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[PMID]:29242203
[Au] Autor:Odame I
[Ad] Endereço:THE HOSPITAL FOR SICK CHILDREN.
[Ti] Título:Hydroxyurea for SCA in Africa: no malaria harm.
[So] Source:Blood;130(24):2575-2576, 2017 12 14.
[Is] ISSN:1528-0020
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Antidrepanocíticos
Hidroxiureia
[Mh] Termos MeSH secundário: África
Anemia Falciforme
Seres Humanos
Malária
[Pt] Tipo de publicação:JOURNAL ARTICLE; COMMENT
[Nm] Nome de substância:
0 (Antisickling Agents); X6Q56QN5QC (Hydroxyurea)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180118
[Lr] Data última revisão:
180118
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171216
[St] Status:MEDLINE
[do] DOI:10.1182/blood-2017-10-812974


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[PMID]:28863145
[Au] Autor:Teixeira RS; Terse-Ramos R; Ferreira TA; Machado VR; Perdiz MI; Lyra IM; Nascimento VL; Boa-Sorte N; Andrade BB; Ladeia AM
[Ad] Endereço:Bahiana School of Medicine and Public Health, Bahia Foundation for the Development of Sciences Salvador, Salvador, Bahia, Brazil.
[Ti] Título:Associations between endothelial dysfunction and clinical and laboratory parameters in children and adolescents with sickle cell anemia.
[So] Source:PLoS One;12(9):e0184076, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Hematological changes can drive damage of endothelial cells, which potentially lead to an early endothelial dysfunction in patients with sickle cell anemia (SCA). An association may exist between endothelial dysfunction and several clinical manifestations of SCA. The present study aims to evaluate the links between changes in endothelial function and clinical and laboratory parameters in children and adolescents with SCA. METHODS: This study included 40 children and adolescents with stable SCA as well as 25 healthy children; aged 6-18 years. All study subjects were evaluated for endothelial function using Doppler ultrasonography. In addition, a number of laboratory assays were performed, including reticulocyte and leukocyte counts as well as measurement of circulating levels of total bilirubin, C-reactive protein (CRP), glucose, lipoproteins and peripheral oxyhemoglobin saturation. These parameters were also compared between SCA patients who were undertaking hydroxyurea (HU) and those who were not. RESULTS: Flow-mediated vasodilation (FMD) values were found to be reduced in SCA patients compared with those detected in healthy controls. SCA individuals with lower FMD values exhibited higher number of hospital admissions due to vaso-occlusive events. Additional analyses revealed that patients who had decreased FMD values exhibited higher odds of acute chest syndrome (ACS) episodes. A preliminary analysis with limited number of individuals failed to demonstrate significant differences in FMD values between SCA individuals who were treated with HU and those who were not. CONCLUSIONS: Children and adolescents with SCA exhibit impaired endothelial function. Reductions in FMD values are associated with ACS. These findings underline the potential use of FMD as screening strategy of SCA patients with severe prognosis at early stages.
[Mh] Termos MeSH primário: Anemia Falciforme/sangue
Anemia Falciforme/complicações
Endotélio Vascular/fisiopatologia
Doenças Vasculares/sangue
Doenças Vasculares/complicações
[Mh] Termos MeSH secundário: Adolescente
Antidrepanocíticos/uso terapêutico
Bilirrubina/sangue
Proteína C-Reativa/análise
Estudos de Casos e Controles
Criança
Células Endoteliais/patologia
Feminino
Glucose/análise
Seres Humanos
Hidroxiureia/uso terapêutico
Contagem de Leucócitos
Lipoproteínas/sangue
Masculino
Oxiemoglobinas/análise
Reticulócitos/citologia
Ultrassonografia Doppler
Doenças Vasculares/diagnóstico por imagem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antisickling Agents); 0 (Lipoproteins); 0 (Oxyhemoglobins); 9007-41-4 (C-Reactive Protein); IY9XDZ35W2 (Glucose); RFM9X3LJ49 (Bilirubin); X6Q56QN5QC (Hydroxyurea)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170902
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0184076


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[PMID]:28727801
[Au] Autor:Bakshi N; Sinha CB; Ross D; Khemani K; Loewenstein G; Krishnamurti L
[Ad] Endereço:Division of Pediatric Hematology-Oncology, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
[Ti] Título:Proponent or collaborative: Physician perspectives and approaches to disease modifying therapies in sickle cell disease.
[So] Source:PLoS One;12(7):e0178413, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Sickle cell disease (SCD) is an inherited blood disorder that primarily affects African-American and other ethnic minority populations. There are three available disease-modifying therapies for sickle cell disease: hydroxyurea (HU), bone marrow transplantation (BMT), and chronic blood transfusion (CBT). Since these treatments vary in their therapeutic intent, efficacy in preventing progression of the disease, short and long-term adverse effects, costs and patient burden, the decision-making process regarding these therapies is complicated for both the patient and healthcare provider. While previous research has focused on the patient perspective of treatment-related decision making, there is a paucity of research investigating the physician perspective of treatment-related decision making. We conducted a qualitative study with physicians who were experts in the field of SCD. Interviews focused on physician perceptions of patient decisional needs as well as physicians' approach to decision making regarding disease-modifying therapies in SCD. Thirty-six physician interviews were analyzed, with a focus on their perspectives regarding available treatment options and on how they approach decision making with patients. We identified two narrative approaches. The Collaborative approach (CA) was characterized by emphasizing the need to discuss all possible treatment options to ensure that the patient and/or family was equipped to make an informed decision. The Proponent approach (PA) was characterized by strongly advocating a pre-determined treatment plan and providing patients/families with information, with the objective of convincing them to accept the treatment. An interplay of patient-related and disease-related factors, decision type and physician-related factors, as well as institutional frameworks, influenced physician perspectives on treatment options and decision making regarding these therapies. These findings point to the potential value of developing systems to foster patient engagement as a way of facilitating shared decision making.
[Mh] Termos MeSH primário: Anemia Falciforme/terapia
Antidrepanocíticos/uso terapêutico
Transfusão de Sangue/métodos
Transplante de Medula Óssea
Hidroxiureia/uso terapêutico
Relações Médico-Paciente
Padrões de Prática Médica
[Mh] Termos MeSH secundário: Adulto
Anemia Falciforme/tratamento farmacológico
Criança
Tomada de Decisões
Feminino
Pesquisas sobre Serviços de Saúde
Seres Humanos
Masculino
Participação do Paciente
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antisickling Agents); X6Q56QN5QC (Hydroxyurea)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170927
[Lr] Data última revisão:
170927
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170721
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0178413


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[PMID]:28679417
[Au] Autor:Badawy SM; Thompson AA; Lai JS; Penedo FJ; Rychlik K; Liem RI
[Ad] Endereço:Department of Pediatrics, Division of Hematology, Oncology and Stem Cell Transplant, Ann & Robert H. Lurie Children's Hospital, Northwestern University Feinberg School of Medicine, 225 E. Chicago Ave., Box #30, Chicago, IL, 60611, USA. sbadawy@luriechildrens.org.
[Ti] Título:Adherence to hydroxyurea, health-related quality of life domains, and patients' perceptions of sickle cell disease and hydroxyurea: a cross-sectional study in adolescents and young adults.
[So] Source:Health Qual Life Outcomes;15(1):136, 2017 Jul 05.
[Is] ISSN:1477-7525
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Sickle cell disease (SCD) patients have impaired domains of health-related quality of life (HRQOL). Hydroxyurea is safe and efficacious in SCD; however, adherence is suboptimal, and patients' perceptions are poorly understood amongst adolescents and young adults (AYA). Study objectives were to: (1) examine patients' perceptions of SCD and hydroxyurea; and (2) explore the relationship of their perceptions to clinical characteristics, HRQOL domains and hydroxyurea adherence. METHODS: Thirty-four SCD patients on hydroxyurea (≥6 months) participated in a single-institution study. Study measures included Brief-Illness Perceptions Questionnaire, ©Modified Morisky Adherence Scale 8-items, and Patient Reported Outcomes Measurement Information System (PROMIS®). We assessed the relationship of patients' perceptions to hydroxyurea adherence using Wilcoxon rank-sum test, the number of hospitalizations using Kruskal-Wallis test, and the number of ED visits, adherence level, HRQOL domain scores using Spearman's rho correlations. We conducted a sub-analysis in HbSS patients to evaluate the relationship of patients' perceptions to laboratory markers of hydroxyurea adherence. RESULTS: Participants were 59% male and 91% Black, and had a median age of 13.5 (range 12-18) years. Participants with ≥4 hospitalizations over 1-year prior (using electronic medical chart review) reported more negative perceptions of SCD-related symptoms and emotional response, and perceived hydroxyurea as less beneficial; all p-values ≤0.01. Most participants (74%) reported low hydroxyurea adherence. Participants with higher hydroxyurea adherence perceived more hydroxyurea benefits (r  = 0.44, p < 0.01) and had better emotional response to SCD (r  = -0.44, p = 0.01). In a sub-analysis of HbSS patients, perceived benefits of hydroxyurea positively correlated with HbF (r  = 0.37, p = 0.05) and MCV values (r  = 0.35, p = 0.05). Participants with more negative perceptions of SCD-related consequences, concerns, and emotional response, and fewer perceived hydroxyurea benefits reported worse fatigue (r  = 0.68; r  = 0.44; r  = 0.74; r  = -0.60), pain (r  = 0.56; r  = 0.54; r  = 0.63; r  = -0.39), anxiety (r  = 0.55; r  = 0.58; r  = 0.56; r  = -0.47), and depression (r  = 0.64; r  = 0.49; r  = 0.70; r  = -0.62), respectively, all p-values <0.05. CONCLUSIONS: Dynamics influencing hydroxyurea adherence are multifactorial, and understanding patients' perceptions is critical to overcoming adherence barriers. Patients' favorable perceptions correlated with greater adherence and better HRQOL domain scores. Prospective evaluation of patients' perceptions of SCD and hydroxyurea in relation adherence, HRQOL domains and clinical outcomes is warranted.
[Mh] Termos MeSH primário: Anemia Falciforme/psicologia
Antidrepanocíticos/uso terapêutico
Hidroxiureia/uso terapêutico
Adesão à Medicação
Qualidade de Vida
[Mh] Termos MeSH secundário: Adolescente
Criança
Estudos Transversais
Serviço Hospitalar de Emergência/estatística & dados numéricos
Feminino
Hospitalização/estatística & dados numéricos
Seres Humanos
Masculino
Percepção
Estudos Prospectivos
Inquéritos e Questionários
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antisickling Agents); X6Q56QN5QC (Hydroxyurea)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170707
[St] Status:MEDLINE
[do] DOI:10.1186/s12955-017-0713-x


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[PMID]:28672087
[Au] Autor:Roy NB; Fortin PM; Bull KR; Doree C; Trivella M; Hopewell S; Estcourt LJ
[Ad] Endereço:Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford, UK, OX3 9DU.
[Ti] Título:Interventions for chronic kidney disease in people with sickle cell disease.
[So] Source:Cochrane Database Syst Rev;7:CD012380, 2017 07 03.
[Is] ISSN:1469-493X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Sickle cell disease (SCD) is one of the commonest severe monogenic disorders in the world, due to the inheritance of two abnormal haemoglobin (beta-globin) genes. SCD can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Kidney disease is a frequent and potentially severe complication in people with SCD.Chronic kidney disease is defined as abnormalities of kidney structure or function, present for more than three months. Sickle cell nephropathy refers to the spectrum of kidney complications in SCD.Glomerular damage is a cause of microalbuminuria and can develop at an early age in children with SCD, and increases in prevalence in adulthood. In people with sickle cell nephropathy, outcomes are poor as a result of the progression to proteinuria and chronic kidney insufficiency. Up to 12% of people who develop sickle cell nephropathy will develop end-stage renal disease. OBJECTIVES: To assess the effectiveness of any intervention in preventing or reducing kidney complications or chronic kidney disease in people with SCD (including red blood cell transfusions, hydroxyurea and angiotensin-converting enzyme inhibitor (ACEI)), either alone or in combination with each other. SEARCH METHODS: We searched for relevant trials in the Cochrane Library, MEDLINE (from 1946), Embase (from 1974), the Transfusion Evidence Library (from 1980), and ongoing trial databases; all searches current to 05 April 2016. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register: 13 April 2017. SELECTION CRITERIA: Randomised controlled trials comparing interventions to prevent or reduce kidney complications or chronic kidney disease in people with SCD. There were no restrictions by outcomes examined, language or publication status. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial eligibility, extracted data and assessed the risk of bias. MAIN RESULTS: We included two trials with 215 participants. One trial was published in 2011 and included 193 children aged 9 months to 18 months, and compared treatment with hydroxyurea to placebo. The second trial was published in 1998 and included 22 adults with normal blood pressure and microalbuminuria and compared ACEI to placebo.We rated the quality of evidence as low to very low across different outcomes according to GRADE methodology. This was due to trials having: a high or unclear risk of bias including attrition and detection bias; indirectness (the available evidence was for children aged 9 months to 18 months in one trial and a small and select adult sample size in a second trial); and imprecise outcome effect estimates of significant benefit or harm. Hydroxyurea versus placebo We are very uncertain if hydroxyurea reduces or prevents progression of kidney disease (assessed by change in glomerular filtration rate), or reduces hyperfiltration in children aged 9 to 18 months, mean difference (MD) 0.58 (95% confidence interval (CI) -14.60 to 15.76 (mL/min per 1.73 m²)) (one study; 142 participants; very low-quality evidence).In children aged 9 to 18 months, hydroxyurea may improve the ability to concentrate urine, MD 42.23 (95% CI 12.14 to 72.32 (mOsm/kg)) (one study; 178 participants; low-quality evidence).Hydroxyurea may make little or no difference to SCD-related serious adverse events including: incidence of acute chest syndrome, risk ratio (RR) 0.39 (99% CI 0.13 to 1.16); painful crisis, RR 0.68 (99% CI 0.45 to 1.02); and hospitalisations, RR 0.83 (99% CI 0.68 to 1.01) (one study, 193 participants; low-quality evidence).No deaths occurred in the trial. Quality of life was not reported. ACEI versus placeboWe are very uncertain if ACEI reduces proteinuria in adults with SCD who have normal blood pressure and microalbuminuria, MD -49.00 (95% CI -124.10 to 26.10 (mg per day)) (one study; 22 participants; very low-quality evidence). We are very uncertain if ACEI reduce or prevent kidney disease as measured by creatinine clearance. The authors state that creatinine clearance remained constant over six months in both groups, but no comparative data were provided (very low-quality evidence).All-cause mortality, serious adverse events and quality of life were not reported. AUTHORS' CONCLUSIONS: In young children aged 9 months to 18 months, we are very uncertain if hydroxyurea improves glomerular filtration rate or reduces hyperfiltration, but it may improve young children's ability to concentrate urine and may make little or no difference on the incidence of acute chest syndrome, painful crises and hospitalisations.We are very uncertain if giving ACEI to adults with normal blood pressure and microalbuminuria has any effect on preventing or reducing kidney complications.This review identified no trials that looked at red cell transfusions nor any combinations of interventions to prevent or reduce kidney complications.Due to lack of evidence this review cannot comment on the management of either children aged over 18 months or adults with any known genotype of SCD.We have identified a lack of adequately-designed and powered studies, and no ongoing trials which address this critical question. Trials of hydroxyurea, ACEI or red blood cell transfusion in older children and adults are urgently needed to determine any effect on prevention or reduction kidney complications in people with SCD.
[Mh] Termos MeSH primário: Anemia Falciforme/complicações
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico
Antidrepanocíticos/uso terapêutico
Hidroxiureia/uso terapêutico
Falência Renal Crônica/prevenção & controle
[Mh] Termos MeSH secundário: Adulto
Albuminúria/complicações
Anemia Falciforme/tratamento farmacológico
Creatinina/metabolismo
Taxa de Filtração Glomerular/efeitos dos fármacos
Hospitalização/estatística & dados numéricos
Seres Humanos
Lactente
Falência Renal Crônica/tratamento farmacológico
Falência Renal Crônica/etiologia
Placebos
Ensaios Clínicos Controlados Aleatórios como Assunto
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (Angiotensin-Converting Enzyme Inhibitors); 0 (Antisickling Agents); 0 (Placebos); AYI8EX34EU (Creatinine); X6Q56QN5QC (Hydroxyurea)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170908
[Lr] Data última revisão:
170908
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170704
[St] Status:MEDLINE
[do] DOI:10.1002/14651858.CD012380.pub2


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[PMID]:28556441
[Au] Autor:King AA; Baumann AA
[Ad] Endereço:Program in Occupational Therapy, Washington University School of Medicine, St. Louis, Missouri.
[Ti] Título:Sickle cell disease and implementation science: A partnership to accelerate advances.
[So] Source:Pediatr Blood Cancer;64(11), 2017 Nov.
[Is] ISSN:1545-5017
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Sickle cell disease (SCD) results in end organ damage and a shortened lifespan. Both the pathophysiology of the disease and the social determinants of health affect patient outcomes. Randomized controlled trials have been completed among this population and resulted in medical advances; however, the gestation of these advances and the lack of penetrance into clinical practice have limited advancements in clinical improvements for many people with SCD. We discuss the role of implementation science in SCD and highlight the need for this science to shorten the length of time to implement evidence-based care for more people with SCD.
[Mh] Termos MeSH primário: Anemia Falciforme/diagnóstico
Anemia Falciforme/prevenção & controle
Antidrepanocíticos/uso terapêutico
[Mh] Termos MeSH secundário: Seres Humanos
Prognóstico
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antisickling Agents)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170531
[St] Status:MEDLINE
[do] DOI:10.1002/pbc.26649


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[PMID]:28500860
[Au] Autor:Estcourt LJ; Fortin PM; Hopewell S; Trivella M; Doree C; Abboud MR
[Ad] Endereço:Haematology/Transfusion Medicine, NHS Blood and Transplant, Level 2, John Radcliffe Hospital, Headington, Oxford, UK, OX3 9BQ.
[Ti] Título:Interventions for preventing silent cerebral infarcts in people with sickle cell disease.
[So] Source:Cochrane Database Syst Rev;5:CD012389, 2017 05 13.
[Is] ISSN:1469-493X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Sickle cell disease (SCD) is one of the commonest severe monogenic disorders in the world, due to the inheritance of two abnormal haemoglobin (beta globin) genes. SCD can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Silent cerebral infarcts are the commonest neurological complication in children and probably adults with SCD. Silent cerebral infarcts also affect academic performance, increase cognitive deficits and may lower intelligence quotient. OBJECTIVES: To assess the effectiveness of interventions to reduce or prevent silent cerebral infarcts in people with SCD. SEARCH METHODS: We searched for relevant trials in the Cochrane Library, MEDLINE (from 1946), Embase (from 1974), the Transfusion Evidence Library (from 1980), and ongoing trial databases; all searches current to 19 September 2016. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register: 06 October 2016. SELECTION CRITERIA: Randomised controlled trials comparing interventions to prevent silent cerebral infarcts in people with SCD. There were no restrictions by outcomes examined, language or publication status. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. MAIN RESULTS: We included five trials (660 children or adolescents) published between 1998 and 2016. Four of the five trials were terminated early. The vast majority of participants had the haemoglobin (Hb)SS form of SCD. One trial focused on preventing silent cerebral infarcts or stroke; three trials were for primary stroke prevention and one trial dealt with secondary stroke prevention.Three trials compared the use of regular long-term red blood cell transfusions to standard care. Two of these trials included children with no previous long-term transfusions: one in children with normal transcranial doppler (TCD) velocities; and one in children with abnormal TCD velocities. The third trial included children and adolescents on long-term transfusion.Two trials compared the drug hydroxyurea and phlebotomy to long-term transfusions and iron chelation therapy: one in primary prevention (children), and one in secondary prevention (children and adolescents).The quality of the evidence was moderate to very low across different outcomes according to GRADE methodology. This was due to trials being at high risk of bias because they were unblinded; indirectness (available evidence was only for children with HbSS); and imprecise outcome estimates. Long-term red blood cell transfusions versus standard care Children with no previous long-term transfusions and higher risk of stroke (abnormal TCD velocities or previous history of silent cerebral infarcts) Long-term red blood cell transfusions may reduce the incidence of silent cerebral infarcts in children with abnormal TCD velocities, risk ratio (RR) 0.11 (95% confidence interval (CI) 0.02 to 0.86) (one trial, 124 participants, low-quality evidence); but make little or no difference to the incidence of silent cerebral infarcts in children with previous silent cerebral infarcts on magnetic resonance imaging and normal or conditional TCDs, RR 0.70 (95% CI 0.23 to 2.13) (one trial, 196 participants, low-quality evidence).No deaths were reported in either trial.Long-term red blood cell transfusions may reduce the incidence of: acute chest syndrome, RR 0.24 (95% CI 0.12 to 0.49) (two trials, 326 participants, low-quality evidence); and painful crisis, RR 0.63 (95% CI 0.42 to 0.95) (two trials, 326 participants, low-quality evidence); and probably reduces the incidence of clinical stroke, RR 0.12 (95% CI 0.03 to 0.49) (two trials, 326 participants, moderate-quality evidence).Long-term red blood cell transfusions may improve quality of life in children with previous silent cerebral infarcts (difference estimate -0.54; 95% confidence interval -0.92 to -0.17; one trial; 166 participants), but may have no effect on cognitive function (least squares means: 1.7, 95% CI -1.1 to 4.4) (one trial, 166 participants, low-quality evidence). Transfusions continued versus transfusions halted: children and adolescents with normalised TCD velocities (79 participants; one trial)Continuing red blood cell transfusions may reduce the incidence of silent cerebral infarcts, RR 0.29 (95% CI 0.09 to 0.97 (low-quality evidence).We are very uncertain whether continuing red blood cell transfusions has any effect on all-cause mortality, Peto odds ratio (OR) 8.00 (95% CI 0.16 to 404.12); or clinical stroke, RR 0.22 (95% CI 0.01 to 4.35) (very low-quality evidence).The trial did not report: comparative numbers for SCD-related adverse events; quality of life; or cognitive function. Hydroxyurea and phlebotomy versus transfusions and chelation Primary prevention, children (121 participants; one trial)We are very uncertain whether switching to hydroxyurea and phlebotomy has any effect on: silent cerebral infarcts (no infarcts); all-cause mortality (no deaths); risk of stroke (no strokes); or SCD-related complications, RR 1.52 (95% CI 0.58 to 4.02) (very low-quality evidence). Secondary prevention, children and adolescents with a history of stroke (133 participants; one trial)We are very uncertain whether switching to hydroxyurea and phlebotomy has any effect on: silent cerebral infarcts, Peto OR 7.28 (95% CI 0.14 to 366.91); all-cause mortality, Peto OR 1.02 (95%CI 0.06 to 16.41); or clinical stroke, RR 14.78 (95% CI 0.86 to 253.66) (very low-quality evidence).Switching to hydroxyurea and phlebotomy may increase the risk of SCD-related complications, RR 3.10 (95% CI 1.42 to 6.75) (low-quality evidence).Neither trial reported on quality of life or cognitive function. AUTHORS' CONCLUSIONS: We identified no trials for preventing silent cerebral infarcts in adults, or in children who do not have HbSS SCD.Long-term red blood cell transfusions may reduce the incidence of silent cerebral infarcts in children with abnormal TCD velocities, but may have little or no effect on children with normal TCD velocities. In children who are at higher risk of stroke and have not had previous long-term transfusions, long-term red blood cell transfusions probably reduce the risk of stroke, and other SCD-related complications (acute chest syndrome and painful crises).In children and adolescents at high risk of stroke whose TCD velocities have normalised, continuing red blood cell transfusions may reduce the risk of silent cerebral infarcts. No treatment duration threshold has been established for stopping transfusions.Switching to hydroxyurea with phlebotomy may increase the risk of silent cerebral infarcts and SCD-related serious adverse events in secondary stroke prevention.All other evidence in this review is of very low-quality.
[Mh] Termos MeSH primário: Anemia Falciforme/complicações
Antidrepanocíticos/uso terapêutico
Infarto Encefálico/prevenção & controle
Transfusão de Eritrócitos
Hidroxiureia/uso terapêutico
Flebotomia
[Mh] Termos MeSH secundário: Adolescente
Antidrepanocíticos/efeitos adversos
Infarto Encefálico/etiologia
Causas de Morte
Criança
Cognição/fisiologia
Seres Humanos
Hidroxiureia/efeitos adversos
Flebotomia/efeitos adversos
Prevenção Primária/métodos
Qualidade de Vida
Ensaios Clínicos Controlados Aleatórios como Assunto
Prevenção Secundária/métodos
Acidente Vascular Cerebral/prevenção & controle
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; REVIEW
[Nm] Nome de substância:
0 (Antisickling Agents); X6Q56QN5QC (Hydroxyurea)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171113
[Lr] Data última revisão:
171113
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170514
[St] Status:MEDLINE
[do] DOI:10.1002/14651858.CD012389.pub2


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[PMID]:28439953
[Au] Autor:Galadanci NA; Umar Abdullahi S; Vance LD; Musa Tabari A; Ali S; Belonwu R; Salihu A; Amal Galadanci A; Wudil Jibir B; Bello-Manga H; Neville K; Kirkham FJ; Shyr Y; Phillips S; Covert BV; Kassim AA; Jordan LC; Aliyu MH; DeBaun MR
[Ad] Endereço:Department of Hematology and Blood Transfusion, Bayero University/Aminu Kano Teaching Hospital, Kano, Nigeria.
[Ti] Título:Feasibility trial for primary stroke prevention in children with sickle cell anemia in Nigeria (SPIN trial).
[So] Source:Am J Hematol;92(8):780-788, 2017 Aug.
[Is] ISSN:1096-8652
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The vast majority of children with sickle cell anemia (SCA) live in Africa, where evidence-based guidelines for primary stroke prevention are lacking. In Kano, Nigeria, we conducted a feasibility trial to determine the acceptability of hydroxyurea therapy for primary stroke prevention in children with abnormal transcranial Doppler (TCD) measurements. Children with SCA and abnormal non-imaging TCD measurements (≥200 cm/s) received moderate fixed-dose hydroxyurea therapy (∼20 mg/kg/day). A comparison group of children with TCD measurements <200 cm/s was followed prospectively. Approximately 88% (330 of 375) of families agreed to be screened, while 87% (29 of 33) of those with abnormal TCD measurements, enrolled in the trial. No participant elected to withdraw from the trial. The average mean corpuscular volume increased from 85.7 fl at baseline to 95.5 fl at 24 months (not all of the children who crossed over had a 24 month visit), demonstrating adherence to hydroxyurea. The comparison group consisted of initially 210 children, of which four developed abnormal TCD measurements, and were started on hydroxyurea. None of the monthly research visits were missed (n = total 603 visits). Two and 10 deaths occurred in the treatment and comparison groups, with mortality rates of 2.69 and 1.81 per 100 patient-years, respectively (P = .67). Our results provide strong evidence, for high family recruitment, retention, and adherence rates, to undertake the first randomized controlled trial with hydroxyurea therapy for primary stroke prevention in children with SCA living in Africa.
[Mh] Termos MeSH primário: Anemia Falciforme/complicações
Anemia Falciforme/tratamento farmacológico
Acidente Vascular Cerebral/etiologia
Acidente Vascular Cerebral/prevenção & controle
[Mh] Termos MeSH secundário: Anemia Falciforme/epidemiologia
Antidrepanocíticos/administração & dosagem
Antidrepanocíticos/efeitos adversos
Antidrepanocíticos/uso terapêutico
Criança
Pré-Escolar
Feminino
Seguimentos
Hospitalização
Seres Humanos
Hidroxiureia/administração & dosagem
Hidroxiureia/efeitos adversos
Hidroxiureia/uso terapêutico
Incidência
Masculino
Adesão à Medicação
Nigéria
Reprodutibilidade dos Testes
Sensibilidade e Especificidade
Acidente Vascular Cerebral/diagnóstico
Acidente Vascular Cerebral/epidemiologia
Resultado do Tratamento
Ultrassonografia Doppler Transcraniana
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE III; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antisickling Agents); X6Q56QN5QC (Hydroxyurea)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170728
[Lr] Data última revisão:
170728
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170426
[St] Status:MEDLINE
[do] DOI:10.1002/ajh.24770


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[PMID]:28426137
[Au] Autor:Nevitt SJ; Jones AP; Howard J
[Ad] Endereço:Department of Biostatistics, University of Liverpool, Block F, Waterhouse Building, 1-5 Brownlow Hill, Liverpool, UK, L69 3GL.
[Ti] Título:Hydroxyurea (hydroxycarbamide) for sickle cell disease.
[So] Source:Cochrane Database Syst Rev;4:CD002202, 2017 04 20.
[Is] ISSN:1469-493X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Sickle cell disease (SCD) is one of the most common inherited diseases worldwide. It is associated with lifelong morbidity and a reduced life expectancy. Hydroxyurea (hydroxycarbamide), an oral chemotherapeutic drug, ameliorates some of the clinical problems of SCD, in particular that of pain, by raising fetal haemoglobin. This is an update of a previously published Cochrane Review. OBJECTIVES: To assess the effects of hydroxyurea therapy in people with SCD (all genotypes), of any age, regardless of setting. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Register, comprising of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched online trial registries.Date of the most recent search: 16 January 2017. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials, of one month or longer, comparing hydroxyurea with placebo, standard therapy or other interventions for people with SCD. DATA COLLECTION AND ANALYSIS: Authors independently assessed studies for inclusion, carried out data extraction and assessed the risk of bias. MAIN RESULTS: Seventeen studies were identified in the searches; eight randomised controlled trials were included, recruiting 899 adults and children with SCD (haemoglobin SS (HbSS), haemoglobin SC (HbSC) or haemoglobin Sߺthalassaemia (HbSߺthal) genotypes). Studies lasted from six to 30 months.Four studies (577 adults and children with HbSS or HbSߺthal) compared hydroxyurea to placebo; three recruited individuals with only severe disease and one recruited individuals with all disease severities. There were statistically significant improvements in terms of pain alteration (using measures such as pain crisis frequency, duration, intensity, hospital admissions and opoid use), measures of fetal haemoglobin and neutrophil counts and fewer occurrences of acute chest syndrome and blood transfusions in the hydroxyurea groups. There were no consistent statistically significant differences in terms of quality of life and adverse events (including serious or life-threatening events). Seven deaths occurred during the studies, but the rates by treatment group were not statistically significantly different.Two studies (254 children with HbSS or HbSߺthal also with risk of primary or secondary stroke) compared hydroxyurea and phlebotomy to transfusion and chelation; there were statistically significant improvements in terms of measures of fetal haemoglobin and neutrophil counts, but more occurrences of acute chest syndrome and infections in the hydroxyurea and phlebotomy group. There were no consistent statistically significant differences in terms of pain alteration and adverse events (including serious or life-threatening events). Two deaths occurred during the studies (one in a the hydroxyurea treatment arm and one in the control arm), but the rates by treatment group were not statistically significantly different. In the primary prevention study, no strokes occurred in either treatment group but in the secondary prevention study, seven strokes occurred in the hydroxyurea and phlebotomy group (none in the transfusion and chelation group) and the study was terminated early.The quality of the evidence for the above two comparisons was judged as moderate to low as the studies contributing to these comparisons were mostly large and well designed (and at low risk of bias); however evidence was limited and imprecise for some outcomes such as quality of life, deaths during the studies and adverse events and results are applicable only to individuals with HbSS and HbSߺthal genotypes.Of the remaining two studies, one (22 children with HbSS or HbSߺthal also at risk of stoke) compared hydroxyurea to observation; there were statistically significant improvements in terms of measures of fetal haemoglobin and neutrophil counts but no statistically significant differences in terms of adverse events (including serious or life-threatening events).The final study (44 adults and children with HbSC) compared treatment regimens with and without hydroxyurea - there was statistically significant improvement in terms of measures of fetal haemoglobin, but no statistically significant differences in terms of adverse events (including serious or life-threatening events). No participants died in either of these studies and other outcomes relevant to the review were not reported.The quality of the evidence for the above two comparisons was judged to be very low due to the limited number of participants, the lack of statistical power (as both studies were terminated early with approximately only 20% of their target sample size recruited) and the lack of applicability to all age groups and genotypes. AUTHORS' CONCLUSIONS: There is evidence to suggest that hydroxyurea is effective in decreasing the frequency of pain episodes and other acute complications in adults and children with sickle cell anaemia of HbSS or HbSߺthal genotypes and in preventing life-threatening neurological events in those with sickle cell anaemia at risk of primary stroke by maintaining transcranial doppler velocities. However, there is still insufficient evidence on the long-term benefits of hydroxyurea, particularly in preventing chronic complications of SCD, recommending a standard dose or dose escalation to maximum tolerated dose. There is also insufficient evidence about the long-term risks of hydroxyurea, including its effects on fertility and reproduction. Evidence is also limited on the effects of hydroxyurea on individuals with HbSC genotype. Future studies should be designed to address such uncertainties.
[Mh] Termos MeSH primário: Anemia Falciforme/tratamento farmacológico
Antidrepanocíticos/uso terapêutico
Hidroxiureia/uso terapêutico
[Mh] Termos MeSH secundário: Adulto
Anemia Falciforme/sangue
Anemia Falciforme/mortalidade
Antidrepanocíticos/efeitos adversos
Terapia por Quelação
Criança
Transfusão de Eritrócitos
Genótipo
Doença da Hemoglobina SC/sangue
Doença da Hemoglobina SC/tratamento farmacológico
Seres Humanos
Hidroxiureia/efeitos adversos
Flebotomia/efeitos adversos
Ensaios Clínicos Controlados Aleatórios como Assunto
Conduta Expectante
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; REVIEW
[Nm] Nome de substância:
0 (Antisickling Agents); X6Q56QN5QC (Hydroxyurea)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170801
[Lr] Data última revisão:
170801
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170421
[St] Status:MEDLINE
[do] DOI:10.1002/14651858.CD002202.pub2


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[PMID]:28409830
[Au] Autor:Than NN; Soe HHK; Palaniappan SK; Abas AB; De Franceschi L
[Ad] Endereço:Department of Community Medicine, Melaka-Manipal Medical College, Jalan Batu Hampar, Bukit Baru, Melaka, Malaysia, 75150.
[Ti] Título:Magnesium for treating sickle cell disease.
[So] Source:Cochrane Database Syst Rev;4:CD011358, 2017 Apr 14.
[Is] ISSN:1469-493X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Sickle cell disease is an autosomal recessive inherited haemoglobinopathy which causes painful vaso-occlusive crises due to sickle red blood cell dehydration. Vaso-occlusive crises are common painful events responsible for a variety of clinical complications; overall mortality is increased and life expectancy decreased compared to the general population. Experimental studies suggest that intravenous magnesium has proven to be well-tolerated in individuals hospitalised for the immediate relief of acute (sudden onset) painful crisis and has the potential to decrease the length of hospital stay. Some in vitro studies and open studies of long-term oral magnesium showed promising effect on pain relief but failed to show its efficacy. The studies show that oral magnesium therapy may prevent sickle red blood cell dehydration and prevent recurrent painful episodes. There is a need to access evidence for the impact of oral and intravenous magnesium effect on frequency of pain, length of hospital stay and quality of life. OBJECTIVES: To evaluate the effects of short-term intravenous magnesium on the length of hospital stay and quality of life in children and adults with sickle cell disease. To determine the effects of long-term oral magnesium therapy on the frequency of painful crises and the quality of life in children and adults with sickle cell disease. SEARCH METHODS: We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books.Date of last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register: 01 December 2016.Date of last search of other resources (clinical trials registries): 29 March 2017. SELECTION CRITERIA: We searched for published and unpublished randomized controlled studies of oral or intravenous magnesium compared to placebo or no magnesium. DATA COLLECTION AND ANALYSIS: Authors independently assessed the study quality and extracted the data using standard Cochrane methodologies. MAIN RESULTS: We included five randomized placebo-controlled studies with a total of 386 participants (aged three to 53 years). Two shorter parallel studies (n = 306) compared intravenous magnesium sulphate to placebo (normal saline) for admission to hospital due to a vaso-occlusive crisis, for which we were able to analyse data. The quality of evidence was moderate for studies presenting this comparison mainly due to limitations due to risk of bias and imprecision. Two of the three longer-term studies comparing oral magnesium pidolate to placebo had a cross-over design. The third was a parallel factorial study which compared hydroxyurea and oral magnesium to each other and to placebo over a longer period of time; we only present the comparison of oral magnesium to placebo from this study. The quality of evidence was very low with uncertainty of the estimation.The eight-hourly dose levels in the two studies of intravenous magnesium were different; one used 100 mg/kg while the second used 40 mg/kg. Only one of these studies (n = 104) reported the mean daily pain score while hospitalised (a non-significant difference between groups, moderate quality evidence). The second study (n = 202) reported a number of child- and parent-reported quality of life scores. None of the scores showed any difference between treatment groups (low quality evidence). Data from one study (n = 106) showed no difference in length of stay in hospital between groups (low quality evidence). Both studies reported on adverse events, but not defined by severity as we had planned. One study showed significantly more participants receiving intravenous magnesium experienced warmth at infusion site compared to placebo; there were no differences between groups for other adverse events (low quality evidence).Three studies (n = 80) compared oral magnesium pidolate to placebo. None of them reported data which we were able to analyse. One study (n = 24) reported on the number of painful days and stated there was no difference between two groups (low quality evidence). None of the studies reported on quality of life or length of hospital stay. Two studies (n = 68) reported there were no differences in levels of magnesium in either plasma or red blood cells (moderate quality evidence). Two studies (n = 56) reported adverse events. One reported episodes of mild diarrhoea and headache, all of which resolved without stopping treatment. The second study reported adverse events as gastrointestinal disorders, headache or migraine, upper respiratory infections and rash; which were all evenly distributed across treatment groups (moderate quality evidence). AUTHORS' CONCLUSIONS: Moderate to low quality evidence showed neither intravenous magnesium and oral magnesium therapy has an effect on reducing painful crisis, length of hospital stay and changing quality of life in treating sickle cell disease. Therefore, no definitive conclusions can be made regarding its clinical benefit. Further randomized controlled studies, perhaps multicentre, are necessary to establish whether intravenous and oral magnesium therapies have any effect on improving the health of people with sickle cell disease.
[Mh] Termos MeSH primário: Anemia Falciforme/tratamento farmacológico
Antidrepanocíticos/uso terapêutico
Magnésio/uso terapêutico
[Mh] Termos MeSH secundário: Administração Oral
Adolescente
Adulto
Anemia Falciforme/sangue
Criança
Pré-Escolar
Seres Humanos
Hidroxiureia/uso terapêutico
Injeções Intravenosas
Magnésio/efeitos adversos
Magnésio/sangue
Sulfato de Magnésio/uso terapêutico
Meia-Idade
Medição da Dor
Pais
Ácido Pirrolidonocarboxílico/uso terapêutico
Qualidade de Vida
Ensaios Clínicos Controlados Aleatórios como Assunto
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antisickling Agents); 7487-88-9 (Magnesium Sulfate); I38ZP9992A (Magnesium); SZB83O1W42 (Pyrrolidonecarboxylic Acid); X6Q56QN5QC (Hydroxyurea)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170801
[Lr] Data última revisão:
170801
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170415
[St] Status:MEDLINE
[do] DOI:10.1002/14651858.CD011358.pub2



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