Using Large Language Models to Support Content Analysis: A Case Study of ChatGPT for Adverse Event Detection.

This study explores the potential of using large language models to assist content analysis by conducting a case study to identify adverse events (AEs) in social media posts. The case study compares ChatGPT's performance with human annotators' in detecting AEs associated with delta-8-tetrahydrocannabinol, a cannabis-derived product. Using the identical instructions given to human annotators, ChatGPT closely approximated human results, with a high degree of agreement noted: 94.4% (9436/10,000) for any AE detection (Fleiss κ=0.95) and 99.3% (9931/10,000) for serious AEs (κ=0.96). These findings suggest that ChatGPT has the potential to replicate human annotation accurately and efficiently. The study recognizes possible limitations, including concerns about the generalizability due to ChatGPT's training data, and prompts further research with different models, data sources, and content analysis tasks. The study highlights the promise of large language models for enhancing the efficiency of biomedical research.

AI-Generated Draft Replies Integrated Into Health Records and Physicians' Electronic Communication.

Importance: Timely tests are warranted to assess the association between generative artificial intelligence (GenAI) use and physicians' work efforts. Objective: To investigate the association between GenAI-drafted replies for patient messages and physician time spent on answering messages and the length of replies. Design, Setting, and Participants: Randomized waiting list quality improvement (QI) study from June to August 2023 in an academic health system. Primary care physicians were randomized to an immediate activation group and a delayed activation group. Data were analyzed from August to November 2023. Exposure: Access to GenAI-drafted replies for patient messages. Main Outcomes and Measures: Time spent (1) reading messages, (2) replying to messages, (3) length of replies, and (4) physician likelihood to recommend GenAI drafts. The a priori hypothesis was that GenAI drafts would be associated with less physician time spent reading and replying to messages. A mixed-effects model was used. Results: Fifty-two physicians participated in this QI study, with 25 randomized to the immediate activation group and 27 randomized to the delayed activation group. A contemporary control group included 70 physicians. There were 18 female participants (72.0%) in the immediate group and 17 female participants (63.0%) in the delayed group; the median age range was 35-44 years in the immediate group and 45-54 years in the delayed group. The median (IQR) time spent reading messages in the immediate group was 26 (11-69) seconds at baseline, 31 (15-70) seconds 3 weeks after entry to the intervention, and 31 (14-70) seconds 6 weeks after entry. The delayed group's median (IQR) read time was 25 (10-67) seconds at baseline, 29 (11-77) seconds during the 3-week waiting period, and 32 (15-72) seconds 3 weeks after entry to the intervention. The contemporary control group's median (IQR) read times were 21 (9-54), 22 (9-63), and 23 (9-60) seconds in corresponding periods. The estimated association of GenAI was a 21.8% increase in read time (95% CI, 5.2% to 41.0%; P = .008), a -5.9% change in reply time (95% CI, -16.6% to 6.2%; P = .33), and a 17.9% increase in reply length (95% CI, 10.1% to 26.2%; P < .001). Participants recognized GenAI's value and suggested areas for improvement. Conclusions and Relevance: In this QI study, GenAI-drafted replies were associated with significantly increased read time, no change in reply time, significantly increased reply length, and some perceived benefits. Rigorous empirical tests are necessary to further examine GenAI's performance. Future studies should examine patient experience and compare multiple GenAIs, including those with medical training.

Characteristics of X (Formerly Twitter) Community Notes Addressing COVID-19 Vaccine Misinformation.

This study evaluated the topics, accuracy, and credibility of X (formerly Twitter) Community Notes addressing COVID-19 vaccination.

Regulate Artificial Intelligence in Health Care by Prioritizing Patient Outcomes.

This Viewpoint argues for a shift in focus by the White House executive order on artificial intelligence from regulatory targets to patient outcomes.

Musicogenic seizures-STXBP1 encephalopathy with reflex seizures.

Mutations in the gene encoding syntaxin binding protein 1 (STXBP1) have been implicated in a wide variety of epileptic encephalopathies. Although the recognized phenotypes of patients with STXBP1 encephalopathies have broadened in recent years, no case of reflex seizures, particularly musicogenic seizures, has been reported in the literature. We present an 18-year-old woman with STXBP1 encephalopathy and seizures that are stereotypically reproducible in response to a variety of audible stimuli. An 18-year-old woman with a history of profound intellectual disability, confirmed STXBP1 genetic defect via genetic testing, and seizures beginning as infantile spasms during childhood, who presented to the epilepsy monitoring unit for seizure characterization. Her mother reported reproducible seizures triggered by a particular cell phone ringtone, music from a certain automobile television commercial and certain beeping alarm sounds. In response, the patient had clinically stereotyped seizures associated with staring, behavioral arrest, followed by eye deviation to the left, tonic stiffening in upper and lower extremities, and labored breathing lasting between 30 s and 2 min. These seizures were reliably reproducible within a few seconds of exposure to the auditory stimulus. During hospitalization, mother played one of the cell phone ringtones known to trigger seizures for the patient, which resulted in induction of a seizure characterized by diffuse electrodecrement, subsequent emergence of frontal-predominant theta which was followed by progressive diffuse attenuation and semi-rhythmic slowing over the right posterior quadrant. This is the first case to describe musicogenic or other reflex seizures in a patient with STXBP1 encephalopathy.

Ambulatory EEG: Crossing the divide during a pandemic.

The COVID-19 pandemic forced temporary closure of epilepsy monitoring units across the globe due to potential hospital-based contagion. As COVID-19 exposures and deaths continues to surge in the United States and around the world, other types of long-term EEG monitoring have risen to fill the gap and minimize hospital exposure. AEEG has high yield compared to standard EEG. Prolonged audio-visual video-EEG capability can record events and epileptiform activity with quality like inpatient video-EEG monitoring. Technological advances in AEEG using miniaturized hardware and wireless secure transmission have evolved to small portable devices that are perfect for people forced to stay at home during the pandemic. Application of seizure detection algorithms and Cloud-based storage with real-time access provides connectivity to AEEG interpreters during prolonged "shut-down". In this article we highlight the benefits of AEEG as an alternative to diagnostic inpatient VEM during the paradigm shift to mobile heath forced by the Coronavirus.

Optic Neuritis After a Snakebite: A Diagnostic Dilemma.

Background: Snakebite is one of the major causes of morbidity and mortality in India, particularly in rural regions. Of the 57 known venomous species of snakes in India, the 4 most dangerous snakes are the cobra, the common krait, the Russell viper, and the saw-scaled viper. Of these, the snakes commonly implicated with neurotoxicity are the cobra and the common krait-both elapidae. Acute neuromuscular weakness with respiratory system involvement is the most lethal neurotoxic effect. Case Report: A 24-year-old female was brought to the emergency department in an unresponsive state with a history of snakebite on the left foot. The patient was intubated, mechanically ventilated, and promptly started on snake antivenom and anticholinesterase agents. The patient improved significantly and was extubated. On day 6, she developed blurred vision and slurred speech. She was diagnosed with bilateral optic neuropathy and treated with repeat snake antivenom and steroids. She improved significantly and was discharged on day 14. Conclusion: When a person is bitten by a venomous snake, antivenom is the mainstay of treatment, but clinicians must also consider possible reactions and complications. Optic neuritis following a snakebite is rare but does occur. The prognosis is generally good if clinical suspicion for such a complication is strong, the snake is identified, and the patient receives timely treatment with steroids.

Paradoxical Embolism Causing Myocardial Infarction in a COVID-19 Patient Presenting With Pulmonary Embolism.

The presence of myocardial injury in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection is common. The cardiac complications of SARS-CoV2 infection are varied and distinguishing between them can be complicated.  A 55-year-old man with recent diagnosis of SARS-CoV2 infection presented with chest pain, syncope, and was found to have saddle pulmonary embolism (PE). Marked elevation in cardiac enzymes prompted a coronary angiogram which was normal. Cardiac MRI revealed late gadolinium enhancement (LGE) in the anterolateral wall consistent with myocardial infarction (MI). He was diagnosed with paradoxical embolism causing MI. The differential for elevated cardiac enzymes is wide in patients with SARS-CoV2 infection. This case illustrates that sometimes multiple diagnoses exist, and that a high index of suspicion is required to continue work-up.

Television-induced electronegative photoparoxysmal response: an extratemporal seizure mimic?

Video-EEG monitoring is an established gold-standard procedure for diagnosis and differentiation of epileptic and non-epileptic seizures. Epilepsy misdiagnosis, to which factors such as EEG artifact misinterpretation contribute to, is common, and can have long-lasting iatrogenic repercussions to the clinical management of affected patients. Among the many types of responses to photic stimulation, artifacts and physiologic and epileptic responses are possible. All of these can interfere with EEG interpretation when provoked by a source of illumination. Photic-induced responses are of increasing relevance given the ubiquity of screens and other light-emitting electronics in our modern world. One of these, the photoparoxysmal response, is a frequent finding in photosensitive patients with genetic generalized epilepsies. Various responses beyond abnormal occurrence of cortical spikes or spike-and-wave discharges are known to occur on EEG in response to intermittent photic stimulation (IPS), with different clinical implications. To our knowledge, we report a unique electronegative photoparoxysmal response during video-EEG monitoring induced by fluctuating illumination caused by a distant television screen. This response mimicked an extratemporal seizure in a young woman with frontal lobe epilepsy, admitted for presurgical evaluation. Novel electronegative responses to electronic devices during video-EEG monitoring merit consideration by EEG interpreters to help avoid misdiagnosis.

Crying with depressed affect induced by electrical stimulation of the anterior insula: A stereo EEG case study.

Stereo-EEG (sEEG) is an invasive recording technique used to localize the seizure-onset zone for epilepsy surgery in people with drug-resistant focal seizures. Pathological crying reflects disordered emotional expression and the anterior insula is known to play a role in empathy and socio-emotional processing. We describe a patient where electrical stimulation mapping (ESM) of the anterior insula during sEEG generated pathological crying and profound sadness that was time-locked to the electrical stimulus. We evaluated a 35-year-old left-handed female for repeat epilepsy surgery. The patient had drug resistant focal impaired awareness seizures despite a previous left temporal neocortical resection informed by an invasive study using subdural grid and strip electrodes seven years earlier. She was studied invasively with 10 sEEG electrodes sampling temporal, occipital, and insular targets. In the process of functional mapping, stimulation of the anterior insular cortex provoked tearful crying with sad affect, reproducible upon repeat stimulation. Our case is unique in demonstrating transitory pathological crying with profound sadness provoked by ESM of the left anterior insula. Furthermore we demonstrate repeated time-synched crying from electrical stimulation, which supports the hypothesis that the anterior insula in the brain plays an important role in the biology of emotion, as implicated by previous studies.

Case Report: Unprovoked venous thromboembolism in a young adult male.

A 24-year-old male was presented to us with sudden onset of chest pain and dyspnea for the past one hour. There was no history of calf pain, trauma, surgery, prolonged immobilization, long-haul air travel, bleeding diathesis or any other co-morbidity. The patient denied any addiction history. The heart rate was 114 beats/min, and blood pressure was 106/90 mmHg. Electrocardiogram showed tachycardia with S 1Q 3T 3 pattern. The left arterio-venous Doppler study was suggestive of a thrombus in popliteal vein and sapheno-popliteal junction. The CT-Pulmonary Angiogram scan was suggestive of a massive pulmonary thromboembolism. The patient was thrombolysed with Intravenous Alteplase immediately and was put on tab Rivaroxaban for maintenance. He was later discharged after being stable. Unprovoked venous thromboembolism (VTE) is very rare and has the potential to lead to pulmonary embolism which could be disastrous, especially in young adults. We present such a case where unprovoked VTE was diagnosed and treated. This case suggests that high clinical suspicion is the key for the diagnosis of acute pulmonary embolism, especially in the absence of history suggestive of deep vein thrombosis.

Effectiveness of SIESTA on Objective and Subjective Metrics of Nighttime Hospital Sleep Disruptors.

We created Sleep for Inpatients: Empowering Staff to Act (SIESTA), which combines electronic "nudges" to forgo nocturnal vitals and medications with interprofessional education on improving patient sleep. In one "SIESTAenhanced unit," nurses received coaching and integrated SIESTA into daily huddles; a standard unit did not. Six months pre- and post-SIESTA, sleep-friendly orders rose in both units (foregoing vital signs: SIESTA unit, 4% to 34%; standard, 3% to 22%, P < .001 both; sleeppromoting VTE prophylaxis: SIESTA, 15% to 42%; standard, 12% to 28%, P < .001 both). In the SIESTAenhanced unit, nighttime room entries dropped by 44% (-6.3 disruptions/room, P < .001), and patients were more likely to report no disruptions for nighttime vital signs (70% vs 41%, P = .05) or medications (84% vs 57%, P = .031) than those in the standard unit. The standard unit was not changed. Although sleep-friendly orders were adopted in both units, a unit-based nursing empowerment approach was associated with fewer nighttime room entries and improved patient experience.

C-X-C Motif Chemokine Receptor 3 Splice Variants Differentially Activate Beta-Arrestins to Regulate Downstream Signaling Pathways.

Biased agonism, the ability of different ligands for the same receptor to selectively activate some signaling pathways while blocking others, is now an established paradigm for G protein-coupled receptor signaling. One group of receptors in which endogenous bias is critical is the chemokine system, consisting of over 50 ligands and 20 receptors that bind one another with significant promiscuity. We have previously demonstrated that ligands for the same receptor can cause biased signaling responses. The goal of this study was to identify mechanisms that could underlie biased signaling between different receptor splice variants. The C-X-C motif chemokine receptor 3 (CXCR3) has two splice variants, CXCR3A and CXCR3B, which differ by 51 amino acids at its N-terminus. Consistent with an earlier study, we found that C-X-C motif chemokine ligands 4, 9, 10, and 11 all activated G αi at CXCR3A, while at CXCR3B these ligands demonstrated no measurable G αi or G αs activity. ß-arrestin (ßarr) was recruited at a reduced level to CXCR3B relative to CXCR3A, which was also associated with differences in ßarr2 conformation. ßarr2 recruitment to CXCR3A was attenuated by both G protein receptor kinase (GRK) 2/3 and GRK5/6 knockdown, while only GRK2/3 knockdown blunted recruitment to CXCR3B. Extracellular regulated kinase 1/2 phosphorylation downstream from CXCR3A and CXCR3B was increased and decreased, respectively, by ßarr1/2 knockout. The splice variants also differentially activated transcriptional reporters. These findings demonstrate that differential splicing of CXCR3 results in biased responses associated with distinct patterns of ßarr conformation and recruitment. Differential splicing may serve as a common mechanism for generating biased signaling and provides insights into how chemokine receptor signaling can be modulated post-transcriptionally.

Awakenings? Patient and Hospital Staff Perceptions of Nighttime Disruptions and Their Effect on Patient Sleep.

STUDY OBJECTIVES: Although important to recovery, sleeping in the hospital is difficult because of disruptions. Understanding how patients, hospital physicians, and nurses perceive sleep disruptions and identifying which disruptions are associated with objective sleep loss can help target improvement initiatives. METHODS: Patients and hospital staff completed the Potential Hospital Sleep Disruptions and Noises Questionnaire (PHSDNQ). Cutoff points were defined based on means, and responses were dichotomized. Perceived percent disrupted for each item was calculated, and responses were compared across groups using chi-square tests. Objective sleep time of patients was measured using wrist actigraphy. The association between patient-reported disruptions and objective sleep time was assessed using a multivariable linear regression model controlling for subject random effects. RESULTS: Twenty-eight physicians (78%), 37 nurses (88%), and 166 of their patients completed the PHSDNQ. Patients, physicians, and nurses agreed that pain, vital signs and tests were the top three disrupters to patient sleep. Significant differences among the groups' perceptions existed for alarms [24% (patients) vs. 46% (physicians) vs. 27% (nurses), p < 0.040], room temperature (15% vs. 0% vs. 5%, p < 0.031) and anxiety (18% vs. 21% vs. 38%, p < 0.031). Using survey and actigraphy data from 645 nights and 379 patients, the presence of pain was the only disruption associated with lower objective sleep duration (minutes) [-38.1 (95% confidence interval -63.2, -12.9) p < 0.003]. CONCLUSION: Hospital staff and patients agreed that pain, vital signs and tests were top sleep disrupters. However, pain was associated with the greatest objective sleep loss, highlighting the need for proactive screening and management of patient pain to improve sleep in hospitals.

When Pulmonary Function Test is Available, Should we Wait for the COPD Symptoms to Develop?

Adolescent smokers are more likely to be addicted to nicotine and develop a chronic habit. Chronic smoking has a direct impact on quality of life and life expectancy. Repeated environmental exposure and smoke inhalation can be deleterious to health. In order to evaluate the core functioning of the lungs, Pulmonary Function Tests (PFTs) are conducted. This panel of tests should be advised for all patients complaining of shortness of breath. Since clinical features resulting from chronic smoking tend to appear late in the course of the disease, PFTs are immensely useful for early identification of abnormalities in asymptomatic adult smokers. Numerous studies have shown that normal PFT parameters begin to deteriorate immediately after smoking is initiated. However, most physicians prefer to wait for characteristic signs and symptoms of Chronic Obstructive Pulmonary Disease (COPD) to develop before proceeding with PFTs in the patients. This leads to inadvertent and often dangerous delay in reaching a definitive diagnosis and initiating treatment. Therefore, we undertook this review to determine whether conducting PFTs in asymptomatic adult smokers can facilitate the early detection and/or prevention of COPD. We reviewed and analyzed articles from PubMed, Google Scholar, Index Medicus, WHO Global Health Library and Scopus, which specifically demonstrated the presence of abnormal PFT changes in asymptomatic adult smokers. With PFTs, we now have the advantage of diagnosing early changes in the lung volumes. Hence, we conclude that PFTs should be performed early in smokers and cessation of smoking should be encouraged to check the increasing incidence of COPD.

Heart Rhythm Society members' views on pacemaker and implantable cardioverter-defibrillator reuse.

BACKGROUND: Reuse of cardiac implantable electronic devices (CIEDs) may help address the unmet need among patients in low- and middle-income countries (LMICs). METHODS: To examine Heart Rhythm Society (HRS) physicians' opinions regarding CIED reuse, an online survey eliciting attitudes toward CIED reuse was sent to all 3,380 HRS physician members. RESULTS: There were 429 responses (response rate 13%). A large majority of respondents agreed or strongly agreed that resterilization of devices for reimplantation in patients who cannot afford new devices may be safe (370, 87%) and, if proven to be safe, would be ethical (375, 88%). A total of 340 (81%) respondents would be comfortable asking their patients to consider donating their device, and 353 (84%) would be willing to reimplant a resterilized device if it were legal. The most commonly cited concerns about device reuse were infection (270, 64%) and device malfunction (125, 29%). Respondents from the United States and Canada had more favorable impressions of device reuse than respondents from other high-income countries (P < 0.05 for three of five positive statements regarding reuse), and were less likely to cite ethical concerns (P < 0.001). However, when responses from all high-income countries were compared with lower- and upper-middle income countries, there were no significant differences in the rates of approval. CONCLUSIONS: HRS survey respondents support the concept of CIED reuse for patients in LMICs who cannot afford new devices. Studies are needed to demonstrate the clinical efficacy and safety of this practice and to identify potential barriers to adoption among physicians.

Interaction of ciliary disease protein retinitis pigmentosa GTPase regulator with nephronophthisis-associated proteins in mammalian retinas.

PURPOSE: Retinitis pigmentosa GTPase regulator (RPGR) is a cilia-centrosomal protein that frequently mutates in X-linked retinal degeneration and associated disorders. RPGR interacts with multiple ciliary proteins in the retina. Perturbations in the assembly of RPGR complexes are associated with retinal degeneration. This study was undertaken to delineate the composition and dissection of RPGR complexes in mammalian retinas. METHODS: Immunoprecipitation of RPGR from ciliary fraction of bovine retina was performed, followed by mass spectrometry analysis. The glutathione S-transferase pull-down assay was performed to validate the interaction. Immunodepletion experiments were performed to dissect the partitioning of RPGR in different protein complexes in mammalian retinas. RESULTS: We found that RPGR associates with a ciliary protein nephrocystin-4 (nephroretinin; NPHP4) that is mutated in nephronophthisis (NPH) and RP (Senior-Løken syndrome). This association is abolished in the Rpgr-knockout mouse retina. The RCC1-like domain of RPGR interacts with the N-terminal 316 amino acids of NPHP4. In the retina, RPGR also associates with NPHP1, an NPHP4-interacting protein; RPGR interacts directly with amino acids 243-586 of NPHP1. We further show that, in the retina, RPGR associates with and is partitioned in at least two different complexes with NPHP-associated proteins, (i) NPHP1, NPHP2, and NPHP5, and (ii) NPHP4, NPHP6, and NPHP8. CONCLUSIONS: RPGR may regulate some complexes with NPHP proteins in the mammalian retina. The disruption of these complexes may contribute to the pathogenesis of retinal degeneration in X-linked RP and associated ciliary diseases.