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1.
World Psychiatry ; 21(2): 287-294, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35524614

RESUMO

It is common experience for practising psychiatrists that individuals with schizophrenia vary markedly in their symptomatic response to antipsychotic medication. What is not clear, however, is whether this variation reflects variability of medication-specific effects (also called "treatment effect heterogeneity"), as opposed to variability of non-specific effects such as natural symptom fluctuation or placebo response. Previous meta-analyses found no evidence of treatment effect heterogeneity, suggesting that a "one size fits all" approach may be appropriate and that efforts at developing personalized treatment strategies for schizophrenia are unlikely to succeed. Recent advances indicate, however, that earlier approaches may have been unable to accurately quantify treatment effect heterogeneity due to their neglect of a key parameter: the correlation between placebo response and medication-specific effects. In the present paper, we address this shortcoming by using individual patient data and study-level data to estimate that correlation and quantitatively characterize antipsychotic treatment effect heterogeneity in schizophrenia. Individual patient data (on 384 individuals who were administered antipsychotic treatment and 88 who received placebo) were obtained from the Yale University Open Data Access (YODA) database. Study-level data were obtained from a meta-analysis of 66 clinical trials including 17,202 patients. Both individual patient and study-level analyses yielded a negative correlation between placebo response and treatment effect for the total score on the Positive and Negative Syndrome Scale (PANSS) (ρ=-0.32, p=0.002 and ρ=-0.39, p<0.001, respectively). Using the most conservative of these estimates, a meta-analysis of treatment effect heterogeneity provided evidence of a marked variability in antipsychotic-specific effects between individuals with schizophrenia, with the top quartile of patients experiencing beneficial treatment effects of 17.7 points or more on the PANSS total score, while the bottom quartile presented a detrimental effect of treatment relative to placebo. This evidence of clinically meaningful treatment effect heterogeneity suggests that efforts to personalize antipsychotic treatment of schizophrenia have potential for success.

2.
BMC Psychiatry ; 22(1): 337, 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35578254

RESUMO

BACKGROUND: The debate of whether machine learning models offer advantages over standard statistical methods when making predictions is ongoing. We discuss the use of a meta-learner model combining both approaches as an alternative. METHODS: To illustrate the development of a meta-learner, we used a dataset of 187,757 people with depression. Using 31 variables, we aimed to predict two outcomes measured 60 days after initiation of antidepressant treatment: severity of depressive symptoms (continuous) and all-cause dropouts (binary). We fitted a ridge regression and a multi-layer perceptron (MLP) deep neural network as two separate prediction models ("base-learners"). We then developed two "meta-learners", combining predictions from the two base-learners. To compare the performance across the different methods, we calculated mean absolute error (MAE, for continuous outcome) and the area under the receiver operating characteristic curve (AUC, for binary outcome) using bootstrapping. RESULTS: Compared to the best performing base-learner (MLP base-learner, MAE at 4.63, AUC at 0.59), the best performing meta-learner showed a 2.49% decrease in MAE at 4.52 for the continuous outcome and a 6.47% increase in AUC at 0.60 for the binary outcome. CONCLUSIONS: A meta-learner approach may effectively combine multiple prediction models. Choosing between statistical and machine learning models may not be necessary in practice.

3.
Int J Urol ; 2022 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-35393696

RESUMO

OBJECTIVES: We aimed to develop models to predict new-onset overactive bladder in 5 years using a large prospective cohort of the general population. METHODS: This is a secondary analysis of a longitudinal cohort study in Japan. The baseline characteristics were measured between 2008 and 2010, with follow-ups every 5 years. We included subjects without overactive bladder at baseline and with follow-up data 5 years later. Overactive bladder was assessed using the overactive bladder symptom score. Baseline characteristics (demographics, health behaviors, comorbidities, and overactive bladder symptom scores) and blood test data were included as predictors. We developed two competing prediction models for each sex based on logistic regression with penalized likelihood (LASSO). We chose the best model separately for men and women after evaluating models' performance in terms of discrimination and calibration using an internal validation via 200 bootstrap resamples and a temporal validation. RESULTS: We analyzed 7218 participants (male: 2238, female: 4980). The median age was 60 and 55 years, and the number of new-onset overactive bladder was 223 (10.0%) and 288 (5.8%) per 5 years in males and females, respectively. The in-sample estimates for C-statistic, calibration intercept, and slope for the best performing models were 0.77 (95% confidence interval 0.74-0.80), 0.28 and 1.15 for males, and 0.77 (95% confidence interval 0.74-0.80), 0.20 and 1.08 for females. Internal and temporal validation gave broadly similar estimates of performance, indicating low optimism. CONCLUSION: We developed risk prediction models for new-onset overactive bladder among men and women with good predictive ability.

4.
Stat Methods Med Res ; : 9622802221090759, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35469504

RESUMO

Meta-analysis of randomized controlled trials is generally considered the most reliable source of estimates of relative treatment effects. However, in the last few years, there has been interest in using non-randomized studies to complement evidence from randomized controlled trials. Several meta-analytical models have been proposed to this end. Such models mainly focussed on estimating the average relative effects of interventions. In real-life clinical practice, when deciding on how to treat a patient, it might be of great interest to have personalized predictions of absolute outcomes under several available treatment options. This paper describes a general framework for developing models that combine individual patient data from randomized controlled trials and non-randomized study when aiming to predict outcomes for a set of competing medical interventions applied in real-world clinical settings. We also discuss methods for measuring the models' performance to identify the optimal model to use in each setting. We focus on the case of continuous outcomes and illustrate our methods using a data set from rheumatoid arthritis, comprising patient-level data from three randomized controlled trials and two registries from Switzerland and Britain.

5.
Stat Med ; 2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-35261053

RESUMO

Network meta-analysis can synthesize evidence from studies comparing multiple treatments for the same disease. Sometimes the treatments of a network are complex interventions, comprising several independent components in different combinations. A component network meta-analysis (CNMA) can be used to analyze such data and can in principle disentangle the individual effect of each component. However, components may interact with each other, either synergistically or antagonistically. Deciding which interactions, if any, to include in a CNMA model may be difficult, especially for large networks with many components. In this article, we present two Bayesian CNMA models that can be used to identify prominent interactions between components. Our models utilize Bayesian variable selection methods, namely the stochastic search variable selection and the Bayesian LASSO, and can benefit from the inclusion of prior information about important interactions. Moreover, we extend these models to combine data from studies providing aggregate information and studies providing individual patient data (IPD). We illustrate our models in practice using three real datasets, from studies in panic disorder, depression, and multiple myeloma. Finally, we describe methods for developing web-applications that can utilize results from an IPD-CNMA, to allow for personalized estimates of relative treatment effects given a patient's characteristics.

6.
Am J Epidemiol ; 191(5): 930-938, 2022 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-35146500

RESUMO

Comparative effectiveness research using network meta-analysis can present a hierarchy of competing treatments, from the most to the least preferable option. However, in published reviews, the research question associated with the hierarchy of multiple interventions is typically not clearly defined. Here we introduce the novel notion of a treatment hierarchy question that describes the criterion for choosing a specific treatment over one or more competing alternatives. For example, stakeholders might ask which treatment is most likely to improve mean survival by at least 2 years, or which treatment is associated with the longest mean survival. We discuss the most commonly used ranking metrics (quantities that compare the estimated treatment-specific effects), how the ranking metrics produce a treatment hierarchy, and the type of treatment hierarchy question that each ranking metric can answer. We show that the ranking metrics encompass the uncertainty in the estimation of the treatment effects in different ways, which results in different treatment hierarchies. When using network meta-analyses that aim to rank treatments, investigators should state the treatment hierarchy question they aim to address and employ the appropriate ranking metric to answer it. Following this new proposal will avoid some controversies that have arisen in comparative effectiveness research.


Assuntos
Benchmarking , Humanos , Metanálise em Rede , Incerteza
7.
Lancet Psychiatry ; 9(3): 232-242, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35183280

RESUMO

BACKGROUND: Adverse events can occur after antipsychotic discontinuation but evidence from antipsychotic drug trials is scarce. We aimed to estimate the occurrence of adverse events after discontinuing antipsychotics. METHODS: For this two-stage individual participant data meta-analysis, we searched the Yale University Open Data Access Project's database for randomised controlled trials of antipsychotics from database inception until May 6, 2021. We included placebo-controlled antipsychotic randomised controlled trials with individual participant data of participants (aged ≥ 18 years, of any sex and ethnicity) with schizophrenia, schizoaffective disorder, or bipolar disorder. Studies were excluded if treatment with antidepressants, lithium, or antiepileptic drugs was initiated as additive therapy at the start of the placebo phase. Starting from the screening or washout phase, we divided participants who were randomised to placebo into two groups: the discontinuation group (participants who discontinued prestudy antipsychotics at the start of the screening or washout phase) and control group (participants who did not take prestudy antipsychotics for at least 4 weeks before the start of the screening or washout phase). Participants were excluded from the discontinuation and control groups if they discontinued prestudy treatment with antidepressants, lithium, or antiepileptic drugs up to 4 weeks before baseline, received an antipsychotic as a tolerability test, or received a long-acting injection of an antipsychotic within 12 weeks before baseline. In the discontinuation group, individuals were excluded if they discontinued prestudy antipsychotic treatment more than 3 days before, or any day after, the start of screening or washout phase. The prespecified primary outcome was occurrence of at least one new somatic adverse event with an onset within 4 weeks after the start of the screening or washout phase. We implemented a generalised linear model that accounted for potential confounders, to estimate the effect of antipsychotic discontinuation. This study is registered with PROSPERO (CRD42021224350). FINDINGS: We identified 409 records of which 18 were eligible and included in the analysis. From these 18 studies, 692 individuals (242 [35·0%] women and 450 [65·0%] men) were eligible for the discontinuation group and 935 individuals (339 [36·3%] women and 596 [63·7%] men) were eligible for the control group (median age in both groups: 39 years [IQR 30-47]). New somatic adverse events occurred in 295 (43%) individuals in the discontinuation group and 293 (31%) individuals in the control group (OR 1·74; 95% CI 1·27-2·39; τ2=0·15; moderate strength of evidence). New psychiatric adverse events were also more frequent in the discontinuation group than the control group (OR 2·01; 95% CI 1·38-2·94). Longer duration of treatment before discontinuation (OR for doubling the duration of treatment: 1·08; 95% CI 1·01-1·14) was associated with a higher probability of new somatic adverse events after antipsychotic discontinuation, and tapered discontinuation (compared with abrupt discontinuation: 0·54; 0·32-0·91) and no history of somatic illness (compared with history of somatic illness: 0·63; 0·43-0·91) were associated with lower probabilities of new somatic adverse events after antipsychotic discontinuation. The risk of bias was moderate in 13 (72·2%) studies and serious in five (27·8%) studies. INTERPRETATION: We detected moderate evidence of emerging somatic adverse events after discontinuation of first-generation and second-generation antipsychotics, particularly after discontinuation of longer durations of treatment. Tapered discontinuation can mitigate the risk of emerging somatic adverse events after antipsychotic discontinuation. These findings have implications for the safety of treatment discontinuation and could be used for tailored treatment planning. FUNDING: German Research Foundation.


Assuntos
Antipsicóticos/efeitos adversos , Transtorno Bipolar/tratamento farmacológico , Redução da Medicação/métodos , Esquizofrenia/tratamento farmacológico , Adulto , Antipsicóticos/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto
8.
JAMA Psychiatry ; 79(3): 210-218, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35080618

RESUMO

IMPORTANCE: Most evidence about efficacy and safety of antipsychotics in schizophrenia spectrum disorders relies on randomized clinical trials (RCTs). However, owing to their strict eligibility criteria, RCTs represent only a part of the real-world population (ie, unselected patients seen in everyday clinical practice), which may result in an efficacy-effectiveness gap. OBJECTIVE: To quantify the proportion of real-world individuals with schizophrenia spectrum disorders who would be ineligible for participation in RCTs, and to explore whether clinical outcomes differ between eligible and ineligible individuals. DESIGN, SETTING, AND PARTICIPANTS: This study applied eligibility criteria typically used in RCTs for relapse prevention in schizophrenia spectrum disorders to real-world populations. Individuals with diagnoses of schizophrenia spectrum disorders recorded in national patient registries in Finland and Sweden were identified. Individuals who had used antipsychotics continuously for 12 weeks in outpatient care were selected. Individuals were followed up for up to 1 year while they were receiving maintenance treatment with any second-generation antipsychotic (excluding clozapine). Follow-up was censored at treatment discontinuation, initiation of add-on antipsychotics, death, and end of database linkage. MAIN OUTCOMES AND MEASURES: Proportions of RCT-ineligible individuals with schizophrenia spectrum disorders owing to any and specific RCT exclusion criteria. The risk of hospitalization due to psychosis within 1-year follow-up in ineligible vs eligible persons were compared using hazard ratios (HR) and corresponding 95% CIs. RESULTS: The mean (SD) age in the Finnish cohort (n = 17 801) was 47.5 (13.8) years and 8972 (50.4%) were women; the mean (SD) age in the Swedish cohort (n = 7458) was 44.8 (12.5) years and 3344 (44.8%) were women. A total of 20 060 individuals (79%) with schizophrenia spectrum disorders would be ineligible for RCTs (Finnish cohort: 14 221 of 17 801 [79.9%]; Swedish cohort: 5839 of 7458 [78.3%]). Most frequent reasons for ineligibility were serious somatic comorbidities and concomitant antidepressant/mood stabilizer use. Risks of hospitalization due to psychosis was higher among ineligible than eligible individuals (Finnish cohort: 18.4% vs 17.2%; HR, 1.14 [95% CI, 1.04-1.24]; Swedish cohort: 20.1% vs 14.8%; HR, 1.47 [95% CI, 1.28-1.92]). The largest risks of hospitalization due to psychosis were observed in individuals ineligible owing to treatment resistance, tardive dyskinesia, and history of suicide attempts. Finally, with more ineligibility criteria met, larger risks of hospitalization due to psychosis were observed in both countries. CONCLUSIONS AND RELEVANCE: RCTs may represent only about a fifth of real-world individuals with schizophrenia spectrum disorders. Underrepresented (ineligible) patients with schizophrenia spectrum disorders have moderately higher risks of admission due to psychosis while receiving maintenance treatment than RCT-eligible patients. These findings set the stage for future studies targeting real-world populations currently not represented by RCTs.


Assuntos
Antipsicóticos , Clozapina , Transtornos Psicóticos , Esquizofrenia , Adulto , Antipsicóticos/uso terapêutico , Clozapina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Psicóticos/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Esquizofrenia/induzido quimicamente , Esquizofrenia/tratamento farmacológico
9.
PLoS One ; 16(11): e0257384, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34735442

RESUMO

OBJECTIVE: To evaluate different hypofractionated radiotherapy (HRT) regimens for newly diagnosed elderly glioblastoma (GBM) patients. METHODS: We performed a systematic review with network meta-analysis (NMA), including searches on CENTRAL, Medline, EMBASE, CINAHL, clinical trial databases and manual search. Only randomized clinical trials (RCTs) were included. Primary outcomes: overall survival (OS) and adverse events (AE). Secondary outcomes: progression-free-survival (PFS) and quality of life (QoL). We used the Cochrane Risk of Bias (RoB) table for assessing individual studies and CINeMA for evaluating the certainty of the final body of evidence. RESULTS: Four RCTs (499 patients) were included. For OS, the estimates from NMA did not provide strong evidence of a difference between the HRTs: 40 Gray (Gy) versus 45 Gy (HR: 0.89; CI 95%: 0.42, 1.91); 34 Gy versus 45 Gy (HR: 0.85; CI 95% 0.43, 1.70); 25 Gy versus 45 Gy (HR: 0.81; CI 95% 0.32, 2.02); 34 Gy versus 40 Gy (HR: 0.95; CI 95% 0.57, 1.61); and 25 Gy versus 34 Gy (HR: 0.95; CI 95% 0.46, 1.97). We performed qualitative synthesis for AE and QoL due to data scarcity and clinical heterogeneity among studies. The four studies reported a similar QoL (assessed by different methods) between arms. One RCT reported grade ≥ 3 AE, with no evidence of a difference between arms. PFS was reported in one study (25 Gy versus 40 Gy), with no evidence of a difference between arms. CONCLUSION: This review found no evidence of a difference between the evaluated HRTs for efficacy and safety.


Assuntos
Glioblastoma/epidemiologia , Glioblastoma/radioterapia , Hipofracionamento da Dose de Radiação/normas , Medição de Risco , Idoso , Glioblastoma/patologia , Humanos , Metanálise em Rede , Intervalo Livre de Progressão , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
J Am Heart Assoc ; 10(20): e018828, 2021 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-34622669

RESUMO

Background New-generation drug-eluting stents (DES) reduce target-vessel revascularization compared with bare-metal stents (BMS), and recent data suggest that DES have the potential to decrease the risk of myocardial infarction and cardiovascular mortality. We evaluated the treatment effect of DES versus BMS according to the target artery (left anterior descending [LAD] and/or left main [LM] versus other territories [no-LAD/LM]). Methods and Results The Coronary Stent Trialist (CST) Collaboration gathered individual patient data of randomized trials of DES versus BMS for the treatment of coronary artery disease. The primary outcome was the composite of cardiac death or myocardial infarction. Hazard ratios (HRs) with 95% CIs were derived from a 1-stage individual patient data meta-analysis. We included 26 024 patients across 19 trials: 13 650 (52.4%) in the LAD/LM and 12 373 (47.6%) in the no-LAD/LM group. At 6-year follow-up, there was strong evidence that the treatment effect of DES versus BMS depended on the target vessel (P-interaction=0.024). Compared with BMS, DES reduced the risk of cardiac death or myocardial infarction to a greater extent in the LAD/LM (HR, 0.76; 95% CI, 0.68-0.85) than in the no-LAD/LM territories (HR, 0.93; 95% CI, 0.83-1.05). This benefit was driven by a lower risk of cardiac death (HR, 0.83; 95% CI, 0.70-0.98) and myocardial infarction (HR, 0.74; 95% CI, 0.65-0.85) in patients with LAD/LM disease randomized to DES. An interaction (P=0.004) was also found for all-cause mortality with patients with LAD/LM disease deriving benefit from DES (HR, 0.86; 95% CI, 0.76-0.97). Conclusions As compared with BMS, new-generation DES were associated with sustained reduction in the composite of cardiac death or myocardial infarction if used for the treatment of LAD or left main coronary stenoses. Registration URL: https://www.crd.york.ac.uk/PROSPERO; Unique identifier: CRD42017060520.


Assuntos
Doença da Artéria Coronariana , Stents Farmacológicos , Infarto do Miocárdio , Intervenção Coronária Percutânea , Desenho de Prótese , Doença da Artéria Coronariana/terapia , Morte , Humanos , Metais , Intervenção Coronária Percutânea/efeitos adversos , Fatores de Risco , Stents , Resultado do Tratamento
11.
Journal of the American Heart Association ; 10(20): 018828, Oct. 2021. graf, tab
Artigo em Inglês | Sec. Est. Saúde SP, Sec. Est. Saúde SP, CONASS, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1344305

RESUMO

BACKGROUND: New-generation drug-eluting stents (DES) reduce target-vessel revascularization compared with bare-metal stents (BMS), and recent data suggest that DES have the potential to decrease the risk of myocardial infarction and cardiovascular mortality. We evaluated the treatment effect of DES versus BMS according to the target artery (left anterior descending [LAD] and/or left main [LM] versus other territories [no-LAD/LM]). METHODS AND RESULTS: The Coronary Stent Trialist (CST) Collaboration gathered individual patient data of randomized trials of DES versus BMS for the treatment of coronary artery disease. The primary outcome was the composite of cardiac death or myocardial infarction. Hazard ratios (HRs) with 95% CIs were derived from a 1-stage individual patient data meta-analysis. We included 26 024 patients across 19 trials: 13 650 (52.4%) in the LAD/LM and 12 373 (47.6%) in the no-LAD/LM group. At 6-year follow-up, there was strong evidence that the treatment effect of DES versus BMS depended on the target vessel (P interaction=0.024). Compared with BMS, DES reduced the risk of cardiac death or myocardial infarction to a greater extent in the LAD/LM (HR, 0.76; 95% CI, 0.68­0.85) than in the no-LAD/LM territories (HR, 0.93; 95% CI, 0.83­1.05). This benefit was driven by a lower risk of cardiac death (HR, 0.83; 95% CI, 0.70­0.98) and myocardial infarction (HR, 0.74; 95% CI, 0.65­0.85) in patients with LAD/LM disease randomized to DES. An interaction (P=0.004) was also found for all-cause mortality with patients with LAD/LM disease deriving benefit from DES (HR, 0.86; 95% CI, 0.76­0.97). CONCLUSIONS: As compared with BMS, new-generation DES were associated with sustained reduction in the composite of cardiac death or myocardial infarction if used for the treatment of LAD or left main coronary stenoses.


Assuntos
Stents , Stents Farmacológicos
12.
BMJ Open ; 11(9): e048298, 2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-34588246

RESUMO

INTRODUCTION: Knee osteoarthritis is a chronic degenerative disease associated with significant chronic pain, disability and impaired quality of life and is the most common form of osteoarthritis. There is no cure for knee osteoarthritis, and the main therapeutic goals are pain management and improving quality of life. The objective of this study is to evaluate the relative efficacy and acceptability of available interventions using network meta-analysis (NMA) to provide a comprehensive evidence base to inform future treatment guidelines. METHODS AND ANALYSIS: A comprehensive literature search of major electronic databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials) and clinical trial registries will identify randomised control trials (RCTs) of interventions listed in NICE guidelines for the treatment of knee osteoarthritis in adults. We will perform an NMA to estimate relative intervention effects across the whole treatment network. If any studies use multicomponent intervention packages, we will employ a component NMA model to estimate the contribution of individual components. The quality of evidence will be assessed using the Confidence in Network Meta-Analysis approach, which is based on the traditional GRADE framework adapted for NMA. Risk of bias (RoB) will be assessed using the revised Cochrane RoB 2.0 tool for RCTs. ETHICS AND DISSEMINATION: This study does not require ethical approval. Findings will be submitted to a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42020184192.


Assuntos
Dor Crônica , Osteoartrite do Joelho , Adulto , Doença Crônica , Dor Crônica/terapia , Humanos , Metanálise como Assunto , Metanálise em Rede , Osteoartrite do Joelho/terapia , Manejo da Dor , Ensaios Clínicos Controlados Aleatórios como Assunto
13.
J Consult Clin Psychol ; 89(6): 563-574, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34264703

RESUMO

OBJECTIVE: To examine if cognitive restructuring (CR), behavioral activation (BA), and cognitive-behavioral therapy (CBT) result in differential effects in the treatment of adult depression. METHOD: We extracted randomized controlled trials (RCTs) from a database updated yearly from PubMed, PsycINFO, Embase, and Cochrane Library. Network and pairwise meta-analyses were conducted to investigate the effects of CR, BA, and CBT delivered in a face-to-face individual format, compared with waiting list (WL) and care-as-usual (CAU), on adult depression. The primary outcome was a standardized mean difference (SMD) in posttreatment depression severity. Tolerability of treatments and depression severity at follow-up were also assessed. RESULTS: A total of 45 studies with 3,382 participants were included. There was no evidence of a difference in effectiveness between CR, BA, and CBT. All three interventions were superior to CAU; SMD 0.57, 95% confidence interval [CI 0.08-1.07]; 0.52 [0.34-0.71]; 0.44 [0.28-0.60], respectively and WL 1.20 [0.69-1.70]; 1.15 [0.90-1.40]; 1.07 [0.87-1.26]. No difference in tolerability was found (risk ratio [RR] vs. CAU: 1.01 [0.04-22.81], 0.84 [0.63-1.11], and 0.96 [0.76-1.21], respectively). Metaregression and sensitivity analyses did not produce material differences. CONCLUSIONS: Results suggest that CR or BA alone and their combination (CBT) may be effective interventions in comparison to WL and CAU in the treatment of adult depression. There was no evidence suggesting differences in effectiveness among the three treatments. More research is needed to derive conclusions about the performance of CR. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Assuntos
Terapia Cognitivo-Comportamental/métodos , Depressão/terapia , Adulto , Terapia Comportamental/métodos , Cognição , Humanos , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Listas de Espera
14.
J Alzheimers Dis ; 82(3): 1075-1084, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34120898

RESUMO

BACKGROUND: In patients with Alzheimer's disease, global assessment scales, such as the Clinical Dementia Rating-Sum of Boxes (CDR-SB), the Clinician's Interview-Based Impression Plus Caregiver Input (CIBI plus), and the Clinical Global Impression (CGI) are commonly used. OBJECTIVE: To clinically understand and interpret the associations between these scales, we examined the linkages for the total and change scores of CDR-SB, CIBI plus, and CGI. METHODS: Individual participant data (N = 2,198) from five pivotal randomized placebo-controlled trials of donepezil were included. Data were collected at baseline and scheduled visits for up to 6 months. Spearman's correlation coefficients ρ were examined between corresponding total and change scores of simultaneous CDR-SB, CIBI plus, and CGI ratings. To link between the simultaneous ratings, equipercentile linking was used. RESULTS: We found strong evidence that the Spearman's correlation coefficients between the CDR-SB and CGI, and CDR-SB and CIBI plus total scores were at least adequately correlated (ρ= 0.50 to 0.71, with p < 0.01). The correlation coefficients between the change scores of CDR-SB and CGI were deemed adequate for weeks 6 to 24 (ρ= 0.44 to 0.65); the remaining correlations were smaller in magnitude (ρ= 0.09 to 0.35). Overall, the linkages were in-line with expectations, e.g., CDR-SB range score of 3-4 (= very mild dementia) was linked to a CGI score of 3 (= mildly ill), and an increase of CDR-SB of 1 was linked to a change of 5 (= minimal worsening) in both CGI and CIBI plus. CONCLUSION: The study findings can be useful for clinicians wishing to compare scores of different scales across patients. They can also help researchers understand results of studies using different scales and can facilitate meta-analyses, to increase statistical power.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Cuidadores , Donepezila/uso terapêutico , Entrevista Psicológica/normas , Testes de Estado Mental e Demência/normas , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/psicologia , Cuidadores/psicologia , Análise de Dados , Feminino , Humanos , Masculino , Nootrópicos/uso terapêutico , Participação do Paciente/psicologia
15.
Res Synth Methods ; 12(6): 849-854, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34133079

RESUMO

The Peto odds ratio is a well-known effect measure in meta-analysis of binary outcomes. For pairwise comparisons, the Peto odds ratio estimator can be severely biased in the situation of unbalanced sample sizes in the two treatment groups or large treatment effects. In this publication, we evaluate Peto odds ratio estimators in the setting of multi-arm studies and in network meta-analysis using illustrative examples. We observe that Peto odds ratio estimators in a multi-arm study are inconsistent if the observed event probabilities are different or the sample sizes of treatment groups are unbalanced. The same problem emerges in network meta-analysis including only two-arm studies and translates to indirect comparisons of pairwise meta-analyses. We conclude that the Peto odds ratio should not be used as effect measure in network meta-analysis or indirect comparisons of pairwise meta-analyses.


Assuntos
Razão de Chances , Metanálise em Rede
16.
BMC Urol ; 21(1): 78, 2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-33985490

RESUMO

BACKGROUND: An accurate prediction model could identify high-risk subjects of incident Overactive bladder (OAB) among the general population and enable early prevention which may save on the related medical costs. However, no efficient model has been developed for predicting incident OAB. In this study, we will develop a model for predicting the onset of OAB at 5-year in the general population setting. METHODS: Data will be obtained from the Nagahama Cohort Project, a longitudinal, general population cohort study. The baseline characteristics were measured between Nov 28, 2008 and Nov 28, 2010, and follow-up was performed every 5 years. From the total of 9,764 participants (male: 3,208, female: 6,556) at baseline, we will exclude participants who could not attend the follow-up assessment and those who were defined as having OAB at baseline. The outcome will be incident OAB defined using the Overactive Bladder Symptom Score (OABSS) at follow-up assessment. Baseline questionnaires (demographic, health behavior, comorbidities and OABSS) and blood test data will be included as predictors. We will develop a logistic regression model utilizing shrinkage methods (LASSO penalization method). Model performance will be evaluated by discrimination and calibration. Net benefit will be evaluated by decision curve analysis. We will perform an internal validation and a temporal validation of the model. We will develop a web-based application to visualize the prediction model and facilitate its use in clinical practice. DISCUSSION: This will be the first study to develop a model to predict the incidence of OAB.


Assuntos
Modelos Estatísticos , Projetos de Pesquisa , Bexiga Urinária Hiperativa/epidemiologia , Estudos de Validação como Assunto , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Prognóstico , Medição de Risco , Fatores de Tempo
17.
Artigo em Inglês | MEDLINE | ID: mdl-33849995

RESUMO

INTRODUCTION: Structural MRI is the most frequently used method to investigate brain volume alterations in neuropsychiatric disease. Previous meta-analyses have typically focused on a single diagnosis, thereby precluding transdiagnostic comparisons. METHODS AND ANALYSIS: We will include all structural MRI studies of adults that report brain volumes for participants from at least two of the following diagnostic groups: healthy controls, schizophrenia, schizoaffective disorder, delusional disorder, psychotic depression, clinical high risk for psychosis, schizotypal personality disorder, psychosis unspecified, bipolar disorder, autism spectrum disorder, major depressive disorder, attention deficit hyperactivity disorder, obsessive compulsive disorder, post-traumatic stress disorder, emotionally unstable personality disorder, 22q11 deletion syndrome, generalised anxiety disorder, social anxiety disorder, panic disorder, mixed anxiety and depression. Network meta-analysis will be used to synthesise eligible studies. The primary analysis will examine standardised mean difference in average volume, a secondary analysis will examine differences in variability of volumes. DISCUSSION: This network meta-analysis will provide a transdiagnostic integration of structural neuroimaging studies, providing researchers with a valuable summary of a large literature. PROSPERO REGISTRATION NUMBER: CRD42020221143.

18.
Clin Infect Dis ; 73(3): e735-e744, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-33530095

RESUMO

BACKGROUND: We analyzed associations between immunodeficiency and cancer incidence in a nationwide cohort of people living with human immunodeficiency virus (HIV; PLWH) in South Africa. METHODS: We used data from the South African HIV Cancer Match Study built on HIV-related laboratory measurements from the National Health Laboratory Services and cancer records from the National Cancer Registry. We evaluated associations between time-updated CD4 cell count and cancer incidence rates using Cox proportional hazards models. We reported adjusted hazard ratios (aHRs) over a grid of CD4 values and estimated the aHR per 100 CD4 cells/µL decrease. RESULTS: Of 3 532 266 PLWH, 15 078 developed cancer. The most common cancers were cervical cancer (4150 cases), Kaposi sarcoma (2262 cases), and non-Hodgkin lymphoma (1060 cases). The association between lower CD4 cell count and higher cancer incidence rates was strongest for conjunctival cancer (aHR per 100 CD4 cells/µL decrease: 1.46; 95% confidence interval [CI], 1.38-1.54), Kaposi sarcoma (aHR, 1.23; 95% CI, 1.20-1.26), and non-Hodgkin lymphoma (aHR, 1.18; 95% CI, 1.14-1.22). Among infection-unrelated cancers, lower CD4 cell counts were associated with higher incidence rates of esophageal cancer (aHR, 1.06; 95% CI, 1.00-1.11) but not breast, lung, or prostate cancer. CONCLUSIONS: Lower CD4 cell counts were associated with an increased risk of developing various infection-related cancers among PLWH. Reducing HIV-induced immunodeficiency may be a potent cancer-prevention strategy among PLWH in sub-Saharan Africa, a region heavily burdened by cancers attributable to infections.


Assuntos
Infecções por HIV , Neoplasias do Colo do Útero , Contagem de Linfócito CD4 , Feminino , HIV , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Humanos , Incidência , Masculino , África do Sul/epidemiologia
19.
PLoS One ; 16(2): e0246631, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33556155

RESUMO

Many healthcare interventions are complex, consisting of multiple, possibly interacting, components. Several methodological articles addressing complex interventions in the meta-analytical context have been published. We hereby provide an overview of methods used to evaluate the effects of complex interventions with meta-analytical models. We summarized the methodology, highlighted new developments, and described the benefits, drawbacks, and potential challenges of each identified method. We expect meta-analytical methods focusing on components of several multicomponent interventions to become increasingly popular due to recently developed, easy-to-use, software tools that can be used to conduct the relevant analyses. The different meta-analytical methods are illustrated through two examples comparing psychotherapies for panic disorder.


Assuntos
Análise de Dados , Atenção à Saúde/métodos , Projetos de Pesquisa , Animais , Humanos , Metanálise como Assunto , Software
20.
JAMA Psychiatry ; 78(4): 361-371, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33471111

RESUMO

Importance: Personalized treatment choices would increase the effectiveness of internet-based cognitive behavioral therapy (iCBT) for depression to the extent that patients differ in interventions that better suit them. Objective: To provide personalized estimates of short-term and long-term relative efficacy of guided and unguided iCBT for depression using patient-level information. Data Sources: We searched PubMed, Embase, PsycInfo, and Cochrane Library to identify randomized clinical trials (RCTs) published up to January 1, 2019. Study Selection: Eligible RCTs were those comparing guided or unguided iCBT against each other or against any control intervention in individuals with depression. Available individual patient data (IPD) was collected from all eligible studies. Depression symptom severity was assessed after treatment, 6 months, and 12 months after randomization. Data Extraction and Synthesis: We conducted a systematic review and IPD network meta-analysis and estimated relative treatment effect sizes across different patient characteristics through IPD network meta-regression. Main Outcomes and Measures: Patient Health Questionnaire-9 (PHQ-9) scores. Results: Of 42 eligible RCTs, 39 studies comprising 9751 participants with depression contributed IPD to the IPD network meta-analysis, of which 8107 IPD were synthesized. Overall, both guided and unguided iCBT were associated with more effectiveness as measured by PHQ-9 scores than control treatments over the short term and the long term. Guided iCBT was associated with more effectiveness than unguided iCBT (mean difference [MD] in posttreatment PHQ-9 scores, -0.8; 95% CI, -1.4 to -0.2), but we found no evidence of a difference at 6 or 12 months following randomization. Baseline depression was found to be the most important modifier of the relative association for efficacy of guided vs unguided iCBT. Differences between unguided and guided iCBT in people with baseline symptoms of subthreshold depression (PHQ-9 scores 5-9) were small, while guided iCBT was associated with overall better outcomes in patients with baseline PHQ-9 greater than 9. Conclusions and Relevance: In this network meta-analysis with IPD, guided iCBT was associated with more effectiveness than unguided iCBT for individuals with depression, benefits were more substantial in individuals with moderate to severe depression. Unguided iCBT was associated with similar effectiveness among individuals with symptoms of mild/subthreshold depression. Personalized treatment selection is entirely possible and necessary to ensure the best allocation of treatment resources for depression.


Assuntos
Terapia Cognitivo-Comportamental , Depressão/terapia , Transtorno Depressivo/terapia , Intervenção Baseada em Internet , Metanálise em Rede , Humanos
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