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1.
Public Health Res (Southampt) ; 12(3): 1-192, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38421001

RESUMO

Background: Schools have a duty of care to prevent violence between students but a significant amount of dating and relationship violence and gender-based violence occurs in schools. These are important public health issues with important longitudinal consequences for young people. Objectives: To understand functioning and effectiveness of school-based interventions for the prevention of dating and relationship violence and gender-based violence. Review methods: We undertook a mixed-methods systematic review to synthesise different types of evidence relating to school-based interventions for the prevention of dating and relationship violence and gender-based violence to understand if, how and in what ways these interventions are effective. We searched 21 databases and 2 trial registers and undertook forwards and backwards citation chasing, author contact and other supplementary search methods. Searches identified all literature published to June 2021. All screening was undertaken in duplicate and independently, and we quality appraised all included studies. Results: We included 247 reports (68 outcome evaluations, 137 process evaluations). Synthesis of intervention components produced an intervention typology: single-component, curricular, multicomponent, and multilevel programmes. Synthesis of intervention theories suggested that interventions aiming to increase students' sense of school belonging and sense of safety in the school building could encourage increased learning of prosocial skills and increased prosocial peer norms, and so potentially reducing dating and relationship violence and gender-based violence. Synthesis of factors affecting delivery highlighted school organisation and leaders who believed in the importance of addressing dating and relationship violence/gender-based violence, along with time and resources to deliver the interventions. The ease with which the intervention could be delivered and modified was also important. Meta-analysis found stronger evidence for intervention effectiveness in reducing dating and relationship violence than for gender-based violence, with significant long-term impacts on dating and relationship violence victimisation and perpetration, and some evidence that interventions in high-income countries could be effective for reducing victimisation and perpetration of gender-based violence in the long-term. Impacts on knowledge and attitudes were primarily short-term. Network meta-analysis did not suggest superiority of any intervention type. Moderation evidence suggested interventions reduced dating and relationship violence perpetration in boys more than girls, but reduced gender-based violence perpetration more in girls. Metaregression by intervention component did not explain heterogeneity in effectiveness, but qualitative comparative analysis suggested that reducing perpetration was important to reducing victimisation, and that perpetration could be reduced via focus on interpersonal skills, guided practice and (for gender-based violence) implementation of social structural components. Limitations: Despite an exhaustive search, trials may have been missed and risk of publication bias was high for several analyses. Conclusions: This is the most comprehensive systematic review of school-based interventions for dating and relationship violence and gender-based violence to date. It is clear that the prevention of dating and relationship violence and gender-based violence in schools will require longer-term investment to show benefit. Future work: Future research is needed to understand why intervention effectiveness appears stronger for dating and relationship violence than gender-based violence. Study registration: The study is registered as PROSPERO CRD42020190463. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme (NIHR award ref: NIHR130144) and is published in full in Public Health Research; Vol. 12, No. 3. See the NIHR Funding and Awards website for further award information.


Schools are places where dating and relationship violence and gender-based violence occur. Therefore, interventions conducted within schools are ideally placed to prevent and reduce dating and relationship violence and gender-based violence. We reviewed existing research on these interventions, exploring how they were expected to work, what factors affected their implementation in practice, how they had an impact on dating and relationship violence and gender-based violence, and what specific parts of the interventions were most effective and in what contexts. We defined what sort of evidence to include in the review, carried out a comprehensive search and found 247 reports on school-based interventions to prevent dating and relationship violence or gender-based violence, most of which were conducted in North America. Most interventions aimed to provide students with the knowledge, attitudes and skills needed to prevent perpetration and victimisation. They varied in complexity; some had one activity, others had multiple activities, some were integrated into the existing school curricula and others were complex in that they sought to change how schools as a whole respond to dating and relationship violence or gender-based violence. We theorised that complex interventions would bring about greater and more sustainable change, but this was not supported by our findings. The implementation of interventions was affected by factors such as school organisation and leaders who believed in the importance of addressing dating and relationship violence/gender-based violence, along with time and resources to deliver the interventions. The ease with which the intervention could be delivered and modified was also important. There was stronger evidence for intervention effectiveness in reducing dating and relationship violence than for gender-based violence, with significant long-term impacts on dating and relationship violence victimisation and perpetration. There was some evidence that interventions in high-income countries could be effective for reducing victimisation and perpetration of gender-based violence in the long-term. More complicated interventions were not more effective, and interventions tended to reduce dating and relationship violence perpetration in boys more than in girls. We have also been able to identify where there are gaps in available evidence, which may provide avenues for future research.


Assuntos
Vítimas de Crime , Violência de Gênero , Masculino , Feminino , Humanos , Adolescente , Instituições Acadêmicas , Habilidades Sociais , Violência de Gênero/prevenção & controle , Estudantes
2.
Res Synth Methods ; 14(4): 582-595, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37287195

RESUMO

Conventional systematic reviews offer few insights into for whom and how interventions work. 'Realist reviews' examine such questions via examining 'context-mechanism-outcome configurations' (CMOCs) but are insufficiently rigorous in how evidence is identified, assessed and synthesised. We developed 'realist systematic reviews', addressing similar questions to realist reviews but using rigorous methods. We applied this to synthesising evidence on school-based prevention of dating and relationship violence (DRV) and gender-based violence (GBV). This paper reflects on overall methods and findings, drawing on papers reporting each analysis. Drawing on intervention descriptions, theories of change and process evaluations, we developed initial CMOC hypotheses: interventions triggering 'school-transformation' mechanisms (preventing violence by changing school environments) will achieve larger effects than those triggering 'basic-safety' (stopping violence by emphasising its unacceptability) or 'positive-development' (developing students' broader skills and relationships) mechanisms; however, school transformation would only work in schools with high organisational capacity. We used various innovative analyses, some of which aimed to test these hypotheses and some of which were inductive, drawing on available findings to augment and refine the CMOCs. Overall, interventions were effective in reducing long-term DRV but not GBV or short-term DRV. DRV prevention occurred most effectively via the 'basic-safety' mechanism. 'School-transformation' mechanisms were more effective in preventing GBV but only in high-income countries. Impacts on long-term DRV victimisation were greater when working with a critical mass of participating girls. Impacts on long-term DRV perpetration were greater for boys. Interventions were more effective when focusing on skills, attitudes and relationships, or lacking parental involvement or victim stories. Our method provided novel insights and should be useful to policy-makers seeking the best interventions for their contexts and the most information to inform implementation.


Assuntos
Violência de Gênero , Revisões Sistemáticas como Assunto , Feminino , Humanos , Masculino , Violência de Gênero/prevenção & controle , Instituições Acadêmicas , Estudantes , Violência/prevenção & controle
3.
Prev Med Rep ; 34: 102277, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37387728

RESUMO

School-based interventions for the prevention of dating and relationship violence (DRV) and gender-based violence (GBV) take advantage of universal opportunities for intervention. Information on differential effectiveness of interventions is important to assess if they ameliorate or worsen social gradients in specific outcomes. This is especially important in DRV and GBV prevention given the gendered context of these behaviours and their common aetiologies in patriarchal gender norms, and social acceptance in school contexts of sexual harassment, such as catcalling or unwanted groping. We undertook a systematic review of moderation analyses in randomised trials of school-based interventions for DRV and GBV prevention. We searched 21 databases and used supplementary search methods without regard to publication type, language or year of publication, and synthesised moderation tests relating to equity-relevant characteristics (principally sex and prior history of the outcome) for DRV and GBV perpetration and victimisation. Across 23 included outcome evaluations, programme effects on DRV victimisation were not moderated by gender or prior experience of DRV victimisation, but DRV perpetration outcomes were greater for boys, particularly for emotional and physical DRV perpetration. Findings for GBV outcomes were counterintuitive. Our findings suggest that practitioners should carefully monitor local intervention effectiveness and equity to ensure that interventions are working as intended. However, one of the most surprising findings from our analysis-with clear relevance for uncertainties in practice-was that differential impacts by sexuality or sexual minority status were not frequently evaluated.

4.
Am J Public Health ; 113(3): 320-330, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36791352

RESUMO

Background. Schools are sites of dating and relationship violence (DRV) and of gender-based violence (GBV) victimization and perpetration. School-based interventions can reach a broad range of students, targeting both individual and group processes that may underpin DRV and GBV. Considering DRV and GBV jointly is important because of their shared etiologies. Comparing the effectiveness of interventions using network meta-analysis (NMA) can support decision-making on optimal resource use. Objectives. To evaluate the comparative effectiveness of school-based interventions for children aged 5 to 18 years on DRV and GBV victimization, perpetration, and related mediators. Search Methods. We searched 21 databases in July 2020 and June 2021, alongside extensive supplementary search methods, including gray literature searches, forward and backward citation chasing, and searches on first and last author names. Selection Criteria. We included randomized-controlled trials of interventions for children of compulsory school age implemented within the school setting, and either partially or wholly aimed at changing DRV or GBV outcomes. Data Collection and Analysis. Pairwise meta-analyses using random-effects robust variance estimation considered intervention effectiveness on DRV and GBV victimization and perpetration using odds ratios, and on mediators (e.g., knowledge and attitudes) using standardized mean differences. Effects were divided into short-term (< 12 months postbaseline) and long-term (≥ 12 months postbaseline). NMAs on victimization and perpetration outcomes compared interventions categorized by breadth of mechanism and complexity of delivery and implementation. Meta-regression tested sensitivity to percentage of girls in the trial sample and country context. Main Results. Our analysis included 68 trials. Evidence was stronger overall for effects on DRV than for GBV, with significant long-term impacts on DRV victimization (odds ratio [OR] = 0.82; 95% confidence interval [CI] = 0.68, 0.99) and DRV perpetration (OR = 0.78; 95% CI = 0.64, 0.94). Knowledge and attitudinal effects were predominantly short-term (e.g., for DRV-related violence acceptance, d = 0.16; 95% CI = 0.08, 0.24). NMAs did not suggest the superiority of any intervention type; however, most analyses for GBV outcomes were inconsistent. A higher proportion of girls in the sample was associated with increased effectiveness on long-term victimization outcomes. Author's Conclusions. Evidence is stronger for DRV than for GBV, despite considerable heterogeneity. Certainty of findings was low or very low overall. Public Health Implications. Violence reductions may require more than 1 school year to become apparent. More extensive interventions may not be more effective. A possible reason for stronger effectiveness for DRV is that whereas GBV is ingrained in school cultures and practices, DRV is potentially more open to change via addressing individual knowledge and attitudes. (Am J Public Health. 2023;113(3):320-330. https://doi.org/10.2105/10.2105/AJPH.2022.307153).


Assuntos
Vítimas de Crime , Violência de Gênero , Criança , Feminino , Humanos , Metanálise em Rede , Violência/prevenção & controle , Atitude
5.
Arch Dis Child ; 108(4): 296-299, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36599626

RESUMO

OBJECTIVE: In 2021, centres across all seven NHS-England regions were selected to develop pilot clinics with the aim of treating children and young people (CYP) living with complications relating to excess weight (CEW). We led a process to develop core outcomes to enable the evaluation of these clinics. METHODS: A two-round Delphi process, virtual steering group meetings and two patient representation workshops were used to agree the most important outcomes for both clinicians/allied professionals and representative prospective service users. RESULTS: A total of 119 clinicians/allied professionals were invited to contribute to the Delphi process: 62 (52%) agreed and completed round 1 and 47 of these (76%) went on to complete round 2. Six young people (age range 13-17 years) and six parents were involved in two patient representation workshops and their experiences fed into virtual steering group meetings, via a representative.There were 44 outcomes assessed in round 1 and 21 outcomes assessed in round 2. There were 16 core outcomes selected: anthropometric, glucose tolerance/insulin resistance/type 2 diabetes, blood pressure, lipid profile, breathing problems, identification of aetiology, non-alcoholic fatty liver disease, idiopathic intracranial hypertension, anxiety, depression, self-esteem, quality of life, school attendance, dietary habits including disordered eating, exercise and activity habits. CONCLUSIONS: Use of an online Delphi process, patient representation workshops and virtual steering group meetings has enabled the development of core outcomes for clinical obesity services with eight physical health, five mental health and three self-management outcomes. Further work is needed to develop outcome measures to complete a core outcome set. These will be used to guide the evaluation of novel regional clinics for the treatment of complications of excess weight.


Assuntos
Diabetes Mellitus Tipo 2 , Criança , Humanos , Adolescente , Consenso , Qualidade de Vida , Estudos Prospectivos , Avaliação de Resultados em Cuidados de Saúde , Técnica Delphi , Resultado do Tratamento , Projetos de Pesquisa
6.
Health Educ Behav ; 50(3): 339-346, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36503294

RESUMO

Dating and relationship violence (DRV) and gender-based violence (GBV) among children and young people incur a high cost to individuals and society. School-based interventions present an opportunity to prevent DRV and GBV early in individuals' lives. However, with school resources under pressure, policymakers require guidance on the economics of implementing interventions. As part of a large systematic review funded by the National Institute for Health and Care Research (NIHR), we searched for economic evaluations and costing studies of school-based interventions for DRV and GBV. No formal economic evaluations were identified. Seven studies reporting costs, cost savings, or resource use for eight interventions were identified. The largest costs of implementing interventions were related to staff training and salaries but savings could be made by implementing interventions on a large scale. The potential cost savings of avoided DRV and GBV far outweighed the costs of implementation.


Assuntos
Violência de Gênero , Violência por Parceiro Íntimo , Adolescente , Criança , Humanos , Análise Custo-Benefício , Violência de Gênero/prevenção & controle , Violência por Parceiro Íntimo/prevenção & controle , Instituições Acadêmicas
7.
Trauma Violence Abuse ; 24(5): 3593-3614, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-36448544

RESUMO

Adolescents are at an increased risk for experiencing dating and relationship violence (DRV) and gender-based violence (GBV). School-based interventions remain an important and frequently used method for DRV/GBV prevention. A clear understanding and description of the different components of school-based interventions specific to DRV/GBV is needed to organize and advance the array of prevention efforts being utilized in school settings. We conducted an intervention component analysis to create a taxonomy for school-based interventions addressing DRV and GBV. We searched 21 databases in July 2020 and updated searches in June 2021, alongside extensive supplementary search methods. We included randomized controlled trials (RCTs) in adolescents of compulsory school-age that were implemented within the school setting which partially or wholly focused on DRV and GBV topics. Our analysis included 68 studies describing 76 different school-based interventions. Through an iterative coding process we identified 40 intervention components organized within 13 activity categories, including both student-directed components and non-student-directed components such as activities for school personnel and family members of students. We also identified components addressing higher levels of the social-ecological model including structural-social and structural-environmental aspects of DRV/GBV which prior reviews have not considered. This taxonomy of components and synthesis of intervention efficacy for DRV/GBV school-based interventions provides a framework for comparing past intervention evaluations and constructing new interventions to address these issues at multiple levels within a community.


Assuntos
Violência de Gênero , Violência por Parceiro Íntimo , Adolescente , Humanos , Violência por Parceiro Íntimo/prevenção & controle , Violência de Gênero/prevenção & controle , Instituições Acadêmicas , Estudantes , Família
8.
Artigo em Inglês | MEDLINE | ID: mdl-35329365

RESUMO

Meaningful inclusion of young people's perceptions and experiences of inequalities is argued to be critical in the development of pro-equity policies. Our study explored young people's perceptions of what influences their opportunities to be healthy within their local area and their understandings of health inequalities. Three interlinked qualitative focus group discussions, each lasting 90 to 100 min, with the same six groups of young people (n = 42) aged 13-21, were conducted between February and June 2021. Participants were recruited from six youth groups in areas of high deprivation across three geographical locations in England (South Yorkshire, the North East and London). Our study demonstrates that young people understand that health inequalities are generated by social determinants of health, which in turn influence behaviours. They highlight a complex interweaving of pathways between social determinants and health outcomes. However, they do not tend to think in terms of the social determinants and their distribution as resulting from the power and influence of those who create and benefit from health and social inequalities. An informed understanding of the causes of health inequalities, influenced by their own unique generational experiences, is important to help young people contribute to the development of pro-equity policies of the future.


Assuntos
Nível de Saúde , Adolescente , Inglaterra , Humanos , Londres , Fatores Socioeconômicos
9.
Rev Educ ; 10(3): e3382, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37090159

RESUMO

School-based interventions for preventing dating and relationship violence (DRV) and gender-based violence (GBV) are an important way of attempting to prevent and reduce the significant amount of DRV and GBV that occurs in schools. A theoretical understanding of how these interventions are likely to cause change is essential for developing and evaluating effectiveness, so developing an overarching theory of change for school-based interventions to prevent DRV and GBV was the first step in our systematic review. Theoretical data were synthesised from 68 outcome evaluations using methods common to qualitative synthesis. Specifically, we used a meta-ethnographic approach to develop a line-of-argument for an overarching theory of change and Markham and Aveyard's (2003, Social Science & Medicine, 56, 1209) theory of human functioning and school organisation as a framework for structuring the concepts. The overall theory of change generated was that by strengthening relationships between and among staff and students, between the classroom and the wider school, and between schools and communities, and by increasing students' sense of belonging with student-centred learning opportunities, schools would encourage student commitment to the school and its values, prosocial behaviour and avoidance of violence and aggression. The theory of human functioning informed our understanding of the mechanisms of action but from our analysis we found that it required refinement to address the importance of context and student agency.

10.
Arch Dis Child ; 106(1): 9-13, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32561543

RESUMO

The 2019 NHS England Long Term Plan set out the ambition to work across the 0-25 age range to support children and young people as they make the transition to early adulthood. Within this broad age bracket, how do we ensure we get health services right for 16-25 year-olds including the transfer to adult services? In this paper, we explore the evidence supporting youth-friendly and developmentally appropriate healthcare approaches and what these mean in practice for young people and healthcare professionals. Examples from primary and secondary care, as well as the perspectives of a young person, illustrate the challenges and solutions.


Assuntos
Serviços de Saúde do Adolescente , Transição para Assistência do Adulto , Adolescente , Humanos , Garantia da Qualidade dos Cuidados de Saúde , Medicina Estatal , Reino Unido , Adulto Jovem
11.
Kidney Int ; 95(3): 666-679, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30784662

RESUMO

Autoantibodies against phospholipase A2 receptor 1 (PLA2R1) and thrombospondin type 1 domain-containing 7A (THSD7A) are emerging as biomarkers to classify membranous nephropathy (MN) and to predict outcome or response to treatment. Anti-THSD7A autoantibodies are detected by Western blot and indirect immunofluorescence test (IIFT). Here, we developed a sensitive enzyme-linked immunosorbent assay (ELISA) optimized for quantitative detection of anti-THSD7A autoantibodies. Among 1012 biopsy-proven MN patients from 6 cohorts, 28 THSD7A-positive patients were identified by ELISA, indicating a prevalence of 2.8%. By screening additional patients, mostly referred because of PLA2R1-unrelated MN, we identified 21 more cases, establishing a cohort of 49 THSD7A-positive patients. Twenty-eight patients (57%) were male, and male patients were older than female patients (67 versus 49 years). Eight patients had a history of malignancy, but only 3 were diagnosed with malignancy within 2 years of MN diagnosis. We compared the results of ELISA, IIFT, Western blot, and biopsy staining, and found a significant correlation between ELISA and IIFT titers. Anti-THSD7A autoantibodies were predominantly IgG4 in all patients. Eight patients were double positive for THSD7A and PLA2R1. Levels of anti-THSD7A autoantibodies correlated with disease activity and with response to treatment. Patients with high titer at baseline had poor clinical outcome. In a subgroup of patients with serial titers, persistently elevated anti-THSD7A autoantibodies were observed in patients who did not respond to treatment or did not achieve remission. We conclude that the novel anti-THSD7A ELISA can be used to identify patients with THSD7A-associated MN and to monitor autoantibody titers during treatment.


Assuntos
Autoanticorpos/análise , Glomerulonefrite Membranosa/diagnóstico , Imunossupressores/uso terapêutico , Trombospondinas/imunologia , Adulto , Idoso , Autoanticorpos/imunologia , Biomarcadores/análise , Biópsia , Monitoramento de Medicamentos/métodos , Ensaio de Imunoadsorção Enzimática/métodos , Estudos de Viabilidade , Feminino , Glomerulonefrite Membranosa/tratamento farmacológico , Glomerulonefrite Membranosa/imunologia , Células HEK293 , Humanos , Masculino , Pessoa de Meia-Idade , Receptores da Fosfolipase A2/imunologia , Estudos Retrospectivos , Sensibilidade e Especificidade , Fatores de Tempo , Resultado do Tratamento
13.
Arch Dis Child Educ Pract Ed ; 103(4): 207-210, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-28798055

RESUMO

Young people from marginalised groups can be excluded from health services because of reduced access, increased stigma and health inequalities. In addition, the stress associated with discrimination and stigma can have serious effects on individual health. This article explores how stigma affects young people's access to services and how health professionals can improve their practice and support for marginalised young people to achieve the best possible health outcomes. A better understanding of local populations of young people and their needs is key to improving services and support. Working in partnership with voluntary and community sector organisations is also important. In addition, improvements can be made by promoting better communication with young people and providing extra support to help them follow treatment plans.


Assuntos
Acessibilidade aos Serviços de Saúde/organização & administração , Pediatras/organização & administração , Saúde Pública , Criança , Humanos
14.
Arch Dis Child ; 97(8): 704-8, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22685052

RESUMO

BACKGROUND: Out-of-hospital measurements of blood pressure (BP) are important for investigating and managing hypertension, but information is limited regarding the right technique to use in infants, small children and those intolerant of ambulatory BP monitoring. The aim of the study was to determine the feasibility and clinical utility of home Doppler BP monitoring (HDBPM). METHODS: This single-centre study included all consecutive patients referred to a tertiary hypertension clinic who underwent HDBPM over a 12-month period. Parents were taught to measure systolic BP using a Doppler instrument. RESULTS: HDBPM was successfully performed in 15 children (median (IQR) age 2.2 (0.9-3.7) years). All six patients referred for confirmation of newly diagnosed hypertension following sustained elevated clinic BP levels were found to be normotensive. Of the nine children referred with 'treated hypertension' for monitoring currently elevated clinic BP levels, four had confirmed hypertension and five were normotensive on HDBPM. In all nine 'treated hypertensive' patients, medication changes and normotensive BP levels were achieved with on-going home Doppler monitoring. 11/15 (73.3%) subjects successfully performed ≥1 BP measurement on at least 24 days of the 28-day monitoring period. The median (IQR) number of BP measurements performed weekly through week 4 of HDBPM were 22 (13-36), 18 (12-38), 18 (11-36) and 16 (8-32) respectively. No patient was hospitalised for further BP monitoring. CONCLUSIONS: HDBPM is acceptable to children and their families, demonstrating its feasibility as an out-of-office measurement technique. The initial results and the reliability of HDBPM need to be explored in larger clinical studies.


Assuntos
Monitorização Ambulatorial da Pressão Arterial/métodos , Pressão Sanguínea/fisiologia , Hipertensão/diagnóstico , Pré-Escolar , Estudos de Viabilidade , Humanos , Lactente , Projetos Piloto
15.
Am J Gastroenterol ; 101(2): 304-10, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16454835

RESUMO

OBJECTIVES: Predisposition to alcoholic liver disease (ALD) may be partly genetic. Heterozygosity for the HFE mutations C282Y and/or H63D has been associated with more severe disease in several liver conditions. Studies in ALD have not used controls matched for alcohol consumption and results have been conflicting. METHODS: HFE genotyping was performed in two Caucasian heavy-drinking cohorts (>60 units/wk (M) or 40 units/wk (F) for >5 yr): (a) 254 patients with decompensated ALD (Child's grade B or C), (b) 130 controls with similar alcohol consumption but without liver disease. Results in males were also compared with those from another study of healthy male blood donors. RESULTS: (1) Genotype distributions for the C282Y and H63D mutations were similar in ALD patients, heavy-drinking controls, and healthy blood donors. (2) ALD patients with and without HFE mutations had similar disease severity, age at presentation, and alcohol consumption. (3) Increased serum ferritin and % transferrin saturation were seen in 63% and 29% of ALD patients, regardless of HFE genotype; the increased % transferrin saturation was due to reduced unsaturated iron binding capacity, rather than increased serum iron. (4) Stainable liver iron was present in 52% of patients; grade was greater in patients with two HFE mutations than in those with one or with none. (5) Only the two C282Y homozygote patients had substantial iron overload. CONCLUSIONS: Although serum iron abnormalities are common, C282Y and H63D mutation frequencies were not increased in heavy drinkers with decompensated liver disease. HFE mutations, although modestly influencing liver iron, do not predispose to clinically significant ALD.


Assuntos
Consumo de Bebidas Alcoólicas/genética , DNA/genética , Expressão Gênica , Antígenos de Histocompatibilidade Classe I/genética , Hepatopatias Alcoólicas/genética , Proteínas de Membrana/genética , Consumo de Bebidas Alcoólicas/sangue , Doadores de Sangue , Progressão da Doença , Feminino , Ferritinas/sangue , Predisposição Genética para Doença , Proteína da Hemocromatose , Humanos , Ferro/sangue , Hepatopatias Alcoólicas/sangue , Masculino , Pessoa de Meia-Idade , Mutação , Fenótipo , Reação em Cadeia da Polimerase , Fatores de Risco , Índice de Gravidade de Doença , Transferrina/metabolismo
16.
Nephrol Dial Transplant ; 21(7): 1848-54, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16311257

RESUMO

BACKGROUND: Severe steroid-dependent nephrotic syndrome (SDNS) is a common type of nephrotic syndrome (NS) observed in childhood. Steroid-sparing agents such as calcineurin inhibitors (CNIs) are used to avoid steroid toxicity in SDNS. Tacrolimus (TAC) has been prescribed for maintaining remission of NS in patients who have developed treatment resistance or adverse effects with cyclosporin A (CYA) at our institution since 1995. The aim of this study was to compare the efficacy and complications of TAC with CYA in the management of severe SDNS. METHODS: We report a retrospective longitudinal clinical series of patients with SDNS, all of whom have been treated with TAC. RESULTS: Ten SDNS children (eight males) were reviewed quarterly from time of initial referral to the present day during 93 completed treatment patient years. Nine patients had minimal change disease and one had focal segmental glomerulosclerosis on their first biopsy. The median age at diagnosis was 2.9 years (range 1.6-12.9). The median age at initial referral was 3.9 years (range 2.2-12.9). All patients initially responded to prednisolone at 60 mg/m2/day, and subsequent frequent relapses were treated sequentially with oral cyclophosphamide 168 mg/kg over 8-12 weeks (n = 10), CYA (n = 10), intravenous mustine or a second course of cyclophosphamide (n = 7) and then TAC (n = 10). The initial daily treatment of CYA and TAC in two divided doses was 5 and 0.1 mg/kg/day, respectively; targeted 12 h blood drug levels were of 50-100 microg/l for CYA and 5-10 microg/l for TAC. Patients underwent renal biopsy and the formal glomerular filtration rate (GFR) was measured using plasma clearance of the Inutest method every 2-3 years while receiving CNIs. Six patients continued with TAC; in four patients, TAC was discontinued because of poor response (n = 2), hypertension (n = 1) and glucose intolerance (n = 1). For CYA and TAC treatment periods, the median NS relapse rate was two and one relapses per year, respectively, and cumulative steroid dosage was 73.9 and 105.2 mg/kg/day, respectively (P = 0.54). The reduction in GFR was 5.8 and 11.7 ml/min/1.73 m2 during these periods. Three of the 10 patients showed histological evidence of mild CNI nephrotoxicity over the whole of the CNI treatment period despite achieving target therapeutic drug levels; no significant change in measured or calculated GFR over this prolonged CNI therapy was observed. Antihypertensive medication was prescribed for 11 of 31 CYA and 22 of 40 TAC treatment years. Growth was maintained during the entire CNI therapy period with median change in height SD scores (SDS) of +0.37 and -0.03 over CYA and TAC, respectively (P = 0.13). CONCLUSION: In conclusion, we observed that the replacement of CYA by TAC does not lead to a better management of severe SDNS.


Assuntos
Imunossupressores/farmacologia , Síndrome Nefrótica/tratamento farmacológico , Esteroides/metabolismo , Tacrolimo/uso terapêutico , Inibidores de Calcineurina , Criança , Pré-Escolar , Ciclosporina/farmacologia , Feminino , Taxa de Filtração Glomerular , Humanos , Lactente , Estudos Longitudinais , Masculino , Síndrome Nefrótica/metabolismo , Estudos Retrospectivos , Fatores de Tempo
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