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Vancomycin and daptomycin are frequently used in outpatient parenteral antimicrobial therapy (OPAT). We analyze health care utilization and cost to the health care system for vancomycin vs daptomycin in the outpatient setting and find that vancomycin results in significantly higher health care utilization and similar cost per course compared with daptomycin in OPAT.
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INTRODUCTION: Ibrexafungerp is a new triterpenoid antifungal agent with activity against a variety of fungal species, including Aspergillus spp. and echinocandin-resistant Candida spp. AREAS COVERED: This evaluation will summarize currently available clinical evidence on the use of ibrexafungerp in the treatment/prevention of vulvovaginal candidiasis (VVC) and detail the mechanism of action, pharmacokinetic/pharmacodynamic parameters, and ongoing/latest research involving ibrexafungerp. EXPERT OPINION: The evidence involving the utilization of ibrexafungerp for the treatment of VVC shows that it is superior when compared to placebo and has comparable clinical cure rates when compared with fluconazole. Ibrexafungerp demonstrates reliable coverage against several Candida spp. including echinocandin-resistant strains, Candida auris, and Aspergillus spp. For VVC, a dose of 300 mg (two 150 mg tablets) twice daily is recommended and does not require dose adjustments based on renal or hepatic function. The use of ibrexafungerp outside of VVC is currently under study with several ongoing trials showing promising interim data.
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PURPOSE: To report the indications and outcomes of emergency keratoplasty over a 21-year period in Greenlane Clinical Centre, the major tertiary eye referral center in Auckland, New Zealand (Aotearoa). METHODS: A retrospective review of medical records of all emergency keratoplasties performed in Greenlane Clinical Centre from January 2000 to September 2021 was conducted. Demographic, preoperative, intraoperative, and 1-year postoperative data were collected. RESULTS: Emergency keratoplasty was performed in 102 eyes of 97 patients (54 men), comprising 5.6% of transplants performed (N = 1830) in this period. The mean age was 53 years (range = 4-95 years, SD = 20). Patients of Maori ethnicity were overrepresented (31%). Corneal perforation was present in 90% of eyes, and microbial keratitis was the most common indication. Bacteria were the most commonly isolated organisms (38%). The mean preoperative and 12-month postoperative best potential corrected distance visual acuity was 1.6 and 1.2 (logMAR), respectively. All cases of therapeutic keratoplasty achieved initial therapeutic success, with no eyes lost or requiring repeat emergency keratoplasty. Complications included nonhealing epithelial defects (19%), cataract (19%), glaucoma (15%), allograft rejection (13%), and corneal melting (5%). Fifteen cases (15%) had documented graft failure at 12 months. Multivariate analysis revealed that younger age was the only statistically significant factor associated with failure at 12 months. CONCLUSIONS: Emergency keratoplasty was the indication for 5.6% of keratoplasties performed. Our results compare favorably with those in the literature, possibly because of early intervention and lower incidence of fungal keratitis. The reported overrepresentation of Maori has important implications for health access and delivery in New Zealand.
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BACKGROUND: Fatigue imposes a socioeconomic burden on patients with Crohn's disease (CD) and ulcerative colitis (UC). We assessed the prevalence of fatigue among patients with CD or UC and identified disease activity measures associated with fatigue. METHODS: Data from the Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease (SPARC IBD) were analyzed separately for CD and UC. Fatigue was defined based on a subjective and dichotomic questionnaire. Patients indicated if they experienced fatigue within the last week. The overall prevalence of fatigue was analyzed using descriptive and contingency tables. Demographics, clinical characteristics, disease activity (measures include Physician's Global Assessment for both CD and UC, short CD Activity Index for CD, and Ulcerative Colitis Disease Activity Index for UC), symptoms, and patient-reported outcomes were compared between patients with and without fatigue. Multivariable logistic regression models were constructed to identify symptoms and disease activity measures associated with fatigue. RESULTS: The study included 903 patients with CD and 443 patients with UC. Fatigue was reported in 47.7% of patients with CD and 40.9% of patients with UC. In patients with CD, abdominal pain, bowel incontinence, depressive symptoms, reduced general well-being, and night-time bowel movements were associated with fatigue. In patients with UC, depressive symptoms, reduced general well-being, moderate or severe disease activity by the physician's global assessment, and night-time bowel movements were significantly associated with fatigue. CONCLUSIONS: Fatigue is a common symptom among patients with CD or UC and is associated with higher levels of disease activity and reduced general well-being.
Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), can lead to fatigue in many patients regardless of their disease severity. Fatigue not only affects patients' quality-of-life but also their ability to work and their mental health. However, research specific to the IBD related symptoms that contribute to fatigue in these patients is not currently available, especially in the United States (US). To address this gap, real-world data was analyzed to understand how common fatigue is among patients with CD and UC in the US and clinical symptoms that co-occur with fatigue. We found that fatigue affects more than 40% of the patients. Our results suggest that fatigue is correlated with more severe disease symptoms and overall lower well-being among patients with CD and UC.
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Articulating clear and achievable expectations is fundamental to both education and organizational management. In this article, we provide a simple intervention for clarifying expectations-and establishing that these expectations have been understood-which proved beneficial both to community college interns and to their internship mentors in biotech-related undergraduate research experiences. Internship mentors were asked to utilize a simple Expectation Clarity Tool to outline the expectations, success metrics, baseline assessments, and training strategy and support that would be foundational to their intern's project. These included expectations around conceptual, technical, performance, and professional skills and behaviors. Concurrently, but independently, community college interns were asked to complete the same type of exercise as a way of identifying gaps in their knowledge and understanding of their mentor's expectations and their internship project. The mentor's completed Expectation Clarity Tool was then shared with their intern. As a result of completing this relatively simple intervention, the majority of mentors reported that it increased their confidence as a mentor, taught them a new mentoring skill, changed how they will mentor trainees moving forward, and positively impacted their relationship with their trainee. On the intern side, the majority of interns reported that engaging in this intervention, both as an independent exercise and in obtaining their mentor's completed Expectation Clarity Tool, increased their confidence as an intern and positively impacted the success of their internship.
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The current work investigated the effects of mass-loading the eardrum on wideband absorbance in humans. A non-invasive approach to mass-loading the eardrum was utilized in which water was placed on the eardrum via ear canal access. The mass-loaded absorbance was compared to absorbance measured for two alternative middle ear states: normal and stiffened. To stiffen the ear, subjects pressurized the middle ear through either exsufflation or insufflation concurrent with Eustachian tube opening. Mass-loading the eardrum was hypothesized to reduce high-frequency absorbance, whereas pressurizing the middle ear was hypothesized to reduce low- to mid-frequency absorbance. Discriminant linear analysis classification was performed to evaluate the utility of absorbance in differentiating between conditions. Water on the eardrum reduced absorbance over the 0.7- to 6-kHz frequency range and increased absorbance at frequencies below approximately 0.5 kHz; these changes approximated the pattern of changes reported in both hearing thresholds and stapes motion upon mass-loading the eardrum. Pressurizing the middle ear reduced the absorbance over the 0.125- to 4-kHz frequency range. Several classification models based on the absorbance in two- or three-frequency bands had accuracy exceeding 88%.
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Orelha Média , Pressão , Membrana Timpânica , Humanos , Masculino , Feminino , Membrana Timpânica/fisiologia , Membrana Timpânica/anatomia & histologia , Orelha Média/fisiologia , Orelha Média/anatomia & histologia , Adulto , Adulto Jovem , Elasticidade , Estimulação Acústica , Tuba Auditiva/fisiologia , Tuba Auditiva/anatomia & histologia , Estribo/fisiologia , Água , Análise DiscriminanteRESUMO
Large-scale microbiome studies are progressively utilizing multiomics designs, which include the collection of microbiome samples together with host genomics and metabolomics data. Despite the increasing number of data sources, there remains a bottleneck in understanding the relationships between different data modalities due to the limited number of statistical and computational methods for analyzing such data. Furthermore, little is known about the portability of general methods to the metagenomic setting and few specialized techniques have been developed. In this review, we summarize and implement some of the commonly used methods. We apply these methods to real data sets where shotgun metagenomic sequencing and metabolomics data are available for microbiome multiomics data integration analysis. We compare results across methods, highlight strengths and limitations of each, and discuss areas where statistical and computational innovation is needed.
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Biologia Computacional , Genômica , Metabolômica , Metagenômica , Microbiota , Metabolômica/métodos , Microbiota/genética , Biologia Computacional/métodos , Metagenômica/métodos , Genômica/métodos , HumanosRESUMO
BACKGROUND: Bowel urgency is a highly burdensome symptom among patients with inflammatory bowel disease (IBD). OBJECTIVES: To assess changes in severity of bowel urgency and identify predictors of worsening or improvement among patients with Crohn's disease (CD) and ulcerative colitis (UC) at 6 months from their enrollment visit. METHODS: Data from patients in the Study of a Prospective Adult Research Cohort with IBD were analyzed. Enrolled patients with CD or UC with 6-month visits were included. Changes and predictors of bowel urgency severity over 6 months in patients with CD or UC were examined using two separate analyses: (a) "worsening" versus "no change" excluding those with moderate-to-severe bowel urgency at enrollment, and (b) "improvement" versus "no change" excluding those with no bowel urgency at enrollment. The enrollment characteristics were compared within these groups. RESULTS: At baseline, in both CD and UC, use of biologics and/or immunomodulators at enrollment was similar across cohorts. Among patients with CD, 206 of 582 (35.4%) reported worsening, and 195 of 457 (42.7%) reported improvement in bowel urgency. Younger age (P = 0.013) and moderate-to-severe bowel urgency (P < 0.001) were associated with improvement. Moderate bowel urgency (P = 0.026) and bowel incontinence while awake (P = 0.022) were associated with worsening. Among patients with UC, 84 of 294 (28.6%) reported worsening, and 111 of 219 (50.7%) reported improvement in bowel urgency. Higher symptomatic disease severity (P = 0.011) and more severe bowel urgency (P < 0.001) were associated with improvement. CONCLUSIONS: Bowel urgency is an unpredictable and unstable symptom among patients with IBD. Over 50% of patients with CD or UC experienced either worsening or improvement at 6 months postenrollment.
WHAT IS KNOWN ABOUT BOWEL URGENCY IN INFLAMMATORY BOWEL DISEASE (IBD)?: Around six to eight in every ten patients with inflammatory bowel disease suffer from bowel urgency, a sudden need to have bowel movement. Many patients with IBD perceive bowel urgency as a bothersome symptom impacting their everyday activities. WHY DID WE DO THIS STUDY?: Despite the importance of bowel urgency, the changes in bowel urgency severity among the IBD-affected US population are yet to be fully known. We aimed to assess changes in severity of bowel urgency in patients with Crohn's disease (CD) or ulcerative colitis (UC) at 6 months. WHAT HAVE WE FOUND FROM THIS STUDY?: Bowel urgency is a common and unpredictable symptom among patients with CD and UC. Over 50% of patients reported that the severity of bowel urgency has either worsened or improved at the 6 months postenrollment. While about 4050% of IBD patients reported improvement, about 30% reported worsening, suggesting a lack of effective therapies to treat bowel urgency. FUTURE IMPLICATION: There is a need for advanced therapies to resolve bowel urgency in patients with CD and UC.
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BACKGROUND: Mobile upright PET devices have the potential to enable previously impossible neuroimaging studies. Currently available options are imagers with deep brain coverage that severely limit head/body movements or imagers with upright/motion enabling properties that are limited to only covering the brain surface. METHODS: In this study, we test the feasibility of an upright, motion-compatible brain imager, our Ambulatory Motion-enabling Positron Emission Tomography (AMPET) helmet prototype, for use as a neuroscience tool by replicating a variant of a published PET/fMRI study of the neurocorrelates of human walking. We validate our AMPET prototype by conducting a walking movement paradigm to determine motion tolerance and assess for appropriate task related activity in motor-related brain regions. Human participants (n = 11 patients) performed a walking-in-place task with simultaneous AMPET imaging, receiving a bolus delivery of F18-Fluorodeoxyglucose. RESULTS: Here we validate three pre-determined measure criteria, including brain alignment motion artifact of less than <2 mm and functional neuroimaging outcomes consistent with existing walking movement literature. CONCLUSIONS: The study extends the potential and utility for use of mobile, upright, and motion-tolerant neuroimaging devices in real-world, ecologically-valid paradigms. Our approach accounts for the real-world logistics of an actual human participant study and can be used to inform experimental physicists, engineers and imaging instrumentation developers undertaking similar future studies. The technical advances described herein help set new priorities for facilitating future neuroimaging devices and research of the human brain in health and disease.
Brain imaging plays an important role in understanding how the human brain functions in both health and disease. However, traditional brain scanners often require people to remain still, limiting the study of the brain in motion, and excluding people who cannot remain still. To overcome this, our team developed an imager that moves with a person's head, which uses a suspended ring of lightweight detectors that fit to the head. Using our imager, we were able to obtain clear brain images of people walking in place that showed the expected brain activity patterns during walking. Further development of our imager could enable it to be used to better understand real-world brain function and behavior, enabling enhanced knowledge and treatment of neurological conditions.
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BACKGROUND AND AIMS: While avoidance of long-term corticosteroids is a common objective in the management of autoimmune hepatitis (AIH), prolonged immunosuppression is usually required to prevent disease progression. This study investigates the patient and provider factors associated with treatment patterns in US patients with AIH. APPROACH AND RESULTS: A retrospective cohort of adults with the incident and prevalent AIH was identified from Optum's deidentified Clinformatics Data Mart Database. All patients were followed for at least 2 years, with exposures assessed during the first year and treatment patterns during the second. Patient and provider factors associated with corticosteroid-sparing monotherapy and cumulative prednisone use were identified using multivariable logistic and linear regression, respectively.The cohort was 81.2% female, 66.3% White, 11.3% Black, 11.2% Hispanic, and with a median age of 61 years. Among 2203 patients with ≥1 AIH prescription fill, 83.1% received a single regimen for >6 months of the observation year, which included 52.2% azathioprine monotherapy, 16.9% azathioprine/prednisone, and 13.3% prednisone monotherapy. Budesonide use was uncommon (2.1% combination and 1.9% monotherapy). Hispanic ethnicity (aOR: 0.56; p = 0.006), cirrhosis (aOR: 0.73; p = 0.019), osteoporosis (aOR: 0.54; p =0.001), and top quintile of provider AIH experience (aOR: 0.66; p = 0.005) were independently associated with lower use of corticosteroid-sparing monotherapy. Cumulative prednisone use was greater with diabetes (+441 mg/y; p = 0.004), osteoporosis (+749 mg/y; p < 0.001), and highly experienced providers (+556 mg/y; p < 0.001). CONCLUSIONS: Long-term prednisone therapy remains common and unexpectedly higher among patients with comorbidities potentially aggravated by corticosteroids. The greater use of corticosteroid-based therapy with highly experienced providers may reflect more treatment-refractory disease.
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SMAD4 is a tumor suppressor mutated or silenced in multiple cancers, including oral cavity squamous cell carcinoma (OSCC). Human clinical samples and cell lines, mouse models and organoid culture were used to investigate the role that SMAD4 plays in progression from benign disease to invasive OSCC. Human OSCC lost detectable SMAD4 protein within tumor epithelium in 24% of cases, and this loss correlated with worse progression-free survival independent of other major clinical and pathological features. A mouse model engineered for KrasG12D expression in the adult oral epithelium induced benign papillomas, however the combination of KrasG12D with loss of epithelial Smad4 expression resulted in rapid development of invasive carcinoma with features of human OSCC. Examination of regulatory pathways in 3D organoid cultures of SMAD4+ and SMAD4- mouse tumors with Kras mutation found that either loss of SMAD4 or inhibition of TGFß signaling upregulated the WNT pathway and altered the extracellular matrix. The gene signature of the mouse tumor organoids lacking SMAD4 was highly similar to the gene signature of human head and neck squamous cell carcinoma. In summary, this work has uncovered novel mechanisms by which SMAD4 acts as a tumor suppressor in OSCC. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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Progressão da Doença , Neoplasias Bucais , Proteína Smad4 , Via de Sinalização Wnt , Proteína Smad4/metabolismo , Proteína Smad4/genética , Humanos , Animais , Via de Sinalização Wnt/fisiologia , Neoplasias Bucais/patologia , Neoplasias Bucais/metabolismo , Neoplasias Bucais/genética , Camundongos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Linhagem Celular Tumoral , Mutação , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Masculino , Organoides/metabolismo , Organoides/patologiaRESUMO
BACKGROUND: Opportunistic infections (OIs) are a significant cause of morbidity and mortality after organ transplantation, though data in the liver transplant (LT) population are limited. METHODS: We performed a retrospective cohort study of LT recipients between January 1, 2007 and Deceber 31, 2016 using Medicare claims data linked to the Organ Procurement and Transplantation Network database. Multivariable Cox regression models evaluated factors independently associated with hospitalizations for early (≤1 year post transplant) and late (>1 year) OIs, with a particular focus on immunosuppression. RESULTS: There were 11 320 LT recipients included in the study, of which 13.2% had at least one OI hospitalization during follow-up. Of the 2638 OI hospitalizations, 61.9% were early post-LT. Cytomegalovirus was the most common OI (45.4% overall), although relative frequency decreased after the first year (25.3%). Neither induction or maintenance immunosuppression were associated with early OI hospitalization (all p > .05). The highest risk of early OI was seen with primary sclerosing cholangitis (aHR 1.74; p = .003 overall). Steroid-based and mechanistic target of rapamycin inhibitor-based immunosuppression at 1 year post LT were independently associated with increased late OI (p < .001 overall). CONCLUSION: This study found OI hospitalizations to be relatively common among LT recipients and frequently occur later than previously reported. Immunosuppression regimen may be an important modifiable risk factor for late OIs.
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Hospitalização , Transplante de Fígado , Medicare , Infecções Oportunistas , Humanos , Estados Unidos/epidemiologia , Masculino , Medicare/estatística & dados numéricos , Feminino , Hospitalização/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Idoso , Infecções Oportunistas/epidemiologia , Pessoa de Meia-Idade , Transplante de Fígado/efeitos adversos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Terapia de Imunossupressão/efeitos adversos , Infecções por Citomegalovirus/epidemiologiaRESUMO
Background: Beta-lactam antibiotics are first-line agents for most patients receiving antimicrobial prophylaxis in surgical procedures. Despite evidence showing low cross-reactivity between penicillins and cephalosporins, patients with beta-lactam allergies commonly receive vancomycin as an alternative to avoid allergic reaction. Methods: Adult patients receiving vancomycin for surgical prophylaxis with a reported beta-lactam allergy at our institution between August 2017 to July 2018 were retrospectively evaluated for potential eligibility for penicillin allergy testing and/or receipt of standard prophylaxis. Results: Among 830 patients who received vancomycin for surgical prophylaxis, 196 reported beta-lactam allergy and were included in the analysis. Approximately 40 % of surgeries were orthopedic. Of patients receiving vancomycin as first-line therapy, 189 (96.4 %) were potentially eligible for beta-lactam prophylaxis. Conclusions: Patients with beta-lactam allergies often qualify for receipt of a first-line antibiotic. An opportunity exists for improved allergy assessment as an antimicrobial stewardship intervention in surgical prophylaxis.
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BACKGROUND & AIMS: Management of inflammatory bowel diseases (IBD) is complex and variation in care has been well-documented. However, the drivers of practice variation remain unexplored. We examined variation based on the treating gastroenterologist's IBD focus (proportion of outpatient visits for IBD). METHODS: We conducted a retrospective cohort of newly diagnosed patients with IBD using data from Optum's deidentified Clinformatics Data Mart Database (2000-2020). The exposure variable was whether the treating gastroenterologist had an IBD focus (>90th percentile of IBD visits/total outpatient visits). We used adjusted regression models to evaluate associations between provider IBD focus and process measures (use of mesalamine, corticosteroid, biologic, and narcotic medications and endoscopic or radiographic imaging) and clinical outcomes (time to IBD-related hospitalization and bowel resection surgery). We tested for change in treatment patterns over time by including an interaction term for study era (2004-2012 vs 2013-2020). RESULTS: The study included 772 children treated by 493 providers and 2864 adults treated by 2076 providers. In children, none of the associations between provider focus and process or outcome measures were significant. In adults, care from an IBD-focused provider was associated with more use of biologics, combination therapy, and imaging and endoscopy, and less mesalamine use for Crohn's disease (P < .05 for all comparisons) but not with other process measures. Biologics were prescribed more frequently and narcotics less frequently during the later era (P < .05 for both). Hospitalization and surgery rates were not associated with IBD focus or era. CONCLUSIONS: IBD care for adults varies by provider specialization. Given the evolving complexity, novel methods may be needed to standardize care.
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INTRODUCTION: Native hip dislocations are defined as traumatic dislocations of the hip, typically high-energy and associated with polytrauma. The majority of these injuries occur following motor vehicle accidents (MVAs). Due to the inherent stability of the hip joint, a significant force is required to cause dislocation. It is critical that such injuries are managed and reduced in a timely manner. We evaluated the current practice in a major trauma centre (MTC) in Cardiff and gathered information from emergency departments (EDs) in Wales and MTCs around the United Kingdom (UK). METHODS: We did an evaluation of the current practice with a retrospective audit of all traumatic native hip dislocations presenting to the MTC at Cardiff from August 2018 to February 2021. Data was obtained from Trauma Audit and Research Network (TARN), medical records, radiology and theatre management systems. An online survey was developed and disseminated to EDs in Wales and MTCs across the UK. RESULTS: There were 15 traumatic hip dislocation cases over the period evaluated. Sixty percent of cases were due to MVA. Eighty-six percent of patients had an associated fracture, with one Pipkin type IV fracture dislocation. The mean time to reduction from injury was 532 minutes (240-804 minutes), with 28.6% reduced within 6 hours and 71.4% reduced within 12 hours. Two patients had reduction performed in the ED (mean time to reduction, 275 minutes). There was one occurrence of avascular necrosis (AVN) and one of chondrolysis at the follow-up. The response rate to the survey was 80% and 83% in Wales and MTCs nationally, respectively. The majority (82%) of departments did not have an established pathway in place for managing traumatic native hip dislocations with a preference for reduction in the operating theatre. CONCLUSION: Native hip dislocations are rare, high-energy injuries associated with significant morbidity. The available evidence suggests time to reduction is imperative in reducing the risk of future complications. The establishment of a pathway to guide management and having a mechanism to perform reductions in the ED may produce significant reductions in this time, impacting outcomes.
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COVID-19 , Máscaras , Pandemias , SARS-CoV-2 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Humanos , Instalações de SaúdeRESUMO
OBJECTIVES: The first objective of the study was to compare approaches to eardrum electrode insertion as they relate to the likelihood of introducing an acoustic leak between the ear canal and eartip. A common method for placing a tympanic membrane electrode involves securing the electrode in the canal by routing it underneath a foam eartip. This method is hypothesized to result in a slit leak between the canal and foam tip due to the added bulk of the electrode wire. An alternative approach involves creating a bore in the wall of the foam tip that the electrode can be threaded through. This method is hypothesized to reduce the likelihood of a slit leak before the electrode wire is integrated into the foam tip. The second objective of the study was to investigate how sound transmission in the ear is affected by placing an electrode on the eardrum. It was hypothesized that an electrode in contact with the eardrum increases the eardrum's mass, with the potential to reduce sound transmission at high frequencies. DESIGN: Wideband acoustic immittance and distortion product otoacoustic emissions (DPOAEs) were measured in eight human ears. Measurements were completed for five different conditions: (1) baseline with no electrode in the canal, (2) dry electrode in the canal but not touching the eardrum, secured underneath the eartip, (3) dry electrode in the canal not touching the eardrum, secured through a bore in the eartip (subsequent conditions were completed using this method), (4) hydrated electrode in the canal but not touching the eardrum, and (5) hydrated electrode touching the eardrum. To create the bore, a technique was developed in which a needle is heated and pushed through the foam eartip. The electrode is then thread through the bore and advanced slowly by hand until contacting the eardrum. Analysis included comparing absorbance, admittance phase angle, and DPOAE levels between measurement conditions. RESULTS: Comparison of the absorbance and admittance phase angle measurements between the electrode placement methods revealed significantly higher absorbance and lower admittance phase angle from 0.125 to 1 kHz when the electrode is routed under the eartip. Absorbance and admittance phase angle were minimally affected when the electrode was inserted through a bore in the eartip. DPOAE levels across the different conditions showed changes approximating test-retest variability. Upon contacting the eardrum, the absorbance tended to decrease below 1 kHz and increase above 1 kHz. However, changes were within the range of test-retest variability. There was evidence of reduced levels below 1 kHz and increased levels above 1 kHz upon the electrode contacting the eardrum. However, differences between conditions approximated test-retest variability. CONCLUSIONS: Routing the eardrum electrode through the foam tip reduces the likelihood of incurring an acoustic leak between the canal walls and eartip, compared with routing the electrode under the eartip. Changes in absorbance and DPOAE levels resulting from electrode contact with the eardrum implicate potential stiffening of eardrum; however, the magnitude of changes suggests minimal effect of the electrode on sound transmission in the ear.
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BACKGROUND: Positive surgical margin rates remain high in head and neck cancer surgery. Relocation is challenging given the complex, three-dimensional (3D) anatomy. METHODS: Prospective, multi-institutional study to determine accuracy of head and neck surgeons and pathologists relocating margins on virtual 3D specimen models using written descriptions from pathology reports. Using 3D models of 10 head and neck surgical specimens, each participant relocated 20 mucosal margins (10 perpendicular, 10 shave). RESULTS: A total of 32 participants, 23 surgeons and 9 pathologists, marked 640 margins. Of the 320 marked perpendicular margins, 49.7% were greater than 1 centimeter from the true margin with a mean relocation error of 10.2 mm. Marked shave margins overlapped with the true margin a mean 54% of the time, with no overlap in 44 of 320 (13.8%) shave margins. CONCLUSIONS: Surgical margin relocation is imprecise and challenging even for experienced surgeons and pathologists. New communication technologies are needed.
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BACKGROUND & AIMS: Crohn's disease is associated with alterations in the gut microbiome and metabolome described as dysbiosis. We characterized the microbial and metabolic consequences of ileal resection, the most common Crohn's disease surgery. METHODS: Patients with and without intestinal resection were identified from the Diet to Induce Remission in Crohn's Disease and Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease studies. Stool samples were analyzed with shotgun metagenomics sequencing. Fecal butyrate was measured with 1H nuclear magnetic resonance spectroscopy. Fecal bile acids and plasma 7α-hydroxy-4-cholesten-3-one (C4) was measured with mass spectrometry. RESULTS: Intestinal resection was associated with reduced alpha diversity and altered beta diversity with increased Proteobacteria and reduced Bacteroidetes and Firmicutes. Surgery was associated with higher representation of genes in the KEGG pathway for ABC transporters and reduction in genes related to bacterial metabolism. Surgery was associated with reduced concentration of the But gene but this did not translate to reduced fecal butyrate concentration. Surgery was associated with decreased abundance of bai operon genes, with increased plasma C4 concentration, increased primary bile acids and reduced secondary bile acids, including isoLCA. Additionally, Egerthella lenta, Adlercreutzia equalofaciens, and Gordonibacter pamelaeae were lower in abundance among patients with prior surgery in both cohorts. CONCLUSIONS: In 2 different populations, prior surgery in Crohn's disease is associated with altered fecal microbiome. Patients who had undergone ileal resection had reduction in the potentially beneficial bacteria E lenta and related actinobacteria and secondary bile acids, including isoLCA, suggesting that these could be biomarkers of patients at higher risk for disease progression.