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1.
Cureus ; 16(6): e61680, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38841294

RESUMO

Background ChatGPT is a language model that has gained widespread popularity for its fine-tuned conversational abilities. However, a known drawback to the artificial intelligence (AI) chatbot is its tendency to confidently present users with inaccurate information. We evaluated the quality of ChatGPT responses to questions pertaining to atrial fibrillation for patient education. Our analysis included the accuracy and estimated grade level of answers and whether references were provided for the answers. Methodology ChatGPT was prompted four times and 16 frequently asked questions on atrial fibrillation from the American Heart Association were asked. Prompts included Form 1 (no prompt), Form 2 (patient-friendly prompt), Form 3 (physician-level prompt), and Form 4 (prompting for statistics/references). Responses were scored as incorrect, partially correct, or correct with references (perfect). Flesch-Kincaid grade-level unique words and response lengths were recorded for answers. Proportions of the responses at differing scores were compared using the chi-square analysis. The relationship between form and grade level was assessed using the analysis of variance. Results Across all forms, scoring frequencies were one (1.6%) incorrect, five (7.8%) partially correct, 55 (85.9%) correct, and three (4.7%) perfect. Proportions of responses that were at least correct did not differ by form (p = 0.350), but perfect responses did (p = 0.001). Form 2 answers had a lower mean grade level (12.80 ± 3.38) than Forms 1 (14.23 ± 2.34), 3 (16.73 ± 2.65), and 4 (14.85 ± 2.76) (p < 0.05). Across all forms, references were provided in only three (4.7%) answers. Notably, when additionally prompted for sources or references, ChatGPT still only provided sources on three responses out of 16 (18.8%). Conclusions ChatGPT holds significant potential for enhancing patient education through accurate, adaptive responses. Its ability to alter response complexity based on user input, combined with high accuracy rates, supports its use as an informational resource in healthcare settings. Future advancements and continuous monitoring of AI capabilities will be crucial in maximizing the benefits while mitigating the risks associated with AI-driven patient education.

2.
Sci Rep ; 14(1): 14305, 2024 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-38906984

RESUMO

Astrocytes play a role in healthy cognitive function and Alzheimer's disease (AD). The transcriptional factor nuclear factor-κB (NF-κB) drives astrocyte diversity, but the mechanisms are not fully understood. By combining studies in human brains and animal models and selectively manipulating NF-κB function in astrocytes, we deepened the understanding of the role of astrocytic NF-κB in brain health and AD. In silico analysis of bulk and cell-specific transcriptomic data revealed the association of NF-κB and astrocytes in AD. Confocal studies validated the higher level of p50 NF-κB and phosphorylated-p65 NF-κB in glial fibrillary acidic protein (GFAP)+-astrocytes in AD versus non-AD subjects. In the healthy mouse brain, chronic activation of astrocytic NF-κB disturbed the proteomic milieu, causing a loss of mitochondrial-associated proteins and the rise of inflammatory-related proteins. Sustained NF-κB signaling also led to microglial reactivity, production of pro-inflammatory mediators, and buildup of senescence-related protein p16INK4A in neurons. However, in an AD mouse model, NF-κB inhibition accelerated ß-amyloid and tau accumulation. Molecular biology studies revealed that astrocytic NF-κB activation drives the increase in GFAP and inflammatory proteins and aquaporin-4, a glymphatic system protein that assists in mitigating AD. Our investigation uncovered fundamental mechanisms by which NF-κB enables astrocytes' neuroprotective and neurotoxic responses in the brain.


Assuntos
Doença de Alzheimer , Astrócitos , Encéfalo , NF-kappa B , Astrócitos/metabolismo , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Doença de Alzheimer/genética , Animais , Humanos , Camundongos , Encéfalo/metabolismo , Encéfalo/patologia , NF-kappa B/metabolismo , Modelos Animais de Doenças , Masculino , Transdução de Sinais , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Proteína Glial Fibrilar Ácida/genética , Peptídeos beta-Amiloides/metabolismo
3.
Cureus ; 16(5): e59898, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38721479

RESUMO

Background Google Gemini (Google, Mountain View, CA) represents the latest advances in the realm of artificial intelligence (AI) and has garnered attention due to its capabilities similar to the increasingly popular ChatGPT (OpenAI, San Francisco, CA). Accurate dissemination of information on common conditions such as hypertension is critical for patient comprehension and management. Despite the ubiquity of AI, comparisons between ChatGPT and Gemini remain unexplored. Methods ChatGPT and Gemini were asked 52 questions derived from the American College of Cardiology's (ACC) frequently asked questions on hypertension, following a specified prompt. Prompts included: no prompting (Form 1), patient-friendly prompting (Form 2), physician-level prompting (Form 3), and prompting for statistics/references (Form 4). Responses were scored as incorrect, partially correct, or correct. Flesch-Kincaid (FK) grade level and word count were recorded. Results Across all forms, scoring frequencies were as follows: 23 (5.5%) incorrect, 162 (38.9%) partially correct, and 231 (55.5%) correct. ChatGPT showed higher rates of partially correct answers than Gemini (p = 0.0346). Physician-level prompts resulted in a higher word count across both platforms (p < 0.001). ChatGPT showed a higher FK grade level (p = 0.033) in physician-friendly prompting. Gemini exhibited a significantly higher mean word count (p < 0.001); however, ChatGPT had a higher FK grade level across all forms (p > 0.001). Conclusion To our knowledge, this study is the first to compare cardiology-related responses from ChatGPT and Gemini, two of the most popular AI chatbots. The grade level for most responses was collegiate level, which was above average for the National Institutes of Health (NIH) recommendations, but on par with most online medical information. Both chatbots responded with a high degree of accuracy, with inaccuracies being rare. Therefore, it is reasonable that cardiologists suggest either chatbot as a source of supplementary education.

4.
Cureus ; 16(5): e61067, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38803402

RESUMO

Introduction Hyperlipidemia is prevalent worldwide and affects a significant number of US adults. It significantly contributes to ischemic heart disease and millions of deaths annually. With the increasing use of the internet for health information, tools like ChatGPT (OpenAI, San Francisco, CA, USA) have gained traction. ChatGPT version 4.0, launched in March 2023, offers enhanced features over its predecessor but requires a monthly fee. This study compares the accuracy, comprehensibility, and response length of the free and paid versions of ChatGPT for patient education on hyperlipidemia. Materials and methods ChatGPT versions 3.5 and 4.0 were prompted in three different ways and 25 questions from the Cleveland Clinic's frequently asked questions (FAQs) on hyperlipidemia. Prompts included no prompting (Form 1), patient-friendly prompting (Form 2), and physician-level prompting (Form 3). Responses were categorized as incorrect, partially correct, or correct. Additionally, the grade level and word count from each response were recorded for analysis. Results Overall, scoring frequencies for ChatGPT version 3.5 were: five (6.67%) incorrect, 18 partially correct (24%), and 52 (69.33%) correct. Scoring frequencies for ChatGPT version 4.0 were: one (1.33%) incorrect, 18 (24.00%) partially correct, and 56 (74.67%) correct. Correct answers did not significantly differ between ChatGPT version 3.5 and ChatGPT version 4.0 (p = 0.586). ChatGPT version 3.5 had a significantly higher grade reading level than version 4.0 (p = 0.0002). ChatGPT version 3.5 had a significantly higher word count than version 4.0 (p = 0.0073). Discussion There was no significant difference in accuracy between the free and paid versions of hyperlipidemia FAQs. Both versions provided accurate but sometimes partially complete responses. Version 4.0 offered more concise and readable information, aligning with the readability of most online medical resources despite exceeding the National Institutes of Health's (NIH's) recommended eighth-grade reading level. The paid version demonstrated superior adaptability in tailoring responses based on the input. Conclusion Both versions of ChatGPT provide reliable medical information, with the paid version offering more adaptable and readable responses. Healthcare providers can recommend ChatGPT as a source of patient education, regardless of the version used. Future research should explore diverse question formulations and ChatGPT's handling of incorrect information.

5.
J Clin Sleep Med ; 20(4): 583-594, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38217478

RESUMO

STUDY OBJECTIVES: We evaluated the accuracy of ChatGPT in addressing insomnia-related queries for patient education and assessed ChatGPT's ability to provide varied responses based on differing prompting scenarios. METHODS: Four identical sets of 20 insomnia-related queries were posed to ChatGPT. Each set differed by the context in which ChatGPT was prompted: no prompt, patient-centered, physician-centered, and with references and statistics. Responses were reviewed by 2 academic sleep surgeons, 1 academic sleep medicine physician, and 2 sleep medicine fellows across 4 domains: clinical accuracy, prompt adherence, referencing, and statistical precision, using a binary grading system. Flesch-Kincaid grade-level scores were calculated to estimate the grade level of the responses, with statistical differences between prompts analyzed via analysis of variance and Tukey's test. Interrater reliability was calculated using Fleiss's kappa. RESULTS: The study revealed significant variations in the Flesch-Kincaid grade-level scores across 4 prompts: unprompted (13.2 ± 2.2), patient-centered (8.1 ± 1.9), physician-centered (15.4 ± 2.8), and with references and statistics (17.3 ± 2.3, P < .001). Despite poor Fleiss kappa scores, indicating low interrater reliability for clinical accuracy and relevance, all evaluators agreed that the majority of ChatGPT's responses were clinically accurate, with the highest variability on Form 4. The responses were also uniformly relevant to the given prompts (100% agreement). Eighty percent of the references ChatGPT cited were verified as both real and relevant, and only 25% of cited statistics were corroborated within referenced articles. CONCLUSIONS: ChatGPT can be used to generate clinically accurate responses to insomnia-related inquiries. CITATION: Alapati R, Campbell D, Molin N, et al. Evaluating insomnia queries from an artificial intelligence chatbot for patient education. J Clin Sleep Med. 2024;20(4):583-594.


Assuntos
Inteligência Artificial , Distúrbios do Início e da Manutenção do Sono , Humanos , Distúrbios do Início e da Manutenção do Sono/diagnóstico , Reprodutibilidade dos Testes , Educação de Pacientes como Assunto , Software
6.
BioTech (Basel) ; 13(1)2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38247731

RESUMO

Gene therapy holds promise as a life-changing option for individuals with genetic variants that give rise to disease. FDA-approved gene therapies for Spinal Muscular Atrophy (SMA), cerebral adrenoleukodystrophy, ß-Thalassemia, hemophilia A/B, retinal dystrophy, and Duchenne Muscular Dystrophy have generated buzz around the ability to change the course of genetic syndromes. However, this excitement risks over-expansion into areas of genetic disease that may not fit the current state of gene therapy. While in situ (targeted to an area) and ex vivo (removal of cells, delivery, and administration of cells) approaches show promise, they have a limited target ability. Broader in vivo gene therapy trials have shown various continued challenges, including immune response, use of immune suppressants correlating to secondary infections, unknown outcomes of overexpression, and challenges in driving tissue-specific corrections. Viral delivery systems can be associated with adverse outcomes such as hepatotoxicity and lethality if uncontrolled. In some cases, these risks are far outweighed by the potentially lethal syndromes for which these systems are being developed. Therefore, it is critical to evaluate the field of genetic diseases to perform cost-benefit analyses for gene therapy. In this work, we present the current state while setting forth tools and resources to guide informed directions to avoid foreseeable issues in gene therapy that could prevent the field from continued success.

7.
Thyroid ; 34(3): 371-377, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38010917

RESUMO

Background: ChatGPT, an artificial intelligence (AI) chatbot, is the fastest growing consumer application in history. Given recent trends identifying increasing patient use of Internet sources for self-education, we seek to evaluate the quality of ChatGPT-generated responses for patient education on thyroid nodules. Methods: ChatGPT was queried 4 times with 30 identical questions. Queries differed by initial chatbot prompting: no prompting, patient-friendly prompting, 8th-grade level prompting, and prompting for references. Answers were scored on a hierarchical score: incorrect, partially correct, correct, or correct with references. Proportions of responses at incremental score thresholds were compared by prompt type using chi-squared analysis. Flesch-Kincaid grade level was calculated for each answer. The relationship between prompt type and grade level was assessed using analysis of variance. References provided within ChatGPT answers were totaled and analyzed for veracity. Results: Across all prompts (n = 120 questions), 83 answers (69.2%) were at least correct. Proportions of responses that were at least partially correct (p = 0.795) and correct (p = 0.402) did not differ by prompt; responses that were correct with references did (p < 0.0001). Responses from 8th-grade level prompting were the lowest mean grade level (13.43 ± 2.86) and were significantly lower than no prompting (14.97 ± 2.01, p = 0.01) and prompting for references (16.43 ± 2.05, p < 0.0001). Prompting for references generated 80/80 (100%) of referenced medical publications within answers. Seventy references (87.5%) were legitimate citations, and 58/80 (72.5%) provided accurately reported information from the referenced publication. Conclusion: ChatGPT overall provides appropriate answers to most questions on thyroid nodules regardless of prompting. Despite targeted prompting strategies, ChatGPT reliably generates responses corresponding to grade levels well-above accepted recommendations for presenting medical information to patients. Significant rates of AI hallucination may preclude clinicians from recommending the current version of ChatGPT as an educational tool for patients at this time.


Assuntos
Nódulo da Glândula Tireoide , Humanos , Nódulo da Glândula Tireoide/diagnóstico , Inteligência Artificial , Educação de Pacientes como Assunto , Escolaridade , Internet
8.
Semin Cell Dev Biol ; 156: 266-275, 2024 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-37919144

RESUMO

If mitochondria are the powerhouses of the cell, then mitochondrial dynamics are the power grid that regulates how that energy output is directed and maintained in response to unique physiological demands. Fission and fusion dynamics are highly regulated processes that fine-tune the mitochondrial networks of cells to enable appropriate responses to intrinsic and extrinsic stimuli, thereby maintaining cellular and organismal homeostasis. These dynamics shape many aspects of an organism's healthspan including development, longevity, stress resistance, immunity, and response to disease. In this review, we discuss the latest findings regarding the mechanisms and roles of mitochondrial dynamics by focussing on the nematode Caenorhabditis elegans. Whole live-animal studies in C. elegans have enabled a true organismal-level understanding of the impact that mitochondrial dynamics play in homeostasis over a lifetime.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Dinâmica Mitocondrial , Mitocôndrias , Longevidade
9.
bioRxiv ; 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38106196

RESUMO

Interleukin-2 (IL-2) variants with increased CD25 dependence that selectively expand Foxp3+ regulatory T (TR) cells are in clinical trials for treating inflammatory diseases. Using an Fc-fused IL-2 mutein (Fc.IL-2 mutein) we developed that prevents diabetes in non-obese diabetic (NOD) mice, we show that Fc.IL-2 mutein induced an activated TR population with elevated proliferation, a transcriptional program associated with Stat5- and TCR-dependent gene modules, and high IL-10 and CTLA-4 expression. Increased IL-10 signaling limited surface MHC class II upregulation during conventional dendritic cell (cDC) maturation, while increased CTLA-4-dependent transendocytosis led to the transfer of CD80 and CD86 costimulatory ligands from maturing cDCs to TR cells. In NOD mice, Fc.IL-2 mutein treatment promoted the suppression of cDCs in the inflamed pancreas and pancreatic lymph nodes resulting in T cell anergy. Thus, IL-2 mutein-expanded TR cells have enhanced functional properties and restrict cDC function, offering promise for targeted immunotherapy use in autoimmune disease.

10.
J Immunother Cancer ; 11(11)2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37940345

RESUMO

BACKGROUND: Multidrug resistance-1 (MDR1) transporter limits the intracellular accumulation of chemotherapies (paclitaxel, anthracyclines) used in breast cancer (BC) treatment. In addition to tumor cells, MDR1 is expressed on immune cell subsets in which it confers chemoresistance. Among human T cells, MDR1 is expressed by most CD8+ T cells, and a subset of CD4+ T helper (Th) cells. Here we explored the expression, function and regulation of MDR1 on CD4+ T cells and investigated the role of this population in response to neoadjuvant chemotherapy (NAC) in BC. METHODS: Phenotypic and functional characteristics of MDR1+ CD4 Th cells were assessed on blood from healthy donors and patients with BC by flow cytometry. These features were extended to CD4+ Th cells from untreated breast tumor by flow cytometry and RNA-sequencing (RNA-seq). We performed in vitro polarization assays to decipher MDR1 regulation on CD4 Th cells. We evaluated in vitro the impact of chemotherapy agents on MDR1+ CD4+ Th cells. We analyzed the impact of NAC treatment on MDR1+ CD4+ Th cells from blood and tumors and their association with treatment efficacy in two independent BC cohorts and in a public RNA-seq data set of BC tumor biopsies before and after NAC. Finally, we performed single cell (sc) RNAseq of blood CD4+ memory T cells from NAC-treated patients and combined them with an scRNAseq public data set. RESULTS: MDR1+ CD4 Th cells were strongly enriched in Th1.17 polyfunctional cells but also in Th17 cells, both in blood and untreated breast tumor tissues. Mechanistically, Tumor growth factor (TGF)-ß1 was required for MDR1 induction during in vitro Th17 or Th1.17 polarization. MDR1 expression conferred a selective advantage to Th1.17 and Th17 cells following paclitaxel treatment in vitro and in vivo in NAC-treated patients. scRNAseq demonstrated MDR1 association with tumor Th1.17 and Th with features of cytotoxic cells. Enrichment in MDR1+ CD4+ Th1.17 and Th17 cells, in blood and tumors positively correlated with pathological response. Absence of early modulation of Th1.17 and Th17 in NAC-resistant patients, argue for its use as a biomarker for chemotherapy regimen adjustment. CONCLUSION: MDR1 favored the enrichment of Th1.17 and Th17 in blood and tumor after NAC that correlated to clinical response.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Linfócitos T CD8-Positivos , Terapia Neoadjuvante , Linfócitos T CD4-Positivos , Células Th17 , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico
12.
JAMA Otolaryngol Head Neck Surg ; 149(11): 980-986, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37422846

RESUMO

Importance: Due to lack of data from high-powered randomized clinical trials, the differences in functional and survival outcomes for patients with oropharyngeal squamous cell carcinoma (OPSCC) undergoing primary transoral robotic surgery (TORS) vs primary radiation therapy and/or chemoradiation therapy (RT/CRT) are unclear. Objectives: To compare 5-year functional (dysphagia, tracheostomy dependence, and gastrostomy tube dependence) and survivorship outcomes in patients with T1-T2 OPSCC receiving primary TORS vs RT/CRT. Design, Setting, and Population: This national multicenter cohort study used data from a global health network (TriNetX) to identify differences in functional and survival outcomes among patients with OPSCC who underwent primary TORS or RT/CRT in 2002 to 2022. After propensity matching, 726 patients with OPSCC met inclusion criteria. In the TORS group, 363 (50%) patients had undergone primary surgery, and in the RT/CRT group, 363 (50%) patients had received primary RT/CRT. Data analyses were performed from December 2022 to January 2023 using the TriNetX platform. Exposure: Primary surgery with TORS or primary treatment with radiation therapy and/or chemoradiation therapy. Main Outcomes and Measures: Propensity score matching was used to balance the 2 groups. Functional outcomes were measured at 6 months, 1 year, 3 years, 5 years, and more than 5 years posttreatment and included dysphagia, gastrostomy tube dependence, and tracheostomy dependence according to standard medical codes. Five-year overall survivorship was compared between patients undergoing primary TORS vs RT/CRT. Results: Propensity score matching allowed a study sample with 2 cohorts comprising statistically similar parameters with 363 (50%) patients in each. Patients in the TORS cohort had a mean (SD) age of 68.5 (9.9) vs 68.8 (9.7) years in RT/CRT cohort; 86% and 88% were White individuals, respectively; 79% of patients were men in both cohorts. Primary TORS was associated with clinically meaningful increased risk of dysphagia at 6 months (OR, 1.37; 95% CI, 1.01-1.84) and 1 year posttreatment (OR, 1.71; 95% CI, 1.22-2.39) compared with primary RT/CRT. Patients receiving surgery were less likely to be gastrostomy tube dependent at 6 months (OR, 0.46; 95% CI, 0.21-1.00) and 5 years posttreatment (risk difference, -0.05; 95% CI, -0.07 to -0.02). Differences in overall rates of tracheostomy dependence (OR, 0.97; 95% CI, 0.51-1.82) between groups were not clinically meaningful. Patients with OPSCC, unmatched for cancer stage or human papillomavirus status, who received RT/CRT had worse 5-year overall survival than those who underwent primary surgery (70.2% vs 58.4%; hazard ratio, 0.56; 95% CI, 0.40-0.79). Conclusions and Relevance: This national multicenter cohort study of patients undergoing primary TORS vs primary RT/CRT for T1-T2 OPSCC found that primary TORS was associated with a clinically meaningful increased risk of short-term dysphagia. Patients treated with primary RT/CRT had an increased risk of short- and long-term gastrostomy tube dependence and worse 5-year overall survival than those who underwent surgery.


Assuntos
Transtornos de Deglutição , Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Procedimentos Cirúrgicos Robóticos , Masculino , Humanos , Idoso , Feminino , Carcinoma de Células Escamosas de Cabeça e Pescoço , Estudos de Coortes , Resultado do Tratamento , Transtornos de Deglutição/etiologia , Neoplasias de Cabeça e Pescoço/terapia
13.
J Clin Sleep Med ; 19(12): 1989-1995, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37485676

RESUMO

STUDY OBJECTIVES: We evaluated the quality of ChatGPT responses to questions on obstructive sleep apnea for patient education and assessed how prompting the chatbot influences correctness, estimated grade level, and references of answers. METHODS: ChatGPT was queried 4 times with 24 identical questions. Queries differed by initial prompting: no prompting, patient-friendly prompting, physician-level prompting, and prompting for statistics/references. Answers were scored on a hierarchical scale: incorrect, partially correct, correct, correct with either statistic or referenced citation ("correct+"), or correct with both a statistic and citation ("perfect"). Flesch-Kincaid grade level and citation publication years were recorded for answers. Proportions of responses at incremental score thresholds were compared by prompt type using chi-squared analysis. The relationship between prompt type and grade level was assessed using analysis of variance. RESULTS: Across all prompts (n = 96 questions), 69 answers (71.9%) were at least correct. Proportions of responses that were at least partially correct (P = .387) or correct (P = .453) did not differ by prompt; responses that were at least correct+ (P < .001) or perfect (P < .001) did. Statistics/references prompting provided 74/77 (96.1%) references. Responses from patient-friendly prompting had a lower mean grade level (12.45 ± 2.32) than no prompting (14.15 ± 1.59), physician-level prompting (14.27 ± 2.09), and statistics/references prompting (15.00 ± 2.26) (P < .0001). CONCLUSIONS: ChatGPT overall provides appropriate answers to most questions on obstructive sleep apnea regardless of prompting. While prompting decreases response grade level, all responses remained above accepted recommendations for presenting medical information to patients. Given ChatGPT's rapid implementation, sleep experts may seek to further scrutinize its medical literacy and utility for patients. CITATION: Campbell DJ, Estephan LE, Mastrolonardo EV, Amin DR, Huntley CT, Boon MS. Evaluating ChatGPT responses on obstructive sleep apnea for patient education. J Clin Sleep Med. 2023;19(12):1989-1995.


Assuntos
Médicos , Apneia Obstrutiva do Sono , Humanos , Educação de Pacientes como Assunto , Apneia Obstrutiva do Sono/terapia , Sono , Software
14.
JCI Insight ; 8(15)2023 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-37338983

RESUMO

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder that causes debilitating swelling and destruction of the joints. People with RA are treated with drugs that actively suppress one or more parts of their immune system, and these may alter the response to vaccination against SARS-CoV-2. In this study, we analyzed blood samples from a cohort of patients with RA after receiving a 2-dose mRNA COVID-19 vaccine regimen. Our data show that individuals on the cytotoxic T lymphocyte antigen 4-Ig therapy abatacept had reduced levels of SARS-CoV-2-neutralizing antibodies after vaccination. At the cellular level, these patients showed reduced activation and class switching of SARS-CoV-2-specific B cells, as well as reduced numbers and impaired helper cytokine production by SARS-CoV-2-specific CD4+ T cells. Individuals on methotrexate showed similar but less severe defects in vaccine response, whereas individuals on the B cell-depleting therapy rituximab had a near-total loss of antibody production after vaccination. These data define a specific cellular phenotype associated with impaired response to SARS-CoV-2 vaccination in patients with RA on different immune-modifying therapies and help inform efforts to improve vaccination strategies in this vulnerable population.


Assuntos
Artrite Reumatoide , COVID-19 , Humanos , Vacinas contra COVID-19 , COVID-19/prevenção & controle , SARS-CoV-2 , Artrite Reumatoide/tratamento farmacológico , Anticorpos Antivirais , RNA Mensageiro
15.
BMJ Open Respir Res ; 10(1)2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37230763

RESUMO

BACKGROUND: Ivacaftor approval was extended to people with cystic fibrosis (CF) and an R117H variant in 2014 in the USA. This observational, real-world, postapproval study evaluated long-term outcomes among people with CF and an R117H variant on ivacaftor using data from the US Cystic Fibrosis Foundation Patient Registry. METHODS: Key outcomes were evaluated in ivacaftor-treated people with CF and an R117H variant for up to 36 months before and after treatment initiation using within-group comparisons. Analyses were descriptive in nature, focused on evaluation of observed outcome patterns over time and were performed both overall and for age groups ≥2 to <6 years, ≥6 to <18 years and ≥18 years. Key outcomes included lung function, body mass index (BMI), pulmonary exacerbations (PEx) and hospitalisations. RESULTS: The ivacaftor cohort included 369 people with CF and an R117H variant who initiated therapy between 1 January 2015 and 31 December 2016. During each of the 12-month intervals following treatment initiation, the mean observed percent predicted forced expiratory volume in 1 s (ppFEV1) and BMI values were higher and the mean annualised number of PEx and hospitalisation events were lower than pretreatment values. Mean change in ppFEV1 from pretreatment baseline was an increase of 1.5 (95% CI 0.8 to 2.3), 1.7 (95% CI 0.7 to 2.7) and 1.8 (95% CI 0.6 to 3.0) percentage points in the first, second and third years of treatment, respectively. Similar trends were observed in adult and paediatric subgroups. CONCLUSIONS: The results support the clinical effectiveness of ivacaftor in people with CF and an R117H variant, including adult and paediatric subgroups.


Assuntos
Fibrose Cística , Adulto , Humanos , Criança , Fibrose Cística/tratamento farmacológico , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Mutação , Sistema de Registros
16.
Laryngoscope Investig Otolaryngol ; 8(1): 82-88, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36846427

RESUMO

Objectives: Patients are increasingly relying on YouTube for health information. We objectively evaluated the quality and comprehensiveness of sialendoscopy YouTube videos available to patients. We further investigated the relationship between video content and video popularity. Methods: We identified 150 videos using the search term "sialendoscopy." Videos were excluded if they were lectures for medical professionals, operating room (OR) recordings, unrelated, non-English, or non-audio. Video quality and comprehensiveness were evaluated using modified DISCERN criterion (range: 5-25) and novel sialendoscopy criterion (NSC, range: 0-7), respectively. Secondary outcomes included standard video metrics and Video Power Index to measure popularity. Videos were classified binarily by uploader type as from an academic medical center or from other sources. Results: Twenty-two (14.7%) of 150 videos were included for review, with 7 (31.8%) uploaded from academic medical institutions. One hundred-nine (72.7%) videos were excluded as lectures for medical professionals or OR recordings. Overall mean modified DISCERN (13.45 ± 3.42) and NSC (3.05 ± 0.96) scores were low; however, videos uploaded by academic medical institutions were significantly more comprehensive (NSC mean difference = 0.98, 95% CI: 0.16-1.80, p = .02). There were no significant correlations between video popularity and objective measures of quality or comprehensiveness. Conclusions: This study highlights the paucity and low quality of sialendoscopy videos for patients. More popular videos are not higher quality, and most videos are targeted more toward physicians rather than patients. As YouTube becomes increasingly used by patients, there is opportunity for otolaryngologists to produce more informative videos for patients while implementing targeted strategies to increase viewership. Level of Evidence: NA.

17.
Ann Otol Rhinol Laryngol ; 132(11): 1349-1354, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36788443

RESUMO

OBJECTIVES: This study evaluated the content and patient educational quality of YouTube videos on facelift surgery for facial rejuvenation. This study investigated the relationship between education quality compared to video content, video metrics, and popularity. METHODS: Two hundred videos were identified across 4 search terms: "facelift surgery," "facelift surgery what to expect," "facelift surgery patient education," and "what is facelift surgery." Unrelated videos, operating room recordings, medical professional lectures, non-English, non-audio, and testimonials were excluded from review. Video quality was assessed using the Global Quality Score (GQS) (range: 1-5), modified DISCERN score (range: 5-25), and JAMA Benchmark Criteria (range: 0-4). Secondary outcomes included upload source, video metrics (views, likes, dislikes, duration, days since upload, comments), and Video Power Indexto measure popularity. The first 10 comments on videos were characterized as positive, neutral, or negative. RESULTS: One hundred forty-three videos were excluded (43 did not meet criteria, 100 duplicates), and 57 videos were included. Fifty-five videos (96.5%) were uploaded by private medical practices. Overall video quality was poor across all 3 scoring systems: GQS (2.92 ± 1.14), modified DISCERN (13.03 ± 3.64), and JAMA Benchmark Criteria (1.78 ± 0.52). Popularity positively correlated with JAMA Benchmark Criteria (R = .49, P < .05) but did not correlate with other quality criteria. CONCLUSIONS: For patients undergoing facelift surgery, there are limited educational videos on YouTube with few videos detailing indications, alternatives, complications, and the postoperative course. YouTube is a growing resource for patient education and opportunities exist for medical institutions to produce higher-quality videos for prospective patients.


Assuntos
Ritidoplastia , Mídias Sociais , Humanos , Estudos Prospectivos , Rejuvenescimento , Face , Gravação em Vídeo , Reprodutibilidade dos Testes
19.
J Cyst Fibros ; 22(3): 464-470, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36581484

RESUMO

BACKGROUND: Study 661-110 (EXTEND) is a phase 3, open-label, three-part rollover study designed to assess the long-term safety and efficacy of tezacaftor/ivacaftor (TEZ/IVA) in participants aged ≥12 years homozygous for F508del (F/F) or heterozygous for F508del and a residual function mutation (F/RF). TEZ/IVA was shown to be safe and efficacious for up to 120 weeks in Part A. Here we report results from Part B, which evaluated safety and efficacy for an additional 96 weeks. METHODS: Part B enrolled participants aged ≥12 years with CF and F/F or F/RF genotypes who completed TEZ/IVA treatment in either Study 661-110 Part A, Study 661-112 (F/F), or Study 661-114 (F/F). Participants received TEZ 100 mg/IVA 150 mg fixed-dose combination once daily (morning) and IVA 150 mg once daily (evening) for 96 weeks. Safety endpoints included adverse events (AEs) and serum liver function tests. Efficacy endpoints included absolute change from baseline in percent predicted forced expiratory volume in 1 second (ppFEV1) and pulmonary exacerbation (PEx) rate. RESULTS: 464 participants were enrolled from Part A (n=377) and other eligible studies (n=87); 463 received ≥1 dose of TEZ/IVA. Overall, 92.2% had ≥1 AE, 0.9% had AEs leading to treatment discontinuation, and 29.4% reported serious AEs. The most common AEs, which were generally consistent with common manifestations of CF, included infective PEx of CF, cough, nasopharyngitis, hemoptysis, and headache. Lung function was maintained over 96 weeks in both genotype groups. PEx rates per year were comparable with Part A. CONCLUSIONS: TEZ/IVA was generally safe and well tolerated over a further 96 weeks; safety data were consistent with Part A. Improvements in ppFEV1 and PEx rates were maintained for an additional 96 weeks in Part B.


Assuntos
Fibrose Cística , Humanos , Aminofenóis/uso terapêutico , Benzodioxóis/uso terapêutico , Agonistas dos Canais de Cloreto/uso terapêutico , Fibrose Cística/diagnóstico , Fibrose Cística/tratamento farmacológico , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/uso terapêutico , Mutação
20.
Cureus ; 14(4): e24352, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35611038

RESUMO

Septic arthritis is a rare but serious complication of both rheumatoid and gouty arthritis and can lead to significant morbidity and even mortality. Here, we report a case of septic arthritis with bacteremia, monosodium urate crystals, and hyperuricemia in a 75-year-old male with long-standing rheumatoid arthritis. Arthrocentesis revealed gram-positive cocci representing group B streptococcus (Streptococcus agalactiae) infection and monosodium urate crystals. A diagnosis of septic arthritis with superimposed acute gouty arthritis was made and the patient was treated accordingly. Management included surgical irrigation and debridement, antibiotic therapy, and systemic glucocorticoids which resulted in a significant improvement in the patient's clinical status.

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