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1.
Blood ; 142(2): 202-209, 2023 07 13.
Artículo en Inglés | MEDLINE | ID: mdl-37172200

RESUMEN

Frequent plateletpheresis is associated with severe lymphopenia of uncertain clinical significance. We assessed the functional impact of frequent platelet donations and associated lymphopenia on the response to neoantigens. We conducted a prospective study of 102 platelet donors (HIV uninfected) who were naive to meningococcal vaccination recruited at Brigham and Women's Hospital. One dose of quadrivalent meningococcal conjugate vaccine was administered. Seroresponse was defined as a fourfold increase of serum bactericidal antibody titers and seroprotection was defined as postvaccination titers of ≥1:8, for each of the 4 vaccine antigens (A, C, W, and Y). Mean age of participants was 61 years, 69% were male, and medial number of platelet donations in prior year was 14 (interquartile range, 4-20). Frequent platelet donors had a low CD4 count (14% with ≤200/µL and 34% with ≤350/µL). Seroresponse rates varied from 68% for serogroup Y to 86% for serogroup A and were higher for participants with baseline titers of <1:8. Postvaccination seroprotection rates varied from 76% for serogroup Y to 96% for serogroup A. After adjustments for age, sex, and frequent donations, lower total lymphocyte or lower CD4 counts were not associated with lower responses. These data suggest no impairment by plateletpheresis-associated lymphopenia on response to these neoantigens. This trial was registered at www.clinicaltrials.gov as #NCT04224311.


Asunto(s)
Linfopenia , Infecciones Meningocócicas , Vacunas Meningococicas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Anticuerpos Antibacterianos , Infecciones Meningocócicas/prevención & control , Estudios Prospectivos , Vacunas Conjugadas
2.
J Urol ; 211(1): 90-100, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37788015

RESUMEN

PURPOSE: Penile cancer is rare, with significant morbidity and limited literature assessing utility of peripheral and deep en face margin assessment (PDEMA) vs traditional margin assessment (vertical sections) on treatment outcomes. MATERIALS AND METHODS: This was a 32-year retrospective multicenter cohort study at 3 academic tertiary care centers. The cohort consisted of 189 patients with histologic diagnosis of in situ or T1a cutaneous squamous cell carcinoma of the penis at Brigham and Women's, Massachusetts General Hospital (1988-2020), and Memorial Sloan Kettering Cancer Center (1995-2020) treated with PDEMA surgical excision, excision/circumcision, or penectomy/glansectomy. Local recurrence, metastasis, and disease-specific death were assessed via multivariable Cox proportional hazard models. RESULTS: The cohort consisted of 189 patients. Median age at diagnosis was 62 years. Median tumor diameter was 1.3 cm. The following outcomes of interest occurred: 30 local recurrences, 13 metastases, and 5 disease-specific deaths. Primary tumors were excised with PDEMA (N = 30), excision/circumcision (N = 110), or penectomy/glansectomy (N = 49). Of patients treated with traditional margin assessment (non-PDEMA), 12% had narrow or positive margins. Five-year proportions were as follows with respect to local recurrence-free survival, metastasis-free survival, and disease-specific survival/progression-free survival, respectively: 100%, 100%, and 100% following PDEMA; 82%, 96%, and 99% following excision/circumcision; 83%, 91%, and 95% following penectomy/glansectomy. A limitation is that this multi-institutional cohort study was not externally validated. CONCLUSIONS: Initial results are encouraging that PDEMA surgical management effectively controls early-stage penile squamous cell carcinoma.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias del Pene , Neoplasias Cutáneas , Masculino , Humanos , Femenino , Persona de Mediana Edad , Neoplasias del Pene/patología , Carcinoma de Células Escamosas/patología , Estudios de Cohortes , Tratamientos Conservadores del Órgano/métodos , Recurrencia Local de Neoplasia/patología , Estudios Retrospectivos
3.
Artículo en Inglés | MEDLINE | ID: mdl-38842227

RESUMEN

BACKGROUND: Penile squamous cell carcinoma (PSCC) carries significant morbidity and mortality. Literature is limited regarding prognostic factors, especially prognostic factors for development of metastasis. OBJECTIVES: To identify independent prognostic factors associated with poor outcomes, defined as local recurrence (LR), metastasis and disease-specific death (DSD) in clinically node-negative PSCC undergoing local therapy. METHODS: Thirty-two-year Retrospective Multicenter Cohort Study of 265 patients with histologically diagnosed PSCC at three tertiary care centres. Predictive models based on patient or tumour characteristics were developed. RESULTS: Local recurrence occurred in 56 patients, metastasis in 52 patients and DSD in 40 patients. In multivariable models, the following five factors were independent prognostic factors based on subhazard ratio (SHR): history of balanitis (LR SHR: 2.3; 95% CI 1.2-4.2), poor differentiation (metastasis SHR 1.9; 95% CI 1.0-3.6), invasion into the corpora (metastasis SHR: 3.0; 95% CI 1.5-5.8 and DSD SHR: 4.5; 95% CI 1.7-12.1), perineural invasion (PNI) (metastasis SHR: 2.8; 95% CI 1.4-5.5 and DSD SHR: 3.5; 95% CI, 1.6-7.8) and a history of phimosis (DSD SHR: 2.5; 95% CI 1.2-5.3). The 5-year cumulative incidence of metastasis was higher for tumours with PNI [cumulative incidence function (CIF) = 55%, 95% CI 38-75 vs. CIF 15%, 95% CI 11-22], corporal invasion (CIF: 35%, 95% CI 26-47 vs. 12%, 95% CI 7-19) and poorly differentiated tumours (CIF = 46%, 95% CI 31-64 vs. CIF 15%, 95% CI 11-22). CONCLUSIONS: History of balanitis, history of phimosis, PNI, corporal invasion and poor differentiation are independent risk factors associated with poor outcomes. Since poor differentiation and PNI currently constitute only T1b disease, prognostic staging can likely be improved.

4.
J Allergy Clin Immunol ; 151(5): 1269-1276, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36740144

RESUMEN

BACKGROUND: Multiple mAbs are currently approved for the treatment of asthma. However, there is limited evidence on their comparative effectiveness. OBJECTIVE: Our aim was to compare the effectiveness of omalizumab, mepolizumab, and dupilumab in individuals with moderate-to-severe asthma. METHODS: We emulated a hypothetical randomized trial using electronic health records from a large US-based academic health care system. Participants aged 18 years or older with baseline IgE levels between 30 and 700 IU/mL and peripheral eosinophil counts of at least 150 cells/µL were eligible for study inclusion. The study period extended from March 2016 to August 2021. Outcomes included the incidence of asthma-related exacerbations and change in baseline FEV1 value over 12 months of follow-up. RESULTS: In all, 68 individuals receiving dupilumab, 68 receiving omalizumab, and 65 receiving mepolizumab met the inclusion criteria. Over 12 months of follow-up, 31 exacerbations occurred over 68 person years (0.46 exacerbations per person year) in the dupilumab group, 63 over 68 person years (0.93 per person year) in the omalizumab group, and 86 over 65 person years (1.32 per person year) in the mepolizumab group (adjusted incidence rate ratios: dupilumab vs mepolizumab, 0.28 [95% CI = 0.09-0.84]; dupilumab vs omalizumab, 0.36 [95% CI = 0.12-1.09]; and omalizumab vs mepolizumab, 0.78 [95% CI = 0.32-1.91]). The differences in the change in FEV1 comparing patients who received the different biologics were as follows: 0.11 L (95% CI = -0.003 to 0.222 L) for dupilumab versus mepolizumab, 0.082 L (95% CI -0.040 to 0.204 L) for dupilumab versus omalizumab, and 0.026 L (95% CI -0.083 to 0.140 L) for omalizumab versus mepolizumab. CONCLUSIONS: Among patients with asthma and eosinophil counts of at least 150 cells/µL and IgE levels of 30 to 700 kU/L, dupilumab was associated with greater improvements in exacerbation and FEV1 value than omalizumab and mepolizumab.


Asunto(s)
Antiasmáticos , Asma , Humanos , Antiasmáticos/uso terapéutico , Asma/etiología , Inmunoglobulina E/uso terapéutico , Omalizumab/uso terapéutico , Investigación sobre la Eficacia Comparativa
5.
Nutr Metab Cardiovasc Dis ; 33(12): 2413-2418, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37580232

RESUMEN

BACKGROUND AND AIMS: While the association of potato consumption with risk factors for coronary artery disease has been inconsistent, no data are available in the literature on the influence of potato consumption on subclinical disease. Thus, we sought to examine whether baked/mashed potato consumption is associated with calcified atherosclerotic plaques in the coronary arteries. METHODS AND RESULTS: In a cross-sectional design, we studied 2208 participants of the NHLBI Family Heart Study. These subjects were selected based on their elevated cardiovascular disease risk compared to the general population. Potato consumption was assessed by a semi-quantitative food frequency questionnaire. We defined prevalent CAC using an Agatston score of at least 100 and fitted generalized estimating equations to calculate prevalence odds ratios of CAC. Mean age at initial clinic visit was 58.2 years and 55% were female. Median consumption of potatoes was 2-4/week. There was no statistically significant association between frequency of potato consumption and prevalent CAC: odds ratios (95% CI) for CAC were 1.0 (reference), 0.85 (0.56-1.30), 0.85 (0.58-1.26), and 0.95 (0.60-1.53) among subjects reporting potato consumption of <1/week, 1/week, 2-4/week, and 5+/week, respectively (p for linear trend 0.83), adjusting for age, sex, BMI, smoking, exercise, diabetes, hypertension, total calories, prevalent coronary heart disease, income, education, and daily red meat intake. CONCLUSIONS: We found no significant association between baked/mashed potato consumption and CAC in older adults. STUDY REGISTRATION NUMBER: NCT00005136. Study registration date: 5/25/2000.


Asunto(s)
Enfermedad de la Arteria Coronaria , Placa Aterosclerótica , Solanum tuberosum , Estados Unidos/epidemiología , Humanos , Femenino , Anciano , Masculino , Vasos Coronarios , National Heart, Lung, and Blood Institute (U.S.) , Estudios Transversales , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/epidemiología , Factores de Riesgo
6.
Clin Exp Dermatol ; 48(3): 225-227, 2023 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-36763721

RESUMEN

Cutaneous diseases are the fourth leading cause of nonfatal disease burden globally. In this study, we aimed to investigate the psychological symptom burden in patients with chronic activity-limiting cutaneous diseases. Our findings suggest that this patient population experience a wide range of interference with their daily lives and exhibit higher psychological burdens and lower quality of life. This study also identified that patients with activity-limiting skin conditions do not seem to seek more professional help or take more medications, which may suggest a potential gap in adequate mental health support and resources.


Asunto(s)
Salud Mental , Calidad de Vida , Humanos , Calidad de Vida/psicología , Enfermedad Crónica
7.
Clin Infect Dis ; 75(1): e920-e923, 2022 08 24.
Artículo en Inglés | MEDLINE | ID: mdl-34726754

RESUMEN

The severe acute respiratory syndrome coronavirus 2 messenger RNA vaccine-induced humoral response and reactogenicity profile are described in allogeneic hematopoietic stem cell transplant (HSCT) recipients. Findings showed that 75.0% (by Simoa assay) or 80.0% (by Roche assay) of the HSCT cohort had a positive antibody response on series completion, compared with 100% in the healthy cohort.


Asunto(s)
COVID-19 , Trasplante de Células Madre Hematopoyéticas , Vacunas de ARNm , COVID-19/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , SARS-CoV-2 , Vacunas , Vacunas Sintéticas , Vacunas de ARNm/efectos adversos
8.
Emerg Infect Dis ; 28(9): 1859-1862, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35868337

RESUMEN

Given widespread use of spike antibody in generating coronavirus disease vaccines, SARS-CoV-2 nucleocapsid antibodies are increasingly used to indicate previous infection in serologic surveys. However, longitudinal kinetics and seroreversion are poorly defined. We found substantial seroreversion of nucleocapsid total immunoglobulin, underscoring the need to account for seroreversion in seroepidemiologic studies.


Asunto(s)
COVID-19 , SARS-CoV-2 , Anticuerpos Antivirales , COVID-19/epidemiología , Proteínas de la Nucleocápside de Coronavirus/inmunología , Humanos , Cinética , Nucleocápside , Fosfoproteínas/inmunología , Estudios Seroepidemiológicos
9.
Haematologica ; 107(5): 1172-1180, 2022 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-34551505

RESUMEN

We conducted a randomized controlled trial in older adults with hematologic malignancies to determine the impact of geriatrician consultation embedded in our oncology clinic alongside standard care. From February 2015 to May 2018, transplant-ineligible patients aged ≥75 years who presented for initial consultation for lymphoma, leukemia, or multiple myeloma at Dana-Farber Cancer Institute (Boston, MA, USA) were eligible. Pre-frail and frail patients, classified based on phenotypic and deficit-accumulation approaches, were randomized to receive either standard oncologic care with or without consultation with a geriatrician. The primary outcome was 1-year overall survival. Secondary outcomes included unplanned care utilization within 6 months of follow-up and documented end-of-life (EOL) goals-of-care discussions. Clinicians were surveyed as to their impressions of geriatric consultation. One hundred sixty patients were randomized to either geriatric consultation plus standard care (n=60) or standard care alone (n=100). The median age of the patients was 80.4 years (standard deviation = 4.2). Of those randomized to geriatric consultation, 48 (80%) completed at least one visit with a geriatrician. Consultation did not improve survival at 1 year compared to standard care (difference: 2.9%, 95% confidence interval: -9.5% to 15.2%, P=0.65), and did not significantly reduce the incidence of emergency department visits, hospital admissions, or days in hospital. Consultation did improve the odds of having EOL goals-of-care discussions (odds ratio = 3.12, 95% confidence interval: 1.03 to 9.41) and was valued by surveyed hematologic-oncology clinicians, with 62.9%-88.2% of them rating consultation as useful in the management of several geriatric domains.


Asunto(s)
Evaluación Geriátrica , Neoplasias Hematológicas , Anciano , Anciano de 80 o más Años , Neoplasias Hematológicas/epidemiología , Neoplasias Hematológicas/terapia , Hospitalización , Humanos , Derivación y Consulta
10.
Microb Cell Fact ; 21(1): 174, 2022 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-36030199

RESUMEN

BACKGROUND: Saccharomyces cerevisiae is often used as a cell factory for the production of S-adenosyl-L-methionine (SAM) for diverse pharmaceutical applications. However, SAM production by S. cerevisiae is negatively influenced by glucose repression, which is regulated by a serine/threonine kinase SNF1 complex. Here, a strategy of alleviating glucose repression by deleting REG1 (encodes the regulatory subunit of protein phosphatase 1) and overexpressing SNF1 (encodes the catalytic subunit of the SNF1 complex) was applied to improve SAM production in S. cerevisiae. SAM production, growth conditions, glucose consumption, ethanol accumulation, lifespan, glycolysis and amino acid metabolism were analyzed in the mutant strains. RESULTS: The results showed that the multiple effects of REG1 deletion and/or SNF1 overexpression exhibited a great potential for improving the SAM production in yeast. Enhanced the expression levels of genes involved in glucose transport and glycolysis, which improved the glucose utilization and then elevated the levels of glycolytic intermediates. The expression levels of ACS1 (encoding acetyl-CoA synthase I) and ALD6 (encoding aldehyde dehydrogenase), and the activity of alcohol dehydrogenase II (ADH2) were enhanced especially in the presence of excessive glucose levels, which probably promoted the conversion of ethanol in fermentation broth into acetyl-CoA. The gene expressions involved in sulfur-containing amino acids were also enhanced for the precursor amino acid biosynthesis. In addition, the lifespan of yeast was extended by REG1 deletion and/or SNF1 overexpression. As expected, the final SAM yield of the mutant YREG1ΔPSNF1 reached 8.28 g/L in a 10-L fermenter, which was 51.6% higher than the yield of the parent strain S. cerevisiae CGMCC 2842. CONCLUSION: This study showed that the multiple effects of REG1 deletion and SNF1 overexpression improved SAM production in S. cerevisiae, providing new insight into the application of the SNF1 complex to abolish glucose repression and redirect carbon flux to nonethanol products in S. cerevisiae.


Asunto(s)
Proteína Fosfatasa 1 , Proteínas Serina-Treonina Quinasas , S-Adenosilmetionina , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Acetilcoenzima A , Etanol , Glucosa , Proteína Fosfatasa 1/genética , Proteína Fosfatasa 1/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , S-Adenosilmetionina/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo
11.
J Am Acad Dermatol ; 86(4): 766-773, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34774657

RESUMEN

BACKGROUND: Lymphovascular invasion (LVI) is an aggressive histologic finding but is excluded from current staging systems due to its lack of demonstrated independent prognostic significance. OBJECTIVE: To evaluate the impact of LVI on cutaneous squamous cell carcinoma tumor outcomes. METHODS: In total, 10,707 cutaneous squamous cell carcinoma tumors from a 20-year, retrospective, multicenter cohort were stratified by the presence (LVI+) or absence (LVI-) of LVI. Outcomes (local recurrence, in-transit metastasis, nodal metastasis, disease-specific death) were compared based on low (Brigham and Women's Hospital [BWH] stage T1/T2a) and high (BWH T2b/T3) tumor stages. RESULTS: Of the 10,707 tumors, 78 had LVI. The analysis of low-stage BWH tumors showed the LVI+ group had a significantly higher 5-year cumulative incidence of local recurrence (LVI+: 12.3%; LVI-: 1.1%; P < .01), metastasis (LVI+: 4.2%; LVI-: 0.4%; P < .01), and disease-specific death (LVI+: 16.2%; LVI-: 0.4%; P < .01). The analysis of BWH high-stage tumors showed the LVI+ group maintained a higher 5-year cumulative incidence of metastasis (LVI+: 28.5%; LVI-: 16.8%; P = .06) and disease-specific death (LVI+: 25.3%; LVI-: 13.9%; P = .03), however, there was no difference in local recurrence (LVI+: 16.3%; LVI-: 15.8%; P = .11). LIMITATIONS: Retrospective study design. CONCLUSION: LVI+ cutaneous squamous cell carcinomas have higher rates of metastasis and death at 5 years. Future staging systems should consider incorporating LVI.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias Cutáneas , Carcinoma de Células Escamosas/patología , Femenino , Humanos , Invasividad Neoplásica/patología , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Neoplasias Cutáneas/patología
12.
J Am Acad Dermatol ; 87(1): 87-94, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35364211

RESUMEN

BACKGROUND: Although adjuvant radiation (ART) following clear margin surgery is recommended for select high-risk cutaneous squamous cell carcinomas, efficacy data are limited. OBJECTIVE: To evaluate the impact of ART on outcomes following clear margin surgery for high T-stage cutaneous squamous cell carcinomas. METHODS: A 20-year retrospective cohort study at 2 academic centers of high T-stage cutaneous squamous cell carcinomas (Brigham and Women's Hospital T2b or T3) with negative histologic margins post resection. Local recurrence (LR) and locoregional recurrence (LRR) were compared by whether tumors received ART or observation. RESULTS: A total of 508 tumors were included, of which 96 underwent ART (ART+). ART+ had a lower 5-year cumulative incidence of LR (ART+, 3.6% [95% CI, 1.6%-7.7%] vs ART-, 8.7% [95% CI, 6.3%-12.0%]) and LRR (ART+, 7.5% [95% CI, 4.4%-11.9%] vs ART-, 15.3% [95% CI, 11.9%-22.1%]). Recurrent tumors ≥6 cm or Brigham and Women's Hospital T3 tumors were classified as high-risk due to a higher 5-year cumulative incidence of LRR (High-risk, 26.3% [95% CI, 19.0%-35.7%]). High-risk tumors treated with ART had a lower 5-year cumulative incidence of LRR (ART+, 17.2% [95% CI, 11.9%-26.4%] vs ART-, 31.0% [95% CI, 26.1%-40.8%]). LIMITATIONS: Retrospective design, heterogeneous population, variations in radiation protocols. CONCLUSION: ART following clear margin surgery for high T-stage cutaneous squamous cell carcinomas resulted in half the risk of LR and LRR.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias Cutáneas , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirugía , Femenino , Humanos , Márgenes de Escisión , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Estudios Retrospectivos , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/radioterapia , Neoplasias Cutáneas/cirugía
13.
Ann Plast Surg ; 88(4): 372-374, 2022 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-34270468

RESUMEN

INTRODUCTION: Limitations in insurance coverage may cause patients to turn to crowdfunding to raise money for gender-affirming procedures. In this study, we analyze the impact of Medicaid insurance coverage on gender-affirming mastectomy campaigns posted on GoFundMe.com. METHODS: Between March 1 and 12, 2021, we accessed GoFundMe.com to analyze available campaigns requesting monetary contributions for gender-affirming mastectomy. Campaigns were identified using the search term "top surgery" followed by the state's name. Duplicate campaigns, campaigns whose primary goal was not gender-affirming mastectomy, and ongoing campaigns were excluded. Campaigns were then categorized according to their state's coverage of gender-affirming surgery: explicit exclusion (EE), explicit inclusion (EI), or no explicit statement of gender-affirming care. We collected data on the number of donors and shares, the fundraising goal, and the total amount raised for each campaign. Common themes within campaign narratives were identified and assessed by each reviewer. Finally, we collected data on the photographs posted by campaign creators. RESULTS: Our search yielded 790 campaigns, with an overall mean of 58 ± 99 donors and 212 ± 288 shares. The mean fundraising goal and amount raised among all campaigns were $6811 ± $5027 and $2579 ± $3072, respectively. Fundraising goals were most likely to be met in an EI state than an EE state (26.3% vs 8.1%; P < 0.001). The mean amount sought was highest in EE states and lowest in EI states, whereas the mean amount raised was lowest in EE states and highest in EI states. Of the campaigns, 97.1% mentioned personal or situational characteristics in the narrative section; 16.2% of all campaigns expressed negative feelings about posting on GoFundMe.com to raise money for their surgeries. CONCLUSION: Disparities in health care coverage of gender-affirming surgeries were seen between state categories, with a decreased need for crowdfunding in states explicitly including coverage of gender-affirming surgery. Many transgender patients used crowdfunding to pay for transition-related health care costs, relying on the kindness of strangers and their social network at the expense of their personal privacy. Expansion of legislative coverage of gender-affirming surgeries may alleviate some of this financial burden and reduce transgender patients' reliance on crowdfunding campaigns.


Asunto(s)
Neoplasias de la Mama , Colaboración de las Masas , Obtención de Fondos , Neoplasias de la Mama/cirugía , Colaboración de las Masas/métodos , Femenino , Obtención de Fondos/métodos , Humanos , Mastectomía , Privacidad , Estados Unidos
14.
J Clin Monit Comput ; 36(6): 1869-1879, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35332406

RESUMEN

Accurate measurement of respiratory rate (RR) in neonates is challenging due to high neonatal RR variability (RRV). There is growing evidence that RRV measurement could inform and guide neonatal care. We sought to quantify neonatal RRV during a clinical study in which we compared multiparameter continuous physiological monitoring (MCPM) devices. Measurements of capnography-recorded exhaled carbon dioxide across 60-s epochs were collected from neonates admitted to the neonatal unit at Aga Khan University-Nairobi hospital. Breaths were manually counted from capnograms and using an automated signal detection algorithm which also calculated mean and median RR for each epoch. Outcome measures were between- and within-neonate RRV, between- and within-epoch RRV, and 95% limits of agreement, bias, and root-mean-square deviation. Twenty-seven neonates were included, with 130 epochs analysed. Mean manual breath count (MBC) was 48 breaths per minute. Median RRV ranged from 11.5% (interquartile range (IQR) 6.8-18.9%) to 28.1% (IQR 23.5-36.7%). Bias and limits of agreement for MBC vs algorithm-derived breath count, MBC vs algorithm-derived median breath rate, MBC vs algorithm-derived mean breath rate were - 0.5 (- 2.7, 1.66), - 3.16 (- 12.12, 5.8), and - 3.99 (- 11.3, 3.32), respectively. The marked RRV highlights the challenge of performing accurate RR measurements in neonates. More research is required to optimize the use of RRV to improve care. When evaluating MCPM devices, accuracy thresholds should be less stringent in newborns due to increased RRV. Lastly, median RR, which discounts the impact of extreme outliers, may be more reflective of the underlying physiological control of breathing.


Asunto(s)
Capnografía , Frecuencia Respiratoria , Recién Nacido , Humanos , Frecuencia Respiratoria/fisiología , Kenia , Monitoreo Fisiológico , Respiración
15.
Stat Med ; 40(13): 3138-3152, 2021 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-33821528

RESUMEN

Nonlinear mixed-effects (NLME) models are commonly used in longitudinal studies such as pharmacokinetics and HIV viral dynamics studies. NLME models are often derived based on underlying data-generating mechanisms, therefore the parameters in these models often have natural physical interpretations that may suggest reasonable constraints on certain parameters. For example, the HIV viral decay rates for populations receiving anti-HIV treatments may be reasonably expected to be nonnegative. Hypothesis testing for these parameters should incorporate practically reasonable constraints to increase statistical power. Motivated from HIV viral dynamic models, in this article we propose multiparameter one-sided or constrained tests for NLME models with censored responses, for example, viral dynamic models with viral loads subject to lower detection limits. We propose approximate likelihood-based tests that are computationally efficient. We evaluate the tests via simulations and show that the proposed tests are more powerful than the corresponding two-sided or unrestricted tests. We apply the proposed tests to two AIDS datasets with new findings.


Asunto(s)
Modelos Estadísticos , Dinámicas no Lineales , Humanos , Funciones de Verosimilitud , Estudios Longitudinales , Carga Viral
16.
J Am Acad Dermatol ; 84(6): 1547-1553, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32389716

RESUMEN

BACKGROUND: Patient outcomes are improved when dermatologists provide inpatient consultations. Inpatient access to dermatologists is limited, illustrating an opportunity to use teledermatology. Little is known about the ability of dermatologists to accurately diagnose disease and manage inpatients with teledermatology, particularly when using nondermatologist-generated clinical data. METHODS: This prospective study assessed the ability of teledermatology to diagnose disease and manage 41 dermatology consultations from a large urban tertiary care center, using internal medicine referral documentation and photographs. Twenty-seven dermatology hospitalists were surveyed. Interrater agreement was assessed by the κ statistic. RESULTS: There was substantial agreement between in-person and teledermatology assessment of the diagnosis with differential diagnosis (median κ = 0.83), substantial agreement in laboratory evaluation decisions (median κ = 0.67), almost perfect agreement in imaging decisions (median κ = 1.0), and moderate agreement in biopsy decisions (median κ = 0.43). There was almost perfect agreement in treatment (median κ = 1.0), but no agreement in follow-up planning (median κ = 0.0). There was no association between raw photograph quality and the primary plus differential diagnosis or primary diagnosis alone. LIMITATIONS: Selection bias and single-center nature. CONCLUSIONS: Teledermatology may be effective in the inpatient setting, with concordant diagnosis, evaluation, and management decisions.


Asunto(s)
Dermatología/métodos , Hospitalización , Consulta Remota/métodos , Enfermedades de la Piel/diagnóstico , Adulto , Anciano , Estudios de Factibilidad , Femenino , Médicos Hospitalarios/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Fotograbar , Estudios Prospectivos , Piel/diagnóstico por imagen , Encuestas y Cuestionarios/estadística & datos numéricos , Centros de Atención Terciaria
17.
Prev Chronic Dis ; 18: E104, 2021 12 23.
Artículo en Inglés | MEDLINE | ID: mdl-34941480

RESUMEN

INTRODUCTION: National obesity prevention strategies may benefit from precision health approaches involving diverse participants in population health studies. We used cohort data from the National Institutes of Health All of Us Research Program (All of Us) Researcher Workbench to estimate population-level obesity prevalence. METHODS: To estimate state-level obesity prevalence we used data from physical measurements made during All of Us enrollment visits and data from participant electronic health records (EHRs) where available. Prevalence estimates were calculated and mapped by state for 2 categories of body mass index (BMI) (kg/m2): obesity (BMI >30) and severe obesity (BMI >35). We calculated and mapped prevalence by state, excluding states with fewer than 100 All of Us participants. RESULTS: Data on height and weight were available for 244,504 All of Us participants from 33 states, and corresponding EHR data were available for 88,840 of these participants. The median and IQR of BMI taken from physical measurements data was 28.4 (24.4- 33.7) and 28.5 (24.5-33.6) from EHR data, where available. Overall obesity prevalence based on physical measurements data was 41.5% (95% CI, 41.3%-41.7%); prevalence of severe obesity was 20.7% (95% CI, 20.6-20.9), with large geographic variations observed across states. Prevalence estimates from states with greater numbers of All of Us participants were more similar to national population-based estimates than states with fewer participants. CONCLUSION: All of Us participants had a high prevalence of obesity, with state-level geographic variation mirroring national trends. The diversity among All of Us participants may support future investigations on obesity prevention and treatment in diverse populations.


Asunto(s)
Obesidad Mórbida , Salud Poblacional , Índice de Masa Corporal , Humanos , Obesidad/epidemiología , Prevalencia , Estados Unidos/epidemiología
18.
Telemed J E Health ; 27(8): 874-880, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33826411

RESUMEN

A unique and sudden need for virtual medical visits created by the coronavirus disease 2019 (COVID-19) pandemic has led to an unprecedented expansion of telemedicine across nearly all medical specialties in the United States. In addition to providing essential medical services during the pandemic, telemedicine has the potential to expand health care access to underserved populations by eliminating traditional barriers to care such as transportation needs, distance from specialty providers, and approved time off from work. However, the literature regarding telehealth accessibility for low-income, non-English-speaking, and minority patients remains limited. Through a cross-sectional analysis comparing 2019 clinic visits with 2020 telehealth visits at the UMass Memorial Medical Center, we demonstrate specialty-specific changes in patient demographics, including a younger population, fewer non-English-speaking patients, and a relative preservation of minority, Medicaid, and Medicare patients among telehealth visits in comparison to clinic visits. We also demonstrate that nonsurgical specialties had significantly lower no-show rates and the greatest number of telehealth visits. Overall, our findings highlight the potential shortcomings of telemedicine in servicing non-English-speaking patients, while maintaining that it is an important tool with the potential to improve access to health care, particularly in nonprocedural specialties.


Asunto(s)
COVID-19 , Telemedicina , Anciano , Estudios Transversales , Humanos , Medicare , Pandemias , SARS-CoV-2 , Estados Unidos , Poblaciones Vulnerables
19.
Eur Respir J ; 54(6)2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31537703

RESUMEN

BACKGROUND: Previous studies have associated marijuana exposure with increased respiratory symptoms and chronic bronchitis among long-term cannabis smokers. The long-term effects of smoked marijuana on lung function remain unclear. METHODS: We determined the association of marijuana smoking with the risk of spirometrically defined chronic obstructive pulmonary disease (COPD) (post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity ratio <0.7) in 5291 population-based individuals and the rate of decline in FEV1 in a subset of 1285 males and females, aged ≥40 years, who self-reported use (or non-use) of marijuana and tobacco cigarettes and performed spirometry before and after inhaled bronchodilator on multiple occasions. Analysis for the decline in FEV1 was performed using random mixed effects regression models adjusted for age, sex and body mass index. Heavy tobacco smoking and marijunana smoking was defined as >20 pack-years and >20 joint-years, respectively. RESULTS: ∼20% of participants had been or were current marijuana smokers with most having smoked tobacco cigarettes in addition (83%). Among heavy marijuana users, the risk of COPD was significantly increased (adjusted OR 2.45, 95% CI 1.55-3.88). Compared to never-smokers of marijuana and tobacco, heavy marijuana smokers and heavy tobacco smokers experienced a faster decline in FEV1 by 29.5 mL·year-1 (p=0.0007) and 21.1 mL·year-1 (p<0.0001), respectively. Those who smoked both substances experienced a decline of 32.31 mL·year-1 (p<0.0001). INTERPRETATION: Heavy marijuana smoking increases the risk of COPD and accelerates FEV1 decline in concomitant tobacco smokers beyond that observed with tobacco alone.


Asunto(s)
Fumar Marihuana/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Fumar/epidemiología , Adulto , Factores de Edad , Anciano , Canadá , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Espirometría , Factores de Tiempo
20.
Pediatr Res ; 86(6): 732-737, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31382268

RESUMEN

BACKGROUND: The relationship between peripheral oxygen saturation (SpO2) and the inspired oxygen concentration is non-linear. SpO2 is frequently used as a dichotomized predictor, to manage this non-linearity. We propose the saturation virtual shunt (VS) as a transformation of SpO2 to a continuous linear variable to improve interpretation of disease severity within clinical prediction models. METHOD: We calculate the saturation VS based on an empirically derived approximation formula between physiological VS and SpO2. We evaluated the utility of the saturation VS in a clinical study predicting the need for facility admission in children in a low resource health-care setting. RESULTS: The transformation was saturation VS = 68.864 × log10(103.711 - SpO2) - 52.110. The ability to predict hospital admission based on a dichotomized SpO2 produced an area under the receiver operating characteristic curve of 0.57, compared to 0.71 based on the untransformed SpO2 and saturation VS. However, the untransformed SpO2 demonstrated a lack of fit compared to the saturation VS (goodness-of-fit test p value < 0.0001 vs 0.098). The observed admission rates varied non-linearly with the untransformed SpO2 but varied linearly with the saturation VS. CONCLUSION: The saturation VS estimates a continuous linearly interpretable disease severity based on SpO2 and improves clinical prediction.


Asunto(s)
Interpretación Estadística de Datos , Modelos Estadísticos , Oxígeno/sangre , Calibración , Preescolar , Femenino , Humanos , Masculino , Oximetría
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