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1.
J Am Acad Dermatol ; 90(2): 328-338, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37714218

RESUMEN

BACKGROUND: There are limited survival data on cutaneous angiosarcoma (CAS), dermatofibrosarcoma protuberans (DFSP), Merkel cell carcinoma (MCC), and sebaceous carcinoma (SC). OBJECTIVE: To analyze survival trends in CAS, DFSP, MCC, and SC among a racially diverse, insured cohort of patients. METHODS: Using data from the Kaiser Permanente Southern California Cancer Registry, we identified adults diagnosed with CAS, DFSP, MCC, or SC between January 1, 1988 and December 31 2018, followed through December 31, 2021. RESULTS: Our cohort consisted of 83 diagnoses of CAS, 490 diagnoses of DFSP, 411 diagnoses of MCC, and 249 diagnoses of SC. Our analysis revealed no significant differences in overall or disease-specific 1000 person-years mortality rates among our populations of non-Hispanic Whites, Hispanics, African American/Blacks, and Asian American/Pacific Islanders diagnosed with CAS, DFSP, MCC, or SC. On multivariate analysis, controlling for patient and tumor characteristics, there was similarly no increased risk of overall mortality for minorities diagnosed with CAS, DFSP, MCC, or SC. LIMITATIONS: Retrospective nature of the analysis and small sample size. CONCLUSION: Contrary to existing literature, our results show a notable lack of racially driven survival disparities among insured individuals with CAS, DFSP, MCC, and SC, emphasizing the importance of health care coverage.


Asunto(s)
Adenocarcinoma Sebáceo , Carcinoma de Células de Merkel , Dermatofibrosarcoma , Neoplasias de las Glándulas Sebáceas , Neoplasias Cutáneas , Adulto , Humanos , Estudios Retrospectivos , Dermatofibrosarcoma/patología , Neoplasias Cutáneas/diagnóstico , Carcinoma de Células de Merkel/terapia
2.
Dermatol Surg ; 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38889101

RESUMEN

BACKGROUND: High-risk cutaneous squamous cell carcinoma (cSCC) is associated with poor clinical outcomes. Traditionally, preoperative clinical tumor size ≥2 cm, based on Brigham and Women's Hospital (BWH) staging criteria, is high risk. OBJECTIVE: To compare outcomes of cSCC treated with Mohs micrographic surgery (MMS) with a preoperative size ≥2 cm (clinically ≥2 cm) versus cSCC with preoperative size <2 cm and postoperative defect size ≥2 cm (histologically ≥2 cm). METHODS: Prospective data were collected from January 1, 2014, to December 31, 2020, on MMS cases for cSCC with a preoperative and/or postoperative size ≥2 cm. Clinical outcomes were followed until March 15, 2023. Data were analyzed using multivariate regression. RESULTS: Three hundred thirty cases of MMS for cSCC were included. Cutaneous squamous cell carcinoma clinically ≥2 cm occurred more frequently in elderly patients; cSCC histologically ≥2 cm were more commonly located in the H region, required wider surgical margins, and more MMS stages to achieve clearance. There were no significant differences in rates of recurrence and metastasis between the groups. CONCLUSION: These data suggest that postoperative (histologic) MMS defect size may allow for better risk stratification of high-risk cSCC and improved staging of cSCC.

3.
Dermatol Surg ; 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38651741

RESUMEN

BACKGROUND: Lasers may present an alternative treatment modality for the management of nonmelanoma skin cancer (NMSC). OBJECTIVE: To investigate lasers as a definitive treatment of NMSC. METHODS: A comprehensive search was performed on MEDLINE, the Cochrane Library, and the National Institutes of Health (www.clinicaltrials.gov). The Preferred Reporting Items for Systematic Reviews and Meta-Analysis was used to finalize a list of relevant literature studies evaluating the role of laser therapy for NMSC. Articles published through May 1, 2023, were included. RESULTS: The authors identified 37 studies investigating nonablative and ablative lasers alone and in combination with other lasers, noninvasive imaging, and additional modalities for the treatment of basal cell carcinomas, 10 focusing on squamous cell carcinoma in situ and 3 focusing on the treatment of both basal and squamous cell carcinomas. CONCLUSION: Although surgical management continues to be superior to laser therapy for the management of high-risk and cosmetically sensitive tumors, laser therapy may be an acceptable alternative for low-risk lesions on the trunk and extremities. However, further studies are needed to optimize parameters, determine maximal efficacy, and provide long-term follow-up before the adoption of laser therapy for NMSC into daily clinical practice.

4.
J Cosmet Laser Ther ; : 1-16, 2024 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-38852607

RESUMEN

We aimed to determine the efficacy of the various available oral, topical, and procedural treatment options for hair loss in individuals with androgenic alopecia. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review of the National Library of Medicine was performed. Overall, 141 unique studies met our inclusion criteria. We demonstrate that many over the counter (e.g. topical minoxidil, supplements, low-level light treatment), prescription (e.g. oral minoxidil, finasteride, dutasteride), and procedural (e.g. platelet-rich plasma, fractionated lasers, hair transplantation) treatments successfully promote hair growth, highlighting the superiority of a multifaceted and individualized approach to management.

5.
J Am Acad Dermatol ; 88(3): 560-567, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36228942

RESUMEN

BACKGROUND: Despite encouraging trends in survival, sociodemographic inequalities persist among patients with melanoma. OBJECTIVE: We sought to quantify the effect of race/ethnicity, socioeconomic status, and health care systems on melanoma-specific mortality within an insured population of patients. METHODS: Using a retrospective cohort study, we identified insured adults diagnosed with Stage I to IV melanoma from January 1, 2009, to December 31, 2014, followed through 2017, from the California Cancer Registry. We compared melanoma-specific mortality between insured patients diagnosed within the largest vertically integrated health care system in California, Kaiser Permanente Southern California, and insured patients with other private insurance (OPI). RESULTS: Our cohort included 14,614 adults diagnosed with melanoma. Multivariable analyses demonstrated that race/ethnicity was not associated with survival disparities, while socioeconomic status was a strong predictor of melanoma-specific mortality, particularly for those with OPI. For example, hazard ratios demonstrate that the poorest patients with OPI have a 70% increased risk of dying from their melanoma compared to their wealthiest counterparts, while the poorest patients in Kaiser Permanente Southern California have no increased risk. LIMITATIONS: Our main limitation includes inadequate data for certain racial/ethnic groups, such as Native Americans. CONCLUSIONS: Our findings underscore the persistence of socioeconomic disparities within an insured population, specifically among those in non-integrated health care systems.


Asunto(s)
Prestación Integrada de Atención de Salud , Melanoma , Adulto , Humanos , Etnicidad , Estudios Retrospectivos , Clase Social , Disparidades en Atención de Salud , Disparidades en el Estado de Salud , Factores Socioeconómicos , California , Melanoma Cutáneo Maligno
6.
Dermatol Surg ; 49(12): 1058-1060, 2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-37656813

RESUMEN

BACKGROUND: With an improved understanding of tumor biology and behavior, the recommended margins for the surgical treatment of melanoma have evolved. OBJECTIVE: We describe the progression of these surgical margins, detailing the historical basis for the 5-cm margin and transitioning to current practice, in which Mohs micrographic surgery (MMS) with immunohistochemistry (IHC) has become increasingly used. METHODS/MATERIALS: We searched PubMed and Google Scholar for articles published between January 2019 and April 2023 describing the use of MMS for melanoma in situ (MIS) and invasive melanomas. RESULTS: We identified 12 articles focusing on the use of MMS for MIS and invasive melanomas: 3 meta-analyses and 9 retrospective studies. Two retrospective analyses documented no differences in overall survival between MMS and wide local excision (WLE) and 2 found improved overall survival for MMS compared with WLE. Three retrospective analyses and 3 meta-analyses demonstrated low recurrence rates after the use of MMS for both MIS and invasive melanomas. Finally, 2 retrospective studies documented the success of MMS with IHC using MART-1. CONCLUSION: Over the past century, the surgical margins for the treatment of melanoma have undergone a marked transformation. MMS with IHC has become increasingly popular given its ability to reliably produce superior clinical outcomes.


Asunto(s)
Melanoma , Neoplasias Cutáneas , Humanos , Márgenes de Escisión , Estudios Retrospectivos , Resultado del Tratamiento , Melanoma/patología , Neoplasias Cutáneas/patología , Cirugía de Mohs , Recurrencia Local de Neoplasia/cirugía , Melanoma Cutáneo Maligno
7.
J Drugs Dermatol ; 22(5): 465-470, 2023 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-37133479

RESUMEN

BACKGROUND: Ultraviolet (UV) radiation leads to deoxyribonucleic acid (DNA) damage and changes in gene expression. Topical DNA repair enzymes in liposomes are capable of undoing this damage. OBJECTIVE: To evaluate gene expression changes induced by ultraviolent B-rays (UVB) light and assess the effect of topical DNA repair enzymes extracted from Micrococcus luteus (M. luteus) and photolyase in modifying these changes. METHODS: Non-invasive, adhesive patch collection kits were used to sample skin on the right and left post-auricular areas before and 24 hours after UVB exposure (n=48). Subjects applied topical DNA repair enzymes to the right post-auricular area daily for 2 weeks. Subjects returned 2 weeks later for repeat non-invasive skin sample collection. RESULTS: Eight of 18 tested genes demonstrated significant changes 24 hours following UVB exposure. DNA repair enzymes from M. luteus or photolyase had no significant effect on genetic expression compared with the control at 2 weeks post UV exposure. CONCLUSION: UVB exposure causes acute changes in gene expression, which may play roles in photo-aging damage and skin cancer growth and regulation. While non-invasive gene expression testing can detect UV damage, additional genomic studies investigating recovery from UV damage at different time periods are needed to establish the potential of DNA repair enzymes to minimize or reverse this damage. J Drugs Dermatol. 2023;22(5): doi:10.36849/JDD.7070.


Asunto(s)
Desoxirribodipirimidina Fotoliasa , Neoplasias Cutáneas , Humanos , Daño del ADN , Desoxirribodipirimidina Fotoliasa/genética , Reparación del ADN , Piel/efectos de la radiación , Rayos Ultravioleta/efectos adversos , Enzimas Reparadoras del ADN/genética
8.
Breast Cancer Res Treat ; 188(1): 21-36, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34115243

RESUMEN

PURPOSE: Despite great success as a targeted breast cancer therapy, trastuzumab use may be complicated by heart failure and loss of left ventricular contractile function. This review summarizes the risk factors, imaging, and prevention of cardiotoxicity associated with trastuzumab and other HER2-targeted therapies. FINDINGS: Cardiovascular disease risk factors, advanced age, and previous anthracycline treatment predispose to trastuzumab-induced cardiotoxicity (TIC), with anthracycline exposure being the most significant risk factor. Cardiac biomarkers such as troponins and pro-BNP and imaging assessments such as echocardiogram before and during trastuzumab therapy may help in early identification of TIC. Initiation of beta-adrenergic antagonists and angiotensin converting enzyme inhibitors may prevent TIC. Cardiotoxicity rates of other HER2-targeted treatments, such as pertuzumab, T-DM1, lapatinib, neratinib, tucatinib, trastuzumab deruxtecan, and margetuximab, appear to be significantly lower as reported in the pivotal trials which led to their approval. CONCLUSIONS: Risk assessment for TIC should include cardiac imaging assessment and should incorporate prior anthracycline use, the strongest risk factor for TIC. Screening and prediction of cardiotoxicity, referral to a cardio-oncology specialist, and initiation of effective prophylactic therapy may all improve prognosis in patients receiving HER2-directed therapy. Beta blockers and ACE inhibitors appear to mitigate risk of TIC. Anthracycline-free regimens have been proven to be efficacious in early HER2-positive breast cancer and should now be considered the standard of care for early HER2-positive breast cancer. Newer HER2-directed therapies appear to have significantly lower cardiotoxicity compared to trastuzumab, but trials are needed in patients who have experienced TIC and patients with pre-existing cardiac dysfunction.


Asunto(s)
Neoplasias de la Mama , Cardiotoxicidad , Femenino , Humanos , Oxazoles , Piridinas , Quinazolinas , Receptor ErbB-2 , Factores de Riesgo , Trastuzumab
9.
J Cosmet Laser Ther ; 22(3): 115-125, 2020 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-32576064

RESUMEN

Despite the increasing knowledge about wound healing mechanisms and the advancements made in laser technology, hypertrophic scars remain difficult to manage. This review intends to discuss the laser devices studied in the prevention and treatment of HS, arising from trauma, surgery, and burns, detail their mechanisms of action, and emphasize those devices with the most promising effects. Most of the suggested mechanisms and explanations for the use of lasers in treating hypertrophic scars are based on selective photothermolysis, in which the light energy emitted from a laser is absorbed by its intended target, thereby disrupting existing collagen and altering the cycle of neocollagenesis. Through our literature review, we have determined that combination therapies, utilizing more than one laser target demonstrate enhanced clinical efficacy. Further, early use of laser devices has been shown to enhance the cosmetic result of sutured wounds and may play a role in preventing the development of hypertrophic scars.


Asunto(s)
Cicatriz Hipertrófica , Terapia por Láser , Quemaduras , Cicatriz Hipertrófica/prevención & control , Cicatriz Hipertrófica/cirugía , Terapia Combinada , Humanos , Rayos Láser , Resultado del Tratamiento , Cicatrización de Heridas
10.
AIDS Behav ; 23(10): 2879-2888, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31468297

RESUMEN

Miami-Dade leads the nation in new HIV infections, and its Black communities experience the greatest disparities in outcomes. Our prior research found that street-based HIV testing facilitated by community health workers improved access to testing and care among Black adults in a controlled trial setting. Herein, we describe our efforts translating this CHW-led intervention into a community service for diverse Blacks in Miami. From December 2016 through August 2017, CHWs educated 1672 individuals about HIV transmission, prevention methods, and risk factor modification; 529 received HIV testing and/or linkage to care services. Approximately 5% of participants (n = 26) had rapid reactive results. This efficacious and culturally-acceptable model represents a powerful change in the delivery of HIV care and demonstrates how public health leaders can foster community engagement in the transition from research to service.


Asunto(s)
Agentes Comunitarios de Salud , Atención a la Salud/métodos , Infecciones por VIH , Accesibilidad a los Servicios de Salud , Adulto , Femenino , Humanos , Masculino , Tamizaje Masivo , Investigación Biomédica Traslacional
11.
J Am Acad Dermatol ; 81(2): 558-567, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30802561

RESUMEN

Radiation dermatitis is a common sequela of radiation therapy; up to 95% of patients will develop moderate-to-severe skin reactions. No criterion standard currently exists for the treatment of acute radiation-induced skin toxicity. It is therefore imperative to develop a greater understanding of management options available to allow clinicians to make informed decisions when managing radiation oncology patients. This literature review discusses the topical agents that have been studied for the treatment of acute radiation dermatitis, reviews their mechanisms of action, and presents a treatment algorithm for clinicians managing patients experiencing radiation dermatitis.


Asunto(s)
Algoritmos , Fármacos Dermatológicos/uso terapéutico , Radiodermatitis/tratamiento farmacológico , Enfermedad Aguda , Corticoesteroides/uso terapéutico , Antiinfecciosos Locales/uso terapéutico , Vendajes , Productos Biológicos/uso terapéutico , Etanolaminas/uso terapéutico , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Preparaciones de Plantas/uso terapéutico , Radiodermatitis/etiología , Radioterapia/efectos adversos , Sulfadiazina de Plata/uso terapéutico , Sucralfato/uso terapéutico , Vitaminas/uso terapéutico
12.
Photodermatol Photoimmunol Photomed ; 35(5): 369-371, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31006143

RESUMEN

Drug-induced photosensitivity develops when the use of oral or topical photosensitizing medications creates a rash after exposure to ultraviolet (UV) radiation. Medications most commonly implicated in photosensitive drug reactions include amiodarone, nonsteroidal anti-inflammatories, thiazides, tetracycline antibiotics, chlorpromazine, and fluoroquinolones. It is generally believed that drug-induced photosensitivity is an UVA phenomenon, caused by UV wavelengths between 315 and 400 nm. Here, we present a case of hydrochlorothiazide (HCTZ)-induced photosensitivity following exposure to 308-nm narrow-band (nb) UVB light emitted from an excimer laser in a patient undergoing treatment for plaque psoriasis. This patient had received biweekly treatments with the excimer laser for years prior without any history of adverse reactions. We believe that our patient suffered an acute photosensitivity to UVB due to new-onset HCTZ. Because nb UVB-emitting lasers are used to treat many dermatologic conditions, physicians should be aware of potential photosensitivity reactions, review medication lists and counsel patients accordingly.


Asunto(s)
Hidroclorotiazida/efectos adversos , Trastornos por Fotosensibilidad/inducido químicamente , Trastornos por Fotosensibilidad/patología , Fármacos Fotosensibilizantes/efectos adversos , Psoriasis/terapia , Terapia Ultravioleta/efectos adversos , Anciano , Femenino , Humanos , Hidroclorotiazida/administración & dosificación , Fármacos Fotosensibilizantes/administración & dosificación , Psoriasis/patología
13.
J Drugs Dermatol ; 18(6): 576, 2019 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-31251551

RESUMEN

Background: DNA repair enzymes have been shown to reduce actinic keratoses and non-melanoma skin cancers, but their use for the treatment of actinic cheilitis has not been studied. Objective: The purpose of this pilot study was to examine the efficacy of a DNA repair enzyme lip balm containing T4 endonuclease in reducing the severity of actinic cheilitis in patients who applied the lip balm twice daily for 3 months. Methods: We performed a prospective study in which 29 patients with a diagnosis of actinic cheilitis underwent a 3-month trial using a topical DNA repair enzyme lip balm containing T4 endonuclease applied to the lips twice daily. The primary, objective outcome was percent of actinic lip involvement, measured using computer software by dividing the calculated affected surface area by the calculated total surface area. Additional outcomes included pre- and post-intervention determination of an actinic cheilitis score on the Actinic Cheilitis Scale, which visually and tactilely quantifies the percentage of lip involvement, amount of roughness, erythema, and tenderness as well as a physician assessment using the Global Aesthetic Improvement Scale. Results: Twenty-five of the 29 enrolled patients completed the trial. The lip balm significantly decreased the percentage of affected lip surface area (P<0.0001). According to the Actinic Cheilitis Scale, data demonstrate that the lip balm significantly decreased the percentage of lip involvement (P=0.002), amount of roughness (P=0.0012)), erythema (P=0.0020), and tenderness (P=0.0175). The total Actinic Cheilitis Scale score also significantly improved after the 3-month treatment period (P<0.0001). According to the Global Aesthetic Improvement Scale, the average score for all 26 patients was 1.04. Conclusion: This study suggests that topical DNA repair enzyme lip balm containing T4 Endonuclease could potentially be a safe and efficacious way to improve and treat actinic cheilitis. J Drugs Dermatol. 2019;18(6):576-579


Asunto(s)
Queilitis/tratamiento farmacológico , Enzimas Reparadoras del ADN/administración & dosificación , Desoxirribonucleasa (Dímero de Pirimidina)/administración & dosificación , Proteínas Virales/administración & dosificación , Administración Tópica , Adulto , Anciano , Anciano de 80 o más Años , Queilitis/diagnóstico , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Adulto Joven
15.
J Racial Ethn Health Disparities ; 9(6): 2404-2411, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-34791613

RESUMEN

Advances in HIV prevention therapies have led to significant reductions in HIV transmission across the USA. However, these resources have not been equally utilized across all populations, with Black communities in the Southeastern USA experiencing among the greatest HIV disparities in the nation. Tailoring HIV programs to align with the cultural norms of minority communities is one approach that can increase uptake of HIV prevention services. However, accomplishing this requires a rich understanding of the unique risk factors and the context of HIV transmission among men and women within culturally distinct communities. To further our understanding, we examined HIV risk behaviors among Black adults living in geographic HIV hotspots of Miami-Dade County. Between December 2016 and April 2019, data on HIV risk behaviors use a standardized HIV assessment developed by the Florida Department of Health. Chi-square and t-test analyses were conducted to examine differences in population demographics and risk factors, and logistic regression was used to test for predictors of HIV status. Results indicate that a significant portion of participants had prior experience with HIV testing, a known protective factor against HIV transmission. Despite this, much of the sample also reported recent engagement in high-risk sexual behaviors. These findings emphasize the need for intervention development within the context of population-specific behaviors. Future research should further consider the importance of transmission behaviors among clusters of demographically similar populations at high risk for or living with HIV.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Infecciones por VIH , Adulto , Masculino , Femenino , Humanos , Población Negra , Conducta Sexual , Infecciones por VIH/epidemiología , Factores de Riesgo
16.
Int J Dermatol ; 59(1): 23-29, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31605389

RESUMEN

The changes in skin and overall appearance that occur with increasing age can be partly attributed to declining hormone levels. While hormonal deficiencies are most commonly associated with postmenopausal females, males are also subject to age-related testosterone decline and may benefit from replacement of deficient hormones. However, great disparities exist between the recommendations of scientific societies and actual use of hormone supplements in aging patients. The purpose of this literature review is to discuss the role of hormones in the aging process of the skin, explain the safety profile of hormone replacement therapy, specifically discussing the superiority of bioidentical hormones, and highlight the benefits of hormone replacement in anti-aging of the skin. In summary, this literature review suggests that hormone replacement with bioidentical hormones is a safe and effective way to prevent skin aging.

17.
Clin Cosmet Investig Dermatol ; 12: 617-624, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31695467

RESUMEN

Concerns over existing sunscreen filters have reinforced the need to examine supplemental sun protection or repair of sun damage. Technology to enhance DNA repair has been available in skincare and sunscreen products for several decades, but skepticism and lack of familiarity with the supporting data remain prevalent. Here, we address six of the main questions raised by medical professionals regarding the efficacy of DNA repair enzymes in sun protection. These include the mode of delivery and mechanism of action, the effect on cellular responses and the amelioration of pre-cancers, cancers and photoaging. The conclusions are that topical DNA repair enzymes do enhance removal of DNA damage and reduce the appearance of new actinic keratoses as well as increase regression of existing lesions. Support for prevention of photoaging and skin cancer is significant but could be strengthened or disproven with additional research.

18.
Cureus ; 11(6): e4967, 2019 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-31453039

RESUMEN

Disseminated tuberculosis (TB) is an uncommon sequela of Mycobacterium TB infection in which bacteria disseminate and form colonies outside of the lungs. Most reports of disseminated TB are found in immunocompromised patients, particularly in patients with human immunodeficiency virus (HIV) infection, malnutrition, genetic susceptibility, diabetes mellitus, smoking, and alcohol abuse. Few case reports describe the finding of disseminated TB in immunocompetent patients, especially in healthy adolescents. The purpose of this report is to present a case in which disseminated TB was found in an otherwise healthy adolescent, female patient, and to explore the effects of pubertal hormonal changes on the immune system. Several studies in the pediatric population have suggested that hormonal changes of estrogen and testosterone associated with puberty may influence the pathogenesis of active TB. While the exact pathogenesis of disseminated TB remains unknown, this case highlights the need for heightened awareness of TB among otherwise healthy adolescents, and specifically, the effect puberty has on disease progression.

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