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1.
Behav Cogn Psychother ; : 1-5, 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33118908

RESUMO

BACKGROUND: Late-life depression issues in developing countries are challenging because of understaffing in mental health. Cognitive behavioural therapy (CBT) is effective for treating depression. AIM: This pilot trial examined the adherence and effectiveness of an eight-session adapted CBT delivered by trained lay health workers for older adults with depressive symptoms living in rural areas of China, compared with the usual care. METHOD: Fifty with screen-positive depression were randomly assigned to the CBT arm or the care as usual (CAU) arm. The primary outcomes were the session completion of older adults and changes in depressive symptoms, assessed using the Geriatric Depression Scale (GDS). RESULTS: The majority (19/24) of participants in the CBT arm completed all sessions. Mixed-effect linear regression showed that the CBT reduced more GDS scores over time compared with CAU. CONCLUSION: Lay-delivered culturally adapted CBT is potentially effective for screen-positive late-life depression.

2.
J Alzheimers Dis ; 76(3): 967-979, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32568196

RESUMO

BACKGROUND: Crenezumab is a fully humanized, monoclonal anti-amyloid-ß immunoglobulin G4 antibody. OBJECTIVE: This Phase Ib study (NCT02353598) evaluated the safety, tolerability, and pharmacokinetics of crenezumabat doses of ≤120 mg/kg administered intravenously every 4 weeks (q4w). Immunogenicity and exploratory biomarkers were also evaluated. METHODS: In this multicenter, double-blind study, participants (aged 50-90 years) with mild-to-moderate Alzheimer's disease (AD) and amyloid-positive positron emission tomography (PET) scan were randomized to receive crenezumab 30 or 45 mg/kg (Cohort 1, n = 21), 60 mg/kg (Cohort 2, n = 21), or 120 mg/kg (Cohort 3, n = 19) or corresponding placebo (n = 14) intravenously q4w for 13 weeks. Seventy-one participants were subsequently enrolled in an optional open-label extension (OLE) and received crenezumab at the originally assigned dose level, except for Cohort 3 (crenezumab 60 mg/kg during OLE). Participants received regular brain MRIs to assess amyloid-related imaging abnormalities (ARIA). Results up to Week 133 are reported. RESULTS: Approximately 94% of participants experienced ≥1 adverse event (AE). Most AEs were mild or moderate; 15.5% experienced a Grade ≥3 AE. No ARIA-edema/effusion (ARIA-E) events were observed. New ARIA-micro hemorrhages and hemosiderosis (ARIA-H) were reported in 4.9% (double-blind treatment period) and 9.9% (combined double-blind treatment and OLE periods) of participants. Steady-state trough concentrations of crenezumab were dose-proportional and maintained for each dose level. CONCLUSION: Crenezumab doses of ≤120 mg/kg intravenously q4w were well tolerated. The observed safety profile for ≤133 weeks of treatment in a mild-to-moderate AD population was similar to that seen in previous trials.

3.
Alzheimers Dement ; 16(7): 1023-1030, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32418361

RESUMO

INTRODUCTION: The API AutosomalDominant AD (ADAD) Colombia Trial is a placebo-controlled clinical trial of crenezumab in 252 cognitively unimpaired 30 to 60-year-old Presenilin 1 (PSEN1) E280A kindred members, including mutation carriers randomized to active treatment or placebo and non-carriers who receive placebo. METHODS: Of the 252 enrolled, we present data on a total of 242 mutation carriers and non-carriers matched by age range, excluding data on 10 participants to protect participant confidentiality, genetic status, and trial integrity. RESULTS: We summarize demographic, clinical, cognitive, and behavioral data from 167 mutation carriers and 75 non-carriers, 30 to 53 years of age. Carriers were significantly younger than non-carriers ((mean age ± SD) 37 ± 5 vs 42 ± 6), had significantly lower Mini Mental Status Exam (MMSE) scores (28.8 ± 1.4 vs 29.2 ± 1.0), and had consistently lower memory scores. DISCUSSION: Although PSEN1 E280A mutation carriers in the Trial are cognitively unimpaired, they have slightly lower MMSE and memory scores than non-carriers. Their demographic characteristics are representative of the local population.

4.
J Evid Based Dent Pract ; 20(1): 101403, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32381410

RESUMO

OBJECTIVES: Dental research typically targets multiple outcomes. Interdental cleaning devices such as interdental brushes (IB) and water jet devices (WJ) share a sizable portion of the medical device market. However, recommendations for device selection are limited by the conflicting evidence from multiple outcomes in available studies and the lack of an appropriate synthesis approach to summarize evidences taken from multiple outcomes. In particular, both pairwise meta-analyses and single-outcome network meta-analyses can give discordant results. The purpose of this multioutcome, Bayesian network meta-analysis is to introduce this innovative method to the dental research community using data from interdental cleaning device studies for illustrative purposes. METHODS: We reanalyzed a network meta-analysis of interproximal oral hygiene methods in the reduction of clinical indices of inflammation, which included 22 trials assessing 10 interproximal oral hygiene aids. We focused on the primary outcome of gingival inflammation, which was measured by 2 correlated outcome variables, the Gingival Index (GI) and bleeding on probing (BOP). RESULTS: In our previous single-outcome analysis, we concluded that IB and WJ rank high for reducing gingival inflammation while toothpick and flossing rank last. In this multioutcome Bayesian network meta-analysis with equal weight on GI and BOP, the surface under the cumulative ranking curve was 0.87 for WJ and 0.85 for IB. WJ and IB remained ranked as the 2 best devices across different sets of weightings for the GI and BOP. CONCLUSION: In conclusion, multioutcome Bayesian network meta-analysis naturally takes the correlations among multiple outcomes into account, which in turn can provide more comprehensive evidence.


Assuntos
Dispositivos para o Cuidado Bucal Domiciliar , Placa Dentária , Teorema de Bayes , Pesquisa em Odontologia , Humanos , Metanálise em Rede , Escovação Dentária
5.
J Am Stat Assoc ; 114(527): 949-961, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31777410

RESUMO

In studies evaluating the accuracy of diagnostic tests, three designs are commonly used, crossover, randomized, and non-comparative. Existing methods for meta-analysis of diagnostic tests mainly consider the simple cases in which the reference test in all or none of the studies can be considered a gold standard test, and in which all studies use either a randomized or non-comparative design. The proliferation of diagnostic instruments and the diversity of study designs create a need for more general methods to combine studies that include or do not include a gold standard test and that use various designs. This paper extends the Bayesian hierarchical summary receiver operating characteristic model to network meta-analysis of diagnostic tests to simultaneously compare multiple tests within a missing data framework. The method accounts for correlations between multiple tests and for heterogeneity between studies. It also allows different studies to include different subsets of diagnostic tests and provides flexibility in the choice of summary statistics. The model is evaluated using simulations and illustrated using real data on tests for deep vein thrombosis, with sensitivity analyses.

6.
Clin Trials ; 16(6): 626-634, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31389723

RESUMO

BACKGROUND: Composite outcomes, which combine multiple types of clinical events into a single outcome, are common in clinical trials. The usual analysis considers the time to first occurrence of any event in the composite. The major criticisms of such an approach are (1) this implicitly treats the outcomes as if they were of equal importance, but they often vary in terms of clinical relevance and severity, (2) study participants often experience more than one type of event, and (3) often less severe events occur before more severe ones, but the usual analysis disregards any information beyond that first event. METHODS: A novel approach, referred to as the win ratio, which addresses the aforementioned criticisms of composite outcomes, is illustrated with a re-analysis of data on fatal and non-fatal cardiovascular disease time-to-event outcomes reported for the Multiple Risk Factor Intervention Trial. In this trial, 12,866 participants were randomized to a special intervention group (n = 6428) or a usual care (n = 6438) group. Non-fatal outcomes were ranked by risk of cardiovascular disease death up to 20 years after trial. In one approach, participants in the special intervention and usual care groups were first matched on coronary heart disease risk at baseline and time of enrollment. Each matched pair was categorized as a winner or loser depending on which one experienced a cardiovascular disease death first. If neither died of cardiovascular disease causes, they were evaluated on the most severe non-fatal outcome. This process continued for all the non-fatal outcomes. A second win ratio statistic, obtained from Cox partial likelihood, was also estimated. This statistic provides a valid estimate of the win ratio using multiple events if the marginal and conditional survivor functions of each outcome satisfy proportional hazards. Loss ratio statistics (inverse of win ratios) are compared to hazard ratios from the usual first event analysis. A larger 11-event composite was also considered. RESULTS: For the 7-event cardiovascular disease composite, the previously reported first event analysis based on 581 events in the special intervention group and 652 events in the usual care group yielded a hazard ratio (95% confidence interval) of 0.89 (0.79-0.99), compared to 0.86 (0.77-0.97) and 0.91 (0.81-1.02) for the severity ranked estimates. Results for the 11-event composite also confirmed the findings of the first event analysis. CONCLUSION: The win ratio analysis was able to leverage information collected past the first experienced event and rank events by severity. The results were similar to and confirmed previously reported traditional first event analysis. The win ratio statistic is a useful adjunct to the traditional first event analysis for trials with composite outcomes.


Assuntos
Doenças Cardiovasculares/mortalidade , Avaliação de Resultados em Cuidados de Saúde , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Adulto , Determinação de Ponto Final , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Fatores de Risco
7.
J Gen Intern Med ; 34(6): 960-968, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30887438

RESUMO

BACKGROUND: Meta-analysis combines multiple independent studies, which can increase power and provide better estimates. However, it is unclear how best to deal with studies with zero events; such studies are also known as double-zero-event studies (DZS). Several statistical methods have been proposed, but the agreement among different approaches has not been systematically assessed using real-world published systematic reviews. METHODS: The agreement of five commonly used methods (i.e., the inverse-variance, Mantel-Haenszel, Peto, Bayesian, and exact methods) was assessed using the Cohen's κ coefficients using 368 meta-analyses with rare events selected from the Cochrane Database of Systematic Reviews. Three continuity corrections, including the correction of a constant 0.5, the treatment arm continuity correction (TACC), and the empirical (EMP) correction, were used to handle DZS when applying inverse-variance and Mantel-Haenszel methods. RESULTS: When the proportion of DZS studies was lower than 50% in a meta-analysis, different methods had moderately high agreement. However, when this proportion was increased to be over 50%, the agreement among the methods decreased to different extents. For the Bayesian, exact, and Peto methods and the inverse-variance and Mantel-Haenszel methods using the EMP correction, their agreement coefficients with the inverse-variance and Mantel-Haenszel methods using a constant 0.5 and TACC decreased from larger than 0.70 to smaller than 0.30. In contrast, the agreement coefficients only decreased slightly among the Bayesian, exact, and Peto methods and the inverse-variance and Mantel-Haenszel methods using the EMP correction. CONCLUSIONS: To utilize all available information and reduce research waste and avoid overestimating the effect, meta-analysts should incorporate DZS, rather than simply removing them. The Peto and other conventional methods with continuity correction should be avoided when the proportion of DZS is extremely high. The exact and Bayesian methods are highly recommended, except when none of the included studies have an event in one or both treatment arms.


Assuntos
Gerenciamento de Dados/métodos , Bases de Dados Factuais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Metanálise como Assunto , Ensaios Clínicos Pragmáticos como Assunto/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Humanos , Resultado do Tratamento
8.
Stat Med ; 38(1): 115-130, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30251263

RESUMO

In observational studies, misclassification of exposure is ubiquitous and can substantially bias the estimated association between an outcome and an exposure. Although misclassification in a single observational study has been well studied, few papers have considered it in a meta-analysis. Meta-analyses of observational studies provide important evidence for health policy decisions, especially when large randomized controlled trials are unethical or unavailable. It is imperative to account properly for misclassification in a meta-analysis to obtain valid point and interval estimates. In this paper, we propose a novel Bayesian approach to filling this methodological gap. We simultaneously synthesize two (or more) meta-analyses, with one on the association between a misclassified exposure and an outcome (main studies), and the other on the association between the misclassified exposure and the true exposure (validation studies). We extend the current scope for using external validation data by relaxing the "transportability" assumption by means of random effects models. Our model accounts for heterogeneity between studies and can be extended to allow different studies to have different exposure measurements. The proposed model is evaluated through simulations and illustrated using real data from a meta-analysis of the effect of cigarette smoking on diabetic peripheral neuropathy.


Assuntos
Teorema de Bayes , Metanálise como Assunto , Neuropatias Diabéticas/etiologia , Humanos , Modelos Estatísticos , Estudos Observacionais como Assunto , Fumar/efeitos adversos
9.
J Periodontol ; 89(5): 558-570, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29520910

RESUMO

BACKGROUND: A wide selection of Interdental Oral Hygiene (IOH) aids is available to consumers. Recommendations for selection are, however, limited by the lack of direct comparisons in available studies. We aimed to assess the comparative efficacy of IOH aids using Bayesian Network Meta-Analysis (BNMA). METHODS: Two independent reviewers performed a systematic literature review of randomized clinical trials assessing IOH aids, based on a focused question. Gingival inflammation (Gingival Index (GI), Bleeding-on-probing (BOP)) was the primary outcome and plaque and probing depth were secondary outcomes A random-effects arm-based BNMA model was run for each outcome; posterior medians and 95% credible-intervals (CIs) summarized marginal distributions of parameters. RESULTS: A two-phase selection process identified 22 trials assessing 10 IOH aids as brushing adjuncts. Interdental brushes (IB) yielded the largest reduction in GI (0.23 [95% CI: 0.09, 0.37]) as toothbrushing adjuncts, followed by water-jet (WJ) (0.19 [95% CI: 0.14, 0.24]). Rankings based on posterior probabilities revealed that IB and WJ had the highest probability of being "best" (64.7% and 27.4%, respectively) for GI reduction, whereas the probability for toothpick and floss being the "best" IOH aids was near zero. Notably, except for toothpicks, all IOH aids were better at reducing GI as compared with control. CONCLUSIONS: BNMA enabled us to quantitatively evaluate IOH aids and provide a global ranking of their efficacy. Interdental brushes and water-jets ranked high for reducing gingival bleeding, whereas toothpicks and floss ranked last. The patient-perceived benefit of IOH aids is not clear because gingival inflammation measures are physical indicators of periodontal health.


Assuntos
Gengivite , Higiene Bucal , Teorema de Bayes , Dispositivos para o Cuidado Bucal Domiciliar , Índice de Placa Dentária , Humanos , Inflamação , Escovação Dentária
10.
PLoS One ; 13(1): e0190362, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29293575

RESUMO

Sepsis continues to be a major problem for hospitalized patients. Opioids are widely used medications for pain management despite recent evidence revealing their adverse effects. The present study evaluates survival differences between opioid-treated patients and non-opioid-treated patients hospitalized with a diagnosis of sepsis. Clinical data was extracted from the University of Minnesota's Clinical Data Repository, which includes Electronic Health Records (EHRs) of the patients seen at 8 hospitals. Among 5,994 patients diagnosed with sepsis, 4,540 opioid-treated patients and 1,454 non-opioid patients were included based on whether they are exposed to prescription opioids during their hospitalization. Cox proportional hazards regression showed that after adjustments for demographics, clinical comorbidities, severity of illness, and types of infection, opioid-treated patients had a significantly higher risk of death at 28 days.


Assuntos
Analgésicos Opioides/administração & dosagem , Registros Eletrônicos de Saúde , Sepse/mortalidade , Analgésicos Opioides/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida
11.
Biostatistics ; 19(1): 87-102, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-28586407

RESUMO

To compare the accuracy of multiple diagnostic tests in a single study, three designs are commonly used (i) the multiple test comparison design; (ii) the randomized design, and (iii) the non-comparative design. Existing meta-analysis methods of diagnostic tests (MA-DT) have been focused on evaluating the performance of a single test by comparing it with a reference test. The increasing number of available diagnostic instruments for a disease condition and the different study designs being used have generated the need to develop efficient and flexible meta-analysis framework to combine all designs for simultaneous inference. In this article, we develop a missing data framework and a Bayesian hierarchical model for network MA-DT (NMA-DT) and offer important promises over traditional MA-DT: (i) It combines studies using all three designs; (ii) It pools both studies with or without a gold standard; (iii) it combines studies with different sets of candidate tests; and (iv) it accounts for heterogeneity across studies and complex correlation structure among multiple tests. We illustrate our method through a case study: network meta-analysis of deep vein thrombosis tests.


Assuntos
Teorema de Bayes , Testes Diagnósticos de Rotina , Modelos Estatísticos , Metanálise em Rede , Humanos , Trombose Venosa/diagnóstico
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