Clinical characteristics and predictors of neonatal outcomes in chorioamnionitis at term gestation: A cohort study.

OBJECTIVE: To investigate the association between clinical and laboratory characteristics of chorioamnionitis in deliveries at term gestation with adverse neonatal outcomes. DESIGN: Retrospective cohort study. SETTING: The study is based on data from the Swedish Pregnancy Register, enriched with clinical data extracted from medical charts. SAMPLE: A cohort of 500 term singleton deliveries in Stockholm County with registered diagnosis of chorioamnionitis (based on the assessment of the responsible obstetrician) in the Swedish Pregnancy Register between 2014 and 2020. METHODS: Logistic regression was used to estimate odds ratios (ORs) as a measurement of the association between clinical and laboratory characteristics and neonatal complications. MAIN OUTCOME MEASURES: Neonatal infection and asphyxia-related complications. RESULTS: The prevalence of neonatal infection and asphyxia-related complications was 10% and 22%, respectively. First leukocyte count in the second tertile (OR 2.14, 95% CI 1.02-4.49), maximum C-reactive protein (CRP) level in the third tertile (OR 4.01, 95% Cl 1.66-9.68) and positive cervical culture (OR 2.22, 95% Cl 1.10-4.48) were associated with an increased risk of neonatal infection. Maximum level of CRP in the third tertile (OR 1.93, 95% Cl 1.09-3.41) and fetal tachycardia (OR 1.63, 95% Cl 1.01-2.65) were associated with an increased risk of asphyxia-related complications. CONCLUSIONS: Elevated inflammatory laboratory markers were associated with both neonatal infection and asphyxia-related complications, and fetal tachycardia was associated with asphyxia-related complications. Based on these findings, the incorporation of maternal CRP in the management of chorioamnionitis should be considered, and a continuous communication between obstetric and neonatal care extending past the delivery time point endorsed.

Diagnostic accuracy of a high-sensitivity troponin I assay and external validation of 0/3 h rule out strategies.

AIMS: The timely diagnosis and exclusion of acute coronary syndromes in the Emergency Department (ED) remains a challenge. This study aims to evaluate the diagnostic accuracy of a high-sensitivity cardiac troponin I assay (Siemens TNIH) on serial sampling for ED patients as standalone test and in rule-out algorithms as recommendations remain assay specific. METHODS AND RESULTS: This secondary analysis from a prospective diagnostic accuracy study at 14 centres included ED patients presenting with chest pain of suspected cardiac nature. Serum drawn on arrival and 3 h later was batchtested for TNIH. The target condition was an adjudicated diagnosis of acute myocardial infarction (AMI). We evaluated the diagnostic accuracy of absolute and relative delta criteria and four rule-out strategies. Of 802 included patients, 13.8% had AMI. Absolute delta criteria had superior accuracy to relative criteria (C-statistic 0.94 vs. 0.76, P < 0.001). However, no delta criteria achieved >95.5% sensitivity for AMI when used alone. Ruling out AMI with TNIH below the 99th percentile at 0 and 3 h had 88.3% (95% confidence interval 80.8-93.6%) sensitivity. The adapted European Society of Cardiology (ESC) 0/2 h algorithm had higher sensitivity (98.2%) than both High-STEACS (93.7%, P = 0.03) and the ESC 0/3 h algorithm (79.3%, P < 0.001). These pathways ruled out 63%, 74%, and 88% patients, respectively. CONCLUSION: With serial sampling over 3 h, the Siemens TNIH assay should be used with a validated algorithm incorporating bespoke cut-offs and absolute delta criteria. In our analysis, the adapted ESC 0/2 h algorithm had greatest sensitivity. 'Ruling out' AMI using the 99th percentile of the assay cannot be recommended.

The prognostic value of emergency department measured hypertension: A systematic review and meta-analysis.

OBJECTIVES: The objective was to assess the prognostic value of hypertension detected in the emergency department (ED). METHODS: The ED presents a unique opportunity to predict long-term cardiovascular disease (CVD) outcomes with its potential for high-footfall, and large-scale routine data collection applied to underserved patient populations. A systematic review and meta-analyses were conducted to assess the prognostic performance and feasibility of ED-measured hypertension as a risk factor for long-term CVD outcomes. We searched MEDLINE and Embase databases and gray literature sources. The target populations were undifferentiated ED patients. The prognostic factor of interest was hypertension. Feasibility outcomes included prevalence, reliability, and follow-up attendance. Meta-analyses were performed for feasibility using a random effect and exact likelihood. RESULTS: The searches identified 1072 studies after title and abstract review, 53 studies had their full text assessed for eligibility, and 26 studies were included. Significant heterogeneity was identified, likely due to the international populations and differing study design. The meta-analyses estimate of prevalence for ED-measured hypertension was 0.31 (95% confidence interval  0.25-0.37). ED hypertension was persistent outside the ED (FE estimate of 0.50). The proportion of patients attending follow-up was low with an exact likelihood estimate of 0.41. Three studies examined the prognostic performance of hypertension and demonstrated an increased risk of long-term CVD outcomes. CONCLUSION: Hypertension can be measured feasibly in the ED and consequently used in a long-term cardiovascular risk prediction model. There is an opportunity to intervene in targeted individuals, using routinely collected data.

A diagnostic evaluation of single screen testing for malaria in the returning traveler: A large retrospective cohort study.

BACKGROUND: Screening for malaria in the returning traveler has often required repeat testing; however, audit data suggest that patients have not been reattending. We sought to ascertain if this was safe by examining the diagnostic efficacy of a single screen consisting of a rapid diagnostic test (RDT) and a thin film. METHODS: We conducted a retrospective cohort study of patients with suspected malaria who attended in the past 5 years from two large teaching hospitals. We assessed the diagnostic accuracy of a single screen, reporting measures of sensitivity and specificity. To establish a reference standard, we cross-linked data with the national malaria registry held at Public Health England and regional centers. RESULTS: The cohort consisted of 1365 patients, of whom 33 opted out of the research and one did not have a complete initial screen. Of those 1331 screens there were 74 cases of Plasmodium falciparum (prevalence of 5.6%) and 104 of any malaria species (prevalence of 7.8%). Sensitivity for the detection of P. falciparum was 100.00% (95% confidence interval [CI] = 95.1 to 100), with a specificity of 99.4% (95% CI = 98.9 to 99.8). For the detection of any species of malaria the sensitivity was slightly lower due to the presence of one false negative; sensitivity was 99.0% (95% CI = 94.8 to 100) and specificity was 99.5% (95% CI = 98.9 to 99.8). CONCLUSIONS: A single thin film and RDT is likely to be sufficient as a first screen for falciparum malaria in the returning traveler with important caveats. For those sent home from emergency departments, appropriate safety netting must be provided. Further prospective study is required to investigate this approach.

Systematic literature search, review and dissemination methodology for the COVID-19 pandemic.

Purpose of the study: SARS-CoV-2 has caused healthcare systems globally to reorganise. A pandemic paradox emerged; while clinicians were desperate for information on a new disease, they had less time to find and evaluate the vast volume of publications at times of significant strain on healthcare systems.A multidisciplinary team undertook a weekly literature search capturing all COVID-19 publications. We also monitored free open access medical education (FOAMed) sources for emerging themes. Title and abstract screening pooled the most relevant papers for emergency medicine. Three summary types were created, a 'Top 5 Flash Update', a journal club and a rapid response to emerging FOAMed themes. From these summaries, three modes of dissemination were used: short written summaries, blogs and podcasts. These were amplified through social media. Study design: A retrospective review was conducted assessing the impact of this knowledge dissemination strategy for the period of March to September 2020. Results: In total, 64 687 papers were identified and screened. Of the papers included in the 'Top 5', 28.3% were on epidemiology, 23.6% treatment, 16.7% diagnostics, 12% prognosis, 8.7% pathophysiology with the remaining 10.7% consisting of PPE, public health, well-being and 'other'. We published 37 blogs, 17 podcasts and 18 Top 5 Flash Updates. The blogs were read 138 343 times, the Top 5 Flash Updates 68 610 times and the podcasts had 72 501 listens. Conclusion: A combination of traditional academic and novel social media approaches can address the pandemic paradox clinicians are facing.

BP1, a potential biomarker for breast cancer prognosis.

Homeobox genes are critical in tumor development. An isoform protein of DLX4 called BP1 is expressed in 80% of invasive ductal breast carcinomas. BP1 overexpression is implicated in an aggressive phenotype and poor prognosis. BP1 upregulation is associated with estrogen receptor negativity so those tumors do not respond to antiestrogens. Breast cancer is the second leading cause of death in women. BP1 could serve as both a novel prognostic biomarker for breast cancer and a therapeutic target. In this review, we address the role of BP1 protein in tumorigenesis of breast cancer and four other malignancies. A number of functions of BP1 in cancer are also discussed.

Association Between Health Beliefs and Gestational Weight Gain.

BACKGROUND: The Institute of Medicine (IOM) provides recommendations for optimal weight gain during pregnancy to minimize complications associated with obesity and excessive weight gain. The Health Belief Model and prior research suggest knowledge of health recommendations and associated risks motivate health behaviors. This study determined whether knowledge of maternal and infant obesity risks during pregnancy (ORDP) and knowledge of IOM gestational weight gain (GWG) recommendations were associated with total GWG and likelihood of adhering to IOM recommendations. MATERIALS AND METHODS: In this prospective survey study, healthy women with a singleton pregnancy were recruited from prenatal clinic waiting rooms of a university medical center to complete a one-time survey of prepregnancy weight and height, demographic variables, knowledge of infant-related ORDP (e.g., large for gestational age), knowledge of maternal-related ORDP (e.g., Cesarean delivery), and knowledge of IOM GWG recommendations. Total GWG was obtained from clinic medical records. Logistic and multiple regression analyses were performed. RESULTS: The sample consisted of 159 women with average age of 25 and prepregnancy body mass index of 28. Women in the sample were predominantly African American (57%) and from low socioeconomic conditions. Results showed (1) knowledge of GWG recommendations was inversely related to total GWG among normal and underweight women and (2) knowledge of infant-related ORDP was positively related to total GWG among overweight and obese women and the likelihood of exceeding recommendations among normal and underweight women. Knowledge of maternal-related ORDP was not related to GWG. CONCLUSION: As the Health Belief Model suggests, knowledge appears to be a modifiable factor in preventing excess GWG. However, there may be misinformation regarding how to adhere to clinical recommendations.

Validation of the (Troponin-only) Manchester ACS decision aid with a contemporary cardiac troponin I assay.

OBJECTIVES: The Manchester Acute Coronary Syndromes (MACS) decision aid can 'rules in' and 'rule out' acute coronary syndromes (ACS) by combining a patient's symptoms with the results of a single blood test taken at the time of arrival in the Emergency Department (ED). The original model (MACS) included two biomarkers: high sensitivity cardiac troponin T (hs-cTnT) and heart-type fatty acid binding protein (h-FABP). A refined model without h-FABP was found to have comparable sensitivity but greater specificity. We sought to validate MACS and T-MACS using the contemporary Siemens Advia Centaur cardiac troponin I assay to increase usability in practice. METHODS: This is a secondary analysis from prospective diagnostic cohort study at Stepping Hill Hospital, United Kingdom. Patients presenting with chest pain of suspected cardiac nature warranting rule out for ACS were included. All patients underwent hs-cTnT testing at least 12h after peak symptoms. The primary outcome was a diagnosis of ACS, defined as either prevalent acute myocardial infarction (AMI) or incident major adverse cardiac events (death, AMI or coronary revascularization) within 30days. RESULTS: Of 405 included patients, 76 (18.8%) had ACS. MACS and T-MACS had similar C-statistics (0.94 for each, p=0.36) and sensitivity (difference 1.3%, 95% CI -1.3 to 3.9%, p=1.00) but T-MACS had significantly greater specificity (difference 16.7%, 95% CI 14.6-18.9%, p<0.0001). T-MACS and MACS would have allowed 36.3% and 22.5% patients to be immediately discharged respectively. Of patients classified as 'very low risk', none had ACS when MACS was used compared to one (0.7%) with T-MACS. CONCLUSION: Both MACS and T-MACS effectively ruled out ACS even with a contemporary troponin I assay and could be used to reduce unnecessary hospital admissions.

The HEART score for early rule out of acute coronary syndromes in the emergency department: a systematic review and meta-analysis.

AIMS: The objective of this systematic review was to summarise the current evidence on the diagnostic accuracy of the HEART score for predicting major adverse cardiac events in patients presenting with undifferentiated chest pain to the emergency department. METHODS AND RESULTS: Two investigators independently searched Medline, Embase and Cochrane databases between 2008 and May 2016 identifying eligible studies providing diagnostic accuracy data on the HEART score for predicting major adverse cardiac events as the primary outcome. For the 12 studies meeting inclusion criteria, study characteristics and diagnostic accuracy measures were systematically extracted and study quality assessed using the QUADAS-2 tool. After quality assessment, nine studies including data from 11,217 patients were combined in the meta-analysis applying a generalised linear mixed model approach with random effects assumption (Stata 13.1). In total, 15.4% of patients (range 7.3-29.1%) developed major adverse cardiac events after a mean of 6 weeks' follow-up. Among patients categorised as 'low risk' and suitable for early discharge (HEART score 0-3), the pooled incidence of 'missed' major adverse cardiac events was 1.6%. The pooled sensitivity and specificity of the HEART score for predicting major adverse cardiac events were 96.7% (95% confidence interval (CI) 94.0-98.2%) and 47.0% (95% CI 41.0-53.5%), respectively. CONCLUSIONS: Patients with a HEART score of 0-3 are at low risk of incident major adverse cardiac events. As 3.3% of patients with major adverse cardiac events are 'missed' by the HEART score, clinicians must ask whether this risk is acceptably low for clinical implementation.

Feasibility of the Manchester Acute Coronary Syndromes (MACS) decision rule to safely reduce unnecessary hospital admissions: a pilot randomised controlled trial.

BACKGROUND: Observational studies suggest that the Manchester Acute Coronary Syndromes (MACS) decision rule can effectively 'rule out' and 'rule in' acute coronary syndromes (ACS) following a single blood test. In a pilot randomised controlled trial, we aimed to determine whether a large trial is feasible. METHODS: Patients presenting to two EDs with suspected cardiac chest pain were randomised to receive care guided by the MACS decision rule (intervention group) or standard care (controls). The primary efficacy outcome was a successful discharge from the ED, defined as a decision to discharge within 4 hours of arrival providing that the patient did not have a missed acute myocardial infarction (AMI) or develop a major adverse cardiac event (MACE: death, AMI or coronary revascularisation) within 30 days. Feasibility outcomes included recruitment and attrition rates. RESULTS: In total, 138 patients were included between October 2013 and October 2014, of whom 131 (95%) were randomised (66 to intervention and 65 controls). Nine (7%) patients had prevalent AMI and six (5%) had incident MACE within 30 days. All 131 patients completed 30-day follow-up and were included in the final analysis with no missing data for the primary analyses. Compared with standard care, a significantly greater proportion of patients whose care was guided by the MACS rule were successfully discharged within 4 hours (26% vs 8%, adjusted OR 5.45, 95% CI 1.73 to 17.11, p=0.004). No patients in either group who were discharged within 4 hours had a diagnosis of AMI or incident MACE within 30 days (0.0%, 95% CI 0% to 20.0% in the intervention group). CONCLUSIONS: In this pilot trial, use of the MACS rule led to a significant increase in safe discharges from the ED but a larger, fully powered trial remains necessary. Our findings seem to support the feasibility of that trial. TRIAL REGISTRATION NUMBER: ISRCTN 86818215. RESEARCH ETHICS COMMITTEE REFERENCE: 13/NW/0081. UKCRN REGISTRATION ID: 14334.

An exploration of patients' experiences of participation in a randomised controlled trial of the Manchester Acute Coronary Syndromes (MACS) decision rule.

BACKGROUND: As an important part of a pilot study to determine the feasibility of a large randomised controlled trial (RCT) comparing use of the Manchester Acute Coronary Syndromes (MACS) decision rule with standard care, we aimed to explore patient attitudes and potential barriers to participation in a trial of this nature. METHODS: We conducted a qualitative study nested within a pilot RCT comparing use of the MACS rule (which could enable some patients with chest pain to be discharged earlier) with standard care. Semi-structured interviews with consenting participants were conducted with reference to a bespoke topic guide. Interviews were audio recorded, transcribed verbatim and analysed using the Framework method with an inductive approach. RESULTS: The 10 interviewees expressed that participation in the trial was generally acceptable. All but one recommended participation to others. Participants who were in pain or anxious at the time of arrival reported that the initial invitation to participate in the trial was sometimes made too early. The approach was welcome, providing they had been given time to settle. Interviewees welcomed the opportunity that trial participation offered for them to play a more active role in their healthcare and to reduce unnecessary waiting time. Participants appeared to like the fact that participation in the trial might mean they could return home sooner and welcomed the provision of follow-up. Although several participants described being generally sceptical of medical research, they were amenable to participation in this trial. This appears to be because they agreed with the need for research in this field and perceived the intervention as non-invasive. CONCLUSIONS: Patients were positive about their participation in this RCT comparing the MACS rule with standard care. A number of areas for improving trial design were identified and should be considered in the planning of future large trials. TRIAL REGISTRATION: ISRCTN 86818215 RESEARCH ETHICS COMMITTEE REFERENCE: 13/NW/0081 UKCRN REGISTRATION ID: 14334.

Beta protein 1 homeoprotein induces cell growth and estrogen-independent tumorigenesis by binding to the estrogen receptor in breast cancer.

Expression of Beta Protein 1 (BP1), a homeotic transcription factor, increases during breast cancer progression and may be associated with tumor aggressiveness. In our present work, we investigate the influence of BP1 on breast tumor formation and size in vitro and in vivo. Cells overexpressing BP1 showed higher viability when grown in the absence of serum (p < 0.05), greater invasive potential (p < 0.05) and formed larger colonies (p < 0.004) compared with the controls. To determine the influence of BP1 overexpression on tumor characteristics, MCF-7 cells transfected with either empty vector (V1) or overexpressor plasmids (O2 and O4) were injected into the fat pads of athymic nude mice. Tumors grew larger in mice receiving O2 or O4 cells than in mice receiving V1 cells. Moreover, BP1 mRNA expression levels were positively correlated with tumor size in patients (p = 0.01). Interestingly, 20% of mice injected with O2 or O4 cells developed tumors in the absence of estrogen, while no mice receiving V1 cells developed tumors. Several mechanisms of estrogen independent tumor formation related to BP1 were established. These data are consistent with the fact that expression of breast cancer anti-estrogen resistance 1 (BCAR1) was increased in O2 compared to V1 cells (p < 0.01). Importantly, O2 cells exhibited increased proliferation when treated with tamoxifen, while V1 cells showed growth inhibition. Overall, BP1 overexpresssion in MCF-7 breast cancer cells leads to increased cell growth, estrogen-independent tumor formation, and increased proliferation. These findings suggest that BP1 may be an important biomarker and therapeutic target in ER positive breast cancer.

Does Body Satisfaction Help or Harm Overweight Teens? A 10-Year Longitudinal Study of the Relationship Between Body Satisfaction and Body Mass Index.

PURPOSE: This study examines the relationship between body satisfaction of overweight adolescents and 10-year changes in body mass index (BMI). METHODS: Participants who were overweight as adolescents (n = 496) were drawn from Project Eating and Activity in Teens and Young Adults (Project EAT), a 10-year longitudinal study. RESULTS: Among overweight girls, a significant difference in 10-year BMI change across baseline body satisfaction quartiles was observed. Overweight girls with the lowest body satisfaction at baseline had a nearly three unit greater increase in BMI at follow-up, compared with overweight girls in the high body satisfaction quartile; this difference has important clinical significance. Among overweight boys, no significant associations between body satisfaction quartile and change in BMI were not observed. CONCLUSION: Overall, findings indicate that among overweight adolescents, a high level of body satisfaction during adolescence was not harmful, and in fact may be beneficial for girls, in terms of long-term weight management. These findings refute the commonly held notion that overweight young people should be dissatisfied with their bodies to motivate positive change.

Factors associated with knowledge of personal gestational weight gain recommendations.

OBJECTIVES: Excess adiposity (obesity and excess gestational weight gain, GWG) during pregnancy (EADP) increases risk for gestational diabetes, preeclampsia, and child and maternal obesity. Personal GWG goals predict total GWG. Some estimates suggest only 30% of pregnant women have personal GWG goals that are congruent with Institute of Medicine GWG recommendations. The primary purpose of this study was to determine the extent to which perceived pre-pregnancy weight status, healthcare provider advice, knowledge of EADP risks, and value for healthy GWG predicted knowledge of GWG recommendations. The secondary purpose was to determine sources of GWG information among pregnant women. METHODS: Pregnant women with a confirmed singleton pregnancy completed a one-time survey in obstetric clinic waiting rooms. Logistic regression analysis was used. RESULTS: 246 predominantly African American, low income, overweight/obese women completed surveys. Average age was 25 (SD 5.3) and gestation age ranged from 7 to 40 weeks. Knowledge of pre-pregnancy weight status was the only unique predictor of GWG recommendation knowledge (B = .642, p = .03). The top three sources of GWG information were physicians, internet, and books. The least frequently reported sources of GWG information were other healthcare providers, community programs, and television. CONCLUSION: In low income diverse overweight/obese pregnant women, accurate pre-pregnancy weight status perception was the only significant unique predictor of knowledge of GWG recommendations. Physicians were the preferred source of GWG information. Clinicians should have frequent, ongoing conversations about weight status with women before, during, and after pregnancy.

Increased copy number of the DLX4 homeobox gene in breast axillary lymph node metastasis.

DLX4 is a homeobox gene strongly implicated in breast tumor progression and invasion. Our main objective was to determine the DLX4 copy number status in sentinel lymph node (SLN) metastasis to assess its involvement in the initial stages of the axillary metastatic process. A total of 37 paired samples of SLN metastasis and primary breast tumors (PBT) were evaluated by fluorescence in situ hybridization, quantitative polymerase chain reaction and array comparative genomic hybridization assays. DLX4 increased copy number was observed in 21.6% of the PBT and 24.3% of the SLN metastasis; regression analysis demonstrated that the DLX4 alterations observed in the SLN metastasis were dependent on the ones in the PBT, indicating that they occur in the primary tumor cell populations and are maintained in the early axillary metastatic site. In addition, regression analysis demonstrated that DLX4 alterations (and other DLX and HOXB family members) occurred independently of the ones in the HER2/NEU gene, the main amplification driver on the 17q region. Additional studies evaluating DLX4 copy number in non-SLN axillary lymph nodes and/or distant breast cancer metastasis are necessary to determine if these alterations are carried on and maintained during more advanced stages of tumor progression and if could be used as a predictive marker for axillary involvement.

Brief report: Teen sexting and psychosocial health.

The current study examines whether adolescents who report sexting exhibit more psychosocial health problems, compared to their non-sexting counterparts. Participants included 937 ethnically diverse male and female adolescents recruited and assessed from multiple high schools in southeast Texas. Measures included self-report of sexting, impulsivity, alcohol and drug use, and depression and anxiety symptoms. Teen sexting was significantly associated with symptoms of depression, impulsivity, and substance use. When adjusted for prior sexual behavior, age, gender, race/ethnicity, and parent education, sexting was only related to impulsivity and substance use. While teen sexting appears to correlate with impulsive and high-risk behaviors (substance use), we did not find sexting to be a marker of mental health.