A 10-year review of presentation, management and outcomes of STEMI in a high-volume regional tertiary Australian centre.

OBJECTIVE: To assess the trends and impact of changes in management of ST Elevation Myocardial Infarction (STEMI) from 2010 to 2019. DESIGN: Retrospective analysis of data from STEMI hospitalisations including demographic, comorbidity, angiographic and outcome data. SETTING/PARTICIPANTS: High-volume non-surgical regional Australian tertiary referral centre. MAIN OUTCOME MEASUREMENTS: Index & 12-month mortality (all-cause & cardiovascular), door-to-balloon time, target-vessel failure, target-vessel revascularisation & procedure-related bleeding. RESULTS: From 2010 to 2019, 1299 patients presented with STEMI. The cardiovascular risk factor profile did not significantly change over the 10-year study period, p = 0.23. There was a significant trend toward culprit vessel percutaneous coronary intervention with stenting, rather than balloon angioplasty followed by surgical revascularisation, p = 0.029. The mean door-to-balloon time was 88 +/- 5.7 min and demonstrated a statistically significant improvement across the decade, p = 0.035. Radial access became the preferred angiographic approach (2010 92% femoral, 2019 91% radial). Drug-eluting stents (DES) replaced bare metal stent use. There was a statistically significant reduction in 12-month cardiovascular mortality across the decade (p = 0.042). However index hospitalisation (cardiovascular and all-cause) and 12-month all-cause mortality did not reduce. Young patients and women are important sub-groups of STEMI presentations with different risk factor profile. CONCLUSIONS: Advances in management of STEMI such as radial access, use of DES and a significant reduction in door-to-balloon time across the decade resulted in a reduction of 12-month cardiovascular mortality over the decade however there was no significant reduction in 12-month all-cause mortality, or index hospitalisation cardiovascular or index hospitalisation all-cause mortality. Further research is needed to ensure non-mortality outcomes, such as heart failure hospitalisation and quality of life, also demonstrate temporal improvement with STEMI management advances. Earlier cardiovascular risk assessment should be considered in smokers than is currently recommended in Australian guidelines (≥45yo for most individuals).

New northerly limit for the sharptail mola in the northeast Atlantic: first sighting of Masturus lanceolatus in the northeast Irish Sea.

The ocean sunfishes are currently represented by five species within three genera: Mola mola (Linnaeus, 1758), Mola alexandrini (Ranzani, 1839), Mola tecta (Nyegaard, Sawai, Gemmell, Gillum, Loneragan, Yamanoue & Stewart, 2017) (Sawai et al., 2018), Masturus lanceolatus (Lienard, 1840), and Ranzania laevis (Pennant, 1776). Growing conservation concerns have led to an ongoing re-examination of their classification status on the International Union for the Conservation of Nature Red Lists, a process requiring the latest data to best support their conservation management on a global scale. Here we report the first sighting of Masturus lanceolatus in the northeast Irish Sea, representing a new northerly range limit for this species in the northeast Atlantic. The species is more commonly reported in tropical seas, and in the Western Atlantic they occur from North Carolina in the United States to southeast Brazil. This sighting increases the most northerly range limit by 2610 km, providing additional insight into the ecology and potentially changing distribution of this generally considered tropical megafaunal species.

Establishing a neonatology consultation program: extending care beyond the neonatal intensive care unit.

Neonates can be cared for in neonatal, pediatric, or cardiac intensive care units, and general and subspecialty pediatric units. Disposition is based on phase of care, gestational and postnatal age, birth weight, specific cardiac or surgical diagnoses, and co-existing medical morbidities. In addition, neonates may transfer between the neonatal intensive care unit (NICU) and other units several times throughout their hospitalization. As such, care for high-risk infants with ongoing neonatal morbidities (often related to prematurity or congenital anomalies) is provided in units with varying neonatal expertise. In this perspective, we provide a framework for the design and implementation of a neonatology consultation service for infants cared for in clinical units outside the NICU. We describe the core principles of effective neonatology consultation and focus on understanding hospital/unit workflow, team composition, patient selection, billing and compliance, and offer suggestions for research initiatives and educational opportunities.

Hair Cortisol Concentrations in Opioid-Exposed versus Nonexposed Mother-Infant Dyads.

OBJECTIVE: To pilot measurement of hair cortisol concentration (HCC) in pregnant women with opioid use disorder and their infants over time and study the potential utility of hair cortisol as a biomarker of chronic stress in this population. STUDY DESIGN: In this pilot prospective cohort study of mother-infant dyads with and without prenatal opioid exposure, we obtained mother-infant HCCs at delivery and again within 1 to 3 months' postpartum. HCCs were compared between the opioid and control groups and between the two time points. RESULTS: There were no significant differences between opioid and control group maternal or infant HCCs at either time point. However, within the opioid-exposed group, there was a significant increase in infant HCCs across the two time points. CONCLUSION: This pilot study describes our experience with the measurement of HCCs in opioid-exposed mother-infant dyads. KEY POINTS: · Maternal stress impacts fetal and child health.. · Many stressors in pregnant women with opioid use disorder.. · Hair cortisol may be a useful stress biomarker..

Drivers of decision-making regarding infant sleep practices among mothers with opioid use disorder.

OBJECTIVE: To understand the perspectives and perceived facilitators of and barriers to following safe infant sleeping practices among mothers with opioid use disorder (OUD). STUDY DESIGN: Using the Theory of Planned Behavior (TPB) framework, we conducted qualitative interviews with mothers with OUD regarding infant sleep practices. We created codes and generated themes, concluding data collection upon achieving thematic saturation. RESULTS: Twenty-three mothers with infants 1-7 months of age were interviewed from 08/2020 to 10/2021. Mothers chose sleeping practices they perceived made their infants safer, more comfortable, and minimized infant withdrawal symptoms. Mothers in residential treatment facilities were influenced by facility infant sleep rules. Hospital sleep modeling and varied advice by providers, friends and family influenced maternal decisions. CONCLUSIONS: Mothers reported factors unique to their experience with OUD that influenced their decisions about infant sleep that should be considered when developing tailored interventions to promote safe infant sleep in this population.

Understanding cigarette smoking among mothers with opioid use disorder.

BACKGROUND: Cigarette smoking is highly prevalent among mothers with opioid use disorder (OUD). Organizations such as the American College of Obstetrics and Gynecology recommend cessation of cigarettes during the pre- and postnatal periods. Factors that inform decisions to continue or stop smoking cigarettes among pregnant and postpartum mothers with OUD are unclear. AIMS: This study aimed to understand (1) the lived experience of mothers with OUD regarding cigarette smoking and (2) barriers and facilitators to reduction of cigarette smoking during the pre- and postnatal periods. METHODS: Guided by the Theory of Planned Behavior (TPB) framework, we completed semi-structured, in-depth interviews with mothers with OUD with infants 2-7 months of age. We used an iterative approach to analysis by conducting interviews and developing and revising codes and themes until we reached thematic saturation. RESULTS: Fifteen of 23 mothers reported smoking cigarettes prenatally and postnatally, 6 of 23 smoked cigarettes during the prenatal period only, and 2 mothers were non-smokers. We found that mothers: 1) believed that smoke exposure had negative health consequences and may exacerbate withdrawal symptoms for their infants; 2) implemented risk mitigation practices, which were dictated both by themselves and by outside rules, to reduce the harmful effects of smoke around infants; 3) were motivated to quit or cut-down on smoking because of the desire to optimize the health and well-being of their infants; 4) continued to smoke because they felt that the stress related to caregiving and their own recovery were a higher priority than quitting smoking; and 5) were influenced by exposure to smokers with whom they lived, as well as by the varied advice of medical providers, family, and friends. CONCLUSION: While mothers with OUD acknowledged the negative health impact of cigarette smoke exposure to their infants, many experienced stressors related to recovery and caregiving unique to those with OUD that impacted their cigarette smoking behaviors.

Breastfeeding Decision-Making Among Mothers with Opioid Use Disorder: A Qualitative Study.

Background: Factors that contribute to low initiation and continuation of breastfeeding among mothers with opioid use disorder (OUD) are poorly understood. Objective: To understand barriers and facilitators to breastfeeding initiation and continuation beyond the birth hospitalization for mothers with OUD. Materials and Methods: We conducted 23 in-depth, semistructured interviews with mothers with OUD who cared for their infants at home 1-7 months after birth. Our interview guide was informed by the Theory of Planned Behavior (TPB) framework, which has been used to understand decision-making regarding breastfeeding. An iterative approach was used to develop codes and themes. Results: Among 23 participants, 16 initiated breastfeeding, 10 continued after hospital discharge, and 4 continued beyond 8 weeks. We identified factors influencing breastfeeding decisions in the four TPB domains. Regarding attitudes, feeding intentions were based on beliefs of the healthiness of breastfeeding particularly pertaining to infant withdrawal or exposure to mothers' medications. Regarding social norms, breastfeeding was widely recommended, but mothers had varying levels of trust in medical professional advice. Regarding perceived control, infant withdrawal and maternal pain caused breastfeeding to be difficult, with decisions to continue modulated by level of outside support. Regarding self-efficacy, mothers weighed their own recovery and well-being against the constant demands of breastfeeding, impacting decisions to continue. Conclusion: Mothers with OUD face unique barriers to breastfeeding related to their infants' withdrawal as well as their own health, recovery, and social context. Overcoming these barriers may serve as future intervention targets for breastfeeding promotion among this high-risk population.

MCB-613 exploits a collateral sensitivity in drug resistant EGFR-mutant non-small cell lung cancer through covalent inhibition of KEAP1.

Targeted therapies have revolutionized cancer chemotherapy. Unfortunately, most patients develop multifocal resistance to these drugs within a matter of months. Here, we used a high-throughput phenotypic small molecule screen to identify MCB-613 as a compound that selectively targets EGFR-mutant, EGFR inhibitor-resistant non-small cell lung cancer (NSCLC) cells harboring diverse resistance mechanisms. Subsequent proteomic and functional genomic screens involving MCB-613 identified its target in this context to be KEAP1, revealing that this gene is selectively essential in the setting of EGFR inhibitor resistance. In-depth molecular characterization demonstrated that (1) MCB-613 binds KEAP1 covalently; (2) a single molecule of MCB-613 is capable of bridging two KEAP1 monomers together; and, (3) this modification interferes with the degradation of canonical KEAP1 substrates such as NRF2. Surprisingly, NRF2 knockout sensitizes cells to MCB-613, suggesting that the drug functions through modulation of an alternative KEAP1 substrate. Together, these findings advance MCB-613 as a new tool for exploiting the selective essentiality of KEAP1 in drug-resistant, EGFR-mutant NSCLC cells.

Physiological and life history changes associated with seasonal adaptation in the cactophilic Drosophila mojavensis.

Many insects inhabiting temperate climates are faced with changing environmental conditions throughout the year. Depending on the species, these environmental fluctuations can be experienced within a single generation or across multiple generations. Strategies for dealing with these seasonal changes vary across populations. Drosophila mojavensis is a cactophilic Drosophila species endemic to the Sonoran Desert. The Sonoran Desert regularly reaches temperatures of 50°C in the summer months. As individuals of this population are rare to collect in the summer months, we simulated the cycling temperatures experienced by D. mojavensis in the Sonoran Desert from April to July (four generations) in a temperature- and light-controlled chamber, to understand the physiological and life history changes that allow this population to withstand these conditions. In contrast to our hypothesis of a summer aestivation, we found that D. mojavensis continue to reproduce during the summer months, albeit with lower viability, but the adult survivorship of the population is highly reduced during this period. As expected, stress resistance increased during the summer months in both the adult and the larval stages. This study examines several strategies for withstanding the Sonoran Desert summer conditions which may be informative in the study of other desert endemic species.

Neonatal Opioid Withdrawal Syndrome: A Comparison of As-Needed Pharmacotherapy.

BACKGROUND AND OBJECTIVE: Methadone and morphine are commonly administered medications for neonatal opioid withdrawal syndrome (NOWS). Infants are increasingly treated with as-needed or "pro re nata" (PRN) medication. The optimal pharmacologic agent for PRN treatment of NOWS has not been examined. This study's objective is to compare NOWS hospital outcomes between infants treated with PRN methadone versus morphine. METHODS: We performed a retrospective cohort study of infants pharmacologically treated for NOWS across 4 Massachusetts hospitals between January 2018 and February 2021. Infants born ≥36 weeks gestation with prenatal opioid exposure treated with PRN methadone or morphine were included. Mixed effects logistic and linear regression models were employed to evaluate differences in transition rates to scheduled dosing, length of stay, and number of PRN doses administered depending on PRN treatment agent. RESULTS: There were 86 infants in the methadone group and 52 in the morphine group. There were no significant differences in NOWS hospital outcomes between groups in adjusted models: transition to scheduled dosing (methadone 31.6% vs morphine 28.6%, adjusted odds ratio 1.21, 95% confidence interval [CI] 0.87-1.19), mean length of stay (methadone 15.5 vs morphine 14.3 days, adjusted risk ratio 1.06, 95% CI 0.80-1.41), and the mean number of PRN doses (methadone 2.3 vs morphine 3.4, adjusted risk ratio 0.65, 95% CI 0.41-1.02). There was an association with nonpharmacologic care practices and improved NOWS hospital outcomes. CONCLUSIONS: There were no significant differences in NOWS hospitalization outcomes based on pharmacologic agent type; nonpharmacologic care practices were most strongly associated with improved NOWS hospitalization outcomes.

Impact of Coronavirus Disease-2019 on Hospital Care for Neonatal Opioid Withdrawal Syndrome.

OBJECTIVE: To compare prenatal exposures, hospital care processes, and hospitalization outcomes for opioid-exposed newborns before and during the coronavirus disease 2019 (COVID-19) pandemic. STUDY DESIGN: In this multicenter retrospective analysis, data were collected from 19 Massachusetts hospitals, including 5 academic and 14 community hospitals. The pre-COVID-19 cohort was defined as births occurring during March 1, 2019-February 28, 2020, and the COVID-19 cohort was defined as births occurring during March 1, 2020-December 31, 2020. Opioid-exposed newborns born at ≥35 weeks of gestation were included. Differences in prenatal substance exposures, hospital care processes, and neonatal opioid withdrawal syndrome (NOWS) outcomes, including pharmacologic treatment for NOWS (PharmTx), length of stay (LOS), and as-needed (prn) treatment failure rates, were evaluated. RESULTS: There were 663 opioid-exposed newborns in the pre-COVID-19 group and 476 in the COVID-19 group. No between-group differences were seen in prenatal substance exposures or the need for PharmTx. Compared with the pre-COVID-19 group, in the COVID-19 group there was less rooming-in after maternal discharge (53.8% vs 63.0%; P = .001) and less care in the pediatric unit setting (23.5% vs 25.3%; P = .001), longer LOS (adjusted risk ratio, 1.04; 95% CI, 1.01-1.08), and a higher rate of breast milk receipt at discharge (aOR, 2.03; 95% CI, 1.22-3.39). Within the subset of academic centers, more infants failed prn treatment in the COVID-19 group (53.8% vs 26.5%, P = .02; aOR, 3.77; 95% CI, 0.98-14.5). CONCLUSIONS: Among the hospitals in our collaborative, hospital processes for NOWS, including care setting, rooming-in, and LOS were negatively impacted in the COVID-19 group, particularly in academic medical centers.

Women in larger bodies' experiences with contraception: a scoping review.

BACKGROUND: As the prevalence of obesity increases and the age of onset decreases, more women of reproductive age will be living in larger bodies. Research on weight-related efficacy and safety has informed clinical guidelines for routine and emergency contraceptive use by women with a higher body mass index; however, patient perspectives are needed to understand women in larger bodies' experiences with contraception and contraceptive care. This scoping review summarizes the literature on women in larger bodies' experiences with contraception with the goal of gaining a better understanding of the nature of these experiences and identifying gaps in the existing research. METHODS: Following Arksey and O'Malley's framework, a scoping review of the literature was conducted. Four databases (PubMed, PsycINFO, SCOPUS, and CINAHL) were searched for peer-reviewed, empirical articles published in English between 2010 and 2020, with a focus on North America, Europe, Australia, and New Zealand. Data were summarized by identifying key themes in the reviewed literature. RESULTS: Twenty-nine articles meeting the eligibility criteria were reviewed. The literature was predominantly quantitative (n = 27), with only one qualitative study and one systematic review, respectively. Five themes were identified, including (1) use of contraception among women in larger bodies; (2) knowledge, attitudes towards and beliefs about contraception; (3) contraceptive (dis)satisfaction among women in larger bodies; (4) contraceptive counseling; and (5) barriers to contraception. The findings revealed that women in larger bodies may have unmet contraceptive care needs. Despite many articles addressing the need to improve contraceptive counseling for women in larger bodies (n = 26), few explored how women felt about their care (n = 2). Finally, only two articles focused on emergency contraception, indicating a need for further research. CONCLUSION: This scoping review emphasizes the pressing need for qualitative research to explore women in larger bodies' experiences with routine and emergency contraception, as well as receiving contraceptive counseling and care. Future research exploring the lived experiences of women in larger bodies is necessary to better characterize their contraceptive needs and identify avenues to improve patient care.

As obesity becomes more prevalent, more women of reproductive age will be living in larger bodies. This review highlights what is known about women in larger bodies' experiences with contraception and suggests where future research is needed. We searched four databases for papers published in English from 2010 to 2020. Our review included 29 articles. Nearly all of the studies were quantitative, with one qualitative study and one review. Most articles talked about contraceptive use, but few of them included emergency contraception. Some papers highlighted women's knowledge and opinions about contraception, whereas others talked about their contraceptive (dis)satisfaction. Many articles discussed contraceptive counseling. Finally, some papers considered potential barriers to contraception. Our findings suggest that women in larger bodies have unmet contraceptive needs. Notably, this review aimed to focus on patient experiences but women's voices were rarely represented. Future qualitative research on women's lived experiences will provide a better understanding of women in larger bodies' contraceptive needs and suggest how care can be improved.

SCN2A channelopathies in the autism spectrum of neuropsychiatric disorders: a role for pluripotent stem cells?

Efforts to identify the causes of autism spectrum disorders have highlighted the importance of both genetics and environment, but the lack of human models for many of these disorders limits researchers' attempts to understand the mechanisms of disease and to develop new treatments. Induced pluripotent stem cells offer the opportunity to study specific genetic and environmental risk factors, but the heterogeneity of donor genetics may obscure important findings. Diseases associated with unusually high rates of autism, such as SCN2A syndromes, provide an opportunity to study specific mutations with high effect sizes in a human genetic context and may reveal biological insights applicable to more common forms of autism. Loss-of-function mutations in the SCN2A gene, which encodes the voltage-gated sodium channel NaV1.2, are associated with autism rates up to 50%. Here, we review the findings from experimental models of SCN2A syndromes, including mouse and human cell studies, highlighting the potential role for patient-derived induced pluripotent stem cell technology to identify the molecular and cellular substrates of autism.

Pathogen displacement during intermittent catheter insertion: a novel in vitro urethra model.

AIM: To develop a novel in vitro urethra model and use it to determine if insertion of an intermittent urinary catheter (IC) displaces pathogenic bacteria from the urethral meatus along the urethra. METHODS: Displacement of microbial growth after catheter insertion was assessed using a novel in vitro urethra model. The in vitro urethra model utilized chromogenic agar and was inoculated with bacteria at one side of the artificial urethra channel, to act as a contaminated urethral meatus, before an IC was inserted into the channel. Three ICs types were used to validate the in vitro urethra model and methodology. RESULTS: When compared to the bacterial growth control, a significant difference in bacterial growth was found after insertion of the uncoated (P ≤ 0·001) and hydrophilic coated (P ≤ 0·009) catheters; no significant difference when a prototype catheter was inserted into the in vitro urethra model with either bacterial species tested (P ≥ 0·423). CONCLUSION: The results presented support the hypothesis that a single catheter insertion can initiate a catheter-associated urinary tract infection. SIGNIFICANCE AND IMPACT OF THE STUDY: The in vitro urethra model and associated methodology were found to be reliable and reproducible (P ≥ 0·265) providing new research tool for the development and validation of emerging technologies in urological healthcare.

Cognitive effects of adjuvant endocrine therapy in older women treated for early-stage breast cancer: a 1-year longitudinal study.

PURPOSE: Evidence suggests endocrine therapy (ET) for breast cancer (BC) has adverse cognitive effects, but its specific effects on older women are unknown. This is despite the fact that older women are at increased risk of both breast cancer (BC) and cognitive decline relative to younger women. This study prospectively examined the cognitive effects of ET in a cohort of older BC patients. Our primary outcome measure was change in verbal memory, the cognitive domain most consistently affected by estrogen deprivation. METHODS: Forty-two chemotherapy-naïve women age 60+, without dementia and recently diagnosed with hormone receptor-positive BC, completed neuropsychological tests at the time of ET initiation and after 1 year of treatment. Change in age-standardized verbal memory performance was examined using paired t tests. To assess a broader range of potential cognitive effects, we also examined changes in visual memory, processing speed, frontal executive function, and perceptual reasoning. RESULTS: Participants exhibited significant decline from baseline to 1 year in verbal memory (p = 0.01). This decline was small to moderate in effect size (d = - 0.40). Performance on other domains did not change significantly over the year (all p > 0.05). CONCLUSIONS: Our findings suggest potentially detrimental effects of ET on verbal memory in older women after just 1 year of treatment. Given that ET is prescribed for courses of 5 to 10 years, additional studies examining longer-term effects of treatment in older women are critical.

Cognitive sequelae of endocrine therapy in women treated for breast cancer: a meta-analysis.

PURPOSE: Evidence suggests anti-estrogen endocrine therapy (ET) is associated with adverse cognitive effects; however, findings are based on small samples and vary in the cognitive abilities affected. We conducted a meta-analysis to quantitatively synthesize the evidence. METHODS: Electronic databases were searched in November 2016. Fourteen studies totaling 911 BC patients on aromatase inhibitors (AIs) or tamoxifen (TAM) and 911 controls (i.e., non-cancer controls and BC controls not using ET) were included. Neuropsychological tests were categorized into six domains. Effect sizes were computed to compare (1) ET patients versus controls and (2) TAM patients versus AI patients. RESULTS: In cross-sectional comparisons, ET patients performed worse than control groups on verbal learning/memory, visual learning/memory, frontal executive function, and processing speed, but did not differ on psychomotor efficiency or visuospatial function. Subgroup analyses revealed that verbal learning/memory was the only domain where ET patients performed worse than both non-cancer and BC controls. In other domains, ET patients and BC controls performed equivalently. Regarding change from pre-treatment performance, ET patients did not differ from controls on any domain. TAM and AI patients did not from one another differ overall; however, subgroup analyses indicated that TAM patients performed better than non-steroidal AI patients on several domains, but showed few performance differences relative to steroidal AI patients. CONCLUSIONS: Verbal learning/memory was the only domain where ET patients performed worse than both non-cancer and BC controls, suggesting specific adverse effects on this domain. Additional studies assessing change from pre-treatment performance and differences between steroidal and non-steroidal AIs are warranted.

Sperm gamma-aminobutyric acid type A receptor delta subunit (GABRD) and its interaction with purinergic P2X2 receptors in progesterone-induced acrosome reaction and male fertility.

The mechanism underlying the non-genomic action of progesterone in sperm functions and related Ca2+ mobilisation remains elusive. Herein we report the expression of gamma-aminobutyric acid type A receptor delta subunit (GABRD) in human and rodent sperm and its involvement in mediating the progesterone-induced acrosome reaction. GABRD was localised in the sperm head/neck region. A δ(392-422)-specific inhibitory peptide against GABRD blocked the progesterone-induced acrosome reaction and the associated increase in intracellular Ca2+. Similarly, an inhibitory effect against both progesterone-induced Ca2+ influx and the acrosome reaction was observed with a P2X2 receptor antagonist. The lack of synergism between the GABRD and P2X2 inhibitors suggests that these two receptors are playing a role in the same pathway. Furthermore, a co-immunoprecipitation experiment demonstrated that GABRD could undergo protein-protein interactions with the Ca2+-conducting P2X2 receptor. This interaction between the receptors could be reduced following progesterone (10µM) inducement. Significantly reduced GABRD expression was observed in spermatozoa from infertile patients with reduced acrosome reaction capacity, suggesting that normal expression of GABRD is critical for the sperm acrosome reaction and thus male fertility. The results of the present study indicate that GABRD represents a novel progesterone receptor or modulator in spermatozoa that is responsible for the progesterone-induced Ca2+ influx required for the acrosome reaction through its interaction with the P2X2 receptor.