Application of a terminal schedule probe method to inform schedule thinning with multiple schedules.

Multiple schedules are effective at decreasing challenging behavior and maintaining alternative behavior at acceptable levels. Currently, no conclusive guidance is available for empirically deriving multiple-schedule components (continuous reinforcement for alternative behavior and extinction for challenging behavior [discriminative stimulus] and extinction for both alternative and challenging behavior [delta stimulus]) during the schedule-thinning process. In the current investigation, we describe a terminal schedule probe method to determine delta stimulus starting points and strategies for subsequent schedule-thinning progressions to reach caregiver-informed terminal schedules. We review schedule-thinning outcomes for a clinical cohort using a consecutive controlled case series approach and report results for two groups: One group included applications of terminal probe thinning (n = 24), and the other involved traditional dense-to-lean thinning (n = 18). Outcomes suggest that the terminal schedule probe method produced effective treatments with less resurgence of challenging behavior and leaner, more feasible, multiple schedules.

Risk of Severe Acute Respiratory Syndrome Coronavirus 2 Infection Following Prior Infection or Vaccination.

BACKGROUND: The extent to which infection versus vaccination has conferred similarly durable severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunity during the Omicron era remains unclear. METHODS: In a cohort of 4496 adults under continued serological surveillance throughout the first year of Omicron-predominant SARS-CoV-2 transmission, we examined incidence of new infection among individuals whose last known antigenic exposure was either recent (<90 days) or remote (≥90 days) infection or vaccination. RESULTS: We adjudicated 2053 new-onset infections occurring between 15 December 2021 through 22 December 2022. In multivariable-adjusted analyses, compared to individuals whose last known exposure was remote vaccination, those with recent vaccination (odds ratio [OR], 0.82 [95% confidence interval {CI}, .73-.93]; P = .002) or recent infection (OR, 0.14 [95% CI, .05-.45]; P = .001) had lower risk for new infection within the subsequent 90-day period. Given a significant age interaction (P = .004), we found that remote infection compared to remote vaccination was associated with significantly greater new infection risk in persons aged ≥60 years (OR, 1.88 [95% CI, 1.13-3.14]; P = .015) with no difference seen in those <60 years (1.03 [95% CI, .69-1.53]; P = .88). CONCLUSIONS: During the initial year of Omicron, prior infection and vaccination both offered protection against new infection. However, remote prior infection was less protective than remote vaccination for individuals aged ≥60 years. In older adults, immunity gained from vaccination appeared more durable than immunity gained from infection.

A Bayesian System to Detect and Track Outbreaks of Influenza-Like Illnesses Including Novel Diseases.

BACKGROUND: The early identification of outbreaks of both known and novel influenza-like illnesses is an important public health problem. OBJECTIVE: The design and testing of a tool that detects and tracks outbreaks of both known and novel influenza-like illness, such as the SARS-CoV-19 worldwide pandemic, accurately and early. METHODS: This paper describes the ILI Tracker algorithm that first models the daily occurrence of a set of known influenza-like illnesses in hospital emergency departments in a monitored region using findings extracted from patient care reports using natural language processing. We then show how the algorithm can be extended to detect and track the presence of an unmodeled disease which may represent a novel disease outbreak. RESULTS: We include results based on modeling the diseases influenza, respiratory syncytial virus, human metapneumovirus, and parainfluenza for five emergency departments in Allegheny County Pennsylvania from June 1, 2014 through May 31, 2015. We also include the results of detecting the outbreak of an unmodeled disease, which in retrospect was very likely an outbreak of the enterovirus EV-D68. CONCLUSIONS: The results reported in this paper provide support that ILI Tracker was able to track well the incidence of four modeled influenza-like diseases over a one-year period, relative to laboratory confirmed cases, and it was computationally efficient in doing so. The system was alsoable to detect a likely novel outbreak of the enterovirus D68 early in an outbreak that occurred in Allegheny County in 2014, as well as clinically characterize that outbreak disease accurately.

Assessment of Outcomes in Patients with Heart Failure and End-Stage Kidney Disease after Fluid Resuscitation for Sepsis and Septic Shock.

BACKGROUND: Sepsis fluid resuscitation is controversial, especially for patients with volume overload risk. The Surviving Sepsis Campaign recommends a 30-mL/kg crystalloid fluid bolus for patients with sepsis-induced hypoperfusion. Criticism of this approach includes excessive fluid resuscitation in certain patients. OBJECTIVE: The aim of this study was to assess the efficacy and safety of guideline-concordant fluid resuscitation in patients with sepsis and heart failure (HF) or end-stage kidney disease (ESKD). METHODS: A retrospective cohort study was conducted in patients with sepsis who qualified for guideline-directed fluid resuscitation and concomitant HF or ESKD. Those receiving crystalloid fluid boluses of at least 30 mL/kg within 3 h of sepsis diagnosis were placed in the concordant group and all others in the nonconcordant group. The primary outcome was in-hospital mortality. Secondary outcomes included intensive care unit (ICU) and hospital length of stay (LOS); vasoactive medications and net volume over 24 h; new mechanical ventilation, new or increased volume removal, and acute kidney injury within 48 h; and shock-free survival at 7 days. RESULTS: One hundred twenty-five patients were included in each group. In-hospital mortality was 34.4% in the concordant group and 44.8% in the nonconcordant group (p = 0.1205). The concordant group had a shorter ICU LOS (7.6 vs. 10.5 days; p = 0.0214) and hospital LOS (12.9 vs. 18.3 days; p = 0.0163), but increased new mechanical ventilation (37.6 vs. 20.8%; p = 0.0052). No differences in other outcomes were observed. CONCLUSIONS: Receipt of a 30-mL/kg fluid bolus did not affect outcomes in a cohort of patients with mixed types of HF and sepsis-induced hypoperfusion.

Late surgical site infections among solid organ transplant recipients: an unrecognized clinical entity.

This study identified 26 late invasive primary surgical site infection (IP-SSI) within 4-12 months of transplantation among 2073 SOT recipients at Duke University Hospital over the period 2015-2019. Thoracic organ transplants accounted for 25 late IP-SSI. Surveillance for late IP-SSI should be maintained for at least one year following transplant.

Novel Definitive Hypofractionated Accelerated Radiation Dose-painting (HARD) for Unresected Soft Tissue Sarcomas.

Purpose: Soft tissue sarcomas (STS) are historically radioresistant, with surgery being an integral component of their treatment. With their low α/ß, STS may be more responsive to hypofractionated radiation therapy (RT), which is often limited by long-term toxicity risk to surrounding normal tissue. An isotoxic approach using a hypofractionated accelerated radiation dose-painting (HARD) regimen allows for dosing based on clinical risk while sparing adjacent organs at risk. Methods and Materials: We retrospectively identified patients from 2019 to 2022 with unresected STS who received HARD with dose-painting to high, intermediate, and low-risk regions of 3.0 Gy, 2.5 Gy, and 2.0 to 2.3 Gy, respectively, in 20 to 22 fractions. Clinical endpoints included local control, locoregional control, progression free survival, overall survival, and toxicity outcomes. Results: Twenty-seven consecutive patients were identified and had a median age of 68 years and tumor size of 7.0 cm (range, 1.2-21.0 cm). Tumors were most often high-grade (70%), stage IV (70%), located in the extremities (59%), and locally recurrent (52%). With a median follow-up of 33.4 months, there was a 3-year locoregional control rate of 100%. The 3-year overall and progression-free survival were 44.9% and 23.3%, respectively. There were 5 (19%) acute and 2 (7%) late grade 3 toxicities, and there were no grade 4 or 5 toxicities at any point. Conclusions: The HARD regimen is a safe method of dose-escalating STS, with durable 3-year locoregional control. This approach is a promising alternative for unresected STS, though further follow-up is required to determine long-term control and toxicity.

The left atrial appendage: An enigmatic friend or foe and implications of closure.

The left atrial appendage (LAA) is often thought of as a vestigial organ serving as a nidus for clot formation in those with atrial fibrillation (A-fib). The LAA, however, has unique anatomy which allows it to serve special functions in the human body. Closing the LAA has been shown to decrease the risk of thromboembolic events in patients who cannot tolerate anticoagulation. Several methods of closure exist including percutaneous endocardial closure, epicardial closure, and surgical clipping. In addition to decreasing stroke risk, there appears to be physiologic changes that occur after LAA closure. This comprehensive review aims to describe the functions of the LAA, compare the different methods of closure, and propose a new method for identifying which patients may benefit from LAA closure versus anticoagulation based on each patients' individual comorbidities rather than their contraindications.

Obesity.

Obesity is a common condition and a major cause of morbidity and mortality. Fortunately, weight loss treatment can reduce obesity-related complications. This review summarizes the evidence-based strategies physicians can employ to identify, prevent, and treat obesity, including best practices to diagnose and counsel patients, to assess and address the burden of weight-related disease including weight stigma, to address secondary causes of weight gain, and to help patients set individualized and realistic weight loss goals and an effective treatment plan. Effective treatments include lifestyle modification and adjunctive therapies such as antiobesity medications and metabolic and bariatric surgery.

Cross-Seal IDE Trial: Prospective, Multicenter, Single-Arm Study of the Cross-Seal Suture-Mediated Vascular Closure Device System.

BACKGROUND: An increasing number of interventional procedures require large-sheath technology (>12F) with a favorable outcome with endovascular rather than open surgical access. However, vascular complications are a limitation for the management of these patients. This trial aimed to determine the effectiveness and safety of the Cross-Seal suture-mediated vascular closure device in obtaining hemostasis at the target limb access site following interventional procedures using 8F to 18F procedural sheaths. METHODS: The Cross-Seal IDE trial (Investigational Device Exemption) was a prospective, single-arm, multicenter study in subjects undergoing percutaneous endovascular procedures utilizing 8F to 18F ID procedural sheaths. The primary efficacy end point was time to hemostasis at the target limb access site. The primary safety end point was freedom from major complications of the target limb access site within 30 days post procedure. RESULTS: A total of 147 subjects were enrolled between August 9, 2019, and March 12, 2020. Transcatheter aortic valve replacement was performed in 53.7% (79/147) and percutaneous endovascular abdominal/thoracic aortic aneurysm repair in 46.3% (68/147) of subjects. The mean sheath ID was 15.5±1.8 mm. The primary effectiveness end point of time to hemostasis was 0.4±1.4 minutes. An adjunctive intervention was required in 9.2% (13/142) of subjects, of which 2.1% (3/142) were surgical and 5.6% (8/142) endovascular. Technical success was achieved in 92.3% (131/142) of subjects. Freedom from major complications of the target limb access site was 94.3% (83/88). CONCLUSIONS: In selected patients undergoing percutaneous endovascular procedures utilizing 8F to 18F ID procedural sheath, Cross-Seal suture-mediated vascular closure device achieved favorable effectiveness and safety in the closure of the large-bore arteriotomy. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03756558.

Novel Method for Sealing Tracheostomies Immediately after Decannulation-An Acute Clinical Feasibility Study.

Tracheostomy decannulation leaves an iatrogenic passage in the upper airways. Inadequate sealing leads to pulmonary dysfunction and reduced voice quality. This study aimed to investigate the feasibility and impact of intratracheal tracheostomy sealing on laryngeal airflow and voice quality immediately after decannulation (ClinicalTrials.gov: NCT06138093). Fifteen adult, tracheostomized, intensive care unit patients were included from our hospital. A temporary, silicone-based sealing disc was inserted in the tracheostomy wound immediately after decannulation. Spirometry with measurement of forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and peak expiratory flow (PEF) were performed as measures of airway flow. Voice recordings were assessed using an equal appearing interval scale from 1 to 5. Median FVC, FEV1, PEF, and voice quality score with interquartile range (IQR) was 883 (510-1910) vs. 1260 (1005-1723) mL (p < 0.001), 790 (465-1255) vs. 870 (617-1297) mL (p < 0.001), 103 (55-211) vs. 107 (62-173) mL (p = 0.720), and 2 (1-2.5) vs. 4 (3-5) points (p < 0.001), respectively, with open tracheostomy vs. after sealing the tracheostomy with the intratracheal sealing disc. This feasibility study showed that tracheostomy sealing with the intratracheal disc was safe and led to immediate improvements in FVC, FEV1, and voice quality.

Alterations of whole body glucose metabolism in a feline SARS-CoV-2 infection model.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been especially devastating to patients with comorbidities, including metabolic and cardiovascular diseases. Elevated blood glucose during SARS-CoV-2 infection increased mortality of patients with COVID-19, although the mechanisms are not well understood. It has been previously demonstrated that glucose transport and utilization is a crucial pathway for other highly infectious RNA viruses. Thus, we hypothesized that SARS-CoV-2 infection could lead to alterations in cellular and whole body glucose metabolism. Specific pathogen-free domestic cats were intratracheally inoculated with USA-WA1/2020 (wild-type) SARS-CoV-2 or vehicle-inoculated, then euthanized at 4- and 8-days postinoculation (dpi). Blood glucose and cortisol concentrations were elevated at 4 and 8 dpi. Blood ketones, insulin, and angiotensin II concentrations remained unchanged throughout the experimental timeline. SARS-CoV-2 RNA was detected in the lung and heart, without changes in angiotensin-converting enzyme 2 (ACE2) RNA expression. In the lung, SARS-CoV-2 infection increased glucose transporter 1 (GLUT1) protein levels at 4 and 8 dpi, whereas GLUT4 level was only upregulated at 8 dpi. In the heart, GLUT-1 and -4 protein levels remained unchanged. Furthermore, GLUT1 level was upregulated in the skeletal muscle at 8 dpi, and AMPK was activated in the hearts of infected cats. SARS-CoV-2 infection increased blood glucose concentration and pulmonary GLUT protein levels. These findings suggest that SARS-CoV-2 infection induces metabolic reprogramming primarily in the lung to support viral replication. Furthermore, this translational feline model mimicked human COVID-19 and could be used to explore novel therapeutic targets to treat metabolic disease during SARS-CoV-2 infection.NEW & NOTEWORTHY Our study on a feline model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, mirroring human COVID-19, revealed alterations in whole body and cellular glucose metabolism. Infected cats developed mild hyperglycemia, increased protein levels of glucose transporters in the lung, and AMPK activation in the heart. These findings suggest that SARS-CoV-2 infection induces metabolic reprogramming in the cardiorespiratory system to support viral replication. Understanding these mechanisms could lead to novel antiviral therapeutic strategies.

Subcostal bilateral internal thoracic artery harvesting with the da Vinci Single Port system: an experimental feasibility study.

We evaluated the feasibility of harvesting bilateral internal thoracic arteries with the da Vinci Single Port system (SP) through a single left-sided subcostal incision. Complete bilateral mobilization with sufficiently long conduits for multivessel grafting was possible in 2 human cadavers and 2 live porcine. Creating the subcostal access and docking the SP system took between 14 and 21 min and the total harvest time ranged from 65 to 125 min in all models. No major bleeding was observed in the live porcine and hemostasis was managed with the available instrumentation. One porcine deceased during surgery due to ventricular fibrillation followed by cardiac arrest. The robotic harvesting was technically easily reproduced by the surgeons and required no additional rib-spreading. Further studies will be required to assess if this subcostal approach with the da Vinci SP system yields true clinical benefits in patients.

Acute kidney failure reveals primary renal non-Hodgkin lymphoma.

A male patient in his 60s was admitted to our hospital with symptoms of dyspnoea, asthenia, diaphoresis and acute kidney failure. No tumour or infection was detected in initial screening. However, laboratory examination suggested that the acute kidney failure was due to an intrarenal cause, exhibiting a tubular injury pattern and indications of tumour lysis syndrome. Initial hydration therapy, paired with intravenous rasburicase, rapidly improved the kidney function. Unfortunately, the kidney function deteriorated once again, prompting a kidney biopsy that revealed an aggressive diffuse large B-cell non-Hodgkin lymphoma of the kidney. The chemotherapy, comprised of R-CHOP scheme, led to a full recovery of the kidney function and complete remission of the lymphoma. Primary renal non-Hodgkin lymphoma without nodal manifestation is rare, and its pathophysiology is poorly understood. Therapy schemes can vary significantly between cases, relying primarily on non-renal-specific haemato-oncological guidelines. Therefore, further studies are needed to develop the best therapeutic approaches.

Persistent Lower Urinary Tract Symptoms After BPH Surgery.

PURPOSE OF REVIEW: Lower urinary tract symptoms (LUTS) after surgical management for BPH pose a significant clinical challenge for urologists. Despite high success rates in relieving LUTS, there is a subset of patients who experience persistent symptoms after intervention. In this review article, we describe the management of patients with new or persistent LUTS after endoscopic bladder outlet surgery. RECENT FINDINGS: Previously, the goal for BPH management was to remove as much adenomatous tissue as possible. While potentially effective, this may lead to unwanted side effects. There has been a recent paradigm shift for new minimally invasive surgical therapies (MIST) that strategically treat adenomatous tissue, adding potential complexity in managing patients with new or residual symptoms in the postoperative setting. There is a paucity of literature to guide optimal workup and care of patients with persistent LUTS after surgical management. We characterize patients into distinct groups, defined by types of symptoms, irritative versus obstructive, and timing of the symptomatology, short term versus long term. By embracing this patient-centered approach with shared decision management, clinicians can optimize outcomes efficiently improving their patients' quality of life.

Lexicon-Based Sentiment Analysis in Behavioral Research.

A complete science of human behavior requires a comprehensive account of the verbal behavior those humans exhibit. Existing behavioral theories of such verbal behavior have produced compelling insight into language's underlying function, but the expansive program of research those theories deserve has unfortunately been slow to develop. We argue that the status quo's manually implemented and study-specific coding systems are too resource intensive to be worthwhile for most behavior analysts. These high input costs in turn discourage research on verbal behavior overall. We propose lexicon-based sentiment analysis as a more modern and efficient approach to the study of human verbal products, especially naturally occurring ones (e.g., psychotherapy transcripts, social media posts). In the present discussion, we introduce the reader to principles of sentiment analysis, highlighting its usefulness as a behavior analytic tool for the study of verbal behavior. We conclude with an outline of approaches for handling some of the more complex forms of speech, like negation, sarcasm, and speculation. The appendix also provides a worked example of how sentiment analysis could be applied to existing questions in behavior analysis, complete with code that readers can incorporate into their own work.

Approach to the Patient Navigating Body Mass Index Requirements for Gender-Affirming Surgery.

Body mass index (BMI) requirements for gender-affirming surgeries (GAS) present an obstacle to gender transition for many transgender and gender diverse (TGD) people. Furthermore, TGD people have unique barriers and preferences in managing their weight that must be considered. TGD patients frequently present to their endocrinologists for individualized, gender-affirming support to meet BMI cutoffs for GAS. This Approach to the Patient article combines expertise from several disciplines, including gender-affirming hormone management, weight management, mental health, gynecology, and plastic surgery. Multidisciplinary management considerations are offered for clinicians to assist TGD patients with obesity navigate BMI requirements to access GAS.

Training Response Abilities of Children With Intellectual Disabilities: A Randomized Controlled Trial.

Response abilities, i.e., response time (RT) and response force (RF), which are essential for efficient motor control, are impaired in children with intellectual disabilities (ID). The study aimed to evaluate the effects of object control skills training, computer-based games training, or standard care on the RT and RF of children with ID when measured across task conditions. A randomized controlled trial was conducted in a special education school where 75 children with ID, between 9 and 17 years of age, were randomly assigned to object control skills training, computer-based games training, or standard care, where intervention groups were provided thrice a week for four weeks. The RT and RF were measured using a response analyzer for simple response task, (passive and active) dual-task, and choice response task at baseline, post-intervention, and four-week follow-up. The RT significantly reduced with object control skills training (ηp2= .325) and computer-based games training (ηp2= .159). Participants who received the object control skills training had greater stability in force production than the other groups. With training, children with ID take less time and show better stability in their ability to modulate force in various task settings, with more pronounced effects with the object control skills training.

Assessing Longitudinal Treatment Efficacies and Alterations in Molecular Markers Associated with Glutamatergic Signaling and Immune Checkpoint Inhibitors in a Spontaneous Melanoma Mouse Model.

Previous work done by our laboratory described the use of an immunocompetent spontaneous melanoma-prone mouse model, TGS (TG-3/SKH-1), to evaluate treatment outcomes using inhibitors of glutamatergic signaling and immune checkpoint for 18 weeks. We showed a significant therapeutic efficacy with a notable sex-biased response in male mice. In this follow-up 18-week study, the dose of the glutamatergic signaling inhibitor was increased (from 1.7 mg/kg to 25 mg/kg), which resulted in improved responses in female mice but not male mice. The greatest reduction in tumor progression was observed in male mice treated with single-agent troriluzole and anti-PD-1. Furthermore, a randomly selected group of mice was removed from treatment after 18 weeks and maintained for up to an additional 48 weeks demonstrating the utility of the TGS mouse model to perform a ≥1-year preclinical therapeutic study in a physiologically relevant tumor-host environment. Digital spatial imaging analyses were performed in tumors and tumor microenvironments across treatment modalities using antibody panels for immune cell types and immune cell activation. The results suggest that immune cell populations and cytotoxic activities of T cells play critical roles in treatment responses in these mice. Examination of a group of molecular protein markers based on the proposed mechanisms of action of inhibitors of glutamatergic signaling and immune checkpoint showed that alterations in expression levels of xCT, γ-H2AX, EAAT2, PD-L1, and PD-1 are likely associated with the loss of treatment responses. These results suggest the importance of tracking changes in molecular markers associated with the mechanism of action of therapeutics over the course of a longitudinal preclinical therapeutic study in spatial and temporal manners.

Norway's Battery Electric Vehicles and Public Health- Findings From the Literature.

The transportation sector is among the highest contributors to the increase in greenhouse gas emissions in European nations, with private cars emerging as the primary source. Although reducing emissions presents a formidable challenge, the emergence of battery electric vehicles (BEVs) offers a promising and sustainable avenue toward achieving zero greenhouse gases within the transportation infrastructure. Since the 1990s, the Norwegian parliament has fervently supported this transition, leveraging public awareness campaigns and a range of financial incentives for its users nationwide. The widespread utilization of BEVs promises substantial health benefits, including ensuring cleaner air for all citizens regardless of their socioeconomic status and fostering improvements in public health outcomes. This transition potentially curtails hundreds of thousands of annual deaths attributed to climate change, enhances the quality of life, bolsters civilian productivity, and fuels economic and population growth. The adoption of BEVs offers a myriad of advantages, including reduced health risks and premature mortality, as well as a quieter environment with diminished noise pollution. Nonetheless, the integration of BEVs necessitates robust road infrastructure with considerable maintenance costs, alongside limitations on driving range for users. Concerns arise regarding potential particle emissions from BEV tire wear due to the increased weight of batteries compared to conventional vehicles. Rapid acceleration capabilities may accelerate tire degradation, contributing to higher particle emissions, of which only 10% to 20% remain suspended in the air, whereas the majority settles on road surfaces, posing a threat to nearby aquatic ecosystems when washed into water bodies and soils. While BEVs hold promise for valuable benefits, successful policy creation and implementation require a detailed awareness of their limitations and challenges to ensure a comprehensive approach to sustainable mobility and public health improvement. Therefore, more research on the limitations of BEVs can help inform improved tactics for maximizing their benefits while limiting potential disadvantages.

A swift transition to electric vehicles is a good public health intervention that benefits the quality of the air and climate systems. It is expedient to know that this new technology will not solve all problems caused by transportation systems, as there will always be some unwanted and unexpected side effects as usual with new technologies. We suggest more advanced research on EVs shortcomings for better understanding and usage.