Same-visit hepatitis C testing and treatment to accelerate cure among people who inject drugs (the QuickStart Study): a cluster randomised cross-over trial protocol.

INTRODUCTION: Despite universal access to government-funded direct-acting antivirals (DAAs) in 2016, the rate of hepatitis C treatment uptake in Australia has declined substantially. Most hepatitis C is related to injecting drug use; reducing the hepatitis C burden among people who inject drugs (PWID) is, therefore, paramount to reach hepatitis C elimination targets. Increasing DAA uptake by PWID is important for interrupting transmission and reducing incidence, as well as reducing morbidity and mortality and improving quality of life of PWID and meeting Australia's hepatitis C elimination targets. METHODS AND ANALYSIS: A cluster randomised cross-over trial will be conducted with three intervention arms and a control arm. Arm A will receive rapid hepatitis C virus (HCV) antibody testing; arm B will receive rapid HCV antibody and rapid RNA testing; arm C will receive rapid HCV antibody testing and same-day treatment initiation for HCV antibody-positive participants; the control arm will receive standard of care. The primary outcomes will be (a) the proportion of participants with HCV commencing treatment and (b) the proportion of participants with HCV achieving cure. Analyses will be conducted on an intention-to-treat basis with mixed-effects logistic regression models. ETHICS AND DISSEMINATION: The study has been approved by the Alfred Ethics Committee (number HREC/64731/Alfred-2020-217547). Each participant will provide written informed consent. Reportable adverse events will be reported to the reviewing ethics committee. The findings will be presented at scientific conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05016609. TRIAL PROGRESSION: The study commenced recruitment on 9 March 2022 and is expected to complete recruitment in December 2024.

In-Hospital Delirium and Disability and Cognitive Impairment After COVID-19 Hospitalization.

Importance: Older adults who are hospitalized for COVID-19 are at risk of delirium. Little is known about the association of in-hospital delirium with functional and cognitive outcomes among older adults who have survived a COVID-19 hospitalization. Objective: To evaluate the association of delirium with functional disability and cognitive impairment over the 6 months after discharge among older adults hospitalized with COVID-19. Design, Setting, and Participants: This prospective cohort study involved patients aged 60 years or older who were hospitalized with COVID-19 between June 18, 2020, and June 30, 2021, at 5 hospitals in a major tertiary care system in the US. Follow-up occurred through January 11, 2022. Data analysis was performed from December 2022 to February 2024. Exposure: Delirium during the COVID-19 hospitalization was assessed using the Chart-based Delirium Identification Instrument (CHART-DEL) and CHART-DEL-ICU. Main Outcomes and Measures: Primary outcomes were disability in 15 functional activities and the presence of cognitive impairment (defined as Montreal Cognitive Assessment score <22) at 1, 3, and 6 months after hospital discharge. The associations of in-hospital delirium with functional disability and cognitive impairment were evaluated using zero-inflated negative binominal and logistic regression models, respectively, with adjustment for age, month of follow-up, and baseline (before COVID-19) measures of the respective outcome. Results: The cohort included 311 older adults (mean [SD] age, 71.3 [8.5] years; 163 female [52.4%]) who survived COVID-19 hospitalization. In the functional disability sample of 311 participants, 49 participants (15.8%) experienced in-hospital delirium. In the cognition sample of 271 participants, 31 (11.4%) experienced in-hospital delirium. In-hospital delirium was associated with both increased functional disability (rate ratio, 1.32; 95% CI, 1.05-1.66) and increased cognitive impairment (odds ratio, 2.48; 95% CI, 1.38-4.82) over the 6 months after discharge from the COVID-19 hospitalization. Conclusions and Relevance: In this cohort study of 311 hospitalized older adults with COVID-19, in-hospital delirium was associated with increased functional disability and cognitive impairment over the 6 months following discharge. Older survivors of a COVID-19 hospitalization who experience in-hospital delirium should be assessed for disability and cognitive impairment during postdischarge follow-up.

Multiple variants of the type VII secretion system in Gram-positive bacteria.

Type VII secretion systems (T7SS) are found in bacteria across the Bacillota and Actinomycetota phyla and have been well described in Staphylococcus aureus, Bacillus subtilis, and pathogenic mycobacteria. The T7SS from Actinomycetota and Bacillota share two common components, a membrane-bound EccC/EssC ATPase and EsxA, a small helical hairpin protein of the WXG100 family. However, they also have additional phylum-specific components, and as a result they are termed the T7SSa (Actinomycetota) and T7SSb (Bacillota), respectively. Here, we identify additional organizations of the T7SS across these two phyla and describe eight additional T7SS subtypes, which we have named T7SSc-T7SSj. T7SSd is found exclusively in Actinomycetota including the Olselnella and Bifodobacterium genus, whereas the other seven are found only in Bacillota. All of the novel subtypes contain the canonical ATPase (TsxC) and the WXG100-family protein (TsxA). Most of them also contain a small ubiquitin-related protein, TsxB, related to the T7SSb EsaB/YukD component. Protein kinases, phosphatases, and forkhead-associated (FHA) proteins are often encoded in the novel T7SS gene clusters. Candidate substrates of these novel T7SS subtypes include LXG-domain and RHS proteins. Predicted substrates are frequently encoded alongside genes for additional small WXG100-related proteins that we speculate serve as cosecretion partners. Collectively our findings reveal unexpected diversity in the T7SS in Gram-positive bacteria.

Multisite Validation of a Functional Assay to Adjudicate SCN5A Brugada Syndrome-Associated Variants.

BACKGROUND: Brugada syndrome is an inheritable arrhythmia condition that is associated with rare, loss-of-function variants in SCN5A. Interpreting the pathogenicity of SCN5A missense variants is challenging, and ≈79% of SCN5A missense variants in ClinVar are currently classified as variants of uncertain significance. Automated patch clamp technology enables high-throughput functional studies of ion channel variants and can provide evidence for variant reclassification. METHODS: An in vitro SCN5A-Brugada syndrome automated patch clamp assay was generated and independently studied at Vanderbilt University Medical Center and Victor Chang Cardiac Research Institute. The assay was calibrated according to ClinGen Sequence Variant Interpretation recommendations using high-confidence variant controls (n=49). Normal and abnormal ranges of function were established based on the distribution of benign variant assay results. Odds of pathogenicity values were derived from the experimental results according to ClinGen Sequence Variant Interpretation recommendations. The calibrated assay was then used to study SCN5A variants of uncertain significance observed in 4 families with Brugada syndrome and other arrhythmia phenotypes associated with SCN5A loss-of-function. RESULTS: Variant channel parameters generated independently at the 2 research sites showed strong correlations, including peak INa density (R2=0.86). The assay accurately distinguished benign controls (24/25 concordant variants) from pathogenic controls (23/24 concordant variants). Odds of pathogenicity values yielded 0.042 for normal function and 24.0 for abnormal function, corresponding to strong evidence for both American College of Medical Genetics and Genomics/Association for Molecular Pathology benign and pathogenic functional criteria (BS3 and PS3, respectively). Application of the assay to 4 clinical SCN5A variants of uncertain significance revealed loss-of-function for 3/4 variants, enabling reclassification to likely pathogenic. CONCLUSIONS: This validated high-throughput assay provides clinical-grade functional evidence to aid the classification of current and future SCN5A-Brugada syndrome variants of uncertain significance.

The chemical assessment of surfaces and air (CASA) study: using chemical and physical perturbations in a test house to investigate indoor processes.

The Chemical Assessment of Surfaces and Air (CASA) study aimed to understand how chemicals transform in the indoor environment using perturbations (e.g., cooking, cleaning) or additions of indoor and outdoor pollutants in a well-controlled test house. Chemical additions ranged from individual compounds (e.g., gaseous ammonia or ozone) to more complex mixtures (e.g., a wildfire smoke proxy and a commercial pesticide). Physical perturbations included varying temperature, ventilation rates, and relative humidity. The objectives for CASA included understanding (i) how outdoor air pollution impacts indoor air chemistry, (ii) how wildfire smoke transports and transforms indoors, (iii) how gases and particles interact with building surfaces, and (iv) how indoor environmental conditions impact indoor chemistry. Further, the combined measurements under unperturbed and experimental conditions enable investigation of mitigation strategies following outdoor and indoor air pollution events. A comprehensive suite of instruments measured different chemical components in the gas, particle, and surface phases throughout the study. We provide an overview of the test house, instrumentation, experimental design, and initial observations - including the role of humidity in controlling the air concentrations of many semi-volatile organic compounds, the potential for ozone to generate indoor nitrogen pentoxide (N2O5), the differences in microbial composition between the test house and other occupied buildings, and the complexity of deposited particles and gases on different indoor surfaces.

Respiratory Arrest in a Late Preterm Infant Presenting for a 2-Week Well-Visit.

A 13-day-old, late preterm male, born appropriate for gestational age, presented to the pediatric clinic for his routine 2-week well visit with less than 1-day history of decreased oral intake and lethargy. During the baby's well exam, he acutely decompensated and required resuscitation and transfer to the emergency department, where he was intubated for frequent apneic events. He was admitted to the NICU for management and further workup. Physical examination and initial laboratory tests were unremarkable. An EEG demonstrated electrographic and clinical seizures. His initial MRI was unremarkable, and infection studies revealed the diagnosis. We review the patient's initial presentation, evaluation, hospital course, and the long-term implications of his diagnosis.

Dilute concentrations of maritime fuel can modify sediment reworking activity of high-latitude marine invertebrates.

Multiple expressions of climate change, in particular warming-induced reductions in the type, extent and thickness of sea ice, are opening access and providing new viable development opportunities in high-latitude regions. Coastal margins are facing these challenges, but the vulnerability of species and ecosystems to the effects of fuel contamination associated with increased maritime traffic is largely unknown. Here, we show that low concentrations of the water-accommodated fraction of marine fuel oil, representative of a dilute fuel oil spill, can alter functionally important aspects of the behaviour of sediment-dwelling invertebrates. We find that the response to contamination is species specific, but that the range in response among individuals is modified by increasing fuel concentrations. Our study provides evidence that species responses to novel and/or unprecedented levels of anthropogenic activity associated with the opening up of high-latitude regions can have substantive ecological effects, even when human impacts are at, or below, commonly accepted safe thresholds. These secondary responses are often overlooked in broad-scale environmental assessments and marine planning yet, critically, they may act as an early warning signal for impending and more pronounced ecological transitions.

Escalation to Anti-CD20 Treatment for Multiple Sclerosis Following Natalizumab-Associated Progressive Multifocal Leukoencephalopathy.

Objectives: Disease-modifying therapy (DMT) for multiple sclerosis (MS) after natalizumab-associated progressive multifocal leukoencephalopathy (PML) is controversial due to concern for recurrent PML. We describe DMT utilization for over a decade in a patient with MS who survived PML. Methods: Case report. Results: A 36-year-old woman was diagnosed with MS in 2002 and treated with interferon beta-1a until 2006, when she transitioned to natalizumab due to relapses. She presented in 2012 with 2 months of progressive cognitive and gait concerns and was diagnosed with PML by positive CSF JC virus testing with concordant clinical and MRI findings. She was treated with plasma exchange and then corticosteroids for PML immune reconstitution inflammatory syndrome before starting glatiramer acetate for DMT. She transitioned to dimethyl fumarate in 2013 after MS activity on MRI with negative CSF JC virus testing. Owing to worsening footdrop consistent with progression, she transitioned to ocrelizumab in 2017 and then to ofatumumab in 2020 due to logistics of medication administration. There has been no clinicoradiographic or CSF evidence of recurrent PML. Discussion: DMT selection is challenging for patients with MS who survive PML. We used an escalation approach extending to ocrelizumab and ofatumumab due to MS progression. Anti-CD20 DMTs are a high-efficacy option post-PML. Classification of Evidence: This provides Class IV evidence. It is a single observational study without controls.

Use of Transient Transfection for cGMP Manufacturing of eOD-GT8 60mer, a Self-Assembling Nanoparticle Germline-Targeting HIV-1 Vaccine Candidate.

We describe the current Good Manufacturing Practice (cGMP) production and subsequent characterization of eOD-GT8 60mer, a glycosylated self-assembling nanoparticle HIV-1 vaccine candidate and germline targeting priming immunogen. Production was carried out via transient expression in the human embryonic kidney 293 (HEK293) cell line followed by a combination of purification techniques. A large-scale cGMP (200 L) production run yielded 354 mg of the purified eOD-GT8 60mer drug product material, which was formulated at 1 mg/mL in 10% sucrose in phosphate-buffered saline (PBS) at pH 7.2. The clinical trial material was comprehensively characterized for purity, antigenicity, glycan composition, amino acid sequence, and aggregation and by several safety-related tests during cGMP lot release. A comparison of the purified products produced at the 1 L scale and 200 L cGMP scale demonstrated the consistency and robustness of the transient transfection upstream process and the downstream purification strategies. The cGMP clinical trial material was tested in a Phase 1 clinical trial (NCT03547245), is currently being stored at -80 °C, and is on a stability testing program as per regulatory guidelines. The methods described here illustrate the utility of transient transfection for cGMP production of complex products such as glycosylated self-assembling nanoparticles.

Predictors and Impact of Prolonged Vasoplegia After Continuous-Flow Left Ventricular Assist Device Implantation.

Background: Vasoplegia after cardiac surgery is associated with adverse outcomes. However, the clinical effects of vasoplegia and the significance of its duration after continuous-flow left ventricular assist device (CF-LVAD) implantation are less known. Objectives: This study aimed to identify predictors of and outcomes from transient vs prolonged vasoplegia after CF-LVAD implantation. Methods: The study was a retrospective review of consecutive patients who underwent CF-LVAD implantation between January 1, 2005, and December 31, 2017. Vasoplegia was defined as the presence of all of the following: mean arterial pressure ≤65 mm Hg, vasopressor (epinephrine, norepinephrine, vasopressin, or dopamine) use for >6 hours within the first 24 hours postoperatively, cardiac index ≥2.2 L/min/m2 and systemic vascular resistance <800 dyne/s/cm5, and vasodilatory shock not attributable to other causes. Prolonged vasoplegia was defined as that lasting 12 to 24 hours; transient vasoplegia was that lasting 6 to <12 hours. Patient characteristics, outcomes, and risk factors were analyzed. Results: Of the 600 patients who underwent CF-LVAD implantation during the study period, 182 (30.3%) developed vasoplegia. Mean patient age was similar between the vasoplegia and no-vasoplegia groups. Prolonged vasoplegia (n = 78; 13.0%), compared with transient vasoplegia (n = 104; 17.3%), was associated with greater 30-day mortality (16.7% vs 5.8%; P = 0.02). Risk factors for prolonged vasoplegia included preoperative dialysis and elevated body mass index. Conclusions: Compared with vasoplegia overall, prolonged vasoplegia was associated with worse survival after CF-LVAD implantation. Treatment to avoid or minimize progression to prolonged vasoplegia may be warranted.

10-Year Cumulative Incidence and Indications for Revision Total Joint Arthroplasty for Patients Who Have Ehlers-Danlos syndrome.

BACKGROUND: Long-term complications following total joint arthroplasty are not well established for patients who have Ehlers-Danlos syndrome (EDS), a group of connective tissue disorders. This study compared 10-year incidence of revision surgery after total hip arthroplasty (THA) and total knee arthroplasty (TKA) in patients who have and do not have EDS. METHODS: A retrospective cohort analysis was conducted using a national all-payer claims database from 2010 to 2021 to identify patients who underwent primary TKA or THA. Patients who had and did not have EDS were propensity-score matched by age, sex, and a comorbidity index. Kaplan-Meier analyses and Cox proportional hazard models were utilized to determine the cumulative incidence and risks of revision experienced by patients who have and do not have EDS. RESULTS: The EDS patients who underwent TKA had a higher risk of all-cause revision (hazard ratio (HR): 1.50, 95% confidence interval (95% CI): 1.09 to 2.07, P < 0.014) and risk of revision due to instability (HR = 2.49, 95% CI: 1.37 to 4.52, P < 0.003). The EDS patients who underwent THA had a higher risk of all-cause revision (HR = 2.32, 95% CI: 1.47 to 3.65, P < 0.001), revision due to instability (HR = 4.26, 95% CI: 2.17 to 8.36, P < 0.001), and mechanical loosening (HR = 3.63, 95% CI: 2.05 to 6.44, P < 0.001). CONCLUSION: Patients who had EDS were found to have a higher incidence of revision within 10 years of undergoing TKA and THA compared to matched controls, especially for instability. Patients who have EDS should be counseled accordingly. Surgical technique and implant selection should include consideration for increased constraint in TKA and larger femoral heads or dual mobility articulations for THA.

Protocol of the HARMONY study: A culturally relevant, randomized-controlled, stress management intervention to reduce cardiometabolic risk in African American women.

BACKGROUND: African American Women (AAW) are at high risk for stress-related cardiometabolic (CM) conditions including obesity, heart disease, and diabetes. Prior interventions lack attention to culturally-nuanced stress phenomena (Superwoman Schema [SWS], contextualized stress, and network stress), which are positively and significantly associated with unhealthy eating and sedentary behavior. PURPOSE: The HARMONY Study is designed to test a culturally tailored mindfulness-based stress management intervention to address SWS, contextualized stress, and network stress as potential barriers to adherence to healthy exercise and eating goals. The study will help AAW build on their strengths to promote cardiometabolic health by enhancing positive reappraisal, self-regulation, and self-efficacy as protective factors against chronic stress-inducing biobehavioral morbidity and mortality risk. METHODS: This two-arm, randomized-controlled trial will test the effects of two group-based, online interventions. HARMONY 1 includes culturally-tailored exercise and nutrition education. HARMONY 2 includes mindfulness-based stress reduction, exercise, and nutrition education. We aim to recruit 200 AAW ≥ 18 years old with CM risk. RESULTS: Primary outcomes (actigraphy and carotenoid levels) and secondary outcomes (body composition, inflammatory markers, glucose metabolism, and stress) are being collected at baseline and 4-, 8-, and 12-months post-intervention. Intent-to-treat, data analytic approaches will be used to test group differences for the primary outcomes. DISCUSSION: This study is the first to address culturally-nuanced stress phenomena in AAW (SWS, network stress, and contextualized stress) using culturally-tailored stress management, exercise, and nutrition educational approaches to reduce biobehavioral CM risk among AAW. Quantitative and qualitative results will inform the development of scalable and sustainable CM risk-reduction programming for AAW. TRIAL REGISTRATION: The Multiple PIs registered the clinical trial (Identifier: NCT04705779) and reporting of summary results in ClinicalTrials.gov in accordance with the NIH Policy on the Dissemination of NIH-Funded Clinical Trial Information, within the required timelines.

High Ankle Brachial Index Participants Experienced Similar Long-Term Mortality as Peripheral Artery Disease in a National Sample of Community-Dwelling Adults.

BACKGROUND: Only a few small studies have shown the association between high ankle-brachial pressure index (ABI>1.4) and adverse cardiovascular (CV) events and mortality. While there is abundant literature depicting the association between ABI and overall systemic atherosclerosis, it typically focuses on low ABI. Furthermore, historically, many studies focusing on peripheral artery disease have excluded high ABI participants. We aim to study the mortality outcomes of persons with high ABI in the National Health and Nutrition Examination Survey (NHANES). METHODS: We obtained ABI from participants aged >40 years for survey years 1999 to 2004. We defined low ABI <0.9, normal ABI 0.9-1.4, and high ABI was >1.4 or if the ankle pressures were >245 mmHg. Demographics, various comorbidities, and laboratory test results were obtained at the time of the survey interview. Multivariable adjusted hazard ratios (HR) along with 95% confidence interval (CI) were calculated for CV and all-cause mortality via cox-proportional hazards regression. Mortality was linked to all NHANES participants for follow-up through December 31, 2019, by the Centers for Disease Control and Prevention. RESULTS: We identified 7639 NHANES participants with available ABI. Of these, 6787 (89%) had normal ABI, 646 (8%) had low ABI, and 206 (3%) had elevated ABI. Of participants with high ABI, 50% were men, 15% were African Americans, 10% were current smokers, 56% had hypertension, 33% had diabetes, 15% had chronic kidney disease (CKD), and 18% had concomitant coronary artery disease (CAD). Diabetes (odds ratio [OR]= 2.4, 95% CI: 1.7-3.2), CAD (OR=1.6, 95% CI: 1.0-2.4), and CKD (OR=1.5, 95% CI: 1.0-2.3) at baseline were associated of having high ABI respectively. High ABI was independently associated with elevated CV (HR= 2.6, 95% CI: 2.1-3.1, p < 0.0001) and all-cause mortality (HR= 2.5, 95% CI: 2.2-2.8, p < 0.0001) after adjusting for co-variates including diabetes, CKD, CAD, current smoking, cancer, and hypertension. CONCLUSION: A high ABI is associated with an elevated CV and all-cause mortality, similar to patients with PAD. High ABI participants should receive the same attention and aggressive medical therapies as the patients with PAD.

Quitting smoking with smoke? Unauthorized claims used by herbal cigarette manufacturers.

INTRODUCTION: Herbal cigarettes are made with non-tobacco plant materials (e.g., tea leaves, hemp), are typically sold pre-rolled in packs and with filters, and are combusted and smoked like tobacco cigarettes. Herbal cigarette manufacturers have a history of making misleading health claims and at least one company has previously settled with the US Federal Trade Commission over deceptive advertising. This study examined current claims and product characteristics of herbal cigarettes sold by a popular online retailer. METHODS: We searched Amazon.com for "herbal cigarettes" and "hemp cigarettes" and identified all herbal cigarette products sold on the first page of search results (n=51). Two coders independently content analyzed each product's Amazon page for claims (e.g., smoking cessation, health), product characteristics (e.g., flavors), and presence of disclaimers and warnings. RESULTS: Overall, 78.4% of product pages made smoking cessation claims (e.g., "A more scientific way to quit smoking", "…decreases nicotine craving symptom and helps to quit tobacco smoking"). Further, 45.1% of product pages included claims describing lower risk/exposure compared to tobacco products (e.g., "…without the addictive nicotine and toxic chemicals found in tobacco cigarettes"). Some herbal products were available in multiple flavors, including menthol (21.6%) and fruit (17.7%). Only 35.3% of products included visible health warnings on product packaging. CONCLUSIONS: Many herbal cigarette products sold on Amazon.com make unauthorized cessation and health claims. Regulatory agencies must act decisively to stop the misleading advertising of these products and develop appropriate warnings to educate the public about the potential harms of herbal cigarettes. IMPLICATIONS: This content analysis documents the use of unauthorized and misleading claims made in the marketing of herbal cigarettes.These findings highlight the need for enforcement of existing federal regulations, which prohibit deceptive advertising.Research is needed to inform the development of appropriate warning labels that can be used to inform consumers of the potential harms of smoking herbal cigarettes.

Alkali cation-induced cathodic corrosion in Cu electrocatalysts.

The reconstruction of Cu catalysts during electrochemical reduction of CO2 is a widely known but poorly understood phenomenon. Herein, we examine the structural evolution of Cu nanocubes under CO2 reduction reaction and its relevant reaction conditions using identical location transmission electron microscopy, cyclic voltammetry, in situ X-ray absorption fine structure spectroscopy and ab initio molecular dynamics simulation. Our results suggest that Cu catalysts reconstruct via a hitherto unexplored yet critical pathway - alkali cation-induced cathodic corrosion, when the electrode potential is more negative than an onset value (e.g., -0.4 VRHE when using 0.1 M KHCO3). Having alkali cations in the electrolyte is critical for such a process. Consequently, Cu catalysts will inevitably undergo surface reconstructions during a typical process of CO2 reduction reaction, resulting in dynamic catalyst morphologies. While having these reconstructions does not necessarily preclude stable electrocatalytic reactions, they will indeed prohibit long-term selectivity and activity enhancement by controlling the morphology of Cu pre-catalysts. Alternatively, by operating Cu catalysts at less negative potentials in the CO electrochemical reduction, we show that Cu nanocubes can provide a much more stable selectivity advantage over spherical Cu nanoparticles.

Ventricular Septation of the Double-Inlet Ventricle: Over Three Decades of Follow-Up.

There is renewed interest in septation of the double-inlet ventricle as an alternative to Fontan palliation. We examined our septation experience with over 30 years of follow-up. We retrospectively reviewed patients with double-inlet ventricle from 1990 to 2011. Patients with two adequate atrioventricular valves, a volume-overloaded ventricle, and no significant subaortic obstruction were septation candidates. Of 98 double-inlet ventricle patients, 9 (9.2%) underwent attempted septation via a one-stage (n = 2, 22.2%) or two-stage (n = 7, 77.8%) approach. Ages at primary septation were 7.5 and 20.2 months. In the staged group, median age at the first and second stage was 8.3 months [range 4.1-14.7] and 22.4 months [range 11.4-195.7], respectively. There were no operative mortalities. Median follow-up was 18.8 years [range 0.4-32.9] and 30-year transplant-free survival was 77.8% ± 13.9%. Both single stage patients are alive and in sinus rhythm; 1 underwent bilateral outflow tract obstruction repair 27 years later. Of 7 patients planned for two-stage septation, there was 1 interval mortality and 1 deferred the second stage. Five patients underwent the second stage; 1 required early reintervention for a residual neo-septal defect and 1 underwent right atrioventricular valve replacement 28 years later. Three patients required a pacemaker preoperatively (n = 1) or after partial septation (n = 2). At latest follow-up, 7 patients have normal biventricular function and no significant valvulopathy. All remain NYHA functional class I. Select double-inlet ventricles may be septated with excellent long-term outcomes. Reconsideration of this strategy is warranted to avoid the sequelae of Fontan circulation.

Hand Surgeon Posture: An Evaluation and Factors That Affect It.

Objective: Approximately 68% of orthopaedic surgeons report occupational related musculoskeletal pain, with back pain being the most common. Poor posture while operating has been proven to contribute to these high rates of musculoskeletal pain. There is little research regarding intraoperative surgeon posture within the field of hand and upper extremity surgery. This prospective study aims to investigate and analyze hand surgeon posture in the operating room. Methods: Posture of three hand surgeons was recorded using the UPRIGHT GO posture tracking device while performing a prospective series of 223 hand and upper extremity surgeries. This device reports posture in terms of overall percentage of time spent slouched versus upright. For this cohort of 223 cases, data were collected including surgical procedure, whether the surgery was performed in a seated or standing position, whether or not loupes were worn during the procedure, and if the surgeon was the primary or assistant surgeon. These data were then analyzed to look for any contributing factors to poor posture. Results: The three hand surgeons in this study spent an average of 40.3% of their time slouched while operating. The average percentage of time slouched was significantly greater with the use of loupes versus no loupes. Additionally, mean time slouching was slightly increased when the surgeon was seated and also when the surgeon was acting as the assistant surgeon. Conclusion: The three orthopaedic hand surgeons in our study spent a significant portion of their operative time slouched. The main variable associated with a significant risk of poor surgical posture was wearing loupes. Slight increases in slouching were seen with operating while seated and as the assistant surgeon. Surgeon awareness of these variables, as well as techniques to improve surgeon posture, should be developed in order to help contribute to better surgeon posture within the field of hand surgery.

Characterizing the safety profile of vagus nerve stimulation devices for epilepsy from 21,448 manufacturer and user reports.

OBJECTIVE: This study summarizes medical device reports (MDRs) associated with adverse events for vagus nerve stimulation (VNS) devices indicated for epilepsy as reported by the Manufacturer and User Facility Device Experience (MAUDE) database of the US Food and Drug Administration. METHODS: The MAUDE database was surveyed for MDRs from November 2013 to September 2022 regarding VNS devices for epilepsy. Event descriptions, device problems, correlated patient consequences, and device models were grouped and analyzed in Python. Based on event description, revision surgeries and other unique events were identified. Revenue from VNS device sales was used to approximate growth in their use over time. RESULTS: A total of 21,448 MDRs met the inclusion criteria. High VNS impedance, the most prevalent device malfunction overall (17.0% of MDRs), was the most common factor for 18 of the 102 encountered patient problems and led to 1001 revision surgeries (3371 total revisions). Included in those 18 device malfunctions were 3 of the top 6 occurring patient problems: seizure recurrence (9.9% associated with high impedance; encompassed focal, absence, and grand mal subtypes), death (1.3%), and generalized pain (7.9%). The next 4 top cited device malfunctions-lead fracture (13.7% of MDRs), operational issue (6.6%), battery problem holding charge (4.2%), and premature end-of-life indicator (2.9%)-differed widely in their percentage of cases that did not impact patients (77.4%, 57.3%, 48.9%, and 92.2%, respectively), highlighting differing malfunction severities. Seizure recurrence, the most prevalent patient impact, was the outcome most associated with 32 of the 68 encountered device problems, including high impedance (12.8%), lead fracture (12.2%), operational issue (18.4%), battery problem holding charge (31.2%), and premature end-of-life indicator (8.9%), which comprised the top 5 occurring device problems. In general, MDRs spanned a diverse range including device age, hardware, software, and surgeon or manufacturer error. Trends were seen over time with declining annual MDRs coupled with a rise in the use of VNS devices as gauged by revenue growth. Shifting device and patient problem profiles were also seen in successive models, reflecting engineering updates. CONCLUSIONS: This study characterizes the most common and consequential side effects of VNS devices for epilepsy while clarifying likely causes. In addition, the outcomes of 68 distinct device malfunctions were identified, including many not ubiquitously present in literature, lending critical perspective to clinical practice.

Coverage of Indoor Smoking and Vaping Restrictions in the US, 1990-2021.

INTRODUCTION: Secondhand smoke exposure increases the risk of premature death and disease in children and non-smoking adults. As a result, many US states and local jurisdictions have enacted comprehensive indoor smoking restrictions (ISR). Indoor vaping restrictions (IVR) have also been adopted to protect against exposure to secondhand e-cigarette aerosol. This study aimed to quantify state and national US coverage of policies restricting indoor cigarette and e-cigarette use over time. METHODS: Data from the American Nonsmokers Rights' Foundation on US ISR from 1990 to 2021 and IVR from 2006 to 2021 were analyzed. Combining these data with 2015 US Census population estimates, the percentage of state and national residents covered by partial and comprehensive restrictions in bars, restaurants, and workplaces, were calculated (analysis in 2023-2024) over time. RESULTS: Between 1990-2021, national coverage of comprehensive ISR increased for bars (0% to 67.3%), restaurants (0% to 78.2%), and workplaces (0% to 77.5%). Partial ISR coverage decreased for bars (14.8% to 13.9%), restaurants (40.2% to 15.4%) and workplaces (40.2% to 22.5%). From 2006 to 2021, comprehensive IVR coverage increased for bars (0% to 43.5%), restaurants (0% to 51.5%), and workplaces (0% to 53.2%). Despite these increases in coverage, by the end of 2021, <50% of the population was protected by comprehensive ISR for bars, restaurants, and workplaces in 19, 12, and 14 states, respectively. CONCLUSIONS: The percentage of the US population protected by ISR and IVR has increased over time. However, gaps in coverage remain, which may contribute to disparities in tobacco-related disease and death.