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Abstract Stigma and other barriers limit harm reduction practice integration by clinicians within acute psychiatric settings. The objective of our study was to explore mental health clinician attitudes towards substance use and associations with clinical experience and education level. The Brief Substance Abuse Attitudes Survey was completed among a convenience sample of mental health clinicians in Vancouver, British Columbia. Five predefined attitude subgroups were evaluated. Respondents’ attitudes towards substance use were associated with level of education on questions from two (non-stereotyping [p = 0.012] and treatment optimism [p = 0.008]) subscales. In pairwise comparisons, postgraduate education was associated with more positive attitudes towards relapse risk (p = 0.004) when compared to diploma-educated respondents. No significant associations were observed between years of clinical experience and participant responses. Our findings highlight important aspects of clinician attitudes that could improve harm reduction education and integration into clinical practice.

Abstract Background /Aims De-implementation, including the removal or reduction of unnecessary or inappropriate prescribing, is crucial to ensure patients receive appropriate evidence-based health care. The utilization of de-implementation efforts is contingent on the quality of strategy reporting. To further understand effective ways to de-implement medical practices, specification of behavioural targets and components of de-implementation strategies are required. This paper aims to critically analyse how well the behavioural targets and strategy components, in studies that focused on de-implementing unnecessary or inappropriate prescribing in secondary healthcare settings, were reported. Methods A supplementary analysis of studies included in a recently published review of de-implementation studies was conducted. Article text was coded verbatim to two established specification frameworks. Behavioural components were coded deductively to the five elements of the Action, Actor, Context, Target, Time (AACTT) framework. Strategy components were mapped to the nine elements of the Proctor’s ‘measuring implementation strategies’ framework. Results The behavioural components of low-value prescribing, as coded to the AACTT framework, were generally specified well. However, the Actor and Time components were often vague or not well reported. Specification of strategy components, as coded to the Proctor framework, were less well reported. Proctor’s Actor, Action target: specifying targets, Dose and Justification elements were not well reported or varied in the amount of detail offered. We also offer suggestions of additional specifications to make, such as the ‘interactions’ participants have with a strategy. Conclusion Specification of behavioural targets and components of de-implementation strategies for prescribing practices can be accommodated by the AACTT and Proctor frameworks when used in conjunction. These essential details are required to understand, replicate and successfully de-implement unnecessary or inappropriate prescribing. In general, standardisation in the reporting quality of these components is required to replicate any de-implementation efforts. Trial registration Not registered.

Abstract Background Major depressive disorder (MDD) is prevalent, yet sub-optimally treated among persons with multiple sclerosis (MS). We propose that exercise training may be a promising approach for treating depression in persons with MS who have MDD. Our primary hypothesis predicts a reduction in depression severity immediately after an exercise training intervention compared with minimal change in an attention control condition, and the reduction will be maintained during a follow-up period. Methods This study involves a parallel-group, assessor-blinded RCT that examines the effect of a 4-month home-based exercise training intervention on depression severity in a sample of persons with MS who have MDD based on the MINI International Neuropsychiatric Interview. The primary outcomes of depression severity are the Patient Health Questionnaire-9 and Hamilton Depression Rating Scale. Participants (N = 146) will be recruited from within 200 miles of the University of Illinois at Chicago and randomized (1:1) into either a home-based exercise training condition or control condition with concealed allocation. The exercise training and social-contact, attention control (i.e., stretching) conditions will be delivered remotely over a 4-month period and supported through eight, 1:1 Zoom-based behavioral coaching sessions guided by social-cognitive theory and conducted by persons who are uninvolved in screening, recruitment, random assignment, and outcome assessment. We will collect outcome data at 0, 4 and 8 months using treatment-blinded assessors, and data analyses will involve intent-to-treat principles. Discussion If successful, the proposed study will provide the first Class I evidence supporting a home-based exercise training program for treating MDD in persons with MS. This is critical as exercise training would likely have positive secondary effects on symptoms, cognition, and quality of life, and provide a powerful, behavioral approach for managing the many negative outcomes of MDD in MS. The program in the proposed research is accessible and scalable for broad treatment of depression in MS, and provides the potential for integration in the clinical management of MS. Trial registration The trial was registered on September 10, 2021 at clinicaltrials.gov with the identifier NCT05051618. The registration occurred before we initiated recruitment on June 2, 2023

Abstract Background Many men with prostate cancer will be exposed to androgen deprivation therapy (ADT). While evidence-based ADT use is common, ADT is also used in cases with no or limited evidence resulting in more harm than benefit, i.e., overuse. Since there are risks of ADT (e.g., diabetes, osteoporosis), it is important to understand the behaviors facilitating overuse to inform de-implementation strategies. For these reasons, we conducted a theory-informed survey study, including a discrete choice experiment (DCE), to better understand ADT overuse and provider preferences for mitigating overuse. Methods Our survey used the Action, Actor, Context, Target, Time (AACTT) framework, the Theoretical Domains Framework (TDF), the Capability, Opportunity, Motivation–Behavior (COM-B) Model, and a DCE to elicit provider de-implementation strategy preferences. We surveyed the Society of Government Service Urologists listserv in December 2020. We stratified respondents based on the likelihood of stopping overuse as ADT monotherapy for localized prostate cancer (“yes”/“probably yes,” “probably no”/“no”), and characterized corresponding Likert scale responses to seven COM-B statements. We used multivariable regression to identify associations between stopping ADT overuse and COM-B responses. Results Our survey was completed by 84 respondents (13% response rate), with 27% indicating “probably no”/“no” to stopping ADT overuse. We found differences across respondents who said they would and would not stop ADT overuse in demographics and COM-B statements. Our model identified 2 COM-B domains (Opportunity–Social, Motivation–Reflective) significantly associated with a lower likelihood of stopping ADT overuse. Our DCE demonstrated in-person communication, multidisciplinary review, and medical record documentation may be effective in reducing ADT overuse. Conclusions Our study used a behavioral theory-informed survey, including a DCE, to identify behaviors and context underpinning ADT overuse. Specifying behaviors supporting and gathering provider preferences in addressing ADT overuse requires a stepwise, stakeholder-engaged approach to support evidence-based cancer care. From this work, we are pursuing targeted improvement strategies. Trial registration ClinicalTrials.gov, NCT03579680

Imaging is increasingly used to capture information on the marine environment thanks to the improvements in imaging equipment, devices for carrying cameras and data storage in recent years. In that context, biologists, geologists, computer specialists and end-users must gather to discuss the methods and procedures for optimising the quality and quantity of data collected from images. The 4th Marine Imaging Workshop was organised from 3-6 October 2022 in Brest (France) in a hybrid mode. More than a hundred participants were welcomed in person and about 80 people attended the online sessions. The workshop was organised in a single plenary session of presentations followed by discussion sessions. These were based on dynamic polls and open questions that allowed recording of the imaging community’s current and future ideas. In addition, a whole day was dedicated to practical sessions on image analysis, data standardisation and communication tools. The format of this edition allowed the participation of a wider community, including lower-income countries, early career scientists, all working on laboratory, benthic and pelagic imaging.This article summarises the topics addressed during the workshop, particularly the outcomes of the discussion sessions for future reference and to make the workshop results available to the open public.

At the time of a mammogram, calcifications may be seen in axillary lymph nodes. Metastatic breast cancer is the most common malignant cause of calcifications in the axillary lymph nodes. Benign causes may include but are not limited to granulomatous disease, fat necrosis, gold deposits in rheumatoid arthritis patients, pigmentation from tattoos, and sarcoidosis. We present a case of a 37-year-old female with axillary lymph node calcifications due to metastatic breast cancer. Calcification morphology seen in the primary breast tumor and the axillary lymph nodes are nearly identical on mammogram, which is seldom seen. The similar morphology almost guarantees metastatic breast cancer, underscoring the importance of identifying the etiology of any calcifications present in axillary lymph nodes on mammography.

Objective: To evaluate the ability of a neural network to identify severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using point-of-care electrocardiography obtained with a portable device. Patient and Methods: We enrolled 2827 patients in a prospective observational study, from December 10, 2020, through June 4, 2021, to determine the accuracy of a point-of-care, handheld, smartphone-compatible, artificial intelligence–enabled electrocardiography (ECG) (POC AI-ECG) in detecting asymptomatic SARS-CoV-2 infection using a modified version of an existing deep learning model framework trained on 12-lead ECG data. Results: Study participants were 48% (n=1067) female, 79% (n=1749) White, and 7% (n=153) endorsed previous COVID-19 infection. We found the POC AI-ECG algorithm was ineffective for detecting asymptomatic SARS-CoV-2 infection (area under curve, 0.56; 95% CI, 0.46-0.66), failing to adequately discriminate between ECGs performed among participants who tested positive compared to those who tested negative. Conclusion: Contrary to the prior 12-lead ECG study, a POC AI-ECG failed to reliably identify asymptomatic SARS-CoV-2 infection among adults. This study underscores the importance of prospective testing, assuring similar populations, and using similar signals or data when developing AI-ECG tools. Trial registration: clinicaltrials.gov Identifier: NCT04725097

Abstract An achiral chromophore can acquire a chiral spectroscopic signature when interacting with a chiral environment. This so-called induced chirality is documented in electronic or vibrational circular dichroism, which arises from the coupling between electric and magnetic transition dipoles. Here, we demonstrate that a chiroptical response is also induced within the electric dipole approximation by observing the asymmetric scattering of a photoelectron ejected from an achiral chromophore in interaction with a chiral host. In a phenol–methyloxirane complex, removing an electron from an achiral aromatic π orbital localised on the phenol moiety results in an intense and opposite photoelectron circular dichroism (PECD) for the two enantiomeric complexes with (R) and (S) methyloxirane, evidencing the long-range effect (~5 Å) of the scattering chiral potential. This induced chirality has important structural and analytical implications, discussed here in the context of growing interest in laser-based PECD, for in situ, real time enantiomer determination.

Abstract Background Short sleep duration, defined as

Abstract Type 2 diabetes (T2D) and its complications can have debilitating, sometimes fatal consequences for afflicted individuals. The disease can be difficult to control, and therapeutic strategies to prevent T2D-induced tissue and organ damage are needed. Here we describe the results of administering a potent and selective inhibitor of Protein Kinase C (PKC) family members PKCα and PKCβ, Cmpd 1, in the ZSF1 obese rat model of hyperphagia-induced, obesity-driven T2D. Although our initial intent was to evaluate the effect of PKCα/β inhibition on renal damage in this model setting, Cmpd 1 unexpectedly caused a marked reduction in the hyperphagic response of ZSF1 obese animals. This halted renal function decline but did so indirectly and indistinguishably from a pair feeding comparator group. However, above and beyond this food intake effect, Cmpd 1 lowered overall animal body weights, reduced liver vacuolation, and reduced inguinal adipose tissue (iWAT) mass, inflammation, and adipocyte size. Taken together, Cmpd 1 had strong effects on multiple disease parameters in this obesity-driven rodent model of T2D. Further evaluation for potential translation of PKCα/β inhibition to T2D and obesity in humans is warranted.

ABSTRACTIron (Fe) and sulfur (S) are required elements for life, and changes in their availability can limit the ecological distribution and function of microorganisms. In anoxic environments, soluble Fe typically exists as ferrous iron [Fe(II)] and S as sulfide (HS−). These species exhibit a strong affinity that ultimately drives the formation of sedimentary pyrite (FeS2). Recently, paradigm-shifting studies indicate that Fe and S in FeS2 can be made bioavailable by methanogens through a reductive dissolution process. However, the impact of the utilization of FeS2, as opposed to canonical Fe and S sources, on the phenotype of cells is not fully understood. Here, shotgun proteomics was utilized to measure changes in the phenotype of Methanosarcina barkeri MS grown with FeS2, Fe(II)/HS−, or Fe(II)/cysteine. Shotgun proteomics tracked 1,019 proteins overall, with 307 observed to change between growth conditions. Functional characterization and pathway analyses revealed these changes to be systemic and largely tangential to Fe/S metabolism. As a final step, the proteomics data were viewed with respect to previously collected transcriptomics data to deepen the analysis. Presented here is evidence that M. barkeri adopts distinct phenotypes to exploit specific sources of Fe and S in its environment. This is supported by observed protein abundance changes across broad categories of cellular biology. DNA adjacent metabolism, central carbon metabolism methanogenesis, metal trafficking, quorum sensing, and porphyrin biosynthesis pathways are all features in the phenotypic differentiation. Differences in trace metal availability attributed to complexation with HS−, either as a component of the growth medium [Fe(II)/HS−] or generated through reduction of FeS2, were likely a major factor underpinning these phenotypic differences.IMPORTANCEThe methanogenic archaeon Methanosarcina barkeri holds great potential for industrial bio-mining and energy generation technologies. Much of the biochemistry of this microbe is poorly understood, and its characterization will provide a glimpse into biological processes that evolved close to life’s origin. The discovery of its ability to extract iron and sulfur from bulk, solid-phase minerals shifted a longstanding paradigm that these elements were inaccessible to biological systems. The full elucidation of this process has the potential to help scientists and engineers extract valuable metals from low-grade ore and mine waste generating energy in the form of methane while doing so.

Abstract Background/aims Considerable efforts have been made to improve guideline adherence in healthcare through de-implementation, such as decreasing the prescription of inappropriate medicines. However, we have limited knowledge about the effectiveness, barriers, facilitators and consequences of de-implementation strategies targeting inappropriate medication prescribing in secondary care settings. This review was conducted to understand these factors to contribute to better replication and optimisation of future de-implementation efforts to reduce low-value care. Methods A systematic review of randomised control trials was conducted. Papers were identified through CINAHL, EMBASE, MEDLINE and Cochrane register of controlled trials to February 2021. Eligible studies were randomised control trials evaluating behavioural strategies to de-implement inappropriate prescribing in secondary healthcare. Risk of bias was assessed using the Cochrane Risk of Bias tool. Intervention characteristics, effectiveness, barriers, facilitators and consequences were identified in the study text and tabulated. Results Eleven studies were included, of which seven were reported as effectively de-implementing low-value prescribing. Included studies were judged to be mainly at low to moderate risk for selection biases and generally high risk for performance and reporting biases. The majority of these strategies were clinical decision support at the ‘point of care’. Clinical decision support tools were the most common and effective. They were found to be a low-cost and simple strategy. However, barriers such as clinician’s reluctance to accept recommendations, or the clinical setting were potential barriers to their success. Educational strategies were the second most reported intervention type however the utility of educational strategies for de-implementation remains varied. Multiple barriers and facilitators relating to the environmental context, resources and knowledge were identified across studies as potentially influencing de-implementation. Various consequences were identified; however, few measured the impact of de-implementation on usual appropriate practice. Conclusion This review offers insight into the intervention strategies, potential barriers, facilitators and consequences that may affect the de-implementation of low-value prescribing in secondary care. Identification of these key features helps understand how and why these strategies are effective and the wider (desirable or undesirable) impact of de-implementation. These findings can contribute to the successful replication or optimisation of strategies used to de-implement low-value prescribing practices in future. Trial registration The review protocol was registered at PROSPERO (ID: CRD42021243944).

Abstract Background When reviewing a protocol, research ethics committees (RECs, equivalent to institutional review boards — IRBs) have the responsibility to consider whether the proposed research is justified. If research is not justified, it can waste participants’ time, researchers’ time and resources. As RECs are not constituted to cover all areas of scientific or academic expertise, it can be difficult for RECs to decide whether research is scientifically or methodologically justified especially in the absence of authoritative (often in the form of systematic) reviews. Where such reviews are absent, some have argued that RECs should insist on a new review of existing evidence as a condition of the REC favourable opinion. However, as RECs review a wide range of research, such requests must be proportionate to the type, and extent, of proposed projects. Risk is one factor that may influence the extent of evidence need for a REC to determine that the new project is justified, but not the only factor. The aim of the work described here was to determine whether REC members and researchers specifically link risk to the type of research methodology, and if so, whether this link could be used to help guide the need for systematic, or other, types of reviews. Method We conducted a cross-sectional study, gathering data between November 2020 and January 2021, to examine whether proposed research methodologies impact how RECs perceive risk to participants. We presented 31 research methodologies to REC members and researchers in the form of an international survey. Results We collected 283 responses that included both qualitative and quantitative data as to how research methodology impacts perceptions of risk to participants. We used the data to conclude that RECs did see a link between risk and type of research. We therefore constructed a hierarchy of risk with Phase 1 and 2 clinical trials, and clinical psychology/psychiatry intervention studies, at the top (i.e. viewed as most risky). Conclusions We discuss whether this hierarchy is useful for guiding RECs as to the level of scientific justification that they should seek when reviewing proposed research protocols, and present a one-page guidance sheet to help RECs during their reviews.

Cognitive enrichment is becoming more prevalent in professional marine mammal facilities. Research with dolphins has suggested that such enrichment provides more welfare benefits than enrichment that does not incorporate cognitive challenge. However, there is little research supporting the use of cognitive enrichment as a means to improve the welfare of sea lions. Recently, a novel form of technological cognitive enrichment, the Enclosure Video Enrichment (EVE) system, was introduced to a population of California sea lions at the US Navy’s Marine Mammal Program as a means to enhance welfare. Two of the initial focal animals introduced to EVE were selected based on their health history and the possible benefits of cognitive enrichment in improving health measures. To evaluate this, information regarding the animals’ consumption of their offered diet was compared to other animals in the population of similar age and the absence of a similar health history. Subsequently, the total diet consumption of the targeted animals was evaluated in the two years prior to the introduction to EVE and compared to the total diet consumption during the initial 2 years of regular EVE sessions. There was a significant decrease in the number of days in which the sea lions did not consume their entire offered diet in the two years after implementing regular EVE sessions, an increase in participation and performance of voluntary husbandry behaviors, and a reduction in the number of days animals were clinically ill. This study provides evidence of cognitive enrichment as a management tool to improve animal health and welfare as well as performance in training sessions.

Abstract A neoadjuvant immunotherapy platform clinical trial allows for rapid evaluation of treatment-related changes in tumors and identifying targets to optimize treatment responses. We enrolled patients with resectable pancreatic adenocarcinoma into such a platform trial (NCT02451982) to receive pancreatic cancer GVAX vaccine with low-dose cyclophosphamide alone (Arm A; n = 16), with anti-PD-1 antibody nivolumab (Arm B; n = 14), and with both nivolumab and anti-CD137 agonist antibody urelumab (Arm C; n = 10), respectively. The primary endpoint for Arms A/B - treatment-related change in IL17A expression in vaccine-induced lymphoid aggregates - was previously published. Here, we report the primary endpoint for Arms B/C: treatment-related change in intratumoral CD8+ CD137+ cells and the secondary outcomes including safety, disease-free and overall survivals for all Arms. Treatment with GVAX+nivolumab+urelumab meets the primary endpoint by significantly increasing intratumoral CD8+ CD137+ cells (p = 0.003) compared to GVAX+Nivolumab. All treatments are well-tolerated. Median disease-free and overall survivals, respectively, are 13.90/14.98/33.51 and 23.59/27.01/35.55 months for Arms A/B/C. GVAX+nivolumab+urelumab demonstrates numerically-improved disease-free survival (HR = 0.55, p = 0.242; HR = 0.51, p = 0.173) and overall survival (HR = 0.59, p = 0.377; HR = 0.53, p = 0.279) compared to GVAX and GVAX+nivolumab, respectively, although not statistically significant due to small sample size. Therefore, neoadjuvant and adjuvant GVAX with PD-1 blockade and CD137 agonist antibody therapy is safe, increases intratumoral activated, cytotoxic T cells, and demonstrates a potentially promising efficacy signal in resectable pancreatic adenocarcinoma that warrants further study.

ABSTRACTSouth Africa is the epicentre of the HIV pandemic. Although there have been health promotion education campaigns to reduce HIV incidence, these have not achieved the desired outcomes. When exploring the effectiveness of these campaigns, it is useful not only to examine HIV knowledge, but also to explore the relationship between that knowledge and health-related behaviour. This study aimed to determine the (1) level of knowledge of HIV prevention, (2) relationship between the level of knowledge and the adoption of these behaviours and (3) barriers to sexual behaviour change of vulnerable women in Durban’s city centre, KwaZulu-Natal, South Africa. A mixed methods approach was used to collect information from a marginalised population of women (n = 109) attending a non-governmental organisation, which provides for the needs of people from low socio-economic strata. Data were collected during September 2018 at a wellness day programme at the centre. A total of 109 women, over the age of 18 years answered the questionnaire. Knowledge of HIV transmission was high, with majority of participants correctly identifying modes of transmission. Almost all the participants (91.2%) had been tested for HIV, with 68.8% tested a minimum of three times. Despite this, sexual risk behaviour was high. Despite the high level of knowledge of HIV transmission, there was no relationship between HIV knowledge and adoption of behaviours for the prevention of HIV transmission (p = .457). However, bivariate analysis showed an association between transactional sex and living in informal housing (OR = 31.94, 95% CI: 5.65–180.63, p

Objectives: The goal of this study was to examine the contribution of sleep extension intervention components (wearable sleep tracker and coaching) on sleep extension outcomes. Patient involvement: This study collected open ended qualitative responses of treatment preference, acceptability, and feasibility as a key outcome. Methods: Adults aged 25 to 65 years with sleep duration

Leveraging the value of real-world evidence (RWE) to make informed regulatory decisions in the field of health care continues to gain momentum. Improving clinical evidence generation by evaluating the outcomes and patient experiences at the point-of-care would help achieve the ultimate aim of ensuring that effective and safe treatments are rapidly approved for patient use. In our previous publication, we assessed the global regulatory landscape with respect to RWE and provided a review of the regional availability of frameworks and guidance through May 2021 on the basis of 3 key regulatory elements: regulatory RWE frameworks, data quality guidance, and study methods guidance. In the current review, we have updated and elaborated upon recent developments in the regulatory RWE environment from a regional perspective under the same 3 regulatory elements stated above. In addition, we have also included a new category on procedural guidance. The review also discusses the perceived gaps and potential opportunities for future development and harmonization in this field to support framework establishment in regions without pre-existing RWE policies. Additionally, the article reviews current developments of health technology assessment (HTA) bodies pertaining to RWE and discusses the status of evidentiary alignment among regulators and HTA agencies.

Background and Aims: Biliary tract cancer (BTC) is a rare, lethal, heterogeneous group of cancers often diagnosed at an advanced stage. While gemcitabine plus cisplatin is the standard of care for first-line treatment of locally advanced or metastatic BTC, no globally accepted standard of care currently exists for second-line treatment of BTC following chemotherapy. However, the treatment landscape is evolving with approvals for therapies targeting actionable mutations. This study aimed to characterize treatment patterns and survival in patients with locally advanced or metastatic BTC. Methods: Patients with advanced or metastatic BTC in the Surveillance, Epidemiology, and End Results Medicare database between 2010 and 2015 (N = 2063) were included; patients with nonprimary BTC were excluded. Patient and clinical characteristics, line and type of therapy, and overall survival of patients were analyzed. Results: Only 45.5% (n = 938) of patients initiated systemic therapy within 90 days of diagnosis. The most common event following diagnosis was initiation of first-line therapy, and the most common event following first-line treatment was death. Median survival ranged from 5.0 months for patients receiving second-line fluoropyrimidine to 9.7 months for patients receiving second-line gemcitabine. Duration of therapy ranged from 0.7 months for patients receiving second-line fluoropyrimidine to 3.7 months for patients receiving first-line gemcitabine plus cisplatin therapy. Conclusion: Overall survival from diagnosis was poor and influenced by age, sex, stage, mobility limitations, comorbidity burden, poverty, and previous cancer. Treatment patterns varied for patients who progressed following first-line therapy, as there was no consensus second-line treatment for locally advanced or metastatic BTC without clinically targetable mutations.

While animal model studies have extensively defined the mechanisms controlling cell diversity in the developing mammalian lung, there exists a significant knowledge gap with regards to late-stage human lung development. The NHLBI Molecular Atlas of Lung Development Program (LungMAP) seeks to fill this gap by creating a structural, cellular and molecular atlas of the human and mouse lung. Transcriptomic profiling at the single-cell level created a cellular atlas of newborn human lungs. Frozen single-cell isolates obtained from two newborn human lungs from the LungMAP Human Tissue Core Biorepository, were captured, and library preparation was completed on the Chromium 10X system. Data was analyzed in Seurat, and cellular annotation was performed using the ToppGene functional analysis tool. Transcriptional interrogation of 5500 newborn human lung cells identified distinct clusters representing multiple populations of epithelial, endothelial, fibroblasts, pericytes, smooth muscle, immune cells and their gene signatures. Computational integration of data from newborn human cells and with 32,000 cells from postnatal days 1 through 10 mouse lungs generated by the LungMAP Cincinnati Research Center facilitated the identification of distinct cellular lineages among all the major cell types. Integration of the newborn human and mouse cellular transcriptomes also demonstrated cell type-specific differences in maturation states of newborn human lung cells. Specifically, newborn human lung matrix fibroblasts could be separated into those representative of younger cells (n = 393), or older cells (n = 158). Cells with each molecular profile were spatially resolved within newborn human lung tissue. This is the first comprehensive molecular map of the cellular landscape of neonatal human lung, including biomarkers for cells at distinct states of maturity.

Background Automatic noninvasive oscillometric blood pressure (NIBP) devices measure mean arterial pressure (MAP); systolic and diastolic blood pressure (SBP, DBP) are algorithmically derived from MAP. The most invalid NIBP measure is SBP, yet stroke practitioners use it to manage blood pressure (BP) in accordance with thrombolysis guidelines. We determined agreement between SBP, DBP, and MAP measured manually and by NIBP in patients treated with alteplase. Methods A multisite prospective observational study of NIBP and manual BP agreement was conducted in patients treated with alteplase immediately after bolus and infusion initiation using methods established in guidelines for the assessment of device agreement. Dual auscultatory stethoscopes were used by 2 investigators to ensure agreement with each manual BP variable and MAP was calculated using the standard formula for manual BP measures. Data were analyzed using Bland–Altman analyses and Lin concordance correlation coefficient. Results A total of 7 hospitals participated, collecting 5 sets of manual/NIBP BPs in 95 patients treated with alteplase (475 paired measures). Range in limits of agreement were SBP: −28.91 to 21.41 mmHg with Lin's concordance correlation coefficient 0.8; DBP: −21.0 to 19.0 mmHg with Lin's concordance correlation coefficient 0.69; and MAP: −27.5 to 16.5 mmHg with Lin's concordance correlation coefficient 0.7. There was no difference in device agreement by BP device manufacturer brand. Differences in SBP, DBP, and MAP between NIBP and manual sphygmomanometry failed to reach guideline recommendations requiring 80% of measures to fall within a 5 mmHg difference and 95% of measures to fall within a 10 mmHg difference. Conclusion NIBP devices produce significantly different BP measures then manual sphygmomanometry auscultated BP. Because NIBP devices rely on the MAP and do not directly measure SBP and DBP, definition of what constitutes safe MAP boundaries in patients treated with alteplase should be determined when automatic BP measurement is used in clinical practice.

Abstract Restriction to analysis of births that survive past a specified gestational age (typically 20 weeks gestation) leads to biased exposure-outcome associations. This bias occurs when the cause of restriction (early pregnancy loss) is influenced by both the exposure and unmeasured factors that also affect the outcome. The aim of this study is to estimate the magnitude of bias resulting from left truncated data in the association between advanced maternal age and stillbirth. We simulated data for the causal pathway under a collider-stratification mechanism. Simulation parameters were based on an observed birth cohort from Western Australia and a range of plausible values for the prevalence of early pregnancy loss, unmeasured factor U and the odds ratios for the selection effects. Selection effects included the effects of maternal age on early pregnancy loss, U on early pregnancy loss, and U on stillbirth. We compared the simulation scenarios to the observed birth cohort that was truncated to pregnancies that survived beyond 20 gestational weeks. We found evidence of marginal downward bias, which was most prominent for women aged 40 + years. Overall, we conclude that the magnitude of bias due to left truncation is minimal in the association between advanced maternal age and stillbirth.

Abstract Background Despite extensive benefits and high intentions, few mothers breastfeed exclusively for the recommended duration. Maternal mental health is an important underlying factor associated with barriers and reduced rates of breastfeeding intent, initiation, and continuation. Given evidence of a bidirectional association between maternal mental health and breastfeeding, it is important to consider both factors when examining the efficacy of interventions to improve these outcomes. The purpose of this manuscript is to review the literature on the efficacy of behavioral interventions focused on both maternal mental health and breastfeeding outcomes, examining the intersection of the two. Methods This systematic review was completed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. Studies were selected if they were available in English, used primary experimental design, and used a behavioral intervention type to examine maternal mental health and breastfeeding outcomes. Articles were identified from PubMed, CINAHL, Embase, and PsycINFO from database inception to 3 March 2022. Study quality was assessed using the Cochrane Risk of Bias tool. Results were synthesized by intervention success for 1. Mental health and breastfeeding, 2. Breastfeeding only, 3. Mental health only, and 4. No intervention effect. PROSPERO CRD42021224228. Results Thirty interventions reported in 33 articles were identified, representing 15 countries. Twelve studies reported statistically significant positive effect of the intervention on both maternal mental health and breastfeeding; most showing a decrease in self-report depressive and/or anxiety symptoms in parallel to an increase in breastfeeding duration and/or exclusivity. Common characteristics of successful interventions were a) occurring across pregnancy and postpartum, b) delivered by hospital staff or multidisciplinary teams, c) offered individually, and d) designed to focus on breastfeeding and maternal mental health or on breastfeeding only. Our results are not representative of all countries, persons, experiences, circumstances, or physiological characteristics. Conclusions Interventions that extend the perinatal period and offer individualized support from both professionals and peers who collaborate through a continuum of settings (e.g., health system, home, and community) are most successful in improving both mental health and breastfeeding outcomes. The benefits of improving these outcomes warrant continued development and implementation of such interventions. Systematic review registration PROSPERO CRD42021224228.

Abstract Background Despite improvements in treatment regimens and technology, less than 20% of adults with type 1 diabetes (T1D) achieve glycemic targets. Sleep is increasingly recognized as a potentially modifiable target for improving glycemic control. Diabetes distress, poor self-management behaviors, and reduced quality of life have also been linked to sleep variability and insufficient sleep duration. A significant gap of knowledge exists regarding interventions to improve sleep and the effects of sleep optimization on glycemic control in T1D. The purpose of this study is to determine the efficacy of a T1D-specific sleep optimization intervention (Sleep-Opt) on the primary outcomes of sleep variability, sleep duration, and glycemic control (A1C); other glycemic parameters (glycemic variability, time-in-range [TIR]); diabetes distress; self-management behaviors; quality of life; and other patient-reported outcomes in adults with T1D and habitual increased sleep variability or short sleep duration. Methods A randomized controlled parallel-arm study will be employed in 120 adults (aged 18 to 65 years) with T1D. Participants will be screened for habitual sleep variability (> 1 h/week) or insufficient sleep duration (< 6.5 h per night). Eligible subjects will be randomized to the Sleep-Opt intervention group or healthy living attention control group for 12 weeks. A 1-week run-in period is planned, with baseline measures of sleep by actigraphy (sleep variability and duration), glycemia (A1C and related glycemic measures: glycemic variability and TIR using continuous glucose monitoring), and other secondary outcomes: diabetes distress, self-management behaviors, quality of life, and additional patient-reported outcomes. Sleep-Opt is a technology-assisted behavioral sleep intervention that we recently developed that leverages the rapidly increasing public interest in sleep tracking. Our behavioral intervention employs four elements: a wearable sleep tracker, didactic content, an interactive smartphone application, and brief telephone counseling. The attention control group will participate in a healthy living information program. Baseline measures will be repeated at midpoint, program completion, and post-program (weeks 6, 12, and 24, respectively) to determine differences between the two groups and sustainability of the intervention. Discussion A better understanding of strategies to improve sleep in persons with T1D has the potential to be an important component of diabetes. Trial registration Clinical Trial Registration: NCT04506151 .

Abstract Background Tropomyosin receptor kinases (TrkA, TrkB, TrkC) are a family of tyrosine kinases primarily expressed in neuronal cells of the brain. Identification of oncogenic alterations in Trk expression as a driver in multiple tumor types has increased interest in their role in human cancers. Recently, first- and second-generation 11C and 18F-labeled Trk inhibitors, e.g., [18F]TRACK, have been developed. The goal of the present study was to analyze the direct interaction of [18F]TRACK with peripheral Trk receptors in vivo to prove its specificity for use as a functional imaging probe. Methods In vitro uptake and competition experiments were carried out using the colorectal cancer cell line KM12. Dynamic PET experiments were performed with [18F]TRACK, either alone or in the presence of amitriptyline, an activator of Trk, entrectinib, a Trk inhibitor, or unlabeled reference compound TRACK in KM12 tumor-bearing athymic nude mice as well as B6129SF2/J and corresponding B6;129S2-Ntrk2 tm1Bbd /J mice. Western blot and immunohistochemistry experiments were done with KM12 tumors, brown adipose tissue (BAT), and brain tissue samples. Results Uptake of [18F]TRACK was increasing over time reaching 208 ± 72% radioactivity per mg protein (n = 6/2) after 60 min incubation time. Entrectinib and TRACK competitively blocked [18F]TRACK uptake in vitro (IC50 30.9 ± 3.6 and 29.4 ± 9.4 nM; both n = 6/2). [18F]TRACK showed uptake into KM12 tumors (SUVmean,60 min 0.43 ± 0.03; n = 6). Tumor-to-muscle ratio reached 0.9 (60 min) and 1.2 (120 min). In TrkB expressing BAT, [18F]TRACK uptake reached SUVmean,60 min 1.32 ± 0.08 (n = 7). Activation of Trk through amitriptyline resulted in a significant radioactivity increase of 21% in KM12 tumor (SUVmean,60 min from 0.53 ± 0.01 to 0.43 ± 0.03; n = 6; p TrkA expression on BAT fat cells, but TrkA > TrkB in whole brain. WB analysis showed sevenfold higher TrkB expression in BAT versus KM12 tumor tissue. Conclusion The present data show that radiotracer [18F]TRACK can target peripheral Trk receptors in human KM12 colon cancer as well as brown adipose tissue as confirmed through in vitro and in vivo blocking experiments. Higher TrkB versus TrkA protein expression was detected in brown adipose tissue of mice confirming a peripheral functional role of brain-derived neurotrophic factor in adipose tissue.

Abstract Objectives Women with a history of gestational diabetes (GDM) are at 7-fold increase in the risk of developing diabetes. Insufficient sleep has also been shown to increase diabetes risk. This study aimed to explore the feasibility of a sleep extension in women with a history of GDM and short sleep, and effects on glucose metabolism. Methods Women age 18–45 years with a history of GDM and actigraphy confirmed short sleep duration (

ABSTRACT: Background: Following a study of predictors of superinfection in viral respiratory tract infections (VRTIs), this study analyzes the predictors of the outcome. Methods: Multicenter retrospective study conducted among adults who tested positive for VRTIs with reverse-transcription polymerase chain reaction. We compared characteristics between influenza virus, Paramyxoviridae, and Pneumoviridae and identified predictors of favorable short-term outcome, admission to the intensive care unit (ICU), and mortality. Results: A total of 590 patients had VRTI, including 347 (59%) influenza infections. Mean (SD) patient age was 71.0 (18.3) years, with a sex ratio of 0.91. In multivariate analyses, predictors of favorable short-term outcome were age ≤75 years (adjusted odds ratio [aOR] 5.38 [95% confidence interval, 1.59-18.2]), absence of respiratory disease (4.94 [1.01-24.37]), and absence of superinfection (aOR 3.91 [1.37-11.13]). The predictors of ICU admission were age ≤75 years (aOR 3.28 [1.71-6.25]), chronic respiratory disease (aOR 2.49 [1.20-5.19]), and procalcitonin level >0.25 ng/mL (aOR 4.25 [1.55-11.67]). Predictors of mortality were use of inhaled corticosteroids (2.49 [1.10-5.63]), influenza infection (2.73 [1.27-5.85]), Charlson score ≥5 (5.35 [1.90-15.05]), superinfection (2.54 [1.05-6.18]), and eosinophil count

Abstract Background Chronic kidney disease (CKD) is a very common long-term condition and powerful risk factor for cardiovascular disease (CVD). Low-dose aspirin is of proven benefit in the secondary prevention of myocardial infarction (MI) and stroke in people with pre-existing CVD. However, in people without CVD, the rates of MI and stroke are much lower, and the benefits of aspirin in the primary prevention of CVD are largely balanced by an increased risk of bleeding. People with CKD are at greatly increased risk of CVD and so the absolute benefits of aspirin are likely to be greater than in lower-risk groups, even if the relative benefits are the same. Post hoc evidence suggests the relative benefits may be greater in the CKD population but the risk of bleeding may also be higher. A definitive study of aspirin for primary prevention in this high-risk group, recommended by the National Institute for Health and Care Excellence (NICE) in 2014, has never been conducted. The question has global significance given the rising burden of CKD worldwide and the low cost of aspirin. Methods ATTACK is a pragmatic multicentre, prospective, randomised, open-label, blinded endpoint adjudication superiority trial of aspirin 75 mg daily vs. standard care for the primary prevention of CVD in 25,210 people aged 18 years and over with CKD recruited from UK Primary Care. Participants aged 18 years and over with CKD (GFR category G1-G4) will be identified in Primary Care and followed up using routinely collected data and annual questionnaires for an average of 5 years. The primary outcome is the time to first major vascular event (composite of non-fatal MI, non-fatal stroke and cardiovascular death [excluding confirmed intracranial haemorrhage and other fatal cardiovascular haemorrhage]). Deaths from other causes (including fatal bleeding) will be treated as competing events. The study will continue until 1827 major vascular events have occurred. The principal safety outcome is major intracranial and extracranial bleeding; this is hypothesised to be increased in those randomised to take aspirin. The key consideration is then whether and to what extent the benefits of aspirin from the expected reduction in CVD events exceed the risks of major bleeding. Discussion This will be the first definitive trial of aspirin for primary CVD prevention in CKD patients. The research will be of great interest to clinicians, guideline groups and policy-makers, in the UK and globally, particularly given the high and rising prevalence of CKD that is driven by population ageing and epidemics of obesity and diabetes. The low cost of aspirin means that a positive result would be of relevance to low- and middle-income countries and the impact in the developed world less diluted by any inequalities in health care access. Trial registration ISRCTN: ISRCTN40920200 . EudraCT: 2018-000644-26 . ClinicalTrials.gov: NCT03796156

Rationale. In-hospital falls and delirium are important events to understand in the hospital setting. Although the link between these events is well described, the impact on patient outcomes and the health system necessitates duplication with the use of accessible delirium screening tools. Aims and Objectives. To understand the association of delirium and falls. Methods. A cross-sectional study using delirium screening and falls reports was used to measure the association between delirium and falls. All inpatient data from August, 2018, to January, 2020, at a large academic medical center were analyzed. A multivariable logistic regression of 29,655 hospital admissions was used to understand the association between in-hospital delirium and falls. Results. Analysis revealed a delirium rate of 12.5% (n = 3,707) of all admissions and 286 (0.9%) admissions with falls; of the falls studied, 37.6% of these patients screened positive for delirium during their admission. Relative to those who screened negative for delirium, admissions that screened positive for delirium had a 2.81 increased odds of falling. Conclusions. Delirium and falls are related. This strong association should motivate health systems to look closely at both problems. Falls and delirium can both have immense impacts on the patient and the health system. The powerful association between them provides a window to reduce these additional patient harms. More specifically, a modern delirium screening tool should be used as part of routine risk assessment focused on reducing in-hospital falls.

Abstract Background Multiple clinical prediction rules have been published to risk-stratify febrile infants ≤60 days of age for serious bacterial infections (SBI), which is present in 8-13% of infants. We evaluate the cost-effectiveness of strategies to identify infants with SBI in the emergency department. Methods We developed a Markov decision model to estimate outcomes in well-appearing, febrile term infants, using the following strategies: Boston, Rochester, Philadelphia, Modified Philadelphia, Pediatric Emergency Care Applied Research Network (PECARN), Step-by-Step, Aronson, and clinical suspicion. Infants were categorized as low risk or not low risk using each strategy. Simulated cohorts were followed for 1 year from a healthcare perspective. Our primary model focused on bacteremia, with secondary models for urinary tract infection and bacterial meningitis. One-way, structural, and probabilistic sensitivity analyses were performed. The main outcomes were SBI correctly diagnosed and incremental cost per quality-adjusted life-year (QALY) gained. Results In the bacteremia model, the PECARN strategy was the least expensive strategy ($3671, 0.779 QALYs). The Boston strategy was the most cost-effective strategy and cost $9799/QALY gained. All other strategies were less effective and more costly. Despite low initial costs, clinical suspicion was among the most expensive and least effective strategies. Results were sensitive to the specificity of selected strategies. In probabilistic sensitivity analyses, the Boston strategy was most likely to be favored at a willingness-to-pay threshold of $100,000/QALY. In the urinary tract infection model, PECARN was preferred compared to other strategies and the Boston strategy was preferred in the bacterial meningitis model. Conclusions The Boston clinical prediction rule offers an economically reasonable strategy compared to alternatives for identification of SBI.

Objective : Pulmonary vein stenosis (PVS) is an emerging cause of pulmonary hypertension in preterm infants. It is an often lethal condition with poor long.term prognosis and high mortality. Previous work suggests an association between necrotizing enterocolitis (NEC) and PVS, supporting a possible role for inflammatory processes due to gastrointestinal (GI) pathology as an associated risk factor for PVS. Study Description : We performed a matched case–control study where infants with PVS were matched for gestational age with infants without PVS. Hospital records were reviewed for prior history of NEC or other gut pathology. Results : Twenty-four PVS patients were matched with 68 controls; 63% of patients (15/24) had prior GI pathology as opposed to 19% (13/68) of controls. The GI pathology group had a significantly higher growth restriction and C-reactive protein. The mean gradient across the pulmonary veins was higher in the gut pathology group versus controls, as was mortality (29% vs. 9%). Conclusions : The previously described association between PVS and intestinal pathology was further strengthened by this study. The presence of GI pathology should lead to early surveillance and intervention for PVS.

Cytogenetically cryptic acute promyelocytic leukemia (APL) is rare, characterized by typical clinical and morphological features, but lacks t(15;17)(q24;q21)/PML::RARA translocation seen in conventional karyotyping or FISH. The prompt diagnosis and treatment of APL are critical due to life-threatening complications associated with this disease. However, cryptic APL cases remain a diagnostic challenge that could mislead the appropriate treatment. We describe four cryptic APL cases and review reported cases in the literature. Reverse transcriptase polymerase chain reaction (RT-PCR) is the most efficient diagnostic modality to detect these cases, and alternative methods are also discussed. This study highlights the importance of using parallel testing methods to diagnose cryptic APL cases accurately and effectively.

BackgroundThe World Health Organization recommends to wait at least 6 months after miscarriage and induced abortion before becoming pregnant again to avoid complications in the next pregnancy, although the evidence-based underlying this recommendation is scarce. We aimed to investigate the risk of adverse pregnancy outcomes-preterm birth (PTB), spontaneous PTB, small for gestational age (SGA) birth, large for gestational age (LGA) birth, preeclampsia, and gestational diabetes mellitus (GDM)-by interpregnancy interval (IPI) for births following a previous miscarriage or induced abortion.Methods and findingsWe conducted a cohort study using a total of 49,058 births following a previous miscarriage and 23,707 births following a previous induced abortion in Norway between 2008 and 2016. We modeled the relationship between IPI and 6 adverse pregnancy outcomes separately for births after miscarriages and births after induced abortions. We used log-binomial regression to estimate unadjusted and adjusted relative risk (aRR) and 95% confidence intervals (CIs). In the adjusted model, we included maternal age, gravidity, and year of birth measured at the time of the index (after interval) births. In a sensitivity analysis, we further adjusted for smoking during pregnancy and prepregnancy body mass index. Compared to births with an IPI of 6 to 11 months after miscarriages (10.1%), there were lower risks of SGA births among births with an IPI of 12 months after either a miscarriage or induced abortion (p > 0.05), with the exception of an increased risk of GDM among women with an IPI of 12 to 17 months (5.8%) (aRR 1.20, 95% CI: 1.02, 1.40, p = 0.02), 18 to 23 months (6.2%) (aRR 1.24, 95% CI: 1.02, 1.50, p = 0.03), and ≥24 months (6.4%) (aRR 1.14, 95% CI: 0.97, 1.34, p = 0.10) compared to an IPI of 6 to 11 months (4.5%) after a miscarriage. Inherent to retrospective registry-based studies, we did not have information on potential confounders such as pregnancy intention and health-seeking bahaviour. Furthermore, we only had information on miscarriages that resulted in contact with the healthcare system.ConclusionsOur study suggests that conceiving within 3 months after a miscarriage or an induced abortion is not associated with increased risks of adverse pregnancy outcomes. In combination with previous research, these results suggest that women could attempt pregnancy soon after a previous miscarriage or induced abortion without increasing perinatal health risks.

Summary Although mechanisms involved in response of Saccharomyces cerevisiae to osmotic challenge are well described for low and sudden stresses, little is known about how cells respond to a gradual increase of the osmotic pressure (reduced water activity; aw) over several generations as it could encounter during drying in nature or in food processes. Using glycerol as a stressor, we propagated S. cerevisiae through a ramp of the osmotic pressure (up to high molar concentrations to achieve testing‐to‐destruction) at the rate of 1.5 MPa day‐1 from 1.38 to 58.5 MPa (0.990–0.635 aw). Cultivability (measured at 1.38 MPa and at the harvest osmotic pressure) and glucose consumption compared with the corresponding sudden stress showed that yeasts were able to grow until about 10.5 MPa (0.926 aw) and to survive until about 58.5 MPa, whereas glucose consumption occurred until 13.5 MPa (about 0.915 aw). Nevertheless, the ramp conferred an advantage since yeasts harvested at 10.5 and 34.5 MPa (0.778 aw) showed a greater cultivability than glycerol‐shocked cells after a subsequent shock at 200 MPa (0.234 aw) for 2 days. FTIR analysis revealed structural changes in wall and proteins in the range 1.38–10.5 MPa, which would be likely to be involved in the resistance at extreme osmotic pressure.

Preparing a scientific poster and presenting it at a conference supports the development of a range of skills in undergraduates that are relevant to further study and the workplace. This investigation focused on an asynchronous online poster session in a final year undergraduate science module at a UK university to assess evidence of higher-order skills development and determine student perceptions of the benefits and challenges of participating in the session. The study analysed 100 randomly selected posters from the 2020 session for evidence of scientific understanding, application, and critical evaluation, together with the feedback received on them. While 73% of the posters demonstrated understanding and 70% application, a lower proportion (42%) demonstrated critical evaluation skills. Seventy-eight percent of posters were considered to have received feedback from peers that gave an effective or partially effective evaluation of scientific content. Focus group discussions involving nine students led to the identification of themes relating to constraints, academic challenges, skills and experience, and personal development. Students recognized the value of the conference for skills development and the experience it gave of “real” science, while acknowledging the challenges involved in producing posters, giving feedback to peers, and managing their time. The asynchronous online poster session enabled students to develop higher-order cognitive and communication skills that are valued by employers. This format provides a pragmatic and easy to implement alternative to synchronous online conferences, which is relevant to the shift toward online learning in higher education, due to the COVID-19 pandemic and increase in distance learning and international students.

Objectives Studies showed that short interpregnancy interval - time between birth of the previous (index) child to the conception of the next - is associated with adverse perinatal and maternal outcomes, impacting sibling relations, parenting, and couple relations. This study aims to investigate the demographic and obstetric determinants of short interpregnancy interval in Western Australia. Approach We used a longitudinal study using data linkage obtained from Western Australian Midwives Notification System and Hospital Morbidity Data System for 150,712 women who gave births between 2006 and 2010. We estimated unadjusted and adjusted hazard ratio (aHR) and 95% CI using Gompertz gamma shared frailty model. In the study, event was deemed when women conceived within 18 months after index (previous) births. Otherwise, we considered as censored when women conceived after 18 months of the index births or if they did not conceive until the last date of the follow up period (31st December 2015). Results We found that 20% (n=30,916) of births in WA conceived within 18 months after the index pregnancy. We found that women aged

Objectives Restriction to the analysis of births that survive past a specified gestational age (typically 20 weeks gestation) can lead to biased exposure-outcome associations. The objective is to estimate the influence of bias resulting from using a left truncated dataset to ascertain exposure-outcome associations in perinatal studies. Approach We simulated the magnitude of bias under a collider-stratification mechanism for the association between the exposure of advancing maternal age (≥ 35 years) and the outcome of stillbirth. This bias occurs when the cause of restriction (early pregnancy loss) is influenced by both the exposure and unmeasured factors that also affect the outcome. Simulation parameters were based on an original birth cohort from Western Australia and a range of plausible values for the prevalence of early pregnancy loss (< 20 gestational weeks), an unmeasured factor U and the odds ratios for the selection effects. Selection effects included the effects of maternal age on early pregnancy loss, U on early pregnancy loss, and U on stillbirth. We then compared the simulated scenarios with the results from the original cohort in which bias was unadjusted. Results We found the overall magnitude of bias to be minimal in the association between advancing maternal age and stillbirth. The findings indicate that the stronger the effect of the unmeasured U on early pregnancy loss and stillbirth, the greater the departure from the null. When we compared the simulated model with the results of the original cohort, we found evidence of marginal downward bias which was most prominent for women aged 40+ years. Discussion Our simulations demonstrated a marginal downward bias in the association between advancing maternal age and stillbirth. We recommend that future studies should quantify the extent of such bias when using left truncated birth datasets to determine exposure-outcome associations.