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BACKGROUND: While the incidence of pregnancy has increased among individuals with adult CHD, little has been described about considerations and experiences of patients with adult CHD regarding pregnancy. OBJECTIVE: We aimed to explore patients' motivations, concerns, and decision-making processes regarding pregnancy. METHODS: In April 2019-January 2020, we conducted in-depth telephone interviews with patients (n = 25) with simple, moderate, or complex adult CHD, who received prenatal care at the University of Washington during 2010-2019 and experienced a live birth. Transcripts were analysed using thematic analysis. RESULTS: Participants described motivations for pregnancy as both internal desires (motherhood, marriage fulfillment, biological connection, fetal personhood, self-efficacy) and external drivers (family or community), as well as concerns for the health and survival of themselves and the fetus. Factors that enabled their decision to maintain a pregnancy included having a desire that outweighed their perceived risk, using available data to guide their decision, planning for contingencies and knowing their beliefs about termination, plus having a trusted healthcare team, social support, and resources. Factors that led to insurmountable risk in subsequent pregnancies included desire having been fulfilled by the first pregnancy, compounding risk with age and additional pregnancies, new responsibility to an existing child, and reduced healthcare team and social support. CONCLUSIONS: Understanding individuals' motivations and concerns, and how they weigh their decisions to become or remain pregnant, can help clinicians better support patients with adult CHD considering pregnancy. Clinician education on patient experiences is warranted.
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Tomada de Decisões , Motivação , Gravidez , Feminino , Criança , Adulto , Humanos , Cuidado Pré-Natal , Apoio Social , FetoRESUMO
Despite clinical guidelines, programs conducting population-based screening and genetic service delivery for hereditary cancer prevention and control are rare in practice. We interviewed individuals (n = 13) instrumental in implementing seven unique clinical programs conducting either universal tumor screening for Lynch Syndrome or routine family history screening and provision of genetic services for hereditary breast and ovarian cancer in the United States. To characterize determinants of readiness to implement population-based cancer genetic service delivery models, interviews and deductive codes drew on Weiner's theory of organizational readiness for change. Qualitative analysis identified themes across programs. The degree to which organizational stakeholders valued moving to a population-based genetic service delivery model depended on the existence of aligned clinical guidelines at the time of program implementation. However, judgments of implementation capacity within the organization, particularly with respect to task demands and resource concerns, were more often barriers to readiness. Program champions were essential to facilitating readiness, frequently taking on substantial uncompensated work. These data suggest that developing interventions targeting change efficacy and cultivating practice change champions may be two promising ways to increase uptake of population-based hereditary cancer screening and genetic service delivery in clinical practice.
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Neoplasias da Mama/genética , Neoplasias Colorretais Hereditárias sem Polipose/genética , Detecção Precoce de Câncer/métodos , Predisposição Genética para Doença , Serviços em Genética/organização & administração , Neoplasias Ovarianas/genética , Neoplasias da Mama/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Atenção à Saúde/organização & administração , Feminino , Humanos , Masculino , Neoplasias Ovarianas/diagnóstico , Estados UnidosRESUMO
BACKGROUND: Apolipoprotein A1 (APOL1) gene variants occurring in people of West African descent contribute to the greater burden of kidney disease among African Americans. These variants are associated with increased risk of nondiabetic nephropathy, more rapid progression of chronic kidney disease, and shorter survival of donor kidneys after transplantation. However, only a minority of people with APOL1-associated risk develops kidney disease and specific clinical measures to address APOL1-associated risk are lacking. Given these uncertainties, we sought to engage members of the African American public in discussions with other stakeholders about the appropriate use of APOL1 testing. METHODS: Formative interviews with community members, researchers, and clinicians in Seattle WA, Nashville TN, and Jackson MS, provided baseline information about views toward APOL1 testing and informed the design of 3 community-based deliberations among African Americans. A national meeting held in March 2018 included 13 community members, 7 scientific advisors and 26 additional researchers, clinicians, bioethicists, patient advocates, and representatives from professional organizations and federal funding agencies. Using small break-out and plenary discussion, the group agreed on recommendations based on current knowledge about APOL1-associated risk. RESULTS: Meeting outcomes included recommendations to develop educational materials about APOL1 for community members and clinicians; to offer APOL1 research results to participants; and on the use of APOL1testing in kidney transplant programs. The group recommended against the routine offer of APOL1 testing in clinical care. Areas of disagreement included whether kidney transplant programs should require APOL1 testing of prospective living donors or bar individuals with APOL1 risk from donating kidneys and whether testing should be available on request in routine clinical care. CONCLUSION: We recommend continued discussion among stakeholders and concerted efforts to ensure active and informed participation of members of the affected community to guide research on APOL1 and kidney disease.
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Apolipoproteína L1/genética , Negro ou Afro-Americano/genética , Participação da Comunidade , Testes Genéticos/métodos , Política de Saúde , Falência Renal Crônica/etnologia , Falência Renal Crônica/genética , Pesquisa Participativa Baseada na Comunidade , Congressos como Assunto , Progressão da Doença , Disparidades nos Níveis de Saúde , Disparidades em Assistência à Saúde , Humanos , Comunicação Interdisciplinar , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/cirurgia , Transplante de Rim/mortalidade , Mississippi , Estudos Prospectivos , Tennessee , Obtenção de Tecidos e Órgãos/legislação & jurisprudência , Obtenção de Tecidos e Órgãos/métodos , Resultado do Tratamento , WashingtonRESUMO
American Indian and Alaska Native (AI/AN) communities harbor understandable mistrust of research. Outside researchers have historically controlled processes, promulgating conclusions and recommended policies with virtually no input from the communities studied. Reservation-based communities can apply sovereignty rights conferred by the federal government to change this research trajectory. Many tribes now require review and approval before allowing research activities to occur, in part through the development of regulatory codes and oversight measures. Tribal oversight ensures that research is directed toward questions of importance to the community and that results are returned in ways that optimize problem solving. Unfortunately, tribal governance protections do not always extend to AI/ANs residing in urban environments. Although they represent the majority of AI/ANs, urban Indians face an ongoing struggle for visibility and access to health care. It is against this backdrop that urban Indians suffer disproportionate health problems. Improved efforts to ensure responsible research with urban Indian populations requires attention to community engagement, research oversight, and capacity building. We consider strategies to offset these limitations and develop a foundation for responsible research with urban Indians.
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Indígena Americano ou Nativo do Alasca , Saúde Pública , Pesquisa/organização & administração , População Urbana , Fortalecimento Institucional/organização & administração , Participação da Comunidade , Pesquisa Participativa Baseada na Comunidade/organização & administração , Competência Cultural , Comitês de Ética em Pesquisa/organização & administração , Disparidades nos Níveis de Saúde , Humanos , Indígenas Norte-Americanos , Inuíte , Poder Psicológico , Pesquisa/economia , Pesquisa/normas , Apoio à Pesquisa como Assunto/organização & administração , Estados Unidos , United States Indian Health ServiceRESUMO
Test results for genetic conditions, such as Lynch Syndrome (LS), have traditionally been returned by genetic counselors or other providers who can explain results implications and provide psychosocial support. Returning genetic results through an Electronic Health Record's patient portal may increase the efficiency of returning results and could activate patient follow-up; however, stakeholder input is necessary to determine acceptability and appropriate implementation for LS. Twenty interviews were conducted with clinicians from six specialties involved in LS screening that represent a range of settings. Data were analyzed using directed content analysis and thematic analysis across content categories. Participants felt that patient portals could supplement personal calls, but the potential sensitive nature of LS screening results indicated the need for caution. Others felt that LS results could be returned through portals if there were clear explanations of the result, reputable additional information available within the portal, urging follow up confirmatory testing, and a referral to a genetics specialist. Patient portals were seen as helpful for prompting patient follow-up and providing resources to notify at-risk family members. There is potential for patient portals to return LS screening and other genetic results, however we raise several issues to resolve before implementation is warranted.
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Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Testes Genéticos , Programas de Rastreamento , Portais do Paciente , Neoplasias Colorretais Hereditárias sem Polipose/genética , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
PurposeLynch syndrome cases are underidentified, and universal colorectal cancer tumor screening for Lynch syndrome (UTS) has been recommended. UTS implementation is challenging and few successful examples exist to date, and colorectal cancer patients and at-risk family members exhibit low uptake of genetic services. This study sought to identify the elements that could guide the choice of specialties to implement UTS through three main stages: initiating the screen, returning positive screen results, and providing follow-up.MethodsTo understand stakeholder views on the UTS process, 20 semistructured interviews were conducted with clinicians from six medical specialties crucial for implementing UTS. Data were analyzed using directed content analysis and additional thematic analysis across content categories.ResultsSeveral clinical specialties could fill necessary roles at each of the main stages of UTS implementation. Participants suggested owners based on attributes of specialty roles, clinical settings, and the routes patients take through the system.ConclusionUTS is considered possible in a range of health-care settings, with tailoring. Health systems need to choose who best fills the role's needs based on local resources and processes. These results offer implementation guidance based on role needs, not clinical specialty, in resolving the issue of UTS "ownership."
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Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Medicina , Papel do Médico , Feminino , Seguimentos , Humanos , Masculino , Programas de Rastreamento , Participação dos InteressadosRESUMO
In Zimbabwe, the ZAZIC consortium employs two-way, text-based (2wT) follow-up to strengthen post-operative care for voluntary medical male circumcision (VMMC). 2wT scaled nationally with evidence of client support and strengthened follow-up. However, 2wT uptake among healthcare providers remains suboptimal. Understanding the gap between mobile health (mHealth) potential for innovation expansion and scale-up realization is critical for 2wT and other mHealth innovations. Therefore, we conducted an exploratory qualitative study with the objective of identifying 2wT program strengths, challenges, and suggestions for scale up as part of routine VMMC services. A total of 16 in-depth interviews (IDIs) with diverse 2wT stakeholders were conducted, including nurses, monitoring & evaluation teams, and technology partners-a combination of perspectives that provide new insights. We used both inductive and deductive coding for thematic analysis. Among 2wT drivers of expansion success, interviewees noted: 2wT care benefits for clients; effective hands-on 2wT training; ease of app use for providers; 2wT saved time and money; and 2wT strengthened client/provider interaction. For 2wT scale-up challenges, staff shortages; network infrastructure constraints; client costs; duplication of paper and electronic reporting; and complexity of digital tools integration. To improve 2wT robustness, respondents suggested: more staff training to offset turnover; making 2wT free for clients; using 2wT to replace paper VMMC reporting; integrating with routine VMMC reporting systems; and expanding 2wT to other health areas. High stakeholder participation in app design, implementation strengthening, and evaluation were appreciated. Several 2wT improvements stemmed from this study, including enrollment of multiple people on one number to account for phone sharing; 2wT inclusion of minors ages 15+; clients provided with $1 to offset SMS costs; and reduced SMS messages to clients. Continued 2wT mentoring for staff, harmonization of 2wT with Ministry e-health data systems, and increased awareness of 2wT's client and provider benefits will help ensure successful 2wT scale-up.
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Circuncisão Masculina , Pesquisa Qualitativa , Envio de Mensagens de Texto , Humanos , Zimbábue , Masculino , Telemedicina/métodos , Pessoal de Saúde , Seguimentos , AdultoRESUMO
OBJECTIVES: We assessed the impact of Launching Native Health Leaders (LNHL), a peer-mentoring and networking program that introduced American Indian/Alaska Native (AI/AN) undergraduates to health and research careers and concepts of community-based participatory research (CBPR). METHODS: We conducted 15 interviews and 1 focus group with students who had attended 1 or more LNHL meetings, which took place during 9 professional health research conferences in 2006 to 2009. We completed data collection in 2010, within 1 to 4 years of LNHL participant engagement in program activities. RESULTS: Participants described identity and cultural challenges they encountered in academic institutions and how their views shifted from perceiving research as an enterprise conducted by community outsiders who were not to be trusted toward an understanding of CBPR as contributing to AI/AN health. CONCLUSIONS: LNHL provided a safe environment for AI/AN students to openly explore their place in the health and research arenas. Programs such as LNHL support AI/AN student development as leaders in building trust for academic-tribal partnerships.
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Conhecimentos, Atitudes e Prática em Saúde , Indígenas Norte-Americanos , Liderança , Mentores , Grupo Associado , Estudantes , Confiança , Pesquisa Participativa Baseada na Comunidade , Grupos Focais , Promoção da Saúde , Humanos , Desenvolvimento de Programas , Pesquisa Qualitativa , UniversidadesRESUMO
The Center for Alaska Native Health Research is a community-based participatory research center that conducts studies involving genetic research with Yup'ik Eskimo community members in Southwest Alaska, where Yup'ik remains the first language for most residents. Cultural equivalents are needed to communicate results of these studies among all partners and members of the participating communities, since many scientific terms have no direct translation in Yup'ik. To inform that effort, we examined local understandings of genetics and heredity in one community. Here, we report results from back-translated Yup'ik interviews, and identify working genetic concepts shared by participants from interviews and focus groups. We suggest issues involved in, and some potential steps toward, developing a concise, scientifically accurate and culturally relevant term for "genetics" and other health concepts.
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BACKGROUND: Racial and ethnic disparities in COVID-19 infection and outcomes have been documented, but few studies have examined disparities in access to testing. METHODS: We conducted a mixed methods study of access to COVID-19 testing in the Somali immigrant community in King County, Washington, USA, early during the COVID-19 pandemic. In September 2020-February 2021, we conducted quantitative surveys in a convenience sample (n = 528) of individuals who had accessed PCR testing, recruited at King County testing sites near Somali population centers and through social media outreach in the Somali community. We compared self-identified Somali and non-Somali responses using Chi-square and Wilcoxon rank sum tests. We also conducted three Somali-language focus groups (n = 26) by video conference to explore Somali experiences with COVID-19 testing, and in-depth interviews with King County-based policymakers and healthcare workers (n = 13) recruited through the research team's professional network to represent key demographics and roles. Data were analyzed using qualitative rapid analysis to explore the county's COVID-19 testing landscape. RESULTS: Among 420 survey respondents who had received COVID-19 testing in the prior 90 days, 29% of 140 Somali vs. 11% of 280 non-Somali respondents tested because of symptoms (p = 0.001), with a trend for longer time from symptom onset to testing (a measure of testing access) among Somali respondents (median 3.0 vs. 2.0 days, p = 0.06). Focus groups revealed barriers to testing, including distrust, misinformation, stigma, language, lack of awareness, and transportation. Stakeholders responding from all sectors highlighted the importance of community partnership to improve access. CONCLUSION: Somali communities experience barriers to COVID-19 testing, as evidenced by the longer time from symptom onset to testing and corroborated by our qualitative findings. These barriers, both structural and community-derived, may be overcome through partnerships between government and community to support community-led, multilingual service delivery and racial representation among medical staff.
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COVID-19 , Pandemias , Humanos , Somália , Teste para COVID-19 , Washington/epidemiologia , COVID-19/diagnóstico , COVID-19/epidemiologia , IdiomaRESUMO
BACKGROUND: Genetic test results will be increasingly made available electronically as more patient-facing tools are developed; however, little research has been done that collects data on patient preferences for content and design before creating results templates. OBJECTIVE: This study identifies patient preferences for the electronic return of genetic test results, including what considerations should be prioritized for content and design. METHODS: Following user-centered design methods, 59 interviews were conducted by using semistructured protocols. The interviews explored the content and design issues of patient portals that facilitated the return of test results to patients. We interviewed patients who received electronic results for specific types of genetics tests (pharmacogenetic tests, hereditary blood disorder tests, and tests for the risk of heritable cancers) or electronically received any type of genetic or nongenetic test results. RESULTS: In general, many of participants felt that there always needed to be some clinician involvement in electronic result returns and that electronic coversheets with simple summaries would be helpful for facilitating this. Coversheet summaries could accompany, but not replace, the more detailed report. Participants had specific suggestions for such results summaries, such as only reporting the information that was the most important for patients to understand, including next steps, and doing so by using clear language that is free of medical jargon. Electronic result returns should also include explicit encouragement for patients to contact health care providers about questions. Finally, many participants preferred to manage their care by using their smartphones, particularly in instances when they needed to access health information on the go. CONCLUSIONS: Participants recommended that a patient-friendly front section should accompany the more detailed report and made suggestions for organization, content, and wording. Many used their smartphones regularly to access test results; therefore, health systems and patient portal software vendors should accommodate smartphone app design and web portal design concomitantly when developing platforms for returning results.
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The ethics of returning nonactionable genetic research results to individuals are unclear. Apolipoprotein L1 (APOL1) genetic variants are nonactionable, predominantly found in people of West African ancestry, and contribute to kidney disease disparities. To inform ethical research practice, we interviewed researchers, clinicians, and African American community members (n = 76) about the potential risks and benefits of returning APOL1 research results. Stakeholders strongly supported returning APOL1 results. Benefits include reciprocity for participants, community education and rebuilding trust in research, and expectation of future actionability. Risks include analytic validity, misunderstanding, psychological burdens, stigma and discrimination, and questionable resource tradeoffs.Conclusions:APOL1 results should be offered to participants. Responsibly fulfilling this offer requires careful identification of best communication practices, broader education about the topic, and ongoing community engagement.
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Apolipoproteína L1 , Transplante de Rim , Negro ou Afro-Americano/psicologia , Apolipoproteína L1/genética , Predisposição Genética para Doença , Testes Genéticos/métodos , HumanosRESUMO
Pulmonary complications post-hematopoietic stem cell transplantation (HSCT) such as diffuse alveolar hemorrhage (DAH) can occur in 2% to 14% of HSCT patients and have a mortality greater than 80%. Diffuse alveolar hemorrhage is considered to be an inflammatory response; therefore, HSCT patients are primarily treated with different types of systemic corticosteroids with varying dosages. Other treatments currently reported in the literature in conjunction with corticosteroids include aminocaproic acid, recombinant factor VIIa (rFVIIa), and etanercept. This review highlights appropriate frontline and adjunctive treatment options for HSCT patients with DAH and outcomes for each intervention. To perform the review, the PubMed database was searched from inception through March 19, 2021, to identify potential studies using the search terms DAH and HSCT, DAH and hematopoietic cell transplant (HCT), DAH and stem cell, lung injury and HSCT, and lung injury and HCT. When applicable, references from articles identified in the search were also reviewed for inclusion. Much of the data identified were limited to retrospective cohort studies and case series. Based on the data available, the treatment approach should consist of corticosteroid therapy with a suggested methylprednisolone dose of 250 mg daily followed by a 50% taper every 3 days. Intrapulmonary administration of rFVIIa and intravenous administration of aminocaproic acid could be considered as adjunctive agents in those patients who do not promptly respond to corticosteroid therapy. Due to a lack of data specific to HSCT patients who develop DAH and the risk of infectious complications, etanercept should be avoided. Future studies should be designed as randomized controlled trials and examine the use of adjunctive therapies in the upfront setting for HSCT patients with DAH.
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Transplante de Células-Tronco Hematopoéticas , Hemorragia , Pneumopatias , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hemorragia/tratamento farmacológico , Hemorragia/etiologia , Humanos , Pneumopatias/tratamento farmacológico , Pneumopatias/etiologiaRESUMO
CONTEXT: Women with adult congenital heart disease (ACHD) have an increased risk of adverse events during pregnancy. Advance care planning may therefore be an appropriate component of prenatal care. OBJECTIVE: The aim of this study was to describe the perspectives of women with ACHD surrounding advance care planning during pregnancy. METHODS: We conducted a thematic analysis of 25 semi-structured interviews with women with ACHD who had been pregnant. Purposive sampling was used to gain diversity in ACHD lesion complexity, race, age at pregnancy, and marital status. RESULTS: Mean age at pregnancy was 29 years (range 15-41 years), and ACHD was classified as simple (24%), moderate (44%), or complex (32%). We identified three primary themes: 1) the role of advance care planning in being prepared and providing security for family; 2) reasons for avoiding advance care planning, including its lower priority among more pressing concerns and the impact it might have on their current psychological state; and 3) varied openness to advance care planning discussions during pregnancy. CONCLUSION: Advance care planning is not a routine part of prenatal care in ACHD, and its role in this population requires further assessment.
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Planejamento Antecipado de Cuidados , Cardiopatias Congênitas , Adolescente , Adulto , Feminino , Cardiopatias Congênitas/terapia , Humanos , Gravidez , Gestantes , Adulto JovemRESUMO
Bone mineral density (BMD) loss occurs commonly in patients after allogeneic hematopoietic cell transplantation (HCT), primarily because of steroid use, but little is known about BMD change post-autologous HCT. In a prospective study of 206 consecutive first HCT patients, we measured acute BMD change at the lumbar spine and dual femur between baseline and day +100, and evaluated risk factors for bone loss. Accelerated BMD loss in this 4-month period occurred after both autologous and allogeneic HCT with similar severity (median, 0.03 g/cm(2) versus 0.03 g/cm(2) at the spine; 0.03 g/cm(2) versus 0.05 g/cm(2) at the femur, respectively). This is equivalent to 7 to 17 years' worth of bone loss by aging. Risk factors for BMD loss were different between autologous and allogeneic HCT patients: lymphoma was associated with greater bone loss after autologous HCT than myeloma, whereas higher steroid dose was the most significant risk factor after allogeneic HCT. Multivariable risk models explained 11% to 30% of the variation in HCT-related BMD change. Surprisingly, BMD loss post-autologous HCT occurred with similar incidence and severity to allogeneic HCT, even in the absence of steroid use. Evaluation of clinical strategies to prevent and reverse HCT-related BMD loss is necessary in both autologous and allogeneic HCT patients.
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Densidade Óssea , Doenças Ósseas Metabólicas/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Adolescente , Adulto , Idoso , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Transplante Autólogo/efeitos adversos , Transplante Homólogo/efeitos adversos , Adulto JovemRESUMO
Whether individual results of genetic research studies ought to be disclosed to study participants has been debated in recent decades. Previously, the prevailing expert view discouraged the return of individual research results to participants because of the potential lack of analytic validity, questionable clinical validity and medical actionability, and questions about whether it is the role of research to provide participants with their data. With additional knowledge of participant perspectives and shifting views about the benefits of research and respect for participants, current expert consensus is moving toward support of returning such results. Significant ethical controversies remain, and there are many practical questions left to address, including appropriate procedures for returning results and the potential burden to clinicians when patients seek guidance about the clinical implications of research results. In this review, we describe current views regarding the return of genetic research results, including controversies and practical challenges, and consider the application of these issues to research on apolipoprotein L1 (APOL1), a gene recently associated with health disparities in kidney disease. Although this case is unique, it illustrates the complexities involved in returning results and highlights remaining questions.
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Apolipoproteína L1/genética , Aconselhamento Genético , Testes Genéticos , Variação Genética , Falência Renal Crônica/genética , Projetos de Pesquisa , Sujeitos da Pesquisa , Aconselhamento Genético/ética , Predisposição Genética para Doença , Testes Genéticos/ética , Humanos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/terapia , Fenótipo , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Fatores de RiscoRESUMO
Enoxaparin is a low molecular weight heparin (LMWH) that has been shown to be effective in deep vein thrombosis, pulmonary embolism, and unstable angina. Because renal function plays an important role in the clearance of LMWH, the authors sought to investigate the effect of renal function on enoxaparin. This prospective multiple-dose study evaluated 18 patients with varying degrees of renal function initiated on enoxaparin 1 mg/kg subcutaneously every 12 hours. Peak blood levels of anti-Xa concentrations were obtained 4 +/- 0.5 hours postdose after receiving at least three doses of enoxaparin. The median antifactor Xa levels were higher in patients with creatinine clearance (CLCr) < or = 30 mL/min compared to CLCr > or = 31 mL/min (1.34 IU/mL vs. 0.91 IU/mL, respectively, p < 0.05). A linear correlation was established between creatinine clearance and anti-Xa concentrations (p < 0.0005). On the basis of the data, the authors believe that a dose adjustment is necessary in patients receiving repeated doses of enoxaparin with CLCr < or = 30 mL/min.
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Anticoagulantes , Doenças Cardiovasculares/tratamento farmacológico , Enoxaparina , Rim/efeitos dos fármacos , Insuficiência Renal/metabolismo , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Anticoagulantes/farmacologia , Anticoagulantes/uso terapêutico , Doenças Cardiovasculares/complicações , Enoxaparina/efeitos adversos , Enoxaparina/farmacologia , Enoxaparina/uso terapêutico , Fator Xa/metabolismo , Feminino , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Insuficiência Renal/classificação , Insuficiência Renal/complicações , Índice de Gravidade de DoençaRESUMO
Tacrolimus, a macrolide immunosuppressant, is used topically for the treatment of cutaneous manifestations of graft-versus-host disease (GVHD) for rapid, symptomatic relief of pruritus and erythema. Despite the manufacturer's product information reporting minimal systemic effects of topical tacrolimus, this has not been evaluated in patients with cutaneous GVHD and with occlusive dressings. We describe two patients with cutaneous GVHD who developed toxic tacrolimus levels after receiving several applications of tacrolimus ointment along with occlusive dressings to enhance skin effectiveness. The first patient was a 62-year-old woman with a history of acute myelogenous leukemia (AML) who underwent allogeneic bone marrow transplantation and developed chronic GVHD involving 70% of her body surface area. Her GVHD treatment plan consisted of oral corticosteroids, oral tacrolimus, topical corticosteroids, topical tacrolimus 0.1% ointment twice/day, emollient creams, intravenous rituximab, and photopheresis. The patient's tacrolimus trough levels rose rapidly over the course of 6 days from less than 2 ng/ml to 23 ng/ml, despite oral tacrolimus dosage adjustments. The second patient was a 25-year-old man who developed severe, chronic skin GVHD after undergoing allogeneic sibling bone marrow transplantation for AML. In addition to intravenous corticosteroids, corticosteroid creams, and oral tacrolimus, the patient also received topical tacrolimus twice/day with occlusive dressings. Over the course of 2 days, his tacrolimus trough levels increased from 7.10 ng/ml to 22.10 ng/ml. Although improvement was noted in both patients' skin GVHD with application of the occlusive dressings, the practice was discontinued due to increased and erratic systemic tacrolimus absorption. These case reports suggest that substantial use of topical tacrolimus with occlusive dressings in patients with cutaneous GVHD may contribute to increased systemic absorption resulting in toxic tacrolimus levels. Based on the findings from our two patients as well as published case reports, systemic absorption appears to increase with greater skin permeability, skin barrier dysfunction, amount of body surface area applied, and use of occlusive dressings. When one or more of these factors are present, it may be prudent to monitor tacrolimus levels.