RESUMO
BACKGROUND: Suboptimal medication adherence is common across youth with chronic health conditions and may contribute to health disparities and adverse health outcomes, especially in underserved communities. METHODS: Using pharmacy prescription records and guided by the World Health Organization Multidimensional Adherence Model, we examined patient-, treatment-, and health system-related factors that may affect hydroxyurea adherence in 72 youth with sickle cell disease (SCD), 10-18 years who had participated in the multisite "Hydroxyurea Adherence for Personal Best in SCD" (HABIT) feasibility (6 months) and efficacy (12 months) trials. Pharmacy data were collected from the year prior to study entry through the duration of each trial. We also examined hydroxyurea dose at baseline, prescribing patterns (hydroxyurea formulation and dose prescribed), quantity of hydroxyurea dispensed, and number of daily capsules/tablets prescribed. Data were analyzed using descriptive statistics. RESULTS: On average, youth were prescribed 1095 ± 402 mg hydroxyurea per day, requiring ingestion of 3 or more capsules for 39.4% of youth. Frequently identified potential barriers were complex medication regimens in which dose of hydroxyurea differed by day of week (47.2%); receipt of an inadequate (< 30 days) supply of hydroxyurea from the pharmacy ≥ 3 times during record collection period (29.2%); and prescription of hydroxyurea suspension suggesting problems swallowing capsules (22.2%). In this sample, most youth were exclusively prescribed 500 mg capsules (62.5%), which was associated with complex medication regimens (RR 3.0, 95% CI 1.4-6.7). Potential barriers were common, occurred at all levels and are potentially modifiable with targeted interventions at the treatment- and health system-related levels.
Assuntos
Anemia Falciforme , Antidrepanocíticos , Hidroxiureia , Adesão à Medicação , Humanos , Hidroxiureia/uso terapêutico , Hidroxiureia/administração & dosagem , Anemia Falciforme/tratamento farmacológico , Adolescente , Masculino , Criança , Feminino , Adesão à Medicação/estatística & dados numéricos , Antidrepanocíticos/uso terapêutico , Prescrições de Medicamentos/estatística & dados numéricosRESUMO
BACKGROUND: Adolescence and young adulthood are vulnerable developmental periods for individuals with sickle cell disease (SCD), particularly given the impact of social inequities, challenges with transitioning to adult healthcare services, and increased risk for morbidity and mortality. Systems of power, such as institutionalized and interpersonal manifestations of bias, could impact SCD transfer and engagement in adult care through their influence on healthcare transition readiness; yet research in this area is limited. OBJECTIVE: To characterize how systems of power impact transition readiness factors described in the Social-ecological Model of AYA Readiness for Transition to Promote Health Equity (SMART-E) framework at the patient, caregiver, and practitioner levels. METHODS: Pediatric adolescents and young adults (AYA), transferred AYA, caregivers, and practitioners participated in semi-structured focus groups and individual interviews examining health equity and systems of power during healthcare transition. Focus groups/interviews were transcribed and coded using a deductive approach via the updated SMART-E framework. RESULTS: Ten pediatric AYA with SCD, nine transferred AYA with SCD, eight caregivers, and nine practitioners participated in a focus group or interview. Qualitative findings across reporters emphasize the impact of systems of power (e.g., racial bias and disease stigma) on knowledge, skills and self-efficacy, beliefs and expectations, goals and motivation, and emotions and psychosocial functioning at the patient, caregiver, and practitioner levels. CONCLUSION: Systems of power are prevalent with respect to transition barriers for AYA with SCD and their supports. Structural, institutional, and individual factors with potential to reduce the influence of systems of power should be further identified and targeted for intervention.
Assuntos
Anemia Falciforme , Pesquisa Qualitativa , Transição para Assistência do Adulto , Humanos , Anemia Falciforme/terapia , Anemia Falciforme/psicologia , Masculino , Feminino , Adolescente , Adulto , Adulto Jovem , Grupos Focais , Cuidadores/psicologia , SeguimentosRESUMO
Despite disease-modifying effects of hydroxyurea on sickle cell disease (SCD), poor adherence among affected youth commonly impedes treatment impact. Following our prior feasibility trial, the "Hydroxyurea Adherence for Personal Best in Sickle Cell Treatment (HABIT)" multi-site randomized controlled efficacy trial aimed to increase hydroxyurea adherence for youth with SCD ages 10-18 years. Impaired adherence was identified primarily through flagging hydroxyurea-induced fetal hemoglobin (HbF) levels compared to prior highest treatment-related HbF. Eligible youth were enrolled as dyads with their primary caregivers for the 1-year trial. This novel semi-structured supportive, multidimensional dyad intervention led by community health workers (CHW), was augmented by daily tailored text message reminders, compared to standard care during a 6-month intervention phase, followed by a 6-month sustainability phase. Primary outcomes from the intervention phase were improved Month 6 HbF levels compared to enrollment and proportion of days covered (PDC) for hydroxyurea versus pre-trial year. The secondary outcome was sustainability of changes up to Month 12. The 2020-2021 peak coronavirus disease 2019 (COVID-19) pandemic disrupted enrollment and clinic-based procedures; CHW in-person visits shifted to virtual scheduled interactions. We enrolled 50 dyads, missing target enrollment. Compared to enrollment levels, both HbF level and PDC significantly - but not sustainably - improved within the intervention group (p = .03 and .01, respectively) with parallel increased mean corpuscular volume (MCV) (p = .05), but not within controls. No significant between-group differences were found at Months 6 or 12. These findings suggest that our community-based, multimodal support for youth-caregiver dyads had temporarily improved hydroxyurea usage. Durability of impact should be tested in a trial with longer duration of CHW-led and mobile health support.
Assuntos
Anemia Falciforme , Hidroxiureia , Adolescente , Humanos , Anemia Falciforme/tratamento farmacológico , Antidrepanocíticos/uso terapêutico , Agentes Comunitários de Saúde , Hemoglobina Fetal/análise , Hábitos , Hidroxiureia/uso terapêutico , Adesão à Medicação , Criança , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Sickle cell disease (SCD), which occurs primarily in individuals of African descent, has been identified as a preexisting health condition for COVID-19 with higher rates of hospitalization, intensive care unit admissions, and death. National data indicate Black individuals have higher rates of vaccine hesitancy and lower COVID-19 vaccination rates. Understanding the key predictors of intention to receive a COVID-19 vaccine is essential as intention is strongly associated with vaccination behavior. This multisite study examined attitudes, beliefs, intentions to receive COVID-19 vaccines, and educational preferences among adolescents, young adults, and caregivers of children living with SCD. Participants completed an online survey between July 2021 and March 2022. Multivariate logistic regression was used to examine the association between participant age and COVID-19 vaccine attitudes, beliefs, and vaccine intentions. Of the 200 participants, 65.1% of adolescents, 62.5% of young adults, and 48.4% of caregivers intended to receive a COVID-19 vaccine for themselves or their child. Perception that the vaccine was safe was statistically significant and associated with patient and caregiver intention to receive the COVID-19 vaccine for themselves or their child. Participant age was also statistically significant and associated with the intent to get a booster for patients. Study findings highlight key concerns and influencers identified by patients with SCD and their caregivers that are essential for framing COVID-19 vaccine education during clinical encounters. Study results can also inform the design of messaging campaigns for the broader pediatric SCD population and targeted interventions for SCD subpopulations (eg, adolescents, caregivers).
Assuntos
Anemia Falciforme , Vacinas contra COVID-19 , COVID-19 , Conhecimentos, Atitudes e Prática em Saúde , Intenção , SARS-CoV-2 , Humanos , Anemia Falciforme/psicologia , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/uso terapêutico , Adolescente , Masculino , Feminino , COVID-19/prevenção & controle , Adulto , Adulto Jovem , Criança , Inquéritos e Questionários , Vacinação/psicologia , Hesitação Vacinal/psicologia , Cuidadores/psicologiaRESUMO
Sickle cell disease (SCD) requires coordinated, specialized medical care for optimal outcomes. There are no United States (US) guidelines that define a pediatric comprehensive SCD program. We report a modified Delphi consensus-seeking process to determine essential, optimal, and suggested elements of a comprehensive pediatric SCD center. Nineteen pediatric SCD specialists participated from the US. Consensus was predefined as 2/3 agreement on each element's categorization. Twenty-six elements were considered essential (required for guideline-based SCD care), 10 were optimal (recommended but not required), and five were suggested. This work lays the foundation for a formal recognition process of pediatric comprehensive SCD centers.
Assuntos
Anemia Falciforme , Criança , Humanos , Consenso , Anemia Falciforme/terapiaRESUMO
BACKGROUND: Children with sickle cell disease (SCD) have an increased risk for gallstones due to chronic hyperbilirubinemia from hemolysis. Although gallstones are a known complication, there is variability in estimates of disease burden and uncertainty in the association between sex and gall bladder disease (GBD). METHODS: This was a retrospective cohort study of children with SCD using administrative claims data (January 1, 2014-December 31, 2018). Population-averaged multivariable panel-data logistic regression models were used to evaluate the association between GBD clinical encounters (outcome) and two exposures (age and sex). Annual GBD risk was calculated using predictive margins, adjusting for disease severity, transfusion frequency, and hydroxyurea exposure. RESULTS: A total of 13,745 individuals (of 21,487 possible) met inclusion criteria. The population was evenly split across sex (49.5% female) with predominantly Medicaid insurance (69%). A total of 946 individuals (6.9%) had GBD, 432 (3.1%) had a gallstone complication, and 487 (3.5%) underwent cholecystectomy. The annual risk of GBD rose nonlinearly from 1 to 5% between ages 1 and 19 years with no difference between males and females. Cholecystectomy occurred primarily in individuals with GBD (87%), and neither age nor sex was associated with cholecystectomy in this population. High disease severity (compared with low) more than doubled the annual risk of GBD at all ages. CONCLUSIONS: GBD is associated with age but not sex in children with SCD. Neither age nor sex is associated with risk of cholecystectomy. High disease severity increases the rate of GBD at all ages.
Assuntos
Anemia Falciforme , Doenças da Vesícula Biliar , Cálculos Biliares , Adolescente , Adulto , Anemia Falciforme/complicações , Anemia Falciforme/epidemiologia , Criança , Pré-Escolar , Feminino , Doenças da Vesícula Biliar/complicações , Doenças da Vesícula Biliar/epidemiologia , Cálculos Biliares/complicações , Cálculos Biliares/epidemiologia , Humanos , Hidroxiureia , Lactente , Masculino , Estudos Retrospectivos , Adulto JovemRESUMO
Youth with sickle cell disease (SCD) and their caregivers are susceptible to stress and depression, perhaps exacerbated by pandemic-associated health and economic concerns. Most of the 50 youth-caregiver dyads enrolled in the multisite trial, Hydroxyurea Adherence for Personal Best in Sickle Cell Treatment (HABIT), took an online survey of self-reported mental health symptoms and food insecurity during the 2020 COVID-19 pandemic. Compared to largely pre-pandemic results, prevalence of mental health symptoms in dyad members appeared to have shifted: fewer youth and more caregivers were affected during the pandemic; many of both groups lacked optimism. Pandemic/post-pandemic screening of youth with SCD for mental health symptoms and food insecurity appears warranted.
Assuntos
Anemia Falciforme , COVID-19 , Adolescente , Anemia Falciforme/epidemiologia , Anemia Falciforme/psicologia , COVID-19/epidemiologia , Cuidadores/psicologia , Depressão/epidemiologia , Depressão/etiologia , Depressão/psicologia , Humanos , Saúde Mental , PandemiasRESUMO
BACKGROUND: Adolescent and young adult (AYA) women with sickle cell disease (SCD) have increased pregnancy-related health risks and are prescribed potentially teratogenic medications, yet limited data are available regarding pediatric SCD provider contraceptive practices. We aimed to assess pediatric hematology providers' beliefs, practices, motivators, and barriers for providing contraceptive care to female AYAs with SCD. METHODS: Guided by the Health Belief Model (HBM), we developed a 25-question, web-based survey to assess practices. Survey links were distributed nationwide to pediatric SCD and/or general hematology providers through their publicly available emails and by request to directors of U.S.-accredited Pediatric Hematology-Oncology fellowship programs for distribution to their SCD providers. Data analysis included descriptive statistics, chi-square analysis, and logistic regression. RESULTS: Of 177 respondents, 160 surveys meeting inclusion criteria were analyzed. Most providers reported counseling (77.5%) and referring female AYA patients for contraception (90.8%), but fewer reported prescribing contraception (41.8%). Proportionally fewer trainees provided counseling compared with established providers (54% vs. 85%, p < .001), with a similar trend for prescribing (p = .05). Prescription practices did not differ significantly by provider beliefs regarding potential teratogenicity of hydroxyurea. Key motivators included patient request and disclosure of sexual activity. Key barriers included inadequate provider training, limited visit time, and perceived patient/parent interest. CONCLUSION: Provider contraceptive practices for female AYAs with SCD varied, especially by provider status. Health beliefs regarding teratogenic potential of hydroxyurea did not correlate with contraceptive practices. Clinical guidelines, provider training, and patient/parent decision-making tools may be tested to assess whether provider contraceptive practices could be improved.
Assuntos
Anemia Falciforme , Hematologia , Adolescente , Criança , Anticoncepção/psicologia , Anticoncepcionais , Feminino , Humanos , Hidroxiureia , Gravidez , Adulto JovemRESUMO
BACKGROUND: Sickle cell disease (SCD) is a devastating, multisystemic disorder that affects millions of people worldwide. The earliest clinical manifestations of SCD can affect infants as young as 6 months of age, and pediatric patients are at risk for acute and life-threatening complications. Early intervention with treatments that target the underlying pathophysiological mechanism of SCD, sickle hemoglobin (HbS) polymerization, are expected to slow disease progression and circumvent disease-associated morbidity and mortality. PROCEDURE: The HOPE-KIDS 1 trial (NCT02850406) is an ongoing four-part, phase 2a, open-label, single- and multiple-dose study to evaluate the pharmacokinetics, efficacy, and safety of voxelotor-a first-in-class HbS polymerization inhibitor-in patients aged 6 months to 17 years with SCD. Initial findings from a cohort of 45 patients aged 4 to 11 years who received voxelotor treatment for up to 48 weeks are reported. RESULTS: Hemoglobin (Hb) response, defined as a >1.0 g/dl increase from baseline, was achieved at week 24 by 47% (n = 16/34) of patients with Hb measurements at baseline and week 24. At week 24, 35% (n = 12/34) and 21% (n = 7/34) of patients had a >1.5 g/dl increase and a >2.0 g/dl increase from baseline in Hb concentration, respectively. Concurrent improvements in hemolytic markers were observed. Voxelotor was well tolerated in this young cohort, with no newly emerging safety signals. CONCLUSIONS: Based on its mechanism as an HbS polymerization inhibitor, voxelotor improves Hb levels and markers of hemolysis and has the potential to mitigate SCD-related complications; these results support its use in patients aged ≥4 years.
Assuntos
Anemia Falciforme , Hemoglobina Falciforme , Anemia Falciforme/tratamento farmacológico , Benzaldeídos/farmacocinética , Benzaldeídos/uso terapêutico , Biomarcadores , Criança , Pré-Escolar , Feminino , Hemólise , Humanos , Masculino , Pirazinas , PirazóisRESUMO
Ongoing clinical trials for treatment of beta-globinopathies by gene therapy involve the transfer of the beta-globin gene, which requires integration of three to four copies per genome in most target cells. This high proviral load may increase genome toxicity, potentially limiting the safety of this therapy and relegating its use to total body myeloablation. We hypothesized that introducing an additional hypersensitive site from the locus control region, the complete sequence of the second intron of the beta-globin gene, and the ankyrin insulator may enhance beta-globin expression. We identified a construct, ALS20, that synthesized significantly higher adult hemoglobin levels than those of other constructs currently used in clinical trials. These findings were confirmed in erythroblastic cell lines and in primary cells isolated from sickle cell disease patients. Bone marrow transplantation studies in beta-thalassemia mice revealed that ALS20 was curative at less than one copy per genome. Injection of human CD34+ cells transduced with ALS20 led to safe, long-term, and high polyclonal engraftment in xenograft experiments. Successful treatment of beta-globinopathies with ALS20 could potentially be achieved at less than two copies per genome, minimizing the risk of cytotoxic events and lowering the intensity of myeloablation.
Assuntos
Anemia Falciforme/genética , Transplante de Medula Óssea , Terapia Genética , Globinas beta/genética , Talassemia beta/genética , Anemia Falciforme/sangue , Anemia Falciforme/patologia , Anemia Falciforme/terapia , Animais , Expressão Gênica/genética , Vetores Genéticos/genética , Vetores Genéticos/farmacologia , Hemoglobinas/genética , Xenoenxertos , Humanos , Lentivirus/genética , Região de Controle de Locus Gênico/genética , Camundongos , Transdução Genética , Globinas beta/uso terapêutico , Talassemia beta/sangue , Talassemia beta/patologia , Talassemia beta/terapiaRESUMO
There is an immediate need to address long-standing questions about the reproductive health of girls and women with sickle cell disease (SCD). There are many SCD-related reproductive risks and uncertainties across girls' and women's reproductive life span, with particularly outstanding concerns about menstruation, contraception, fertility and pregnancy. Extant literature addressing women's reproductive health topics is mostly descriptive; there are few high-quality interventional studies. In 2020, the Centers for Disease Control and Prevention and the Foundation for Women and Girls with Blood Disorders convened an expert panel to assess the knowledge gaps in women's reproductive health in SCD. The panel identified significant limitations to clinical care due to the need for research. The panel also identified prominent barriers to research and care. In this report, we frame these issues, providing a roadmap for investigators, funding agencies, and policy makers to advance care for girls and women with SCD.
Assuntos
Anemia Falciforme , Saúde Reprodutiva , Saúde Sexual , Anemia Falciforme/epidemiologia , Anemia Falciforme/fisiopatologia , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Saúde da MulherRESUMO
BACKGROUND: Sickle cell disease (SCD) is an autosomal recessive hemoglobinopathy associated with morbidity and mortality. We sought to understand family planning intentions of parents of young children with SCD including the awareness of three reproductive options (adoption, in vitro fertilization with egg/sperm donation [IVFD], in vitro fertilization [IVF] with preimplantation genetic testing [IVF/PGT]) to decrease the risk of having a child with SCD. PROCEDURE: Qualitative, semistructured, one-on-one interviews with 18 female parents of young children with SCD at an urban, tertiary care pediatric hospital. RESULTS: Half of the parents knew their hemoglobinopathy status or their partner's status before pregnancy. Eight parents chose to have no further children because of fear of SCD in another child. Awareness of reproductive options prior to study enrollment was limited. After brief introduction, 7 parents would consider adoption, 2 IVFD, and 10 IVF/PGT. Desire for a biological child, fear of parental jealousy, ethical or religious considerations, and cost affected the acceptability of these options. Participants universally wanted information about reproductive options available to others prior to pregnancy. CONCLUSIONS: There is limited awareness and variable acceptability of alternative reproductive options available to decrease the risk of a future child having SCD. Participants universally endorsed the need for education regarding hemoglobinopathy status, SCD, and reproductive options prior to pregnancy because for many participants having a child with SCD affected their reproductive intentions. Educational interventions to ensure informed reproductive decision making should be sensitive to desires for a biological child, and ethical and financial considerations.
Assuntos
Anemia Falciforme , Testes Genéticos , Intenção , Mães , Reprodução , Adulto , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , MasculinoRESUMO
Suboptimal vitamin A status (serum retinol <30 µg/dL) is associated with poor clinical outcomes in children with the hemoglobin-SS disease (HbSS), and supplementation with the recommended daily allowance of retinol is ineffective in improving vitamin A status. In a single-center randomized blinded dose-finding pilot study, we compared vitamin A and nutritional status in children with HbSS to healthy children and explored the impact of high-dose supplementation on the primary outcome serum vitamin A status. Exploratory outcomes included hematologic, nutritional, immunologic, and muscle function status in children with HbSS. A mixed-effects linear regression model evaluated associations between vitamin A dose, serum retinol, and exploratory outcomes. Twenty healthy children participated, and 22 subjects with HbSS were randomized to oral 3000 or 6000 IU/d retinol for 8 weeks; 21 subjects completed all evaluations. Serum retinol, growth, and nutritional status were all suboptimal in HbSS subjects at baseline, and supplementation did not change vitamin A status. Fetal hemoglobin (Δ=2.5, 95% confidence interval [CI], 0.5-4.3), mean corpuscular volume (Δ=2.7, 95% CI, 0.7-4.7), mean corpuscular hemoglobin (Δ=1.4, 95% CI, 0.5-2.3), and mean corpuscular hemoglobin concentration (Δ=0.5, 95% CI, 0.1-0.9) all improved with supplementation. Mild improvements in erythrocyte indices, growth status, and muscle function occurred independent of hydroxyurea use.
Assuntos
Anemia Falciforme/tratamento farmacológico , Suplementos Nutricionais , Índices de Eritrócitos/efeitos dos fármacos , Vitamina A/administração & dosagem , Adolescente , Anemia Falciforme/metabolismo , Anemia Falciforme/patologia , Estudos de Casos e Controles , Método Duplo-Cego , Feminino , Seguimentos , Hemoglobina Falciforme/metabolismo , Humanos , Masculino , Estado Nutricional , Projetos Piloto , PrognósticoRESUMO
ß-thalassemia is a disorder caused by altered hemoglobin protein synthesis and affects individuals worldwide. Severe forms of the disease, left untreated, can result in death before the age of 3 years (1). The standard of care consists of chronic and costly palliative treatment by blood transfusion combined with iron chelation. This dual approach suppresses anemia and reduces iron-related toxicities in patients. Allogeneic bone marrow transplant is an option, but limited by the availability of a highly compatible HSC donor. While gene therapy is been explored in several trials, its use is highly limited to developed regions with centers of excellence and well-established healthcare systems (2). Hence, there remains a tremendous unmet medical need to develop alternative treatment strategies for ß-thalassemia (3). Occurrence of aberrant splicing is one of the processes that affects ß-globin synthesis in ß-thalassemia. The (C>G) IVS-2-745 is a splicing mutation within intron 2 of the ß-globin gene. It leads to an aberrantly spliced mRNA that incorporates an intron fragment. This results in an in-frame premature termination codon that inhibits ß-globin production. Here, we propose the use of uniform 2'-O-methoxyethyl (2'-MOE) splice switching oligos (SSOs) to reverse this aberrant splicing in the pre-mRNA. With these lead SSOs we show aberrant to wild type splice switching. This switching leads to an increase of adult hemoglobin (HbA) up to 80% in erythroid cells from patients with the IVS-2-745 mutation. Furthermore, we demonstrate a restoration of the balance between ß-like- and α-globin chains, and up to an 87% reduction in toxic α-heme aggregates. While examining the potential benefit of 2'-MOE-SSOs in a mixed sickle-thalassemic phenotypic setting, we found reduced HbS synthesis and sickle cell formation due to HbA induction. In summary, 2'-MOE-SSOs are a promising therapy for forms of ß-thalassemia caused by mutations leading to aberrant splicing.
RESUMO
Uptake of prenatal genetic testing (PGT) is low among those with sickle cell disease (SCD). This study evaluated the association of knowledge and attitudes towards prenatal genetic counseling (PGC), awareness of posttesting intervention options and omission bias with attitudes towards PGT. In addition, we explored changes among knowledge, attitudes, and awareness of options following exposure to an educational, clinical vignette among parents of children with SCD. Parents (n=44) completed a questionnaire and an educational, clinical vignette presenting a detailed account of a pregnant woman with sickle cell trait seeking PGT and PGC was read to each participant. t Tests, Spearman correlations, multivariable regressions, and moderation/mediation analyses were used. More positive attitudes towards PGC (P=0.01), lesser tendency of omission bias (P<0.01) and private insurance (P=0.04) were significant correlates of more positive attitudes towards PGT. Omission bias mediated the relationship of attitudes towards PGC and attitudes towards PGT (95% confidence interval: 0.13, 3.03). Awareness of options (P=0.02), knowledge of PGC (P=0.01) and knowledge of PGT (P=0.01) significantly improved after exposure to the clinical vignette. Patients and families with SCD can benefit from education about the importance of prenatal diagnosis to improve attitudes, address omission bias and promote more informed decisions of PGT.
Assuntos
Atitude Frente a Saúde , Teste Pré-Natal não Invasivo , Pais , Traço Falciforme , Feminino , Humanos , Masculino , GravidezRESUMO
BACKGROUND: Hydroxyurea (HU) is recommended as standard practice for youth with sickle cell disease (SCD). Yet, despite its efficacy, HU adherence in adolescents and young adults is often poor. Poor medication adherence increases disease burden, healthcare cost and widens health disparities. Adolescence is a critical time to improve adherence through improved chronic disease self-management. This study aims to test the efficacy of an intervention delivered to youth/parent dyads by community health workers (CHWs), augmented by tailored text messages on HU adherence (primary outcome). Secondary outcomes are intervention sustainability, youth health-related quality of life, self-management responsibility concordance, acute hospital use and self-reported disease symptoms. METHODS: Hydroxyurea Adherence for Personal Best in Sickle Cell Disease, "HABIT," is a 12 month multi-center randomized controlled trial. One hundred four youth, 10 to 18 years of age prescribed HU who meet eligibility criteria, enrolled with their parent as dyads, will be randomized 1:1 to either the HABIT intervention or to usual clinical care plus education handouts. All subjects will complete clinic visits at months 0, 2, 4, 6 (efficacy component), 9 and 12 (sustainability component) for assessment of HbF biomarker, other hematologic parameters, and to complete questionnaires. In addition, dyads assigned to the HABIT intervention will work with CHWs to identify a daily habit (e.g., brushing teeth) on which to build a HU adherence habit. Tailored daily text message reminders to support the habit will be developed by the dyad in collaboration with the CHWs and sent to parent and youth. At the 6 month visit, the intervention will end and the sustainability portion of the trial will begin. All data analyses will be based on intention to treat with all randomized subjects included in the analyses. DISCUSSION: Prior retrospective studies demonstrate that a majority of adolescents are poorly adherent to HU. If efficacious, the HABIT intervention has the potential to improve the lives of youth with SCD. TRIAL REGISTRATION: Clinicaltrials.gov NCT03462511 . Registered March 6, 2018, last updated July 26, 2019.
Assuntos
Anemia Falciforme/tratamento farmacológico , Antidrepanocíticos/uso terapêutico , Hidroxiureia/uso terapêutico , Adesão à Medicação/estatística & dados numéricos , Adolescente , Criança , Humanos , Estudos Multicêntricos como Assunto/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Resultado do TratamentoRESUMO
Background: Although sickle cell trait (SCT) is largely a benign carrier state, it may increase risk for certain clinical outcomes. Purpose: To evaluate associations between SCT and clinical outcomes in children and adults. Data Sources: English-language searches of PubMed, CINAHL, the Cochrane Library, Current Contents Connect, Scopus, and Embase (1 January 1970 to 30 June 2018) and bibliographies of review articles. Study Selection: Observational controlled studies (published in English) in children or adults that examined an association between SCT and any of 24 clinical outcomes specified a priori in the following 6 categories: exertion-related injury; renal, vascular, pediatric, and surgery- or trauma-related outcomes; and overall mortality. Data Extraction: A single reviewer extracted study data, which was checked by another; 2 reviewers independently assessed study quality; and strength of evidence was assessed by consensus. Data Synthesis: Of 7083 screened studies, 41 met inclusion criteria. High-strength evidence supported a positive association between SCT and risk for pulmonary embolism, proteinuria, and chronic kidney disease. Moderate-strength evidence supported a positive association between SCT and exertional rhabdomyolysis and a null association between SCT and deep venous thrombosis, heart failure or cardiomyopathy, stroke, and pediatric height or weight. Absolute risks for thromboembolism and rhabdomyolysis were small. For the remaining 15 clinical outcomes, data were insufficient or strength of evidence was low. Limitation: Publication bias was possible, and high-quality evidence was scant. Conclusion: Sickle cell trait is a risk factor for a few adverse health outcomes, such as pulmonary embolism, kidney disease, and exertional rhabdomyolysis, but does not seem to be associated with such complications as heart failure and stroke. Insufficient data or low-strength evidence exists for most speculated complications of SCT. Primary Funding Source: National Human Genome Research Institute.
Assuntos
Traço Falciforme/complicações , Adulto , Estatura , Peso Corporal , Doenças Cardiovasculares/complicações , Criança , Humanos , Complicações Pós-Operatórias , Proteinúria/complicações , Insuficiência Renal Crônica/complicações , Rabdomiólise/complicações , Fatores de Risco , Ferimentos e Lesões/complicaçõesRESUMO
Although elevated right ventricular pressure and left ventricular diastolic dysfunction measured by echocardiogram are independent predictors of death in adults with sickle cell disease (SCD), the utility of routine echocardiographic screening in the pediatric population is controversial. We performed a 3-year retrospective review of children ≥ 10 years of age with SCD who underwent an outpatient transthoracic echocardiogram as part of a screening program. Of 172 patients referred for screening, 105 (61%) had a measurable tricuspid regurgitation jet velocity (TRV): median 2.4 m/s (IQR 2.3-2.5). Elevated right ventricular (RV) pressure (TRV ≥ 2.5 m/s, 25 mmHg), documented in 30% (32/105), was significantly associated with chronic transfusion therapy and elevated lactate dehydrogenase. Left ventricle (LV) dilation, documented in 25% (44/172), was significantly associated with lower hemoglobin, and higher reticulocyte count, lactate dehydrogenase level, and bilirubin level. There was no association between elevated right ventricular pressure or left ventricle dilation and indices of biventricular systolic or diastolic function. The one death in the cohort during the study period had normal echocardiographic findings. In conclusion, mild RV pressure elevation and LV dilation in children with SCD is associated with abnormal laboratory markers of disease severity, but not with ventricular dysfunction over the 3-year study period.
Assuntos
Anemia Falciforme/fisiopatologia , Função Ventricular Esquerda/fisiologia , Função Ventricular Direita/fisiologia , Adolescente , Anemia Falciforme/complicações , Criança , Progressão da Doença , Ecocardiografia , Feminino , Humanos , Masculino , Estudos Retrospectivos , Medição de RiscoRESUMO
Patients with autoimmune multilineage cytopenias are often refractory to standard therapies requiring chronic immunosuppression with medications with limited efficacy and high toxicity. We present data on 30 patients treated on a multicenter prospective clinical trial using sirolimus as monotherapy. All children (N = 12) with autoimmune lymphoproliferative syndrome (ALPS) achieved a durable complete response (CR), including rapid improvement in autoimmune disease, lymphadenopathy, and splenomegaly within 1 to 3 months of starting sirolimus. Double-negative T cells were no longer detectable in most, yet other lymphocyte populations were spared, suggesting a targeted effect of sirolimus. We also treated 12 patients with multilineage cytopenias secondary to common variable immunodeficiency (CVID), Evans syndrome (ES), or systemic lupus erythematosus (SLE), and most achieved a CR (N = 8), although the time to CR was often slower than was seen in ALPS. Six children with single-lineage autoimmune cytopenias were treated and only 2 responded. Sirolimus was well tolerated with very few side effects. All of the responding patients have remained on therapy for over 1 year (median, 2 years; range, 1 to 4.5 years). In summary, sirolimus led to CR and durable responses in a majority of children with refractory multilineage autoimmune cytopenias. The responses seen in ALPS patients were profound, suggesting that sirolimus should be considered as a first-line, steroid-sparing treatment of patients needing chronic therapy. The results in other multilineage autoimmune cytopenia cohorts were encouraging, and sirolimus should be considered in children with SLE, ES, and CVID. This trial was registered at www.clinicaltrials.gov as #NCT00392951.
Assuntos
Doenças Autoimunes/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Doenças Hematológicas/tratamento farmacológico , Imunossupressores/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Terapia de Salvação , Sirolimo/uso terapêutico , Adolescente , Adulto , Doenças Autoimunes/mortalidade , Doenças Autoimunes/patologia , Criança , Pré-Escolar , Feminino , Seguimentos , Doenças Hematológicas/mortalidade , Doenças Hematológicas/patologia , Humanos , Imunossupressores/farmacocinética , Lactente , Masculino , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Sirolimo/farmacocinética , Taxa de Sobrevida , Distribuição Tecidual , Adulto JovemRESUMO
Although musculoskeletal pain in patients with sickle cell disease (SCD) is most frequently the result of vaso-occlusive episodes, clinicians often consider other etiologies including osteomyelitis, avascular necrosis, and trauma. In this study, we report the case of a young female with SCD with hip and back pain secondary to a nontraumatic iliopsoas periosteal hematoma with evidence of adjacent bone infarction. The pathophysiology, diagnostic considerations, and management of periosteal hematomas in SCD are reviewed. This case highlights the need for recognition of unusual causes of musculoskeletal pain in SCD.