESULTS: There is always potential for a patient to have a reaction to any medication, with both infusion reactions and hypersensitivity reactions potentially occurring in the treatment of gynecologic cancers. Premedication to prevent reactions should be given at least prior to infusion for regimens that include the most common agents associated with reactions. At the time when reaction is occurring it might be difficult to distinguish between an infusion reaction versus true hypersensitivity given the similarities in signs and symptoms, therefore it is important that orders to manage reactions be included in every chemotherapy order set so the infusion nurse can provide immediate interventions while waiting for the provider to arrive to assess the patient. Desensitization is a potential option to allow the patient to continue to receive the offending agent. While a variety of desensitization regimens have been presented in the literature, the goal is to minimize steps and variability to decrease opportunity for errors during chemotherapy preparation or administration. CONCLUSION: Incorporating a review of the literature and clinical experience from the SGO Education Committee, this paper provides an overview of current approaches for prevention and management of reactions to commonly used chemotherapy agents for gynecologic cancers.

Forward hysteresis and Hopf bifurcation in an Npzd model with application to harmful algal blooms.

Nutrient-Phytoplankton-Zooplankton-Detritus (NPZD) models, describing the interactions between phytoplankton, zooplankton systems, and their ecosystem, are used to predict their ecological and evolutionary population dynamics. These organisms form the base two trophic levels of aquatic ecosystems. Hence understanding their population dynamics and how disturbances can affect these systems is crucial. Here, starting from a base NPZ modeling framework, we incorporate the harmful effects of phytoplankton overpopulation on zooplankton-representing a crucial next step in harmful algal bloom (HAB) modeling-and split the nutrient compartment to formulate an NPZD model. We then mathematically analyze the NPZ system upon which this new model is based, including local and global stability of equilibria, Hopf bifurcation condition, and forward hysteresis, where the bi-stability occurs with multiple attractors. Finally, we extend the threshold analysis to the NPZD model, which displays both forward hysteresis with bi-stability and Hopf bifurcation under different parameter regimes. We also examine ecological implications after incorporating seasonality and ecological disturbances. Ultimately, we quantify ecosystem health in terms of the relative values of the robust persistence thresholds for phytoplankton and zooplankton and find (i) ecosystems sufficiently favoring phytoplankton, as quantified by the relative values of the plankton persistence numbers, are vulnerable to both HABs and (local) zooplankton extinction (ii) even healthy ecosystems are extremely sensitive to nutrient depletion over relatively short time scales.

A national assessment of urban forest carbon storage and sequestration in Canada.

During a time of rapid urban growth and development, it is becoming ever more important to monitor the carbon fluxes of our cities. Unlike Canada's commercially managed forests that have a long history of inventory and modelling tools, there is both a lack of coordinated data and considerable uncertainty on assessment procedures for urban forest carbon. Nonetheless, independent studies have been carried out across Canada. To improve upon Canada's federal government reporting on carbon storage and sequestration by urban forests, this study builds on existing data to develop an updated assessment of carbon storage and sequestration for Canada's urban forests. Using canopy cover estimates derived from ortho-imagery and satellite imagery ranging from 2008 to 2012 and field-based urban forest inventory and assessment data from 16 Canadian cities and one US city, this study found that Canadian urban forests store approximately 27,297.8 kt C (- 37%, + 45%) in above and belowground biomass and sequester approximately 1497.7 kt C year-1 (- 26%, + 28%). In comparison with the previous national assessment of urban forest carbon, this study suggested that in urban areas carbon storage has been overestimated and carbon sequestration has been underestimated. Maximizing urban forest carbon sinks will contribute to Canada's mitigation efforts and, while being a smaller carbon sink compared to commercial forests, will also provide important ecosystem services and co-benefits to approximately 83% of Canadian people.

Rapid, sensitive, and specific, low-resource molecular detection of Hendra virus.

Efficient and accurate diagnosis of Hendra virus (HeV), a biosafety level 4 (BSL-4) pathogen and zoonotic disease, is of primary importance for surveillance and outbreak control in the Australian equine industry. Sporadic HeV spillover events pose a serious public health concern and are predicted to expand geographically, aligning with the moving distribution of the main reservoir hosts, the flying-foxes. Here we describe the development of a low-resource rapid Hendra test. The test used a fast and simple sample processing protocol followed by reverse transcription isothermal recombinase polymerase amplification (RT-RPA) combined with lateral flow detection (LFD) technology. Results were obtained in 30 min and required only a heating block, ice, and pipettes for liquid handling. The one-step sample processing protocol inactivated HeV in 2 min, providing a simple protocol that could enable safe testing outside of a laboratory. Analytical sensitivity testing demonstrated a detection limit of 1000 copies/µL of synthetic HeV RNA, and analytical specificity testing indicated assays did not detect other pathogens. Gamma-irradiated HeV-spiked in viral transport medium was detected with high sensitivity, down to 10,000 TCID50/mL, the equivalent of 18 RNA copies per reaction. Collectively, our data suggests that our rapid Hendra test offers a potential first-line screening on-site alternative to gold-standard RT-PCR detection, which requires samples to be shipped to central containment laboratories, thermocyclers and labour-intensive viral RNA purification, with testing time of approximately four hours. Our rapid Hendra test provided performance and speed without compromising sensitivity and specificity, and could become a promising more accessible tool for testing under resource-limited conditions for the veterinary community and thoroughbred industry.

The effect of a novel, digital physical activity and emotional well-being intervention on health-related quality of life in people with chronic kidney disease: trial design and baseline data from a multicentre prospective, wait-list randomised controlled trial (kidney BEAM).

BACKGROUND: Physical activity and emotional self-management has the potential to enhance health-related quality of life (HRQoL), but few people with chronic kidney disease (CKD) have access to resources and support. The Kidney BEAM trial aims to evaluate whether an evidence-based physical activity and emotional wellbeing self-management programme (Kidney BEAM) leads to improvements in HRQoL in people with CKD. METHODS: This was a prospective, multicentre, randomised waitlist-controlled trial, with health economic analysis and nested qualitative studies. In total, three hundred and four adults with established CKD were recruited from 11 UK kidney units. Participants were randomly assigned to the intervention (Kidney BEAM) or a wait list control group (1:1). The primary outcome was the between-group difference in Kidney Disease Quality of Life (KDQoL) mental component summary score (MCS) at 12 weeks. Secondary outcomes included the KDQoL physical component summary score, kidney-specific scores, fatigue, life participation, depression and anxiety, physical function, clinical chemistry, healthcare utilisation and harms. All outcomes were measured at baseline and 12 weeks, with long-term HRQoL and adherence also collected at six months follow-up. A nested qualitative study explored experience and impact of using Kidney BEAM. RESULTS: 340 participants were randomised to Kidney BEAM (n = 173) and waiting list (n = 167) groups. There were 96 (55%) and 89 (53%) males in the intervention and waiting list groups respectively, and the mean (SD) age was 53 (14) years in both groups. Ethnicity, body mass, CKD stage, and history of diabetes and hypertension were comparable across groups. The mean (SD) of the MCS was similar in both groups, 44.7 (10.8) and 45.9 (10.6) in the intervention and waiting list groups respectively. CONCLUSION: Results from this trial will establish whether the Kidney BEAM self management programme is a cost-effective method of enhancing mental and physical wellbeing of people with CKD. TRIAL REGISTRATION: NCT04872933. Registered 5th May 2021.

Child, parent, and family mental health and functioning in Australia during COVID-19: comparison to pre-pandemic data.

The COVID-19 pandemic presents significant risks to population mental health. Despite evidence of detrimental effects for adults, there has been limited examination of the impact of COVID-19 on parents and children specifically. We aim to examine patterns of parent and child (0-18 years) mental health, parent substance use, couple conflict, parenting practices, and family functioning during COVID-19, compared to pre-pandemic data, and to identify families most at risk of poor outcomes according to pre-existing demographic and individual factors, and COVID-19 stressors. Participants were Australian mothers (81%) and fathers aged 18 years and over who were parents of a child 0-18 years (N = 2365). Parents completed an online self-report survey during 'stage three' COVID-19 restrictions in April 2020. Data were compared to pre-pandemic data from four Australian population-based cohorts. Compared to pre-pandemic estimates, during the pandemic period parents reported higher rates of parent depression, anxiety, and stress (Cohen's d = 0.26-0.81, all p < 0.001), higher parenting irritability (d = 0.17-0.46, all p < 0.001), lower family positive expressiveness (d = - 0.18, p < 0.001), and higher alcohol consumption (22% vs 12% drinking four or more days per week, p < 0.001). In multivariable analyses, we consistently found that younger parent age, increased financial deprivation, pre-existing parent and child physical and mental health conditions, COVID-19 psychological and environmental stressors, and housing dissatisfaction were associated with worse parent and child functioning and more strained family relationships. Our data suggest wide-ranging, detrimental family impacts associated with the COVID-19 pandemic; and support policy actions to assist families with financial supports, leave entitlements, and social housing.

Spinal glycinergic currents are reduced in a rat model of neuropathic pain following partial nerve ligation but not chronic constriction injury.

Animal models have consistently indicated that central sensitization and the development of chronic neuropathic pain are linked to changes to inhibitory signaling in the dorsal horn of the spinal cord. However, replication of data investigating the cellular mechanisms that underlie these changes remains a challenge and there is still a lack of understanding about what aspects of spinal inhibitory transmission most strongly contribute to the disease. Here, we compared the effect of two different sciatic nerve injuries commonly used to generate rodent models of neuropathic pain on spinal glycinergic signaling. Using whole cell patch-clamp electrophysiology in spinal slices, we recorded from neurons in the lamina II of the dorsal horn and evoked inhibitory postsynaptic currents with a stimulator in lamina III, where glycinergic cell bodies are concentrated. We found that glycine inputs onto radial neurons were reduced following partial nerve ligation (PNL) of the sciatic nerve, consistent with a previous report. However, this finding was not replicated in animals that underwent chronic constriction injury (CCI) to the same nerve region. To limit the between-experiment variability, we kept the rat species, sex, and age consistent and had a single investigator carry out the surgeries. These data show that PNL and CCI cause divergent spinal signaling outcomes in the cord and add to the body of evidence suggesting that treatments for neuropathic pain should be triaged according to nerve injury or cellular dysfunction rather than the symptoms of the disease.NEW & NOTEWORTHY Neuropathic pain models are used in preclinical research to investigate the mechanisms underlying allodynia, a common symptom of neuropathic pain, and to test, develop, and validate therapies for persistent pain. We demonstrate that a glycinergic dysfunction is consistently associated with partial nerve ligation but not the chronic constriction injury model. This suggests that the cellular effects produced by each injury are distinct and that data from different neuropathic pain models should be considered separately.

Alcohol use among Australian parents during the COVID-19 pandemic - April-2020 to May 2021.

AIMS: This study examined the trajectory of alcohol use frequency among parents from April-2020 to May-2021 during the COVID-19 pandemic in the state of Victoria, Australia (who experienced one of the longest lockdowns in the world), compared to parents from the other states of Australia (who experienced relatively fewer restrictions). We further examined the extent to which baseline demographic factors were associated with changes in alcohol use trajectories among parents. METHOD: Data were from the COVID-19 Pandemic Adjustment Survey (2,261 parents of children 0-18 years). Alcohol use frequency was assessed over 13 waves. Baseline demographic predictors included parent gender, age, speaking a language other than English, number of children, partnership status, education, employment, and income. RESULTS: Overall, alcohol trajectories declined over time. Victorian parents, in comparison to parents from other states, reported a smaller reduction in alcohol use frequency across 2020, with a more notable decline during 2021. Female/other gender, speaking a language other than English at home, unemployment, and lower income (Victoria only) were associated with alcohol trajectories of less frequent use, and older age was associated with a trajectory of more frequent use. CONCLUSIONS: Results suggest subtle difference in alcohol trajectories reflecting COVID-19 restrictions, when comparing Victoria and other states in Australia. Socioeconomically advantaged groups were most at risk for elevated trajectories of alcohol use frequency. Population level support may beneficial to reduce drinking behaviours.

Peripheral Administration of Selective Glycine Transporter-2 Inhibitor, Oleoyl-D-Lysine, Reverses Chronic Neuropathic Pain but Not Acute or Inflammatory Pain in Male Mice.

Aberrations in spinal glycinergic signaling are a feature of pain chronification. Normalizing these changes by inhibiting glycine transporter (GlyT)-2 is a promising treatment strategy. However, existing GlyT2 inhibitors (e.g., ORG25543) are limited by narrow therapeutic windows and severe dose-limiting side effects, such as convulsions, and are therefore poor candidates for clinical development. Here, intraperitoneally administered oleoyl-D-lysine, a lipid-based GlyT2 inhibitor, was characterized in mouse models of acute (hot plate), inflammatory (complete Freund's adjuvant), and chronic neuropathic (chronic constriction injury) pain. Side effects were also assessed on a numerical rating score, convulsions score, for motor incoordination (rotarod), and for respiratory depression (whole body plethysmography). Oleoyl-D-lysine produced near complete antiallodynia for chronic neuropathic pain, but no antiallodynia/analgesia in inflammatory or acute pain. No side effects were seen at the peak analgesic dose, 30 mg/kg. Mild side effects were observed at the highest dose, 100 mg/kg, on the numerical rating score, but no convulsions. These results contrasted markedly with ORG25543, which reached less than 50% reduction in allodynia score only at the lethal/near-lethal dose of 50 mg/kg. At this dose, ORG25543 caused maximal side effects on the numerical rating score and severe convulsions. Oleoyl-D-lysine (30 mg/kg) did not cause any respiratory depression, a problematic side effect of opiates. These results show the safe and effective reversal of neuropathic pain in mice by oleoyl-D-lysine and provide evidence for a distinct role of glycine in chronic pain over acute or short-term pain conditions. SIGNIFICANCE STATEMENT: Partially inhibiting glycine transporter (GlyT)-2 can alleviate chronic pain by restoring lost glycinergic function. Novel lipid-based GlyT2 inhibitor ol-D-lys is safe and effective in alleviating neuropathic pain, but not inflammatory or acute pain. Clinical application of GlyT2 inhibitors may be better suited to chronic neuropathic pain over other pain aetiologies.

Glycinergic Modulation of Pain in Behavioral Animal Models.

Animal models of human pain conditions allow for detailed interrogation of known and hypothesized mechanisms of pain physiology in awake, behaving organisms. The importance of the glycinergic system for pain modulation is well known; however, manipulation of this system to treat and alleviate pain has not yet reached the sophistication required for the clinic. Here, we review the current literature on what animal behavioral studies have allowed us to elucidate about glycinergic pain modulation, and the progress toward clinical treatments so far. First, we outline the animal pain models that have been used, such as nerve injury models for neuropathic pain, chemogenic pain models for acute and inflammatory pain, and other models that mimic painful human pathologies such as diabetic neuropathy. We then discuss the genetic approaches to animal models that have identified the crucial glycinergic machinery involved in neuropathic and inflammatory pain. Specifically, two glycine receptor (GlyR) subtypes, GlyRα1(ß) and GlyRα3(ß), and the two glycine transporters (GlyT), GlyT1 and GlyT2. Finally, we review the different pharmacological approaches to manipulating the glycinergic system for pain management in animal models, such as partial vs. full agonism, reversibility, and multi-target approaches. We discuss the benefits and pitfalls of using animal models in drug development broadly, as well as the progress of glycinergic treatments from preclinical to clinical trials.

Near-infrared spectroscopy during cardiopulmonary resuscitation for pediatric cardiac arrest: A prospective, observational study.

AIM: Cerebral oxygenation (rSO2) is not routinely measured during pediatric cardiopulmonary resuscitation (CPR). We aimed to determine whether higher intra-arrest rSO2 was associated with return of spontaneous circulation (ROSC) and survival to hospital discharge. METHODS: Prospective, single-center observational study of cerebral oximetry using near-infrared spectroscopy (NIRS) during pediatric cardiac arrest from 2016 to 2020. Eligible patients had ≥30 s of rSO2 data recorded during CPR. We compared median rSO2 and percentage of rSO2 measurements above a priori thresholds for the entire event and the final five minutes of the CPR event between patients with and without ROSC and survival to discharge. RESULTS: Twenty-one patients with 23 CPR events were analyzed. ROSC was achieved in 17/23 (73.9%) events and five/21 (23.8%) patients survived to discharge. The median rSO2 was higher for events with ROSC vs. no ROSC for the overall event (62% [56%, 70%] vs. 45% [35%, 51%], p = 0.025) and for the final 5 minutes of the event (66% [55%, 72%] vs. 43% [35%, 44%], p = 0.01). Patients with ROSC had a higher percentage of measurements above 50% during the final five minutes of CPR (100% [100%, 100%] vs. 0% [0%, 29%], p = 0.01). There was no association between rSO2 and survival to discharge. CONCLUSIONS: Higher cerebral rSO2 during CPR for pediatric cardiac arrest was associated with higher rates of ROSC but not with survival to discharge.

From adolescence to parenthood: a multi-decade study of preconception mental health problems and postpartum parent-infant bonds.

PURPOSE: To examine associations between anxiety and depressive symptoms across adolescence and young adulthood with subsequent maternal- and paternal-infant bonding at 1 year postpartum. METHODS: The data were from a prospective, intergenerational cohort study. Participants (381 mothers of 648 infants; 277 fathers of 421 infants) self-reported depression and anxiety at three adolescent waves (ages 13, 15 and 17 years) and three young adult waves (ages 19, 23 and 27 years). Subsequent parent-infant bonds with infants were reported at 1 year postpartum (parent age 29-35 years). Generalised estimating equations (GEE) separately assessed associations for mothers and fathers. RESULTS: Mean postpartum bonding scores were approximately half a standard deviation lower in parents with a history of persistent adolescent and young adult depressive symptoms (maternal ßadj = - 0.45, 95% CI - 0.69, - 0.21; paternal ßadj = - 0.55, 95% CI - 0.90, 0.20) or anxiety (maternal ßadj = - 0.42, 95% CI - 0.66, - 0.18; paternal ßadj = - 0.49, 95% CI - 0.95, 0.03). Associations were still mostly evident, but attenuated after further adjustment for postpartum mental health concurrent with measurement of bonding. CONCLUSIONS: Persistent symptoms of depression or anxiety spanning adolescence and young adulthood predict poorer emotional bonding with infants 1-year postbirth for both mothers and fathers.

Effectiveness of the DROP training for military behavioral health providers targeting therapeutic alliance and premature dropout.

AbstractPremature discontinuation from behavioral health treatment is a major problem reducing effectiveness of care in military populations. A training was developed and delivered to 622 behavioral health providers across 15 sites within the Army behavioral healthcare system. The training taught two techniques to foster treatment engagement: (1) Progress Informed Treatment, consisting of reviewing symptom assessments and outcome measures, and (2) assessment and discussion of the treatment alliance via a paper survey given near the end of each session. Eighty-five percent of providers indicated the training was useful and 89% of providers incorporated a technique into their practice. Dropout before the fourth session was significantly reduced in the six months following training, from 72.5% to 67.1% in Service Members (SM; X2(1, N=9127) = 39.58, p < .001). In both the pre and post-training periods, providers working at the Master's level, SM aged 17 or 46 or older, and clients receiving a mood, PTSD, anxiety, adjustment, substance or childhood/adolescent psychiatric diagnosis experienced significantly less dropout, while SM aged 18-21 had significantly more dropout. This training is a feasible and available option to increase treatment engagement and improve treatment outcomes for service members.

Positive allosteric mechanisms of adenosine A1 receptor-mediated analgesia.

The adenosine A1 receptor (A1R) is a promising therapeutic target for non-opioid analgesic agents to treat neuropathic pain1,2. However, development of analgesic orthosteric A1R agonists has failed because of a lack of sufficient on-target selectivity as well as off-tissue adverse effects3. Here we show that [2-amino-4-(3,5-bis(trifluoromethyl)phenyl)thiophen-3-yl)(4-chlorophenyl)methanone] (MIPS521), a positive allosteric modulator of the A1R, exhibits analgesic efficacy in rats in vivo through modulation of the increased levels of endogenous adenosine that occur in the spinal cord of rats with neuropathic pain. We also report the structure of the A1R co-bound to adenosine, MIPS521 and a Gi2 heterotrimer, revealing an extrahelical lipid-detergent-facing allosteric binding pocket that involves transmembrane helixes 1, 6 and 7. Molecular dynamics simulations and ligand kinetic binding experiments support a mechanism whereby MIPS521 stabilizes the adenosine-receptor-G protein complex. This study provides proof of concept for structure-based allosteric drug design of non-opioid analgesic agents that are specific to disease contexts.

Modelling COVID-19 outbreaks in USA with distinct testing, lockdown speed and fatigue rates.

Each state in the USA exhibited a unique response to the COVID-19 outbreak, along with variable levels of testing, leading to different actual case burdens in the country. In this study, via per capita testing dependent ascertainment rates, along with case and death data, we fit a minimal epidemic model for each state. We estimate infection-level responsive lockdown/self-quarantine entry and exit rates (representing government and behavioural reaction), along with the true number of cases as of 31 May 2020. Ultimately, we provide error-corrected estimates for commonly used metrics such as infection fatality ratio and overall case ascertainment for all 55 states and territories considered, along with the USA in aggregate, in order to correlate outbreak severity with first wave intervention attributes and suggest potential management strategies for future outbreaks. We observe a theoretically predicted inverse proportionality relation between outbreak size and lockdown rate, with scale dependent on the underlying reproduction number and simulations suggesting a critical population quarantine 'half-life' of 30 days independent of other model parameters.

Psychosocial predictors of binge-drinking residual harm in adolescence and young adulthood: Findings from the Australian Temperament Project.

AIMS: We examine the extent to which adolescent and young adult psychosocial factors are associated with variation in the experience of common types of harm (e.g., injuries, violence, sexual regrets) with respect to binge-drinking frequency - termed residual harm. METHODS: Data were from the Australian Temperament Project, a population-based cohort study that has followed a sample of young Australians from infancy to adulthood since 1983. The current sample comprised 1,081 (565 women). Residual harm was operationalised by saving residuals from models regressing number of alcohol harms onto binge-drinking frequency at each of 5 waves, two in adolescence (15-16 and 17-18 years) and three in young adulthood (19-20, 23-24, and 27-28 years). Psychosocial factors (mental health, social skills, quality of parent and peer relationships) were assessed prior to binge drinking in early adolescence (13-14 years) and then again in young adulthood (19-20 years). RESULTS: Adolescent predictors of decreased residual harm were lower depressive symptoms, and higher cooperation, self-control, and peer and parent attachment. Young adult predictors of decreased residual harm were lower depressive, anxiety, and stress symptoms and peer and parent negative appraisal, and higher responsibility, and peer and parent emotional support. Associations were evident in males and females, although the strength of some associations diminished with age. CONCLUSIONS: Adolescents and young adults with better mental health, social skills, and relationship quality experienced less harm with respect to their binge-drinking frequency. Future research should examine the potential of investment in strength-based interventions for young people.

Atypical presentation of Takayasu aortitis and myocarditis contributing to sudden death in a young Canadian first nations adult.

This is a rare presentation of Takayasu arteritis in a 30-year-old Canadian First Nations woman with cardiac and aortic root-predominant disease, which manifested in complete heart block. She had a past medical history significant for substance misuse. At presentation, cardiac magnetic resonance imaging identified diffuse thickening of the left atrium and ventricular outflow tract with left ventricular cavity dilation and preserved systolic function. A pacemaker was inserted at this time. Nine months later, the patient died following an out-of-hospital cardiac arrest in the context of cocaine intoxication. At autopsy, the cardiac thickening was also found to involve the proximal aortic root, which on microscopy demonstrated non-infectious aortitis and myocarditis with a granulomatous inflammatory pattern and dense fibrosis indicative of Takayasu arteritis. Important clinical clues to the diagnosis include age, sex, and Pacific Islands, American indigenous and Asian ethnicity. The case also underscores the need to rule out secondary causes of complete heart block, including systemic vasculitides, for all patients regardless of substance use history.