Informed consent is poorly documented when obtaining toxicology testing at delivery in a Massachusetts cohort.

BACKGROUND: Positive toxicology testing at delivery can have enormous consequences for birthing persons and their families, including charges of child abuse or neglect and potential loss of custody for the birthing parent. Therefore state and national guidelines stipulate that, clinicians must obtain consent before toxicology testing at delivery. OBJECTIVE: This study aimed (1) to determine clinician documentation of patient consent for peripartum toxicology testing and (2) to characterize the extent to which patient and hospital characteristics were associated with documented consent. STUDY DESIGN: This was a retrospective cohort of individuals who underwent toxicology testing within 96 hours of delivery between April 2016 and April 2020 at 5 affiliated hospitals across Massachusetts. Medical records were reviewed for documentation of clinician intent to obtain maternal toxicology, testing indication, verbal consent to testing, and child protective services involvement. Hierarchical multivariable logistic regression was used to examine the association between patient and hospital characteristics and documentation of verbal consent. RESULTS: Among 60,718 deliveries, 1562 maternal toxicology tests were obtained. Verbal consent for testing was documented in 466 cases (29.8%). Documented consent was lacking across most demographic groups. Consent was no more likely to be documented when a report was filed with child protective services and less likely in cases where the birthing parent lost custody before discharge (P=.003). In our multivariable model, consent was least likely to be documented when a maternal complication (abruption, hypertension, preterm labor, preterm premature rupture of membranes, or intrauterine fetal demise) was the indication for testing (adjusted odds ratio, 0.46; 95% confidence interval, 0.28-0.76). Verbal consent was twice as likely to be documented in delivery hospitals with established consent policies (adjusted odds ratio, 2.10; 95% confidence interval, 1.01-4.37). CONCLUSION: Consent for toxicology testing at delivery seemed to be infrequently obtained on the basis of clinician documentation. Provider education and hospital policies for obtaining informed consent are needed to protect the rights of birthing individuals.

Subtle Cerebellar Features in Relatives of Essential Tremor Cases.

Background: Essential tremor (ET) cases often exhibit a range of mild cerebellar signs. Their unaffected relatives have been shown in prior studies to exhibit subtle (i.e., preclinical) disease features. Objective: To quantify subtle cerebellar signs in unaffected first-degree relatives of ET cases stratified based on their tremor severity. Methods: Two hundred sixty-nine first-degree relatives of ET cases, none of whom reported tremor or a diagnosis of ET, or were diagnosed with ET based on detailed neurological examination, were stratified based on total tremor score (TTS) into two groups (lower TTS vs. higher TTS) and quartiles. Changes in gait, balance, and intention tremor were quantified on neurological examination. Results: Higher TTS performed worse on the tandem stance task (p = 0.011). When stratified into TTS quartiles, higher quartile was associated with worse performance in tandem stance (p = 0.011) and stance with feet together (p = 0.028). Similarly, intention tremor in the arms (p = 0.0002) and legs (p = 0.047) were higher in the groups with more tremor. Discussion: The links between ET and the cerebellum are multiple. These data provide intriguing evidence that subtle cerebellar signs (i.e., changes in balance and intention tremor) are more prevalent among first-degree relatives of ET cases with more tremor (i.e., those who may be themselves on the pathway to developing ET). These data contribute to a better characterization of what may be an early subclinical stage of the disease.

A Time-Series Analysis of Firearm Purchasing After Mass Shooting Events in the United States.

Importance: Increased understanding of public response to mass shootings could guide public health planning regarding firearms. Objectives: To test the hypothesis that mass shootings are associated with gun purchasing in the United States and to determine factors associated with gun purchasing changes. Design and Setting: In a cross-sectional study, monthly data on US background checks for all firearm purchases, handgun permits, and long gun permits between November 1, 1998, and April 30, 2016, were obtained from the National Instant Criminal Background Check System. All mass shootings resulting in 5 or more individuals injured or killed during the study period were also identified. Interrupted autoregressive integrated moving average time-series modeling was used to identify events associated with changes in gun purchase volume. Then, logistic regression was used to identify event characteristics associated with changes in gun purchases. Analyses were performed between June 6, 2016, and February 5, 2019. Exposures: For the time-series analysis, each mass shooting was modeled as an exposure. In the logistic regression, examined factors were the shooter's race/ethnicity, the region in the United States in which a shooting occurred, whether a shooting was school related, fatalities, handgun use, long gun use, automatic or semiautomatic gun use, media coverage level, and state political affiliation. Main Outcomes and Measures: Identification of major mass shootings significantly associated with changes in gun purchases, and the identification of event-specific factors associated with changes in gun purchases. Results: Between November 1998 and April 2016, 124 major mass shootings and 233 996 385 total background checks occurred. A total of 26 shootings (21.0%) were associated with increases in gun purchases and 22 shootings (17.7%) were associated with decreases in gun purchasing. Shootings receiving extensive media coverage were associated with handgun purchase increases (odds ratio, 5.28; 95% CI, 1.30-21.41; P = .02). Higher-fatality shootings had an inverse association with handgun purchase decreases (odds ratio, 0.73; 95% CI, 0.53-1.00; P = .049). Conclusions and Relevance: The findings of this study suggest an association between mass shootings and changes in gun purchases, observed on a comprehensive timescale. Identification of media coverage and fatalities as significant factors underlying this association invites further study into the mechanisms driving gun purchase changes, holding implications for public health response to future gun violence.

Under-Recognition of Cervical Dystonia: An Essential Tremor Patient with Numerous Textbook Features of Cervical Dystonia.

Background: Physical examination findings of dystonia are often underrecognized, especially in the setting of other movement disorders such as essential tremor (ET). Phenomenology Shown: A patient with ET exhibited numerous textbook features of cervical dystonia, which were misattributed to ET by a primary care physician and two neurologists. Educational Value: To provide a clear and unmistakable visual example of the clinically significant characteristics of cervical dystonia in the setting of concomitant ET.

Genetic Counselors' Approach To Postmortem Genetic Testing After Sudden Death: An Exploratory Study.

A significant portion of sudden death cases result from an underlying genetic etiology, which may be determined through postmortem genetic testing. The National Association of Medical Examiners (NAME) recommends that an appropriate postmortem sample is saved on all sudden death cases under the age of 40. Genetic counselors (GCs) play an important role in this process by working with medical examiners and coroners (ME/Cs) to recommend and interpret specific testing and to guide family members. A survey sent to the National Society of Genetic Counselors was designed and implemented to learn more about the experiences of genetic counselors who had considered or ordered postmortem genetic testing. Results showed that cardiovascular GCs were significantly more willing to recommend genetic testing in younger age decedents (ages 10, 18, 30, 40, and 50) compared to other specialty GCs (p<0.05, Chi-square). Thirty-seven percent (7 of 19) of GCs reported insurance covering some portion of genetic testing. Participants also reported highest success for DNA extractions with fresh and frozen blood, reinforcing NAME recommendations for appropriate sample collection for postmortem genetic testing. Overall, participating GCs demonstrated a very good understanding for the appropriate use of postmortem genetic testing and did identify suspected barriers of cost and lack of insurance coverage as deterrents. With the rapid decrease in costs for diagnostic genetic testing, ME/C awareness of NAME recommendations for sample collection and storage remain important to facilitate postmortem genetic testing.

Periodic-shRNA molecules are capable of gene silencing, cytotoxicity and innate immune activation in cancer cells.

Large dsRNA molecules can cause potent cytotoxic and immunostimulatory effects through the activation of pattern recognition receptors; however, synthetic versions of these molecules are mostly limited to simple sequences like poly-I:C and poly-A:U. Here we show that large RNA molecules generated by rolling circle transcription fold into periodic-shRNA (p-shRNA) structures and cause potent cytotoxicity and gene silencing when delivered to cancer cells. We determined structural requirements for the dumbbell templates used to synthesize p-shRNA, and showed that these molecules likely adopt a co-transcriptionally folded structure. The cytotoxicity of p-shRNA was robustly observed across four different cancer cell lines using two different delivery systems. Despite having a considerably different folded structure than conventional dsRNA, the cytotoxicity of p-shRNA was either equal to or substantially greater than that of poly-I:C depending on the delivery vehicle. Furthermore, p-shRNA caused greater NF-κB activation in SKOV3 cells compared to poly-I:C, indicating that it is a powerful activator of innate immunity. The tuneable sequence and combined gene silencing, immunostimulatory and cytotoxic capacity of p-shRNA make it an attractive platform for cancer immunotherapy.

GenePro: a Cytoscape plug-in for advanced visualization and analysis of interaction networks.

MOTIVATION: Analyzing the networks of interactions between genes and proteins has become a central theme in systems biology. Versatile software tools for interactively displaying and analyzing these networks are therefore very much in demand. The public-domain open software environment Cytoscape has been developed with the goal of facilitating the design and development of such software tools by the scientific community. RESULTS: We present GenePro, a plugin to Cytoscape featuring a set of versatile tools that greatly facilitates the visualization and analysis of protein networks derived from high-throughput interactions data and the validation of various methods for parsing these networks into meaningful functional modules. AVAILABILITY: The GenePro plugin is available at the website http://genepro.ccb.sickkids.ca.