Project description:In network meta-analysis (NMA), treatments can be complex interventions, for example, some treatments may be combinations of others or of common components. In standard NMA, all existing (single or combined) treatments are different nodes in the network. However, sometimes an alternative model is of interest that utilizes the information that some treatments are combinations of common components, called component network meta-analysis (CNMA) model. The additive CNMA model assumes that the effect of a treatment combined of two components A and B is the sum of the effects of A and B, which is easily extended to treatments composed of more than two components. This implies that in comparisons equal components cancel out. Interaction CNMA models also allow interactions between the components. Bayesian analyses have been suggested. We report an implementation of CNMA models in the frequentist R package netmeta. All parameters are estimated using weighted least squares regression. We illustrate the application of CNMA models using an NMA of treatments for depression in primary care. Moreover, we show that these models can even be applied to disconnected networks, if the composite treatments in the subnetworks contain common components.
Project description:BackgroundWe recently reported that convergence insufficiency (CI)-type visual symptomatology was more prevalent in participants with Parkinson's disease (PD), compared to controls. The objective of this work was to determine the prevalence of a confirmed clinical diagnosis of CI in PD, compared to controls.MethodsParticipants with (n = 80) and without (n = 80) PD were recruited and received an eye exam. Published criteria were used to arrive at a clinical diagnosis of CI. The Convergence Insufficiency Symptom Survey (CISS-15) questionnaire was administered to each participant, with a score of ≥21 being considered positive for CI symptomatology. Student t test, chi-square, or nonparametric tests at the 0.05 level were used for statistical significance.ResultsA total of 43.8% of participants with versus 16.3% without PD had a clinical diagnosis of CI (P ≤ 0.001). A total of 53.8% of participants with versus 18.8% without PD had scores on the CISS-15 of ≥21 (P ≤ 0.001).ConclusionsThese results indicate that individuals with PD have a higher prevalence of CI and CI symptomatology than controls. These data provide evidence supporting the notion that treatment for symptomatic CI should be investigated in individuals with PD.
Project description:SignificanceThese data confirm the effectiveness of office-based vergence/accommodative therapy for improving convergence in children with symptomatic convergence insufficiency. They also highlight the importance of using a primary outcome measure that is as objective as possible rather than relying solely on self-reported symptoms for studies of binocular vision in children.PurposeThe purpose of this study was to report changes in clinical signs and symptoms of convergence insufficiency (secondary outcome measures) from a multicenter clinical trial (Convergence Insufficiency Treatment Trial-Attention & Reading Trial [CITT-ART]) evaluating the effectiveness of vergence/accommodative therapy for improving reading and attention in children with symptomatic convergence insufficiency.MethodsThree hundred eleven children aged 9 to 14 years with symptomatic convergence insufficiency were randomly assigned to 16 weeks of office-based vergence/accommodative therapy or to placebo therapy. Improvements in (1) near point of convergence (NPC), (2) positive fusional vergence (PFV), and (3) self-reported symptoms (Convergence Insufficiency Symptom Survey [CISS] score) were compared after 16 weeks of treatment.ResultsMean NPC improved 10.4 cm in the vergence/accommodative and 6.2 cm in the placebo therapy group (mean difference of -4.2 cm [95% confidence interval {CI}, -5.2 to -3.2 cm; P < .001]); mean PFV increased 23.2 and 8.8Δ in the vergence/accommodative and placebo therapy groups, respectively (mean difference of 14.4Δ [95% CI, 12.1 to 16.8Δ; P < .001]). The mean CISS score improved 11.8 and 10.4 points in the vergence/accommodative and placebo therapy groups, respectively (mean difference of 1.5 points [95% CI, -3.8 to +0.8 points; P = .21]).ConclusionsOur results demonstrate that office-based vergence/accommodative therapy is effective for improving the NPC and PFV in children with symptomatic convergence insufficiency. However, given that both treatment groups had a similar reduction in self-reported symptoms, it may not be prudent to use the CISS alone as a measure of successful treatment.
Project description:Preventing psychosis in patients at clinical high risk may be a promising avenue for pre-emptively ameliorating outcomes of the most severe psychiatric disorder. However, information on how each preventive intervention fares against other currently available treatment options remains unavailable. The aim of the current study was to quantify the consistency and magnitude of effects of specific preventive interventions for psychosis, comparing different treatments in a network meta-analysis. PsycINFO, Web of Science, Cochrane Central Register of Controlled Trials, and unpublished/grey literature were searched up to July 18, 2017, to identify randomized controlled trials conducted in individuals at clinical high risk for psychosis, comparing different types of intervention and reporting transition to psychosis. Two reviewers independently extracted data. Data were synthesized using network meta-analyses. The primary outcome was transition to psychosis at different time points and the secondary outcome was treatment acceptability (dropout due to any cause). Effect sizes were reported as odds ratios and 95% confidence intervals (CIs). Sixteen studies (2,035 patients, 57% male, mean age 20.1 years) reported on risk of transition. The treatments tested were needs-based interventions (NBI); omega-3?+?NBI; ziprasidone?+?NBI; olanzapine?+?NBI; aripiprazole?+?NBI; integrated psychological interventions; family therapy?+?NBI; D-serine?+?NBI; cognitive behavioural therapy, French & Morrison protocol (CBT-F)?+?NBI; CBT-F?+?risperidone?+?NBI; and cognitive behavioural therapy, van der Gaag protocol (CBT-V)?+?CBT-F?+?NBI. The network meta-analysis showed no evidence of significantly superior efficacy of any one intervention over the others at 6 and 12 months (insufficient data were available after 12 months). Similarly, there was no evidence for intervention differences in acceptability at either time point. Tests for inconsistency were non-significant and sensitivity analyses controlling for different clustering of interventions and biases did not materially affect the interpretation of the results. In summary, this study indicates that, to date, there is no evidence that any specific intervention is particularly effective over the others in preventing transition to psychosis. Further experimental research is needed.
Project description:The goal of this study was to compare the safety and effectiveness of individual antiembolic interventions in nonvalvular atrial fibrillation (AF): novel oral anticoagulants (NOACs) (apixaban, dabigatran, edoxaban, and rivaroxaban); vitamin K antagonists (VKA); aspirin; and the Watchman device.A network meta-analysis of randomized, clinical trials (RCTs) was performed. RCTs that included patients with prosthetic cardiac valves or mitral stenosis, mean or median follow-up <6 months, <200 participants, without published report in English language, and NOAC phase II studies were excluded. The placebo/control arm received either placebo or no treatment. The primary efficacy outcome was the combination of stroke (of any type) and systemic embolism. All-cause mortality served as a secondary efficacy outcome. The primary safety outcome was the combination of major extracranial bleeding and intracranial hemorrhage. A total of 21 RCTs (96 017 nonvalvular AF patients; median age, 72 years; 65% males; median follow-up, 1.7 years) were included. In comparison to placebo/control, use of aspirin (odds ratio [OR], 0.75 [95% CI, 0.60-0.95]), VKA (0.38 [0.29-0.49]), apixaban (0.31 [0.22-0.45]), dabigatran (0.29 [0.20-0.43]), edoxaban (0.38 [0.26-0.54]), rivaroxaban (0.27 [0.18-0.42]), and the Watchman device (0.36 [0.16-0.80]) significantly reduced the risk of any stroke or systemic embolism in nonvalvular AF patients, as well as all-cause mortality (aspirin: OR, 0.82 [0.68-0.99]; VKA: 0.69 [0.57-0.85]; apixaban: 0.62 [0.50-0.78]; dabigatran: 0.62 [0.50-0.78]; edoxaban: 0.62 [0.50-0.77]; rivaroxaban: 0.58 [0.44-0.77]; and the Watchman device: 0.47 [0.25-0.88]). Apixaban (0.89 [0.80-0.99]), dabigatran (0.90 [0.82-0.99]), and edoxaban (0.89 [0.82-0.96]) reduced risk of all-cause death as compared to VKA.The entire spectrum of therapy to prevent thromboembolism in nonvalvular AF significantly reduced stroke/systemic embolism events and mortality.
Project description:Convergence insufficiency (CI) is the most common binocular vision problem, associated with blurred/double vision, headaches, and sore eyes that are exacerbated when doing prolonged near work, such as reading. The Convergence Insufficiency Neuro-mechanism Adult Population Study (NCT03593031) investigates the mechanistic neural differences between 50 binocularly normal controls (BNC) and 50 symptomatic CI participants by examining the fast and slow fusional disparity vergence systems. The fast fusional system is preprogrammed and is assessed with convergence peak velocity. The slow fusional system optimizes vergence effort and is assessed by measuring the phoria adaptation magnitude and rate. For the fast fusional system, significant differences are observed between the BNC and CI groups for convergence peak velocity, final position amplitude, and functional imaging activity within the secondary visual cortex, right cuneus, and oculomotor vermis. For the slow fusional system, the phoria adaptation magnitude and rate, and the medial cuneus functional activity, are significantly different between the groups. Significant correlations are observed between vergence peak velocity and right cuneus functional activity (p = 0.002) and the rate of phoria adaptation and medial cuneus functional activity (p = 0.02). These results map the brain-behavior of vergence. Future therapeutic interventions may consider implementing procedures that increase cuneus activity for this debilitating disorder.
Project description:PurposeTo culturally and linguistically adapt the Convergence Insufficiency Symptom Survey (CISS) to Spanish and assess the psychometric performance of the new version through Rasch analysis and classical test theory methods.MethodsThe Spanish version of the CISS (CISSVE) was completed by 449 subjects (9-30 years old) from the general population. The validity and reliability of CISSVE were assessed through Rasch statistics (precision, targeting, item fit, unidimensionality, and differential item functioning). To test construct validity, we calculated the coefficients of correlation between the CISSVE and the Computer-Vision Symptom Scale (CVSS17) or Warwick-Edinburgh Mental Well-Being Scale (WEMWBS). We determined test-retest reliability in a subset of 229 subjects. We used differential item functioning (DIF) to compare the CISSSVE and the CISS after administering the CISS to 216 English children.ResultsAfter applying exclusion criteria, the responses of 420 participants (mean age, 18.62 years; female, 54.95%) revealed good Rasch model fit, good precision (person separation = 2.33), and suboptimal targeting (-1.37). There was some evidence of multidimensionality, but disattenuated correlations between the Rasch dimension and a possible secondary dimension were high, suggesting they were measuring similar constructs. No item bias according to gender or age was detected. Spearman's correlation was 0.34 (P < 0.001) for CISSVE-CVSS17 and non-significant for CISSVE-WEMWBS. The limits of agreement for test-retest reliability were 9.67 and -8.71. Rasch analysis results indicated no difference between CISS and CISSVE.ConclusionsAccording to our results, CISSVE is a valid and reliable tool for measuring the symptoms assessed by CISS in Spanish people 9 to 30 years of age.Translational relevanceCISSVE can measure convergence insufficiency symptoms in Spanish-speaking subjects.
Project description:AimsTo perform network meta-analysis for a head-to-head comparison of various interventions used in coronavirus disease 2019 (COVID-19) on mortality, clinical recovery, time to clinical improvement and the occurrence of serious adverse events.MethodsSystematic search was performed using online databases with suitable MeSH terms including coronavirus, COVID-19, randomized controlled trial, hydroxychloroquine, lopinavir/ritonavir, tocilizumab, remdesivir, favipiravir, dexamethasone and interferon-β. Data were independently extracted by 2 study investigators and analysed.ResultsOut of 1225 studies screened, 23 were included for qualitative and quantitative analysis. Among the drugs studied, dexamethasone reduces mortality by 10%, with a relative risk of 0.90 (95% confidence interval [0.82-0.97]) and increases clinical recovery by 6% (relative risk 1.06, 95% confidence interval [1.02-1.10]) compared to standard of care. Similarly, remdesivir administered for 10 days increased clinical recovery by 10%, reduced time to clinical improvement by 4 days and lowered the occurrence of serious adverse events by 27% as compared to standard of care.ConclusionIn comparison to standard of care, dexamethasone was found to increase clinical recovery and lower mortality; remdesivir was significantly associated with a lower risk of mortality as compared to tocilizumab and higher clinical recovery and shorter time to clinical improvement as compared to hydroxychloroquine and tocilizumab; remdesivir followed by tocilizumab were found to have lesser occurrence of serious adverse events in patients with moderate to severe COVID-19.