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Orphanet J Rare Dis ; 15(1): 12, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31937333


BACKGROUND: Inherited metabolic diseases (IMDs) are a group of individually rare single-gene diseases. For many IMDs, there is a paucity of high-quality evidence that evaluates the effectiveness of clinical interventions. Clinical effectiveness trials of IMD interventions could be supported through the development of core outcome sets (COSs), a recommended minimum set of standardized, high-quality outcomes and associated outcome measurement instruments to be incorporated by all trials in an area of study. We began the process of establishing pediatric COSs for two IMDs, medium-chain acyl-CoA dehydrogenase (MCAD) deficiency and phenylketonuria (PKU), by reviewing published literature to describe outcomes reported by authors, identify heterogeneity in outcomes across studies, and assemble a candidate list of outcomes. METHODS: We used a comprehensive search strategy to identify primary studies and guidelines relevant to children with MCAD deficiency and PKU, extracting study characteristics and outcome information from eligible studies including outcome measurement instruments for select outcomes. Informed by an established framework and a previously published pediatric COS, outcomes were grouped into five, mutually-exclusive, a priori core areas: growth and development, life impact, pathophysiological manifestations, resource use, and death. RESULTS: For MCAD deficiency, we identified 83 outcomes from 52 articles. The most frequently represented core area was pathophysiological manifestations, with 33 outcomes reported in 29/52 articles (56%). Death was the most frequently reported outcome. One-third of outcomes were reported by a single study. The most diversely measured outcome was cognition and intelligence/IQ for which eight unique measurement instruments were reported among 14 articles. For PKU, we identified 97 outcomes from 343 articles. The most frequently represented core area was pathophysiological manifestations with 31 outcomes reported in 281/343 articles (82%). Phenylalanine concentration was the most frequently reported outcome. Sixteen percent of outcomes were reported by a single study. Similar to MCAD deficiency, the most diversely measured PKU outcome was cognition and intelligence/IQ with 39 different instruments reported among 82 articles. CONCLUSIONS: Heterogeneity of reported outcomes and outcome measurement instruments across published studies for both MCAD deficiency and PKU highlights the need for COSs for these diseases, to promote the use of meaningful outcomes and facilitate comparisons across studies.

BMJ ; 366: l4363, 2019 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-31340984


OBJECTIVES: To determine the rate of a first recurrent venous thromboembolism (VTE) event after discontinuation of anticoagulant treatment in patients with a first episode of unprovoked VTE, and the cumulative incidence for recurrent VTE up to 10 years. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, Embase, and the Cochrane Central Register of Controlled Trials (from inception to 15 March 2019). STUDY SELECTION: Randomised controlled trials and prospective cohort studies reporting symptomatic recurrent VTE after discontinuation of anticoagulant treatment in patients with a first unprovoked VTE event who had completed at least three months of treatment. DATA EXTRACTION AND SYNTHESIS: Two investigators independently screened studies, extracted data, and appraised risk of bias. Data clarifications were sought from authors of eligible studies. Recurrent VTE events and person years of follow-up after discontinuation of anticoagulant treatment were used to calculate rates for individual studies, and data were pooled using random effects meta-analysis. Sex and site of initial VTE were investigated as potential sources of between study heterogeneity. RESULTS: 18 studies involving 7515 patients were included in the analysis. The pooled rate of recurrent VTE per 100 person years after discontinuation of anticoagulant treatment was 10.3 events (95% confidence interval 8.6 to 12.1) in the first year, 6.3 (5.1 to 7.7) in the second year, 3.8 events/year (95% confidence interval 3.2 to 4.5) in years 3-5, and 3.1 events/year (1.7 to 4.9) in years 6-10. The cumulative incidence for recurrent VTE was 16% (95% confidence interval 13% to 19%) at 2 years, 25% (21% to 29%) at 5 years, and 36% (28% to 45%) at 10 years. The pooled rate of recurrent VTE per 100 person years in the first year was 11.9 events (9.6 to 14.4) for men and 8.9 events (6.8 to 11.3) for women, with a cumulative incidence for recurrent VTE of 41% (28% to 56%) and 29% (20% to 38%), respectively, at 10 years. Compared to patients with isolated pulmonary embolism, the rate of recurrent VTE was higher in patients with proximal deep vein thrombosis (rate ratio 1.4, 95% confidence interval 1.1 to 1.7) and in patients with pulmonary embolism plus deep vein thrombosis (1.5, 1.1 to 1.9). In patients with distal deep vein thrombosis, the pooled rate of recurrent VTE per 100 person years was 1.9 events (95% confidence interval 0.5 to 4.3) in the first year after anticoagulation had stopped. The case fatality rate for recurrent VTE was 4% (95% confidence interval 2% to 6%). CONCLUSIONS: In patients with a first episode of unprovoked VTE who completed at least three months of anticoagulant treatment, the risk of recurrent VTE was 10% in the first year after treatment, 16% at two years, 25% at five years, and 36% at 10 years, with 4% of recurrent VTE events resulting in death. These estimates should inform clinical practice guidelines, enhance confidence in counselling patients of their prognosis, and help guide decision making about long term management of unprovoked VTE. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017056309.

Anticoagulantes/uso terapêutico , Medição de Risco/métodos , Tromboembolia Venosa , Suspensão de Tratamento , Humanos , Recidiva , Tempo , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/fisiopatologia
Artigo em Inglês | MEDLINE | ID: mdl-31067692


Stair and bathroom falls contribute to injuries among older adults. This review examined which features of stairs and bathrooms have been assessed in epidemiological, ergonomic, and national aging studies on falls or their risk factors. Epidemiological and ergonomic studies were eligible if published from 2006-2017, written in English, included older persons, and reported built environment measures. The data extracted included the following: study population and design, outcome measures, and stair and bathroom features. National aging studies were eligible if English questionnaires were available, and if data were collected within the last 10 years. Sample characteristics; data collection methods; and data about falls, the environment, and assistive device use were extracted. There were 114 eligible articles assessed-38 epidemiologic and 76 ergonomic. Among epidemiological studies, 2 assessed stair falls only, 4 assessed bathroom falls only, and 32 assessed falls in both locations. Among ergonomic studies, 67 simulated stairs and 9 simulated bathrooms. Specific environmental features were described in 14 (36.8%) epidemiological studies and 73 (96%) ergonomic studies. Thirteen national aging studies were identified-four had stair data and six had bathroom data. Most epidemiologic and national aging studies did not include specific measures of stairs or bathrooms; the built environment descriptions in ergonomic studies were more detailed. More consistent and detailed environmental measures in epidemiologic and national aging studies would better inform fall prevention approaches targeting the built environment.

Acidentes por Quedas/estatística & dados numéricos , Ambiente Construído , Toaletes , Ergonomia , Humanos , Estudos Longitudinais , Fatores de Risco
Trials ; 18(1): 603, 2017 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-29258568


BACKGROUND: Inherited metabolic diseases (IMD) are a large group of rare single-gene disorders that are typically diagnosed early in life. There are important evidence gaps related to the comparative effectiveness of therapies for IMD, which are in part due to challenges in conducting randomized controlled trials (RCTs) for rare diseases. Registry-based RCTs present a unique opportunity to address these challenges provided the registries implement standardized collection of outcomes that are important to patients and their caregivers and to clinical providers and healthcare systems. Currently there is no core outcome set (COS) for studies evaluating interventions for paediatric IMD. This protocol outlines a study that will establish COS for each of two relatively common IMD in children, phenylketonuria (PKU) and medium-chain acyl-CoA dehydrogenase (MCAD) deficiency. METHODS: This two-part study is registered with the Core Outcome Measures in Effectiveness Trials (COMET) initiative. Part 1 includes a rapid review and development of an evidence map to identify a comprehensive listing of outcomes reported in past studies of PKU and MCAD deficiency. The review follows established methods for knowledge synthesis, including a comprehensive search strategy, two stages of screening citations against inclusion/exclusion criteria by two reviewers working independently, and extraction of important data elements from eligible studies, including details of the outcomes collected and outcome measurement instruments. The review findings will inform part 2 of our study, a set of Delphi surveys to establish consensus on the highest priority outcomes for each condition. Healthcare providers, families of children with PKU or MCAD deficiency, and health system decision-makers will be invited to participate in two to three rounds of Delphi surveys. The design of the surveys will involve parents of children with IMD who are part of a family advisory forum. DISCUSSION: This protocol is a crucial step in developing the capacity to launch RCTs with meaningful outcomes that address comparative effectiveness questions in the field of paediatric IMD. Such trials will contribute high-quality evidence to inform decision-making by patients and their family members, clinicians, and policy-makers.

Acil-CoA Desidrogenase/deficiência , Técnica Delfos , Determinação de Ponto Final/normas , Erros Inatos do Metabolismo Lipídico/terapia , Fenilcetonúrias/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Projetos de Pesquisa/normas , Consenso , Humanos , Erros Inatos do Metabolismo Lipídico/diagnóstico , Fenilcetonúrias/diagnóstico , Participação dos Interessados , Resultado do Tratamento
BMJ Open ; 7(9): 16950, 2017 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-28939565


INTRODUCTION: For patients with a first unprovoked venous thromboembolism (VTE), the optimal duration of anticoagulation is a crucial clinical dilemma which has yet to be resolved. The decision to stop anticoagulant therapy (AT) after the initial 3-6 months or to continue AT indefinitely, is primarily governed by the long-term risk of recurrence when treatment is discontinued. This risk however, is not well established, hindering decision making. METHODS AND ANALYSIS: We will conduct a systematic review and a meta-analysis of studies involving patients diagnosed with a first, symptomatic unprovoked VTE or VTE provoked by minor transient risk factors, who have completed at least 3 months of initial AT; and who were followed-up for standardised time intervals of 1, 2, 5, 10 and 20 years (±3 months) after stopping AT. We will search (from inception to January 2017) MEDLINE, Embase and the Cochrane library for randomised controlled trials and prospective observational studies. Two reviewers will conduct all screening and data collection independently. The primary outcome of the rate of recurrent VTE at the standardised time intervals will be calculated for each study from the total number of recurrent events and the corresponding number of patient-years of follow-up. We will use a random-effects model to pool study results and report a weighted estimate of the absolute rate of recurrent VTE (events per 100 patient-years) over standardised time intervals of 1, 2, 5, 10 and 20 years after discontinuing anticoagulants. ETHICS AND DISSEMINATION: Ethical approval is not applicable for this study. Findings from this study will be disseminated through peer-reviewed journal publication as well as relevant national and international conference presentations. PROSPERO REGISTRATION NUMBER: CRD42017056309.

Anticoagulantes/uso terapêutico , Tromboembolia Venosa/tratamento farmacológico , Esquema de Medicação , Humanos , Recidiva , Projetos de Pesquisa , Fatores de Risco , Revisão Sistemática como Assunto
Res Pract Thromb Haemost ; 1(1): 9-13, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30046669


Unprovoked venous thromboembolism (VTE) can be the first manifestation of an undiagnosed cancer. Recently published studies have suggested that approximately 4-5% of patients with new unprovoked VTE will be diagnosed with cancer within 12 months of follow-up. Therefore, it is important for clinicians to keep a low threshold of suspicion for occult cancer in this patient population. After an unprovoked VTE diagnosis, patients should undergo a thorough medical history, physical examination, basic laboratory investigations (ie, complete blood count and liver function tests), chest X-ray, as well as age- and gender-specific cancer screening (breast, cervical, colon, and prostate). More intensive cancer screening including additional investigations (eg, computed tomography of the abdomen/pelvis) does not seem to increase the rate of occult cancer detection, decrease cancer-related morbidity, or increase survival or cost-effectiveness.