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Prediction of remission in pharmacotherapy of untreated major depression: development and validation of multivariable prediction models.

ABSTRACT: BACKGROUND:Depression is increasingly recognized as a chronic and relapsing disorder. However, an important minority of patients who start treatment for their major depressive episode recover to euthymia. It is clinically important to be able to predict such individuals. METHODS:The study is a secondary analysis of a recently completed pragmatic megatrial examining first- and second-line treatments for hitherto untreated episodes of non-psychotic unipolar major depression (n = 2011). Using the first half of the cohort as the derivation set, we applied multiply-imputed stepwise logistic regression with backward selection to build a prediction model to predict remission, defined as scoring 4 or less on the Patient Health Quetionnaire-9 at week 9. We used three successively richer sets of predictors at baseline only, up to week 1, and up to week 3. We examined the external validity of the derived prediction models with the second half of the cohort. RESULTS:In total, 37.0% (95% confidence interval 34.8-39.1%) were in remission at week 9. Only the models using data up to week 1 or 3 showed reasonable performance. Age, education, length of episode and depression severity remained in the multivariable prediction models. In the validation set, the discrimination of the prediction model was satisfactory with the area under the curve of 0.73 (0.70-0.77) and 0.82 (0.79-0.85), while the calibration was excellent with non-significant goodness-of-fit ?2 values (p = 0.41 and p = 0.29), respectively. CONCLUSIONS:Patients and clinicians can use these prediction models to estimate their predicted probability of achieving remission after acute antidepressant therapy.

SUBMITTER: Furukawa TA

PROVIDER: S-EPMC6763536 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Prediction of remission in pharmacotherapy of untreated major depression: development and validation of multivariable prediction models.

Furukawa Toshi A TA Kato Tadashi T Shinagawa Yoshihiro Y Miki Kazuhira K Fujita Hirokazu H Tsujino Naohisa N Kondo Masaki M Inagaki Masatoshi M Yamada Mitsuhiko M

Psychological medicine 20181115 14

<h4>Background</h4>Depression is increasingly recognized as a chronic and relapsing disorder. However, an important minority of patients who start treatment for their major depressive episode recover to euthymia. It is clinically important to be able to predict such individuals.<h4>Methods</h4>The study is a secondary analysis of a recently completed pragmatic megatrial examining first- and second-line treatments for hitherto untreated episodes of non-psychotic unipolar major depression (n = 201 ...[more]

PMID: 30430961

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Project description:Risk calculators can facilitate shared medical decision-making 1 . Demographics, comorbidities, medication use, geographic region, and other factors may increase the risk for COVID-19-related complications among patients with IBD 2,3 . Develop an individualized prognostic risk prediction tool for predicting the probability of adverse COVID-19 outcomes in patients with IBD. This study developed and validated prognostic penalized logistic regression models 4 using reports to Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) from March-October 2020. Model development was done using a training data set (85% of cases reported March 13 - September 15, 2020), and model validation was conducted using a test data set (the remaining 15% of cases plus all cases reported September 16-October 20, 2020). COVID-19 related:Hospitalization+: composite outcome of hospitalization, ICU admission, mechanical ventilation, or deathICU+: composite outcome of ICU admission, mechanical ventilation, or deathDeathWe assessed the resulting models' discrimination using the area under the curve (AUC) of the receiver-operator characteristic (ROC) curves and reported the corresponding 95% confidence intervals (CIs). We included 2709 cases from 59 countries (mean age 41.2 years [s.d. 18], 50.2% male). A total of 633 (24%) were hospitalized, 137 (5%) were admitted to the ICU or intubated, and 69 (3%) died. 2009 patients comprised the training set and 700 the test set.The models demonstrated excellent discrimination, with a test set AUC (95% CI) of 0.79 (0.75, 0.83) for Hospitalization+, 0.88 (0.82, 0.95) for ICU+, and 0.94 (0.89, 0.99) for Death. Age, comorbidities, corticosteroid use, and male gender were associated with higher risk of death, while use of biologic therapies was associated with a lower risk. Prognostic models can effectively predict who is at higher risk for COVID-19-related adverse outcomes in a population of IBD patients. A free online risk calculator ( https://covidibd.org/covid-19-risk-calculator/ ) is available for healthcare providers to facilitate discussion of risks due to COVID-19 with IBD patients. The tool numerically and visually summarizes the patient's probabilities of adverse outcomes and associated CIs. Helping physicians identify their highest-risk patients will be important in the coming months as cases rise in the US and worldwide. This tool can also serve as a model for risk stratification in other chronic diseases. Question: How well can a multivariable risk model predict the risk of hospitalization, intensive care unit (ICU) stay, or death due to COVID-19 in patients with inflammatory bowel disease (IBD)?Findings: Multivariable prediction models developed using data from an international voluntary registry of IBD patients and available for use online ( https://covidibd.org/ ) have very good discrimination for predicting hospitalization (Test set AUC 0.79) and excellent discrimination for ICU admission (Test set AUC 0.88) and death (Test set AUC 0.94). The models were developed with a training sample of 2009 cases and validated in an independent test sample of 700 cases comprised of a random sub-sample of cases and all cases entered in the registry during a one-month period after model development. Meaning: This risk prediction model may serve as an effective tool for healthcare providers to facilitate conversations about COVID-19-related risks with IBD patients.

Project description:ObjectivesDevelop an individualised prognostic risk prediction tool for predicting the probability of adverse COVID-19 outcomes in patients with inflammatory bowel disease (IBD).Design and settingThis study developed and validated prognostic penalised logistic regression models using reports to the international Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease voluntary registry from March to October 2020. Model development was done using a training data set (85% of cases reported 13 March-15 September 2020), and model validation was conducted using a test data set (the remaining 15% of cases plus all cases reported 16 September-20 October 2020).ParticipantsWe included 2709 cases from 59 countries (mean age 41.2 years (SD 18), 50.2% male). All submitted cases after removing duplicates were included.Primary and secondary outcome measuresCOVID-19 related: (1) Hospitalisation+: composite outcome of hospitalisation, ICU admission, mechanical ventilation or death; (2) Intensive Care Unit+ (ICU+): composite outcome of ICU admission, mechanical ventilation or death; (3) Death. We assessed the resulting models' discrimination using the area under the curve of the receiver operator characteristic curves and reported the corresponding 95% CIs.ResultsOf the submitted cases, a total of 633 (24%) were hospitalised, 137 (5%) were admitted to the ICU or intubated and 69 (3%) died. 2009 patients comprised the training set and 700 the test set. The models demonstrated excellent discrimination, with a test set area under the curve (95% CI) of 0.79 (0.75 to 0.83) for Hospitalisation+, 0.88 (0.82 to 0.95) for ICU+ and 0.94 (0.89 to 0.99) for Death. Age, comorbidities, corticosteroid use and male gender were associated with a higher risk of death, while the use of biological therapies was associated with a lower risk.ConclusionsPrognostic models can effectively predict who is at higher risk for COVID-19-related adverse outcomes in a population of patients with IBD. A free online risk calculator (https://covidibd.org/covid-19-risk-calculator/) is available for healthcare providers to facilitate discussion of risks due to COVID-19 with patients with IBD.

Project description:BACKGROUND:Clinical guidelines recommend screening for depression in the general adult population but recognizes that the optimum interval for screening is unknown. Ideal screening intervals should match the patient risk profiles. OBJECTIVE:This study describes a predictive analytics approach for mining clinical and patient-reported data from a large clinical study for the identification of primary care patients at high risk for depression to match depression screening intervals with patient risk profiles. METHODS:This paper analyzed data from a large safety-net primary care study for diabetes and depression. A regression-based data mining technique was used to examine 53 demographics, clinical variables, and patient-reported variables to develop three prediction models for major depression at 6, 12, and 18 months from baseline. Predictors with the strongest predictive power that require low information collection efforts were selected to develop the prediction models. Predictive accuracy was measured by the area under the receiver operating curve (AUROC) and was evaluated by 10-fold cross-validation. The effectiveness of the prediction algorithms in supporting clinical decision making for six "typical" types of patients was demonstrated. RESULTS:The analysis included 923 patients who were nondepressed at the study baseline. Five patient-reported variables were selected in the prediction models to predict major depression at 6, 12, and 18 months: (1) Patient Health Questionnaire 2-item score; (2) the Sheehan Disability Scale; (3) previous problems with depression; (4) the diabetes symptoms scale; and (5) emotional burden of diabetes. All three depression prediction models had an AUROC>0.80, comparable with published depression prediction studies. Among the 6 "typical" types of patients, the algorithms suggest that patients who reported impaired daily functioning by health status are at an elevated risk for depression in all three periods. CONCLUSIONS:This study demonstrated that leveraging patient-reported data and prediction models can help improve identification of high-risk patients and clinical decisions about the depression screening interval for diabetes patients. Implementation of this approach can be coupled with application of modern technologies such as telehealth and mobile health assessment for collecting patient-reported data to improve privacy, reducing stigma and costs, and promoting a personalized depression screening that matches screening intervals with patient risk profiles.

Project description:BackgroundBefore considering whether to use a multivariable (diagnostic or prognostic) prediction model, it is essential that its performance be evaluated in data that were not used to develop the model (referred to as external validation). We critically appraised the methodological conduct and reporting of external validation studies of multivariable prediction models.MethodsWe conducted a systematic review of articles describing some form of external validation of one or more multivariable prediction models indexed in PubMed core clinical journals published in 2010. Study data were extracted in duplicate on design, sample size, handling of missing data, reference to the original study developing the prediction models and predictive performance measures.Results11,826 articles were identified and 78 were included for full review, which described the evaluation of 120 prediction models. in participant data that were not used to develop the model. Thirty-three articles described both the development of a prediction model and an evaluation of its performance on a separate dataset, and 45 articles described only the evaluation of an existing published prediction model on another dataset. Fifty-seven percent of the prediction models were presented and evaluated as simplified scoring systems. Sixteen percent of articles failed to report the number of outcome events in the validation datasets. Fifty-four percent of studies made no explicit mention of missing data. Sixty-seven percent did not report evaluating model calibration whilst most studies evaluated model discrimination. It was often unclear whether the reported performance measures were for the full regression model or for the simplified models.ConclusionsThe vast majority of studies describing some form of external validation of a multivariable prediction model were poorly reported with key details frequently not presented. The validation studies were characterised by poor design, inappropriate handling and acknowledgement of missing data and one of the most key performance measures of prediction models i.e. calibration often omitted from the publication. It may therefore not be surprising that an overwhelming majority of developed prediction models are not used in practice, when there is a dearth of well-conducted and clearly reported (external validation) studies describing their performance on independent participant data.

Project description:ImportanceBiological therapies have revolutionized inflammatory bowel disease management, but many patients do not respond to biological monotherapy. Identification of likely responders could reduce costs and delays in remission.ObjectiveTo identify patients with Crohn disease likely to be durable responders to ustekinumab before committing to long-term treatment.Design, setting, and participantsThis cohort study analyzed data from 3 phase 3 randomized clinical trials (UNITI-1, UNITI-2, and IM-UNITI) conducted from 2011 to 2015. Participants (n = 401) were individuals with active (C-reactive protein [CRP] measurement of ≥5 mg/L at enrollment) Crohn disease who received ustekinumab therapy. Data analysis was performed from November 1, 2017, to June 1, 2018.ExposuresAll included patients were exposed to 1 or more dose of ustekinumab for 8 weeks or more.Main outcomes and measuresRandom forest methods were used in building 2 models for predicting Crohn disease remission, with a CRP level lower than 5 mg/dL as a proxy for biological remission, beyond week 42 of ustekinumab treatment. The first model used only baseline data, and the second used data through week 8.ResultsIn total, 401 participants, with a mean (SD) age of 36.3 (12.6) years and 170 male (42.4%), were included. The week-8 model had a mean area under the receiver operating characteristic curve (AUROC) of 0.78 (95% CI, 0.69-0.87). In the testing data set, 27 of 55 participants (49.1%) classified as likely to have treatment success achieved success with a CRP level lower than 5 mg/L after week 42, and 7 of 65 participants (10.8%) classified as likely to have treatment failure achieved this outcome. In the full cohort, 87 patients (21.7%) attained remission after week 42. A prediction model using the week-6 albumin to CRP ratio had an AUROC of 0.76 (95% CI, 0.71-0.82). Baseline ustekinumab serum levels did not improve the model's prediction performance.Conclusions and relevanceIn patients with active Crohn disease, demographic and laboratory data before week 8 of treatment appeared to allow the prompt identification of likely nonresponders to ustekinumab without the need for costly drug-level monitoring.

Project description:Pharmacological treatment of major depressive disorder (MDD) typically involves a lengthy trial and error process to identify an effective intervention. This lengthy period prolongs suffering and worsens all-cause mortality, including from suicide, and is typically longer in late-life depression (LLD). Our group has recently demonstrated that during an open-label venlafaxine (serotonin-norepinephrine reuptake inhibitor) trial, significant changes in functional resting state connectivity occurred following a single dose of treatment, which persisted until the end of the trial. In this work, we propose an analysis framework to translate these perturbations in functional networks into predictors of clinical remission. Participants with LLD (N?=?49) completed 12-weeks of treatment with venlafaxine and underwent functional magnetic resonance imaging (fMRI) at baseline and a day following a single dose of venlafaxine. Data was collected at rest as well as during an emotion reactivity task and an emotion regulation task. Remission was defined as a Montgomery-Asberg Depression Rating Scale (MADRS) ?10 for two weeks. We computed eigenvector centrality (whole brain connectivity) and activation during the emotion regulation and emotion reactivity tasks. We employed principal components analysis, Tikhonov-regularized logistic classification, and least angle regression feature selection to predict remission by the end of the 12-week trial. We utilized ten-fold cross-validation and Receiver Operator Curves (ROC) curve analysis. To determine task-region pairs that significantly contributed to the algorithm's ability to predict remission, we used permutation testing. Using the fMRI data at both baseline and after the first dose of treatment yielded a sensitivity of 72% and a specificity of 68% (AUC?=?0.77), a 15% increase in accuracy over baseline MADRS. In general, the accuracy at baseline was further improved by using the change in activation following a single dose. Activation of the frontal cortex, hippocampus, parahippocampus, caudate, thalamus, medial temporal cortex, middle cingulate, and visual cortex predicted treatment remission. Acute, dynamic trajectories of functional imaging metrics in response to a pharmacological intervention are a valuable tool for predicting treatment response in late-life depression and elucidating the mechanism of pharmacological therapies in the context of the brain's functional architecture.

Dataset Information

Prediction of remission in pharmacotherapy of untreated major depression: development and validation of multivariable prediction models.

Publications

Prediction of remission in pharmacotherapy of untreated major depression: development and validation of multivariable prediction models.

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