Convex Treatment Response and Treatment Selection

This paper analyzes the identifying power of weak convexity assumptions in treatment effect models with endogenous selection. The counterfactual distributions are constrained either in terms of the response function, or conditional on the realized treatment, and sharp bounds on the potential outcome distributions are derived. The methods are applied to bound the effect of education on smoking.nonparametric bounds, causality, endogeneity, instrumental variables

Assessment of treatment response in tuberculosis

Antibiotic treatment of tuberculosis has a duration of several months. There is significant variability of the host immune response and the pharmacokinetic-pharmacodynamic properties of Mycobacterium tuberculosis sub-populations at the site of disease. A limitation of sputum-based measures of treatment response may be sub-optimal detection and monitoring of Mycobacterium tuberculosis sub-populations. Potential biomarkers and surrogate endpoints should be benchmarked against hard clinical outcomes (failure/relapse/death) and may need tailoring to specific patient populations. Here, we assess the evidence supporting currently utilized and future potential host and pathogen-based models and biomarkers for monitoring treatment response in active and latent tuberculosis. Biomarkers for monitoring treatment response in extrapulmonary, pediatric and drug resistant tuberculosis are research priorities

HPA axis related genes and response to psychological therapies: genetics and epigenetics

Background Hypothalamic–pituitary–adrenal (HPA) axis functioning has been implicated in the development of stress-related psychiatric diagnoses and response to adverse life experiences. This study aimed to investigate the association between genetic and epigenetics in HPA axis and response to cognitive behavior therapy (CBT). Methods Children with anxiety disorders were recruited into the Genes for Treatment project (GxT, N = 1,152). Polymorphisms of FKBP5 and GR were analyzed for association with response to CBT. Percentage DNA methylation at the FKBP5 and GR promoter regions was measured before and after CBT in a subset (n = 98). Linear mixed effect models were used to investigate the relationship between genotype, DNA methylation, and change in primary anxiety disorder severity (treatment response). Results Treatment response was not associated with FKBP5 and GR polymorphisms, or pretreatment percentage DNA methylation. However, change in FKBP5 DNA methylation was nominally significantly associated with treatment response. Participants who demonstrated the greatest reduction in severity decreased in percentage DNA methylation during treatment, whereas those with little/no reduction in severity increased in percentage DNA methylation. This effect was driven by those with one or more FKBP5 risk alleles, with no association seen in those with no FKBP5 risk alleles. No significant association was found between GR methylation and response. Conclusions Allele-specific change in FKBP5 methylation was associated with treatment response. This is the largest study to date investigating the role of HPA axis related genes in response to a psychological therapy. Furthermore, this is the first study to demonstrate that DNA methylation changes may be associated with response to psychological therapies in a genotype-dependent manner

Antipsychotic Response in the First Week Predicts Later Efficacy

Background and Aims: Time of onset of antipsychotic action is still a debated matter. We aimed to replicate and extend previous findings that early response can predict subsequent non-response. Methods: 86 acutely psychotic patients treated with haloperidol were studied. Results: A PANSS reduction = 23% at 1 week of treatment predicts response at 3 weeks, with a specificity of 84% and a sensitivity of 86%. Conclusion: Our results confirm that an early response to antipsychotic treatment accurately predicts the treatment effectiveness and extends it to a prediction performed as early as 1 week. Copyright (c) 2012 S. Karger AG, Base

Direct administration of 2-hydroxypropyl-beta-cyclodextrin into guinea pig cochleae: Effects on physiological and histological measurements

<p>Cochlear response measurements from two different animals made before (red) and after (blue) treatment with HPβCD (Panel A) and TTX (Panel B) to 80 dB SPL 4 kHz tone bursts. Cochlear response waveform maintained CAP-like morphology after HPβCD treatment, consistent with reduced mechanical drive to neural excitation (Panel B, blue). In contrast, response waveform is EPSP-like following TTX treatment. Unlike TTX, results from HPβCD do not support the hypothesis that the auditory nerve is a site of action for 13 mM HPβCD.</p

Socioeconomic status and anxiety as predictors of antidepressant treatment response and suicidal ideation in older adults.

BACKGROUND: Separate reports from the maintenance treatment for late-life depression (MTLD) trials have shown that low socioeconomic status (SES) and anxiety symptoms at the time of treatment initiation predict lower levels of response to antidepressant treatment and higher levels of suicidal ideation in older adults. AIM: To determine whether SES and anxiety independently contribute to worse treatment outcomes, as indicated by persistence of depressive symptoms during treatment and the persistence of suicidal ideation. Consistent with prior evidence that sociodemographic factors and clinical history are both prognostic of depression treatment efficacy, we hypothesized that SES and pre-existing anxiety symptoms will both predict lower levels of response to treatment and higher levels of suicidal ideation. METHOD: Secondary analyses of data from the MTLD trials. RESULTS: Regression analyses which controlled for comorbid anxiety indicated that residents of middle- and high-income census tracts were more likely to respond to treatment (HR, 1.63; 95%CI, 1.08-2.46) and less likely to report suicidal ideation during treatment (OR, 0.51; 95%CI, 0.28-0.90) than residents of low income census tracts. The same regression models indicated that pre-existing anxiety symptoms were independently related to lower treatment response (HR, 0.73; 95%CI, 0.60-0.89) and higher risk of suicidal ideation (OR, 1.45; 95%CI, 0.98-2.14). CONCLUSION: These findings demonstrate the importance of treating anxiety symptoms during the course of treatment for late-life depression and, at the same time, addressing barriers to treatment response related to low SES

Neurocognitive Predictors of Treatment Response to Randomized Treatment in Adults with Tic Disorders

Tourette\u27s disorder (TS) and chronic tic disorder (CTD) are neurodevelopmental disorders characterized by involuntary vocal and motor tics. Consequently, TS/CTD have been conceptualized as disorders of cognitive and motor inhibitory control. However, most neurocognitive studies have found comparable or superior inhibitory capacity among individuals with TS/CTD relative to healthy controls. These findings have led to the hypothesis that individuals with TS/CTD develop increased inhibitory control due to the constant need to inhibit tics. However, the role of cognitive control in TS/CTD is not yet understood, particularly in adults. To examine the role of inhibitory control in TS/CTD, the present study investigated this association by assessing the relationship between inhibitory control and treatment response in a large sample of adults with TS/CTD. As part of a large randomized trial comparing behavior therapy versus supportive psychotherapy for TS/CTD, a battery of tests, including tests of inhibitory control was administered to 122 adults with TS/CTD at baseline. We assessed the association between neuropsychological test performance and change in symptom severity, as well as compared the performance of treatment responders and non-responders as defined by the Clinical Global Impression Scale. Results indicated that change in symptoms, and treatment response were not associated with neuropsychological performance on tests of inhibitory control, intellectual ability, or motor function, regardless of type of treatment. The finding that significant change in symptom severity of TS/CTD patients is not associated with impairment or change in inhibitory control regardless of treatment type suggests that inhibitory control may not be a clinically relevant facet of these disorders in adults