Measurement Invariance and Response Bias: A Stochastic Frontier Approach

The goals of the present paper were to assess measurement invariance using a common econometric method and to illustrate the approach with self-reported measures of parenting behaviors before and after a family intervention. Most recent literature on measurement invariance (MI) in psychological research 1) explores the use of structural equation modeling (SEM) and confirmatory factor analysis to identify measurement invariance, and 2) tests for measurement invariance across groups rather than across time. We use method, Stochastic Frontier Estimation, or SFE, to identify response bias and covariates of response bias both across individuals at a single point in time and across two measurement occasions (before and after participation in a family intervention). We examined the effects of participant demographics (N = 1437) on response bias; gender and race/ethnicity were related to magnitude of bias and to changes in bias across time, and bias was lower at posttest than at pretest. We discuss analytic advantages and disadvantages of SFE relative to SEM approaches and note that the technique may be particularly useful in addressing the problem of “response shift bias” or “recalibration” in program evaluation -- that is, a shift in metric from before to after an intervention which is caused by the intervention itself and may lead to underestimates of program effects.Measurement invariance, measurement equivalence, response bias, response-shift bias, stochastic frontier analysis

Estimating treatment effectiveness with sample selection

We consider a situation where treatment outcome is observed after two stages of selection; first of participation into the treatment, then in completion of the treatment. Estimates were obtained using two methods. First, three different binary response selection models were estimated sequentially in multiple steps. Second, all three equations were estimated jointly. All methods produce similar parameter estimates. We find evidence of selection effects from completion to outcome that could bias parameter estimates of the outcome equation, but not from participation to outcome, indicating that correcting only for participation may be insufficient to avoid biased estimates in the outcome equation.selection bias, trivariate probit, bivariate probit, treatment effects

Anti-Inflammatory Activity Is a Possible Mechanism by Which the Polyherbal Formulation Comprised of Nigella sativa

The present study investigated the anti-inflammatory effects of a polyherbal decoction comprised of Nigella sativa, Hemidesmus indicus, and Smilax glabra in order to justify its claimed antihepatocarcinogenic activity. Activation of hepatic nuclear factor-kappa B (NF-κB), IκB kinase (IKK α/β) proteins, and TNFα and IL-6 expression was investigated in diethylnitrosamine- (DEN-) induced C3H mice-bearing early hepatocarcinogenic changes. Acute phase inflammatory response was evaluated by carrageenan-induced rat paw edema formation. Anti-inflammatory mechanisms were also assessed by determining effect on (a) membrane stabilization, (b) nitric oxide (NO) inhibitory activity, and (c) inhibition of leukocyte migration. A significant inhibition of the paw edema formation was observed in healthy rats as well as in rats bearing early hepatocarcinogenic changes with oral administration of the decoction. As with the positive control, indomethacin (10 mg/kg b.w.) the inhibitory effect was pronounced at 3rd and 4th h after carrageenan injection. A notable IKK α/β mediated hepatic NF-κB inactivation was associated with a significant hepatic TNFα downregulation among mice-bearing hepatocarcinogenic changes subjected to decoction treatment. Inhibition of NO production, leukocyte migration, and membrane stabilization are possible mechanisms by which anti-inflammatory effect is mediated by the decoction. Overall findings imply that anti-inflammatory activity could be one of the mechanisms by which the decoction mediates its antihepatocarcinogenic effects

Dengue type 1 viruses circulating in humans are highly infectious and poorly neutralized by human antibodies

The four dengue virus (DENV) serotypes are mosquito-borne flaviviruses of humans. The interactions between DENVs and the human host that lead to asymptomatic, mild, or severe disease are poorly understood, in part, because laboratory models are poor surrogates for human DENV disease. Virologists are interested in how the properties of DENVs replicating in people compare with virions propagated on laboratory cell lines, which are widely used for research and vaccine development. Using clinical samples from a DENV type 1 epidemic in Sri Lanka and new ultrasensitive assays, we compared the properties of DENVs in human plasma and after one passage on laboratory cell lines. DENVs in plasma were 50- to 700-fold more infectious than cell culture-grown viruses. DENVs produced by laboratory cell lines were structurally immature and hypersensitive to neutralization by human antibodies compared with DENVs circulating in people. Human plasma and cell culture-derived virions had identical genome sequences, indicating that these phenotypic differences were due to the mature state of plasma virions. Several dengue vaccines are under development. Recent studies indicate that vaccine-induced antibodies that neutralized DENVs in cell culture assays were not sufficient for protecting people from DENV infections. Our results about structural differences between DENVs produced in humans versus cell lines may be key to understanding vaccine failure and developing better models for vaccine evaluation

Modulation of apoptosis in human hepatocellular carcinoma (HepG2 cells) by a standardized herbal decoction of Nigella sativa seeds, Hemidesmus indicus roots and Smilax glabra rhizomes with anti- hepatocarcinogenic effects

<p>Abstract</p> <p>Background</p> <p>A standardized poly-herbal decoction of <it>Nigella sativa </it>seeds, <it>Hemidesmus indicus </it>roots and <it>Smilax glabra </it>rhizomes used traditionally in Sri Lanka for cancer therapy has been demonstrated previously, to have anti-hepatocarcinogenic potential. Cytotoxicity, antioxidant activity, anti-inflammatory activity, and up regulation of p53 and p21 activities are considered to be some of the possible mechanisms through which the above decoction may mediate its anti-hepatocarcinogenic action. The main aim of the present study was to determine whether apoptosis is also a major mechanism by which the decoction mediates its anti-hepatocarcinogenic action.</p> <p>Methods</p> <p>Evaluation of apoptosis in HepG2 cells was carried out by (a) microscopic observations of cell morphology, (b) DNA fragmentation analysis, (c) activities of caspase 3 and 9, as well as by (d) analysis of the expression of pro-apoptotic (Bax) and anti-apoptotic (Bcl-2) proteins associated with cell death.</p> <p>Results</p> <p>The results demonstrated that in HepG2 cells, the decoction can induce (a) DNA fragmentation and (b) characteristic morphological changes associated with apoptosis (nuclear condensation, membrane blebbing, nuclear fragmentation and apoptotic bodies). The decoction could also, in a time and dose dependent manner, up regulate the expression of the pro-apoptotic gene <it>Bax </it>and down regulate expression of anti-apoptotic <it>Bcl-2 </it>gene (as evident from RT-PCR analysis, immunohistochemistry and western blotting). Further, the decoction significantly (<it>p </it>< .001) enhanced the activities of caspase-3 and caspase-9 in a time and dose dependent manner.</p> <p>Conclusions</p> <p>Overall findings provide confirmatory evidence to demonstrate that the decoction may mediate its reported anti-hepatocarcinogenic effect, at least in part, through modulation of apoptosis.</p

Characterization of pulmonary function in 10â18 year old patients with Duchenne muscular dystrophy

Pulmonary function loss in patients with Duchenne muscular dystrophy (DMD) is progressive and leads to pulmonary insufficiency. The purpose of this study in 10â18 year old patients with DMD is the assessment of the inter-correlation between pulmonary function tests (PFTs), their reliability and the association with the general disease stage measured by the Brooke score. Dynamic PFTs (peak expiratory flow [PEF], forced vital capacity [FVC], forced expiratory volume in one second [FEV1]) and maximum static airway pressures (MIP, MEP) were prospectively collected from 64 DMD patients enrolled in the DELOS trial (ClinicalTrials.gov, number NCT01027884). Baseline PEF percent predicted (PEF%p) was <80% and patients had stopped taking glucocorticoids at least 12 months prior to study start. At baseline PEF%p, FVC%p and FEV1%p correlated well with each other (Spearman's rho: PEF%pâFVC%p: 0.54; PEF%pâFEV1%p: 0.72; FVC%pâFEV1%p: 0.91). MIP%p and MEP%p correlated well with one another (MIP%pâMEP%p: 0.71) but less well with PEF%p (MIP%pâPEF%p: 0.40; MEP%pâPEF%p: 0.41) and slightly better with FVC%p (MIP%pâFVC%p: 0.59; MEP%pâFVC%p: 0.74). The within-subject coefficients of variation (CV) for successive measures were 6.97% for PEF%p, 6.69% for FVC%p and 11.11% for FEV1%p, indicating that these parameters could be more reliably assessed compared to maximum static airway pressures (CV for MIP%p: 18.00%; MEP%p: 15.73%). Yearly rates of PFT decline (placebo group) were larger in dynamic parameters (PEF%p: â8.9% [SD 2.0]; FVC%p: â8.7% [SD 1.1]; FEV1%p: â10.2% [SD 2.0]) than static airway pressures (MIP%p: â4.5 [SD 1.3]; MEP%p: â2.8 [SD 1.1]). A considerable drop in dynamic pulmonary function parameters was associated with loss of upper limb function (transition from Brooke score category 4 to category 5). In conclusion, these findings expand the understanding of the reliability, correlation and evolution of different pulmonary function measures in DMD patients who are in the pulmonary function decline phase

Idebenone reduces respiratory complications in patients with Duchenne muscular dystrophy

In Duchenne muscular dystrophy (DMD), progressive loss of respiratory function leads to restrictive pulmonary disease and places patients at significant risk for severe respiratory complications. Of particular concern are ineffective cough, secretion retention and recurrent respiratory tract infections. In a Phase 3 randomized controlled study (DMD Long-term Idebenone Study, DELOS) in DMD patients 10–18 years of age and not taking concomitant glucocorticoid steroids, idebenone (900 mg/day) reduced significantly the loss of respiratory function over a 1-year study period. In a post-hoc analysis of DELOS we found that more patients in the placebo group compared to the idebenone group experienced bronchopulmonary adverse events (BAEs): placebo: 17 of 33 patients, 28 events; idebenone: 6 of 31 patients, 7 events. The hazard ratios (HR) calculated “by patient” (HR 0.33, p = 0.0187) and for “all BAEs” (HR 0.28, p = 0.0026) indicated a clear idebenone treatment effect. The overall duration of BAEs was 222 days (placebo) vs. 82 days (idebenone). In addition, there was also a difference in the use of systemic antibiotics utilized for the treatment of BAEs. In the placebo group, 13 patients (39.4%) reported 17 episodes of antibiotic use compared to 7 patients (22.6%) reporting 8 episodes of antibiotic use in the idebenone group. Furthermore, patients in the placebo group used systemic antibiotics for longer (105 days) compared to patients in the idebenone group (65 days). This post-hoc analysis of DELOS indicates that the protective effect of idebenone on respiratory function is associated with a reduced risk of bronchopulmonary complications and a reduced need for systemic antibiotics

Suitability of external controls for drug evaluation in Duchenne muscular dystrophy

OBJECTIVE: To evaluate the suitability of real-world data (RWD) and natural history data (NHD) for use as external controls in drug evaluations for ambulatory Duchenne muscular dystrophy (DMD). METHODS: The consistency of changes in the 6-minute walk distance (Δ6MWD) was assessed across multiple clinical trial placebo arms and sources of NHD/RWD. Six placebo arms reporting 48-week Δ6MWD were identified via literature review and represented 4 sets of inclusion/exclusion criteria (n = 383 patients in total). Five sources of RWD/NHD were contributed by Universitaire Ziekenhuizen Leuven, DMD Italian Group, The Cooperative International Neuromuscular Research Group, ImagingDMD, and the PRO-DMD-01 study (n = 430 patients, in total). Mean Δ6MWD was compared between each placebo arm and RWD/NHD source after subjecting the latter to the inclusion/exclusion criteria of the trial for baseline age, ambulatory function, and steroid use. Baseline covariate adjustment was investigated in a subset of patients with available data. RESULTS: Analyses included ∼1,200 patient-years of follow-up. Differences in mean Δ6MWD between trial placebo arms and RWD/NHD cohorts ranged from -19.4 m (i.e., better outcomes in RWD/NHD) to 19.5 m (i.e., worse outcomes in RWD/NHD) and were not statistically significant before or after covariate adjustment. CONCLUSIONS: We found that Δ6MWD was consistent between placebo arms and RWD/NHD subjected to equivalent inclusion/exclusion criteria. No evidence for systematic bias was detected. These findings are encouraging for the use of RWD/NHD to augment, or possibly replace, placebo controls in DMD trials. Multi-institution collaboration through the Collaborative Trajectory Analysis Project rendered this study feasible

Measuring bias in self-reported data

Response bias shows up in many fields of behavioural and healthcare research where self-reported data are used. We demonstrate how to use stochastic frontier estimation (SFE) to identify response bias and its covariates. In our application to a family intervention, we examine the effects of participant demographics on response bias before and after participation; gender and race/ethnicity are related to magnitude of bias and to changes in bias across time, and bias is lower at post-test than at pre-test. We discuss how SFE may be used to address the problem of ‘response shift bias’ – that is, a shift in metric from before to after an intervention which is caused by the intervention itself and may lead to underestimates of programme effects