Screening for Intimate Partner Violence in Trauma: Results of a Quality Improvement Project.

INTRODUCTION: Intimate partner violence (IPV) is common, especially among patients presenting with traumatic injury. We implemented an IPV screening program for patients admitted after trauma. We sought to determine whether specific demographic or clinical characteristics were associated with being screened or not screened for IPV and with IPV screen results. METHODS: Retrospective cohort study evaluating all patients admitted after trauma from July 2020-July 2022 in an Adult Level 1 Trauma Center. RESULTS: There were 4147 admissions following traumatic injury, of which 70% were men and 30% were women. The cohort was 46% White, 20% Asian, 15% Black, and 17% other races. Twenty-three percent were Hispanic or Latino/a. Seventy-seven percent were admitted for blunt injuries and 16% for penetrating injuries. Thirteen percent (n = 559) of the cohort was successfully screened for IPV. Screening rates did not differ by gender, race, or ethnicity. After adjustment for demographic and clinical factors, patients admitted to the intensive care unit were significantly less likely to be screened. Of the screened patients, 30% (165) screened positive. These patients were more commonly Hispanic or Latino/a, insured by Medicaid and presented with a penetrating injury. There were no differences in injury severity in patients who screened positive versus those who screened negative. CONCLUSIONS: There are significant barriers to universal screening for IPV, including injury acuity, in patients admitted following trauma. However, the 30% rate of positive screens for IPV in patients admitted following trauma highlights the urgent need to understand and address barriers to screening in trauma settings to enable universal screening.

Validated Calculators Predicting Cesarean Delivery After Induction: Accuracy in an External Population.

OBJECTIVE: To evaluate the performance of two previously published calculators in predicting cesarean delivery after induction of labor in an external population. METHODS: This was a cohort study including all nulliparous pregnant patients with singleton, term, vertex fetuses; intact membranes; and unfavorable cervices who underwent induction of labor between 2015 and 2017 at an academic tertiary care institution. Individual predicted cesarean risk scores were calculated with two previously published calculators. For each calculator, patients were stratified into three risk groups (lower, middle, and upper thirds) of approximately equivalent size. Predicted and observed incidences of cesarean delivery were compared with two-tailed binomial tests of probability in the overall population and in each risk group. RESULTS: A total of 846 patients met inclusion criteria, and 262 (31.0%) had cesarean deliveries, which was significantly lower than overall predicted rates of 40.0% and 36.2% with the two calculators (both P <.01). Both calculators significantly overestimated risk of cesarean delivery in higher risk tertiles (all P <.05). The areas under the receiver operating characteristic for both calculators were 0.57 or less in the overall population and in each risk group, suggesting poor predictive value. Higher predicted risk tertile in both calculators was not associated with any maternal or neonatal outcomes except wound infection. CONCLUSION: Both previously published calculators had poor performance in this population, with neither calculator accurately predicting the incidence of cesarean delivery. Patients and health care professionals might be discouraged regarding trial of labor induction by falsely high predicted risk-of-cesarean scores. We caution against widespread implementation of these calculators without further population-specific refinement and adjustment.

Contraceptive counseling and choices in pregnancies with maternal cardiac disease.

OBJECTIVE: Unplanned pregnancies in women with maternal cardiac disease (MCD) are associated with increased morbidity and mortality, but the majority of these individuals do not use highly reliable contraception on postpartum hospital discharge. Contraceptive counseling in this population outside of pregnancy is incomplete and counseling during pregnancy remains poorly characterized. Our objective was to evaluate the provision and quality of contraceptive counseling for individuals with MCD during pregnancy. METHODS: All individuals with MCD who delivered between 2008 and 2021 at a tertiary care institution with a multidisciplinary cardio-obstetrics team were sent a 27-question survey. A subset of questions were derived from the validated Interpersonal Quality in Family Planning (IQFP) survey, which emphasizes interpersonal connection, adequate information, and decision support for the individual. Each participant received a $15 gift card for survey completion. We performed chart review for clinical and demographic details, including cardiac risk score. RESULTS: Of 522 individuals to whom the survey was sent, 133 responded and met inclusion criteria. Overall, 67% discussed contraception with their general obstetrician, 36% with their maternal-fetal medicine (MFM) specialist, and 24% with their cardiologist. Compared to individuals with low cardiac risk scores, those with high cardiac risk scores had a nonsignificant trend toward being more likely to discuss contraception with a MFM provider (52% vs 33%, p = .08). 65% reported that their provider was 'excellent' or 'good' in all IQFP domains. Respondents valued providers who respected their autonomy and offered thorough counseling. Respondents disliked feeling pressured or uninformed about the safety of contraceptive options. CONCLUSION: Most individuals with MCD reported excellent contraceptive counseling during pregnancy. Additional work is needed to understand barriers to and enablers for effective, patient-centered contraceptive counseling and use in this population.

Million spot binding array platform for exploring and optimizing multiple simultaneous detection events.

Large-scale, high-throughput specificity assays to characterize binding properties within a competitive and complex environment of potential binder-target pairs remain challenging and cost prohibitive. Barcode cycle sequencing (BCS) is a molecular binding assay for proteins, peptides, and other small molecules that is built on a next-generation sequencing (NGS) chip. BCS uses a binder library and targets labeled with unique DNA barcodes. Upon binding, binder barcodes are ligated to target barcodes and sequenced to identify encoded binding events. For complete details on the use and execution of this protocol, please refer to Hong et al. (2022).

Target-switch SELEX: Screening with alternating targets to generate aptamers to conserved terminal dipeptides.

Systematic evolution of ligands by exponential enrichment (SELEX) encompasses a wide variety of high-throughput screening techniques for producing nucleic acid binders to molecular targets through directed evolution. We describe here the design and selection steps for discovery of DNA aptamers with specificity for the two consecutive N-terminal amino acids (AAs) of a small peptide (8-10 amino acids). This bead-based method may be adapted for applications requiring binders which recognize a specific portion of the desired target. For complete details on the use and execution of this protocol, please refer to Hong et al. (2022).

Investigating attitudes toward prenatal diagnosis and fetal therapy for spinal muscular atrophy.

OBJECTIVE: In utero SMA treatment could improve survival and neurologic outcomes. We investigated the attitudes of patients and parents with SMA regarding prenatal diagnosis, fetal therapies, and clinical trials. METHODS: A multidisciplinary team designed a questionnaire that Cure SMA electronically distributed to parents and patients (>18 years old) affected by SMA. Multivariable ordinal logistic regression was used to analyze associations between respondent characteristics and attitudes. RESULTS: Of 114 respondents (60% of whom were patients), only 2 were prenatally diagnosed. However, 91% supported prenatal testing and 81% felt there had been a delay in their diagnosis. Overall, 55% would enroll in a phase I trial for fetal antisense oligonucleotide (ASO) while 79% would choose an established fetal ASO/small molecule therapy. Overall, 61% would enroll in fetal gene therapy trials and 87% would choose fetal gene therapies. Patients were less likely to enroll in a fetal gene therapy trial than parents enrolling a child (OR 0.31, p < 0.05). Older parental age and believing there had been excessive delay in diagnosis were associated with an interest in enrolling in a fetal ASO trial (OR 1.04, 7.38, respectively, p < 0.05). CONCLUSION: In utero therapies are promising for severe genetic diseases. Patients with SMA and their parents view prenatal testing and therapies positively, with gene therapy being favored.

High-level correction of the sickle mutation is amplified in vivo during erythroid differentiation.

Background: A point mutation in sickle cell disease (SCD) alters one amino acid in the ß-globin subunit of hemoglobin, with resultant anemia and multiorgan damage that typically shortens lifespan by decades. Because SCD is caused by a single mutation, and hematopoietic stem cells (HSCs) can be harvested, manipulated, and returned to an individual, it is an attractive target for gene correction. Results: An optimized Cas9 ribonucleoprotein (RNP) with an ssDNA oligonucleotide donor together generated correction of at least one ß-globin allele in more than 30% of long-term engrafting human HSCs. After adopting a high-fidelity Cas9 variant, efficient correction with minimal off-target events also was observed. In vivo erythroid differentiation markedly enriches for corrected ß-globin alleles, indicating that erythroblasts carrying one or more corrected alleles have a survival advantage. Significance: These findings indicate that the sickle mutation can be corrected in autologous HSCs with an optimized protocol suitable for clinical translation.

Role of antibodies, inflammatory markers, and echocardiographic findings in postacute cardiopulmonary symptoms after SARS-CoV-2 infection.

Shortness of breath, chest pain, and palpitations occur as postacute sequelae of COVID-19, but whether symptoms are associated with echocardiographic abnormalities, cardiac biomarkers, or markers of systemic inflammation remains unknown. In a cross-sectional analysis, we assessed symptoms, performed echocardiograms, and measured biomarkers among adults more than 8 weeks after confirmed SARS-CoV-2 infection. We modeled associations between symptoms and baseline characteristics, echocardiographic findings, and biomarkers using logistic regression. We enrolled 102 participants at a median of 7.2 months following COVID-19 onset; 47 individuals reported dyspnea, chest pain, or palpitations. Median age was 52 years, and 41% of participants were women. Female sex, hospitalization, IgG antibody against SARS-CoV-2 receptor binding domain, and C-reactive protein were associated with symptoms. Regarding echocardiographic findings, 4 of 47 participants (9%) with symptoms had pericardial effusions compared with 0 of 55 participants without symptoms; those with effusions had a median of 4 symptoms compared with a median of 1 symptom in those without effusions. There was no strong evidence for a relationship between symptoms and echocardiographic functional parameters or other biomarkers. Among adults more than 8 weeks after SARS-CoV-2 infection, SARS-CoV-2 RBD antibodies, markers of inflammation, and, possibly, pericardial effusions are associated with cardiopulmonary symptoms. Investigation into inflammation as a mechanism underlying postacute sequelae of COVID-19 is warranted.

ProtSeq: Toward high-throughput, single-molecule protein sequencing via amino acid conversion into DNA barcodes.

We demonstrate early progress toward constructing a high-throughput, single-molecule protein sequencing technology utilizing barcoded DNA aptamers (binders) to recognize terminal amino acids of peptides (targets) tethered on a next-generation sequencing chip. DNA binders deposit unique, amino acid-identifying barcodes on the chip. The end goal is that, over multiple binding cycles, a sequential chain of DNA barcodes will identify the amino acid sequence of a peptide. Toward this, we demonstrate successful target identification with two sets of target-binder pairs: DNA-DNA and Peptide-Protein. For DNA-DNA binding, we show assembly and sequencing of DNA barcodes over six consecutive binding cycles. Intriguingly, our computational simulation predicts that a small set of semi-selective DNA binders offers significant coverage of the human proteome. Toward this end, we introduce a binder discovery pipeline that ultimately could merge with the chip assay into a technology called ProtSeq, for future high-throughput, single-molecule protein sequencing.

Operationalizing Human Immunodeficiency Virus Cure-related Trials with Analytic Treatment Interruptions During the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Pandemic: A Collaborative Approach.

Efforts to recognize and minimize the risk to study participants will be necessary to safely and ethically resume scientific research in the context of the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. These efforts are uniquely challenging in the context of human immunodeficiency virus (HIV) cure clinical trials, which often involve complex experimental therapy regimens and perhaps analytic treatment interruption, in which participants pause antiretroviral therapy. In this viewpoint, we discuss our approach to reopening an HIV cure trial in this context, with a focus on key considerations regarding study design, informed consent and participant education, and study implementation. These recommendations might be informative to other groups seeking to resume HIV cure research in settings similar to ours.

Neurotoxic envenomation by the South African coral snake (Aspidelaps lubricus): A case report.

The South African coral snake (Aspidelaps lubricus, Elapidae) has not previously been reported to cause any neurotoxic envenomations in humans. We recently treated a 44-year-old man who was bitten twice, once in each hand, by a captive South African coral snake (Aspidelaps lubricus) while feeding the female snake who had recently laid eggs. Approximately one hour after receiving the bite, he developed vomiting, respiratory failure requiring mechanical ventilation, and paralysis of the bulbar and upper extremity muscles, with retention of voluntary motor control in the lower extremities. Supportive care was provided, and paralysis and respiratory failure resolved spontaneously 12 hours after onset. No antivenom for this species is available. To our knowledge, this is the first published case report of significant human envenomation by Aspidelaps lubricus. Physicians, first responders, and herpetologists should be aware of the potential for neurotoxicity in humans.

A Simplified Protocol for the Treatment of Alcohol Withdrawal.

OBJECTIVES: The aim of the study was to evaluate a novel simplified tool for symptom-triggered treatment of alcohol withdrawal. METHODS: This retrospective cohort study involved inpatients in a county hospital with an International Classification of Diseases, Ninth Revision, Clinical Modification discharge diagnosis of alcohol withdrawal syndrome (AWS) or delirium tremens between January 1, 2007 and December 31, 2008. The study used the Highland Alcohol Withdrawal Protocol (HAWP)-a simplified derivative of the Revised Clinical Institute Withdrawal Assessment for Alcohol. Multivariable regression analysis was performed to compare severity of withdrawal to hospital length of stay, total dose of sedative given, and risk of complications. RESULTS: The study identified 442 patients with a primary diagnosis of AWS or delirium tremens, and those with another primary medical diagnosis complicated by alcohol withdrawal. After adjusting for demographic variables, each one-point increase in the initial and maximum HAWP scores correlated with an increase in the hospital length of stay of 0.3 days [95% confidence interval (95% CI), 0.17 to 0.43 days] and 0.45 days (95% CI, 0.32-0.57 days), and a 15.8 mg (95% CI, 6.6-25.1 mg) and 19.8 mg (95% CI, 11.1-28.5 mg) increase in the total dose of lorazepam given, respectively. The complication rate of seizures, intubations, pneumonia, and death was 13.1%, 12.9%, 6.1% and 0.9%, respectively; a composite endpoint of these outcomes also correlated with initial and maximum HAWP scores (odds ratio 1.09, 95% CI, 1.03%-1.14%). CONCLUSIONS: The HAWP correlates with medication received and complications, and as such appears to give an indication of AWS severity. It is feasible and shorter than prior scales, and merits further study to confirm its effectiveness as part of symptom-triggered protocols to manage alcohol withdrawal in the hospital.

Semiconducting Polymer Nanoparticles with Persistent Near-Infrared Luminescence for In Vivo Optical Imaging.

Materials with persistent luminescence are attractive for in vivo optical imaging since they have a long lifetime that allows the separation of excitation of fluorophores and image acquisition for time-delay imaging, thus eliminating tissue autofluorescence associated with fluorescence imaging. Persistently luminescent nanoparticles have previously been fabricated from toxic rare-earth metals. This work reports that nanoparticles made of the conjugated polymer MEH-PPV can generate luminescence persisting for an hour upon single excitation. A near-infrared dye was encapsulated in the conjugated polymer nanoparticle to successfully generate persistent near-infrared luminescence through resonance energy transfer. This new persistent luminescence nanoparticles have been demonstrated for optical imaging applications in living mice.

Circular retrotransposition products generated by a LINE retrotransposon.

Non-long terminal repeat (non-LTR) retrotransposons are highly abundant elements that are present in chromosomes throughout the eukaryotic domain of life. The long interspersed nuclear element (LINE-1) (L1) clade of non-LTR retrotransposons has been particularly successful in mammals, accounting for 30-40% of human genome sequence. The current model of LINE retrotransposition, target-primed reverse transcription, culminates in a chromosomally integrated end product. Using a budding yeast model of non-LTR retrotransposition, we show that in addition to producing these 'classical', chromosomally integrated products, a fungal L1 clade member (Zorro3) can generate abundant, RNA-derived episomal products. Genetic evidence suggests that these products are likely to be formed via a variation of target-primed reverse transcription. These episomal products are a previously unseen alternative fate of LINE retrotransposition, and may represent an unexpected source for de novo retrotransposition.