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1.
J Natl Compr Canc Netw ; : 1-6, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39079545

RESUMEN

BACKGROUND: Mohs micrographic surgery (MMS) is a promising treatment modality for melanoma in situ (MIS). However, variations in surgical technique limit the generalizability of existing data and may impede future study of MMS in clinical trials. METHODS: A modified Delphi method was selected to establish consensus on optimal MMS techniques for treating MIS in future clinical trials. The Delphi method was selected due to the limited current data, the wide range of techniques used in the field, and the intention to establish a standardized technique for future clinical trials. A literature review and interviews with experienced MMS surgeons were performed to identify dimensions of the MMS technique for MIS that (1) likely impacted costs or outcomes of the procedure, and (2) showed significant variability between surgeons. A total of 8 dimensions of technical variation were selected. The Delphi process consisted of 2 rounds of voting and commentary, during which 44 expert Mohs surgeons across the United States rated their agreement with specific recommendations using a Likert scale. RESULTS: Five of eight recommendations achieved consensus in Round 1. All 3 of the remaining recommendations achieved consensus in Round 2. Techniques achieving consensus in Round 1 included the use of a starting peripheral margin of ≤5 mm, application of immunohistochemistry, frozen tissue processing, and resecting to the depth of subcutaneous fat. Consensus on the use of Wood's lamp, dermatoscope, and negative tissue controls was established in Round 2. CONCLUSIONS: This study generated 8 consensus recommendations intended to offer guidance for Mohs surgeons treating MIS. The adoption of these recommendations will promote standardization to facilitate comparisons of aggregate data in multicenter clinical trials.

2.
Microbiol Spectr ; 12(8): e0420523, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-38940588

RESUMEN

Despite the first-line recommendation of fosfomycin for uncomplicated urinary tract infections (UTIs), there are pressing barriers for optimizing its use for the treatment of non-Escherichia coli Enterobacterales UTI. There are no approved breakpoints for oral use against other Enterobacterales, and the recommended agar dilution (AD) reference method for minimal inhibitory concentration (MIC) determination is largely impractical. Using 160 clinical Klebsiella pneumoniae isolates, we sought to understand rates of skipped wells and MIC imprecision in broth microdilution (BMD) and how that compares to rates of error using AD. Though the Clinical and Laboratory Standards Institute refers to the skipped well phenomena in their recommendation against the use of BMD, there is a paucity of data on its frequency. While AD and BMD produced similar MIC50/90 values (32/256 µg/mL for AD and 64/256 µg/mL for BMD), essential agreement was poor. No-growth wells at concentrations below the MIC occurred in up to 10.9% of wells at a given concentration, as the most frequent scientific error. Growth in concentrations above the measured MIC occurred in up to 3.3% of wells and was seen within three dilutions of the MIC for BMD. Observation of single colonies either at or beyond the measured MIC for AD was also common and occurred up to 8.3% and 2.5% of the time, respectively. The frequent scientific error in both testing methods should prompt re-evaluation of AD guidelines and expansion of MIC testing methods for fosfomycin susceptibility testing, as poor agreement with another method prone to scientific error should not be the main detractor from BMD use.IMPORTANCEDespite the recommendation of fosfomycin for uncomplicated urinary tract infections (UTIs), there are barriers for optimizing its use. There are no approved breakpoints for oral use against other Enterobacterales, and the recommended agar dilution (AD) reference method for MIC determination is largely impractical. The use of broth microdilution (BMD) for fosfomycin testing is not recommended by the Clinical and Laboratory Standards Institute due to unsatisfactory precision and skipped wells-occurrence of no-growth in a single well before the minimal inhibitory concentration (MIC)-and trailing endpoints. We sought to understand rates of skipped wells and growth at concentrations above measured MICs in BMD and how that compares to scientific error using AD. No-growth wells at concentrations below the MIC occurred in up to 10.9% of wells for BMD and single colonies at or beyond measured MICs for AD were also common. Frequent scientific error in both methods should prompt re-evaluation of both AD and BMD for fosfomycin susceptibility testing.


Asunto(s)
Antibacterianos , Fosfomicina , Klebsiella pneumoniae , Pruebas de Sensibilidad Microbiana , Fosfomicina/farmacología , Klebsiella pneumoniae/efectos de los fármacos , Pruebas de Sensibilidad Microbiana/métodos , Antibacterianos/farmacología , Humanos , Infecciones Urinarias/microbiología , Infecciones Urinarias/tratamiento farmacológico , Infecciones por Klebsiella/tratamiento farmacológico , Infecciones por Klebsiella/microbiología , Agar , Medios de Cultivo/química
3.
Dermatol Surg ; 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38843457

RESUMEN

BACKGROUND: As internet access continues to expand, online health care information is increasingly influencing patient decisions. Mohs micrographic surgery (MMS) is commonly used in the field of dermatology but may be unfamiliar to many patients. OBJECTIVE: The purpose of this study was to identify and analyze online educational resources regarding MMS and learn how to optimize the understanding and informational content of MMS for patients and their families. MATERIALS AND METHODS: Thirty-two websites were evaluated for authorship, quality, and readability using DISCERN, JAMA Benchmark Criteria, and Flesch-Kincaid tests. RESULTS: Physician-authored content showed a trend toward higher quality (p = .058). Google scored higher in specific DISCERN questions when overlapping websites were excluded. Bing scored higher in JAMA criteria (p = .03) in criteria such as authorship and currency. Higher DISCERN scores correlated with lower readability. CONCLUSION: Physician involvement improves content quality, raising questions about physicians' responsibility in online resource creation. Correlations between content quality and readability highlight potential challenges for certain demographics. Balancing medical accuracy with comprehensibility is crucial for equitable patient education. This study underscores the need to refine online resources, ensuring accurate, transparent, and accessible health care information.

4.
J Eval Clin Pract ; 30(6): 909-935, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38817022

RESUMEN

OBJECTIVE: The primary aim of this systematic review is to assess the effectiveness of evidence-based healthcare (EBHC) educational interventions on healthcare professionals' knowledge, skills, attitudes, behaviour of EBHC, clinical process and care outcomes. A secondary aim of the review is to assess the effects of important pedagogical moderating factors for EBHC educational interventions. METHOD: This systematic review used a forward and backward citation search strategy on the Web of Science platform (date of inception to 28 April 2023). Only randomised controlled trials (RCTs) and cluster RCTs which compared EBHC educational interventions for healthcare professionals were included. A random effects meta-analysis was undertaken for EBHC compared with an active and nonactive control for all outcomes. RESULTS: Sixty-one RCTs were identified which included a total of 5208 healthcare professionals. There was a large effect for EBHC educational interventions compared with waiting list/no treatment/sham control on knowledge (SMD, 2.69; 95% CI, 1.26-4.14, GRADE Low), skills (SMD, 0.88; 95% CI, 0.25-1.73, Very Low Certainty), attitude (SMD, 0.81; 95% CI, 0.16-1.47, Very Low Certainty) and behaviour of EBHC (SMD, 0.82; 95% CI, 0.25-1.40, Very Low Certainty). Over time the effect of EBHC educational interventions substantially decreased with no evidence of effect at 6 months for any outcome except behaviour (SMD,1.72; 95% CI, 0.74-2.71, Low Certainty). There was some evidence that blended learning, active learning and consistency in the individual delivering the intervention may be important positive moderating factors. CONCLUSION: These findings suggest that EBHC educational interventions may have a large short-term effect on improving healthcare professionals' knowledge, skills, attitude and behaviour of EBHC. These effects may be longer-lasting regarding EBHC behaviour. In terms of pedagogy, blended learning, active learning, and consistency of the individual delivering the intervention may be important positive moderating factors.


Asunto(s)
Competencia Clínica , Práctica Clínica Basada en la Evidencia , Conocimientos, Actitudes y Práctica en Salud , Personal de Salud , Humanos , Personal de Salud/educación , Actitud del Personal de Salud , Ensayos Clínicos Controlados Aleatorios como Asunto
6.
Am J Speech Lang Pathol ; 33(1): 117-134, 2024 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-37889208

RESUMEN

PURPOSE: The intervention of thickened liquids (TL) is commonly used to reduce aspiration in people with dysphagia. Speech-language pathologists (SLPs) have traditionally believed it is an effective intervention. Recent articles highlight limited evidence, poor acceptance, and a variety of unintended consequences. This study explores if current debates have been reflected in SLP practices and perspectives. METHOD: An e-survey was developed. Participants were recruited via professional associations in Australia, New Zealand, Ireland, the United Kingdom, and the United States. Descriptive and inferential statistics were used to explore the data. Principal component analysis was used to summarize SLP practices and perspectives. RESULTS: The 370 respondents represented mainly experienced, confident, hospital-based clinicians. While 20% of respondents frequently recommend TL, 61% believe it to be a burdensome treatment. "Best treatment" and "It works" beliefs continue to underpin decision making. Those who recommend TL most often are most influenced by penetration, coughing, and their own clinical experience. They are more likely to believe TL is evidence based and effective, reduces aspiration, and improves hydration. Person-centeredness is important among all respondents, although significant numbers would implement TL against patient wishes. Improvements in aspiration status and quality of life rank highly as reasons to discontinue TL. CONCLUSIONS: The results of this study suggest that fewer respondents are regularly using TL. Divergent groups are evident with those frequently employing and believing in the efficacy of TL and those who do not. While current debates are influencing practice, there clearly remains a significant number of SLPs continuing to recommend TL. This study's findings highlight both alterations and preservations in the discipline's approach to TL and calls for SLPs to reframe our thinking regarding this intervention as well as consider alternative options in this treatment space. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.24317110.


Asunto(s)
Trastornos de Deglución , Patología del Habla y Lenguaje , Humanos , Estados Unidos , Trastornos de Deglución/diagnóstico , Trastornos de Deglución/terapia , Deglución , Calidad de Vida , Patólogos , Habla , Encuestas y Cuestionarios , Patología del Habla y Lenguaje/métodos
7.
J Am Acad Dermatol ; 90(4): 798-805, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38081390

RESUMEN

BACKGROUND: Amid a movement toward value-based healthcare, increasing emphasis has been placed on outcomes and cost of medical services. To define and demonstrate the quality of services provided by Mohs surgeons, it is important to identify and understand the key aspects of Mohs micrographic surgery (MMS) that contribute to excellence in patient care. OBJECTIVE: The purpose of this study is to develop and identify a comprehensive list of metrics in an initial effort to define excellence in MMS. METHODS: Mohs surgeons participated in a modified Delphi process to reach a consensus on a list of metrics. Patients were administered surveys to gather patient perspectives. RESULTS: Twenty-four of the original 66 metrics met final inclusion criteria. Broad support for the initiative was obtained through physician feedback. LIMITATIONS: Limitations of this study include attrition bias across survey rounds and participation at the consensus meeting. Furthermore, the list of metrics is based on expert consensus instead of quality evidence-based outcomes. CONCLUSION: With the goal of identifying metrics that demonstrate excellence in performance of MMS, this initial effort has shown that Mohs surgeons and patients have unique perspectives and can be engaged in a data-driven approach to help define excellence in the field of MMS.


Asunto(s)
Neoplasias Cutáneas , Cirujanos , Humanos , Neoplasias Cutáneas/cirugía , Cirugía de Mohs , Consenso , Benchmarking
10.
BMC Med Ethics ; 24(1): 7, 2023 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-36750907

RESUMEN

BACKGROUND: Use of modified texture diets-thickening of liquids and modifying the texture of foods-in the hope of preventing aspiration, pneumonia and choking, has become central to the current management of dysphagia. The effectiveness of this intervention has been questioned. We examine requirements for a valid informed consent process for this approach and whether the need for informed consent for this treatment is always understood or applied by practitioners. MAIN TEXT: Valid informed consent requires provision of accurate and balanced information, and that agreement is given freely by someone who knows they have a choice. Current evidence, including surveys of practitioners and patients in different settings, suggests that practice in this area is often inadequate. This may be due to patients' communication difficulties but also poor communication-and no real attempt to obtain consent-by practitioners before people are 'put on' modified texture diets. Even where discussion occurs, recommendations may be influenced by professional misconceptions about the efficacy of this treatment, which in turn may poison the well for the informed consent process. Patients cannot make appropriate decisions for themselves if the information provided is flawed and unbalanced. The voluntariness of patients' decisions is also questionable if they are told 'you must', when 'you might consider' is more appropriate. Where the decision-making capacity of patients is in question, inappropriate judgements and recommendations may be made by substitute decision makers and courts unless based on accurate information. CONCLUSION: Research is required to examine the informed consent processes in different settings, but there is ample reason to suggest that current practice in this area is suboptimal. Staff need to reflect on their current practice regarding use of modified texture diets with an awareness of the current evidence and through the 'lens' of informed consent. Education is required for staff to clarify the importance of, and requirements for, valid informed consent and for decision making that reflects people's preferences and values.


Asunto(s)
Trastornos de Deglución , Humanos , Consentimiento Informado , Comunicación , Dieta
11.
J Antimicrob Chemother ; 77(11): 3180-3186, 2022 10 28.
Artículo en Inglés | MEDLINE | ID: mdl-36101483

RESUMEN

BACKGROUND: Optimal penetration of anti-infectives in the female genital tract (FGT) is paramount in the treatment and prevention of infectious diseases. While exposure of anti-infectives in lower FGT tissues (e.g. cervix, vagina) has been described, little data exist on upper genital tissues (e.g. ovary, uterus). METHODS: Autopsies were performed and post-mortem tissues were collected within 24 h of death for female participants with advanced HIV in Uganda (n = 27). Tenofovir, lamivudine, efavirenz and fluconazole concentrations were measured using LC-MS/MS in plasma, ovarian, uterine, cervical and vaginal tissues. Tissue penetration was calculated as tissue-to-plasma concentration ratios (TPRs). RESULTS: TPRs of tenofovir, lamivudine and fluconazole were highest in vaginal tissue (medians 1.86, 1.83 and 0.94, respectively), while the TPR of efavirenz was highest in ovarian tissue (median 0.65). With cervix as a reference compartment, vaginal TPRs were significantly higher than cervical for all four drugs; TPRs of efavirenz in uterine and ovarian compartments were also significantly higher than cervical. Most of the post-mortem FGT samples had a TPR of greater than 1 for tenofovir and lamivudine, while less than 50% had a TPR of greater than 1 for both efavirenz and fluconazole. CONCLUSIONS: Penetration of anti-infectives was not homogeneous among the FGT compartments. Approximately 70% of FGT tissues had a TPR of greater than 1 for tenofovir and lamivudine, favouring the prevention of local HIV replication and transmission in the FGT.


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Femenino , Humanos , Tenofovir/uso terapéutico , Lamivudine/uso terapéutico , Fluconazol/farmacología , Fluconazol/uso terapéutico , Cromatografía Liquida , Autopsia , Espectrometría de Masas en Tándem , Benzoxazinas/uso terapéutico , Genitales Femeninos , Fármacos Anti-VIH/uso terapéutico
12.
J Plast Reconstr Aesthet Surg ; 75(8): 2757-2774, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35643599

RESUMEN

BACKGROUND: While bilobed and trilobed transposition flaps are established workhorses for nasal reconstruction, their utility is often limited to defects less than 1.5 cm, subjecting patients to more involved multistage or cosmetically less favorable repairs. We highlight the use of bilobed and trilobed transposition flaps for intermediate (≥ 1.5 cm) and large (≥ 2.0 cm) nasal defects. METHODS: Patients reconstructed with multilobed transposition flaps 2017-2020 were identified at two institutions. Validated scar scale (SCAR) and patient component of the patient and observer scar assessment survey (POSAS) were used to assess patient outcomes at a minimum 5-week follow-up. Statistical analyses were performed. RESULTS: Thirty-four patients were identified with mean defect size 1.8 cm diameter. There were no major postoperative events. Scar revision was performed in 9 patients. The mean provider SCAR score was 3.06 (best possible 0, worst possible 13). The mean patient arm of the SCAR scale and POSAS were 0.07 (best possible 0, worst possible 2) and 10.93 (best possible 6, worst possible 60), respectively. CONCLUSION: Bilobed and trilobed flaps have excellent outcomes for intermediate and large nasal defects.


Asunto(s)
Neoplasias Nasales , Procedimientos de Cirugía Plástica , Cicatriz/etiología , Cicatriz/patología , Cicatriz/cirugía , Humanos , Cirugía de Mohs , Nariz/cirugía , Neoplasias Nasales/patología , Neoplasias Nasales/cirugía , Estudios Retrospectivos , Colgajos Quirúrgicos/cirugía
14.
Int J Dermatol ; 61(5): 558-563, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-34287830

RESUMEN

BACKGROUND: Merkel cell carcinoma (MCC) is a rare, highly aggressive malignancy which lacks high-level evidence-based treatment guidelines. METHODS: To determine outcomes of MCC patients and assess the role of radiation in treatment, we performed a retrospective chart review of patients treated for MCC between 2006 and 2016 at a single high-volume academic medical center. The primary outcome was overall survival (OS) for the entire population and for those populations receiving specific therapies. RESULTS: Forty-two patients were evaluable. OS for all patients was not reached since most remain alive at time of analysis. OS for the American Joint Committee on Cancer (AJCC) stage I was not reached. OS for stages II, III, and IV was 37.3 months (6.8, -), 49.5 months (14.2, 49.5), and 14.5 months (10.8, -), respectively. OS could not be reached in the high radiotherapy (RT) dose group (biologically equivalent dose [BED] ≥ 60) and was 49.5 months (10.8, -) in the low-dose group (BED < 60). For surgical margin status, OS was 14.9158 months (6.8008, -) for positive margins and 37.3 months (10.8, -) for negative margins. CONCLUSIONS: No conclusive findings for OS were identified; however, trends for improved OS were associated with lower AJCC staging, negative surgical margins, and high RT doses.


Asunto(s)
Carcinoma de Células de Merkel , Neoplasias Cutáneas , Carcinoma de Células de Merkel/radioterapia , Humanos , Márgenes de Escisión , Estadificación de Neoplasias , Radioterapia Adyuvante , Estudios Retrospectivos , Neoplasias Cutáneas/radioterapia , Resultado del Tratamiento
16.
Health Policy Plan ; 36(9): 1384-1396, 2021 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-34424314

RESUMEN

Previous efforts to estimate the travel time to comprehensive emergency obstetric care (CEmOC) in low- and middle-income countries (LMICs) have either been based on spatial models or self-reported travel time, both with known inaccuracies. The study objectives were to estimate more realistic travel times for pregnant women in emergency situations using Google Maps, determine system-level factors that influence travel time and use these estimates to assess CEmOC geographical accessibility and coverage in Lagos state, Nigeria. Data on demographics, obstetric history and travel to CEmOC facilities of pregnant women with an obstetric emergency, who presented between 1st November 2018 and 31st December 2019 at a public CEmOC facility were collected from hospital records. Estimated travel times were individually extracted from Google Maps for the period of the day of travel. Bivariate and multivariate analyses were used to test associations between travel and health system-related factors with reaching the facility >60 minutes. Mean travel times were compared and geographical coverage mapped to identify 'hotspots' of predominantly >60 minutes travel to facilities. For the 4005 pregnant women with traceable journeys, travel time ranges were 2-240 minutes (without referral) and 7-320 minutes (with referral). Total travel time was within the 60 and 120 minute benchmark for 80 and 96% of women, respectively. The period of the day of travel and having been referred were significantly associated with travelling >60 minutes. Many pregnant women living in the central cities and remote towns typically travelled to CEmOC facilities around them. We identified four hotspots from which pregnant women travelled >60 minutes to facilities. Mean travel time and distance to reach tertiary referral hospitals were significantly higher than the secondary facilities. Our findings suggest that actions taken to address gaps need to be contextualized. Our approach provides a useful guide for stakeholders seeking to comprehensively explore geographical inequities in CEmOC access within urban/peri-urban LMIC settings.


Asunto(s)
Servicios Médicos de Urgencia , Accesibilidad a los Servicios de Salud , Femenino , Geografía , Humanos , Nigeria , Embarazo , Viaje
17.
Dermatol Surg ; 47(3): 355-359, 2021 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-34328287

RESUMEN

BACKGROUND: The skin of color (SOC) population in the United States continues to grow, and these patients are undergoing various cosmetic and surgical procedures at increasing rates. There is a paucity of data on the potential complications associated with surgical and cosmetic procedures in this patient population. OBJECTIVE: We aim to educate dermatologic surgeons and clinicians on surgical and cosmetic procedures in patients of color and increase awareness of the potential complications unique to this patient population. MATERIALS AND METHODS: A thorough PubMed literature search was performed to conduct this review. RESULTS: There are a number of complications in SOC that require special attention, including keloids, postoperative infections, postinflammatory hyperpigmentation, and hypopigmentation. There are also various precautions to consider when performing cosmetic procedures, such as neurotoxin and filler injections, laser therapy, microneedling, and chemical peels. CONCLUSION: Dermatologists should be aware of the potential cosmetic and surgical complications of this growing patient population to provide optimal evidence-based medical care.


Asunto(s)
Técnicas Cosméticas/efectos adversos , Procedimientos Quirúrgicos Dermatologicos/efectos adversos , Pigmentación de la Piel , Quimioexfoliación/efectos adversos , Punción Seca/efectos adversos , Humanos , Hiperpigmentación/etiología , Hipopigmentación/etiología , Queloide/etiología , Terapia por Láser/efectos adversos , Complicaciones Posoperatorias , Factores de Riesgo , Infección de la Herida Quirúrgica/etiología
19.
Cutis ; 107(5): 249-252, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-34288852

RESUMEN

Mohs micrographic surgery (MMS) entails multiple time-consuming surgical and histological examinations for each patient. Efficient communication is key in improving clinic flow, and we surveyed members of the American College of Mohs Surgery to evaluate the efficacy of different techniques utilized by Mohs surgeons across the nation.


Asunto(s)
Cirugía de Mohs , Neoplasias Cutáneas , Comunicación , Humanos , Satisfacción del Paciente , Neoplasias Cutáneas/cirugía , Encuestas y Cuestionarios
20.
Open Forum Infect Dis ; 8(11): ofab506, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35548171

RESUMEN

Background: During the coronavirus disease 2019 (COVID-19) pandemic, clinical trials necessitated rapid testing to be performed remotely. Dried blood spot (DBS) techniques have enabled remote HIV virologic testing globally, and more recently, antibody testing as well. We evaluated DBS testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody testing in outpatients to assess seropositivity. Methods: In 2020, we conducted 3 internet-based randomized clinical trials and offered serologic testing via self-collected DBS as a voluntary substudy. COVID-19 diagnosis was based on the Centers for Disease Control and Prevention case definition with epidemiological link to cases. A minority reported polymerase chain reaction (PCR) testing at an outside facility. We tested for anti-SARS-CoV-2 immunoglobulin via antibody detection by agglutination-PCR (ADAP) and compared the results with enzyme-linked immunosorbent assay (ELISA). Results: Of 2727 participants in the primary studies, 60% (1648/2727) consented for serology testing; 56% (931/1648) returned a usable DBS sample. Of those who were asymptomatic, 5% (33/707) had positive ADAP serology. Of participants with a positive PCR, 67% (36/54) had positive SARS-CoV-2 antibodies. None of those who were PCR-positive and asymptomatic were seropositive (0/7). Of 77 specimens tested for concordance via ELISA, 83% (64/77) were concordant. The challenges of completing a remote testing program during a pandemic included sourcing and assembling collection kits, delivery and return of the kits, and troubleshooting testing. Self-collection was successful for >95% of participants. Delays in US mail with possible sample degradation and timing of DBS collection complicated the analysis. Conclusions: We found remote antibody testing during a global pandemic feasible although challenging. We identified an association between symptomatic COVID-19 and positive antibody results at a similar prevalence as other outpatient cohorts.

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