[Show abstract][Hide abstract] ABSTRACT: To investigate the relationship between multimorbidity and healthcare utilisation patterns among the highest cost patients in a large, integrated healthcare system.
In this retrospective cross-sectional study of all patients in the U.S. Veterans Affairs (VA) Health Care System, we aggregated costs of individuals' outpatient and inpatient care, pharmacy services and VA-sponsored contract care received in 2010. We assessed chronic condition prevalence, multimorbidity as measured by comorbidity count, and multisystem multimorbidity (number of body systems affected by chronic conditions) among the 5% highest cost patients. Using multivariate regression, we examined the association between multimorbidity and healthcare utilisation and costs, adjusting for age, sex, race/ethnicity, marital status, homelessness and health insurance status.
USA VA Health Care System.
5.2 million VA patients.
Annual total costs; absolute and share of costs generated through outpatient, inpatient, pharmacy and VA-sponsored contract care; number of visits to primary, specialty and mental healthcare; number of emergency department visits and hospitalisations.
The 5% highest cost patients (n=261 699) accounted for 47% of total VA costs. Approximately two-thirds of these patients had chronic conditions affecting ≥3 body systems. Patients with cancer and schizophrenia were less likely to have documented comorbid conditions than other high-cost patients. Multimorbidity was generally associated with greater outpatient and inpatient utilisation. However, increased multisystem multimorbidity was associated with a higher outpatient share of total costs (1.6 percentage points per affected body system, p<0.01) but a lower inpatient share of total costs (-0.6 percentage points per affected body system, p<0.01).
Multisystem multimorbidity is common among high-cost VA patients. While some patients might benefit from disease-specific programmes, for most patients with multimorbidity there is a need for interventions that coordinate and maximise efficiency of outpatient services across multiple conditions.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
BMJ Open 04/2015; 5(4):e007771. DOI:10.1136/bmjopen-2015-007771 · 2.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Bupropion was tested for efficacy to achieve methamphetamine (MA) abstinence in dependent, non-daily users.
A randomized, double-blind, placebo-controlled trial, with 12-week treatment and 4-week follow-up, was conducted with 204 treatment-seeking participants having MA dependence per DSM-IV, who used MA on a less-than-daily basis. 104 were randomized to matched placebo and 100 to bupropion, sustained-release 150mg, twice daily. Participants were seen three times weekly to obtain urine for MA and bupropion assays, study assessments, and thrice weekly, 90-min, group psychotherapy. There was no biomarker for placebo adherence. The primary outcome was achievement of abstinence throughout the last two weeks of treatment; 'success' requiring at least two urine samples during each of Weeks 11 and 12, and all samples MA-negative (<300ng/mL).
Bupropion and placebo groups did not differ significantly in the percentage achieving abstinence for the last 2 weeks of treatment (chi-square, p=0.32). Subgroup analysis of participants with lower baseline MA use (≤18 of last 30 days before consent) also revealed no difference in success between groups (p=0.73). Medication adherence per protocol (detectable bupropion, >5ng/mL, in ≥50% of urine samples from Study Weeks 1-10 and ≥66% of urine samples from Weeks 11 to 12) was achieved by 47% of participants taking bupropion.
These data indicate that bupropion did not increase abstinence in dependent participants who were using MA less-than-daily. Medication non-adherence was a limitation in this trial. Psychosocial therapy remains the mainstay of treatment for MA dependence. Further research on subgroups who may respond to bupropion may be warranted.
Published by Elsevier Ireland Ltd.
Drug and Alcohol Dependence 02/2015; 150. DOI:10.1016/j.drugalcdep.2015.01.036 · 3.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Prevalence of cardiovascular disease (CVD) is increased in patients with obstructive sleep apnea (OSA), possibly related to dyslipidemia in these individuals. Insulin resistance is also common in OSA, but its contribution to dyslipidemia of OSA is unclear. The studys aim was to define the relationships among abnormalities of lipoprotein metabolism, clinical measures of OSA, and insulin resistance.
[Show abstract][Hide abstract] ABSTRACT: Mental health condition (MHC) comorbidity is associated with lower intensity care in multiple clinical scenarios. However, little is known about the effect of MHC upon clinicians’ decisions about intensifying antiglycemic medications in diabetic patients with poor glycemic control. We examined whether delay in intensification of antiglycemic medications in response to an elevated Hemoglobin A1c (HbA1c) value is longer for patients with MHC than for those without MHC, and whether any such effect varies by specific MHC type.
In this observational study of diabetic Veterans Health Administration (VA) patients on oral antiglycemics with poor glycemic control (HbA1c ≥8) (N =52,526) identified from national VA databases, we applied Cox regression analysis to examine time to intensification of antiglycemics after an elevated HbA1c value in 2003–2004, by MHC status.
Those with MHC were no less likely to receive intensification: adjusted Hazard Ratio [95% CI] 0.99 [0.96-1.03], 1.13 [1.04-1.23], and 1.12 [1.07-1.18] at 0–14, 15–30 and 31–180 days, respectively. However, patients with substance use disorders were less likely than those without substance use disorders to receive intensification in the first two weeks following a high HbA1c, adjusted Hazard Ratio 0.89 [0.81-0.97], controlling for sex, age, medical comorbidity, other specific MHCs, and index HbA1c value.
For most MHCs, diabetic patients with MHC in the VA health care system do not appear to receive less aggressive antiglycemic management. However, the subgroup with substance use disorders does appear to have excess likelihood of non-intensification; interventions targeting this high risk subgroup merit attention.
BMC Health Services Research 10/2014; 14(1):458. DOI:10.1186/1472-6963-14-458 · 1.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
The human B-cell response to natural influenza virus infection has not been extensively investigated at the polyclonal level.
The overall B-cell response of patients acutely infected with the 2009 pandemic influenza A(H1N1)pdm09 virus (A[H1N1]pdm09) was analyzed by determining the reactivity of plasmablast-derived polyclonal antibodies (PPAbs) to influenza proteins. Recipients of inactivated influenza vaccine containing the same A(H1N1)pdm09 strain were studied for comparison.
During acute infection, robust plasmablast responses to the infecting virus were detected, characterized by a greater PPAb reactivity to the conserved influenza virus nuclear protein and to heterovariant and heterosubtypic hemagglutinins, in comparison to responses to the inactivated A(H1N1)pdm09 vaccine. In A(H1N1)pdm09 vaccinees, the presence of baseline serum neutralizing antibodies against A(H1N1)pdm09, suggesting previous exposure to natural A(H1N1)pdm09 infection, did not affect the plasmablast response to vaccination, whereas repeated immunization with inactivated A(H1N1)pdm09 vaccine resulted in significantly reduced vaccine-specific and cross-reactive PPAb responses.
Natural A(H1N1)pdm09 infection and inactivated A(H1N1)pdm09 vaccination result in very distinct patterns of B-cell activation and priming. These differences are likely to be associated with differences in protective immunity, especially cross-protection against heterovariant and heterosubtypic influenza virus strains.
The Journal of Infectious Diseases 10/2014; 211(7). DOI:10.1093/infdis/jiu580 · 6.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Toxoplasmosis during pregnancy can result in severe neurological damage or death of the fetus or newborn. Immunopathology has been suspected as mechanism of disease. We recently published cytokine profiles in pregnant women infected with Toxoplasma from USA and Colombia and were surprised that a number of cytokines were down regulated in the US cohort (JID 2014 Mar 23). In this study we investigated profiles of 51 cytokines in 15 pregnant women before and after they became infected with Toxoplasma.
Methods: A Luminex (Affymetrix, Santa Clara, CA) human 51-plex assay was performed at the Human Immune Monitoring Center at Stanford University. Plates were read using a Luminex 200 instrument with a lower bound of 100 beads per sample per cytokine. Each sample produces a median of florescent intensities (MFI) and are measured in duplicate. Statistical analysis: Separately by patient, after centering/scaling, a smooth, curve for log (MFI) on time since infection was estimated per cytokine via empirical Bayes shrinkage of -spline coefficients across cytokines.
Sparse clustering on pooled smoothed data across time points (including interpolated values) and patients gave an optimal six-cluster solution for 49 cytokines. IFN-, TNF-, VCAM1 and IL17F contributed most heavily to cluster separation. The two most prevalent clusters across patients and time points were distinct in that most of the 49 cytokines were upregulated in one (immune state 2, 36% of data, Fig. 1) and downregulated in the other (immune state 3, 40% of data, Fig. 2). Prevalence of each cluster was regressed on time since infection using a piecewise linear generalized linear mixed model. Prevalence of immune state 2 decreased prior to infection () and rose after infection (), while prevalence of immune state 3 decreased after infection (; Fig. 3).
Conclusion: Cytokine profiles in pregnant women before and after Toxoplasma infection are reported here for the first time. Upregulation and downregulation are the result of host-parasite interactions in their balancing act to fight the parasite, prevent immunopathology and survival of both
IDWeek 2014 Meeting of the Infectious Diseases Society of America; 10/2014
[Show abstract][Hide abstract] ABSTRACT: Background Congenital cytomegalovirus (CMV) is reported to affect up to 1% of all live births in the United States. T-cell immunity
may be important for controlling CMV replication in congenital CMV-infected infants. We describe the natural history of CMV-specific
T-cell evolution and CMV replication in infants with congenital CMV infection.
[Show abstract][Hide abstract] ABSTRACT: Background:
The preferential citation of studies with the highest success rates could exaggerate perceived effectiveness, particularly for treatments with widely varying published success rates such as radiofrequency catheter ablation for atrial fibrillation.
Methods and results:
We systematically identified observational studies and clinical trials of radiofrequency catheter ablation of atrial fibrillation between 1990 and 2012. Generalized Poisson regression was used to estimate association between study success rate and total citation count, adjusting for sample size, journal impact factor, time since publication, study design, and whether first or last author was a consensus-defined pre-eminent expert. We identified 174 articles meeting our inclusion criteria (36 289 subjects). After adjustment only for time since publication, a 10-point increase above the mean in pooled reported success rates was associated with a 17.8% increase in citation count at 5 years postpublication (95% confidence interval, 7.1-28.4%; P<0.001). After additional adjustment for impact factor, sample size, randomized trial design, and pre-eminent expert authorship, the association remained significant (18.6% increase in citation count; 95% confidence interval, 7.6-29.6%; P<0.0001). In this full model, time since publication, impact factor, and pre-eminent expert authorship were significant covariates, whereas randomized control trial design and study sample size were not.
Among studies of radiofrequency catheter ablation of atrial fibrillation, high success rate was independently associated with citation count, which may indicate citation bias. To readers of the literature, radiofrequency catheter ablation of atrial fibrillation could be perceived to be more effective than the data supports. These findings may have implications for a wide variety of novel cardiovascular therapies.
[Show abstract][Hide abstract] ABSTRACT: Bayesian estimation techniques offer a systematic and quantitative approach for synthesizing data drawn from the literature to model immunological systems. As detailed here, the practitioner begins with a theoretical model and then sequentially draws information from source data sets and/or published findings to inform estimation of model parameters. Options are available to weigh these various sources of information differentially per objective measures of their corresponding scientific strengths. This approach is illustrated in depth through a carefully worked example for a model of decline in T-cell receptor excision circle content of peripheral T cells during development and aging. Estimates from this model indicate that 21years of age is plausible for the developmental timing of mean age of onset of decline in T-cell receptor excision circle content of peripheral T cells.
[Show abstract][Hide abstract] ABSTRACT: Background
Despite endorsement of digoxin in clinical practice guidelines, there exist limited data on its safety in atrial fibrillation/flutter (AF).
The goal of this study was to evaluate the association of digoxin with mortality in AF.
Using complete data of the TREAT-AF (The Retrospective Evaluation and Assessment of Therapies in AF) study from the U.S. Department of Veterans Affairs (VA) healthcare system, we identified patients with newly diagnosed, nonvalvular AF seen within 90 days in an outpatient setting between VA fiscal years 2004 and 2008. We used multivariate and propensity-matched Cox proportional hazards to evaluate the association of digoxin use with death. Residual confounding was assessed by sensitivity analysis.
Of 122,465 patients with 353,168 person-years of follow-up (age 72.1 ± 10.3 years, 98.4% male), 28,679 (23.4%) patients received digoxin. Cumulative mortality rates were higher for digoxin-treated patients than for untreated patients (95 vs. 67 per 1,000 person-years; p < 0.001). Digoxin use was independently associated with mortality after multivariate adjustment (hazard ratio [HR]: 1.26, 95% confidence interval [CI]: 1.23 to 1.29, p < 0.001) and propensity matching (HR: 1.21, 95% CI: 1.17 to 1.25, p < 0.001), even after adjustment for drug adherence. The risk of death was not modified by age, sex, heart failure, kidney function, or concomitant use of beta-blockers, amiodarone, or warfarin.
Digoxin was associated with increased risk of death in patients with newly diagnosed AF, independent of drug adherence, kidney function, cardiovascular comorbidities, and concomitant therapies. These findings challenge current cardiovascular society recommendations on use of digoxin in AF.
Journal of the American College of Cardiology 08/2014; 64(7):660–668. DOI:10.1016/j.jacc.2014.03.060 · 16.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
The immunological bases for the efficacies of the 2 currently licensed influenza vaccines, live attenuated influenza vaccine (LAIV) and inactivated influenza vaccine (IIV), are not fully understood. The goal of this study was to identify specific B-cell responses correlated with the known efficacies of these 2 vaccines.
We compared the B-cell and antibody responses after immunization with 2010/2011 IIV or LAIV in young adults, focusing on peripheral plasmablasts 6-8 days after vaccination.
The quantities of vaccine-specific plasmablasts and plasmablast-derived polyclonal antibodies (PPAbs) in IIV recipients were significantly higher than those in LAIV recipients. No significant difference was detected in the avidity of vaccine-specific PPAbs between the 2 vaccine groups. Proportionally, LAIV induced a greater vaccine-specific immunoglobulin A plasmablast response, as well as a greater plasmablast response to the conserved influenza nuclear protein, than IIV. The cross-reactive plasmablast response to heterovariant strains, as indicated by the relative levels of cross-reactive plasmablasts and the cross-reactive PPAb binding reactivity, was also greater in the LAIV group.
Distinct quantitative and qualitative patterns of plasmablast responses were induced by LAIV and IIV in young adults; a proportionally greater cross-reactive response was induced by LAIV.
The Journal of Infectious Diseases 03/2014; 210(6). DOI:10.1093/infdis/jiu190 · 6.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In North America (NA) and Europe, the majority of toxoplasmosis cases are benign and generally asymptomatic, whereas in South
America (SA) toxoplasmosis is associated with much more severe symptoms in adults and congenitally infected children. The
reasons for these differences remain unknown; currently, there is little information from patients in either region on how
the immune system responds to infection with Toxoplasma gondii. Here, we report the relative abundance of 51 serum cytokines from acute and chronic toxoplasmosis cohorts of pregnant women
from the United States, where approximately one-half of clinical isolates are Type II, and Colombia, where clinical isolates
are generally “atypical” or Type I-like strains. Surprisingly, the results showed notably lower levels of 23 cytokines in
acutely infected patients from the United States, relative to uninfected US controls. In acutely infected Colombian patients,
however, only 8 cytokine levels differed detectably with 4 being lower and 4 higher relative to uninfected controls. Strikingly,
there were also differences in the cytokine profiles of the chronically infected patients relative to uninfected controls
in the US cohort. Hence, Toxoplasma appears to specifically impact levels of circulating cytokines, and our results may partly explain region-specific differences
in the clinical spectrum of toxoplasmosis.
The Journal of Infectious Diseases 03/2014; 210(6). DOI:10.1093/infdis/jiu189 · 6.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Benzodiazepines, other anxiolytics, or sedative hypnotics are prescribed for 30%-50% of posttraumatic stress disorder (PTSD) patients. Prior data and theory suggest that these medications may inhibit response to exposure therapy, one of the most effective PTSD treatments. The present post hoc study reanalyzed results from a psychotherapy trial to assess whether benzodiazepine use was associated with reduced response to exposure therapy.
Between August 2002 and October 2005, 283 female veterans and soldiers meeting DSM-IV criteria for PTSD were randomly assigned to 10 weekly 90-minute sessions of either prolonged exposure (n = 140) or present-centered psychotherapy (n = 143). Benzodiazepine use (n = 57) or non-use (n = 226) at intake was not randomly assigned. Multilevel modeling was used to assess the effects of benzodiazepine status, psychotherapy condition, and their interaction on changes on the Clinician-Administered PTSD Scale and the PTSD Checklist during the treatment and 6-month follow-up periods.
Consistent with prior reports from these data, prolonged exposure psychotherapy produced greater reductions per week in PTSD symptoms than did present-centered psychotherapy (b = -0.48, P = .02). Patients prescribed benzodiazepines did not have weaker response to prolonged exposure, but demonstrated poorer posttreatment maintenance of gains from present-centered psychotherapy (b = -0.78, P < .001).
Prolonged exposure is a sufficiently robust treatment that patients who are taking benzodiazepines can benefit from it. It is unclear whether benzodiazepine use or other patient factors accounted for benzodiazepine recipients' poorer maintenance of gains in present-centered psychotherapy.
ClinicalTrials.gov identifier: NCT00032617.
The Journal of Clinical Psychiatry 12/2013; 74(12):1241-8. DOI:10.4088/JCP.13m08592 · 5.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There has been an increasing tendency for anesthesiologists to be responsible for providing sedation or anesthesia during chest CT imaging in young children. Anesthesia-related atelectasis noted on chest CT imaging has proven to be a common and troublesome problem, affecting image quality and diagnostic sensitivity.
To evaluate the safety and effectiveness of a standardized anesthesia, lung recruitment, controlled-ventilation technique developed at our institution to prevent atelectasis for chest CT imaging in young children.
Fifty-six chest CT scans were obtained in 42 children using a research-based intubation, lung recruitment and controlled-ventilation CT scanning protocol. These studies were compared with 70 non-protocolized chest CT scans under anesthesia taken from 18 of the same children, who were tested at different times, without the specific lung recruitment and controlled-ventilation technique. Two radiology readers scored all inspiratory chest CT scans for overall CT quality and atelectasis. Detailed cardiorespiratory parameters were evaluated at baseline, and during recruitment and inspiratory imaging on 21 controlled-ventilation cases and 8 control cases.
Significant differences were noted between groups for both quality and atelectasis scores with optimal scoring demonstrated in the controlled-ventilation cases where 70% were rated very good to excellent quality scans compared with only 24% of non-protocol cases. There was no or minimal atelectasis in 48% of the controlled ventilation cases compared to 51% of non-protocol cases with segmental, multisegmental or lobar atelectasis present. No significant difference in cardiorespiratory parameters was found between controlled ventilation and other chest CT cases and no procedure-related adverse events occurred.
Controlled-ventilation infant CT scanning under general anesthesia, utilizing intubation and recruitment maneuvers followed by chest CT scans, appears to be a safe and effective method to obtain reliable and reproducible high-quality, motion-free chest CT images in children.
[Show abstract][Hide abstract] ABSTRACT: Study Objective: To determine the neurocognitive effects of continuous positive airway pressure (CPAP) therapy on patients with obstructive sleep apnea (OSA). Design, Setting, and Participants: The Apnea Positive Pressure Long-term Efficacy Study (APPLES) was a 6-month, randomized, double-blind, 2-arm, sham-controlled, multicenter trial conducted at 5 U.S. university, hospital, or private practices. Of 1,516 participants enrolled, 1,105 were randomized, and 1,098 participants diagnosed with OSA contributed to the analysis of the primary outcome measures. Intervention: Active or sham CPAP Measurements: Three neurocognitive variables, each representing a neurocognitive domain: Pathfinder Number Test-Total Time (attention and psychomotor function [A/P]), Buschke Selective Reminding Test-Sum Recall (learning and memory [L/M]), and Sustained Working Memory Test-Overall Mid-Day Score (executive and frontal-lobe function [E/F]) Results: The primary neurocognitive analyses showed a difference between groups for only the E/F variable at the 2 month CPAP visit, but no difference at the 6 month CPAP visit or for the A/P or L/M variables at either the 2 or 6 month visits. When stratified by measures of OSA severity (AHI or oxygen saturation parameters), the primary E/F variable and one secondary E/F neurocognitive variable revealed transient differences between study arms for those with the most severe OSA. Participants in the active CPAP group had a significantly greater ability to remain awake whether measured subjectively by the Epworth Sleepiness Scale or objectively by the maintenance of wakefulness test. Conclusions: CPAP treatment improved both subjectively and objectively measured sleepiness, especially in individuals with severe OSA (AHI > 30). CPAP use resulted in mild, transient improvement in the most sensitive measures of executive and frontal-lobe function for those with severe disease, which suggests the existence of a complex OSA-neurocognitive relationship.
[Show abstract][Hide abstract] ABSTRACT: Background: Clinical Decision Support (CDS) systems that provide health professionals with evidence-based care recommendations have the potential to improve patient-centeredness of care by individualizing recommendations for each patient; however, it is important to know whether health professionals find them useful and usable. We implemented ATHENA-Hypertension (ATHENA-HTN), a CDS for management of primary hypertension, to assist primary care providers (PCPs) in individualizing patient care.
Objective/Purpose: To evaluate the usefulness and usability of ATHNEA-HTN in a primary care clinical environment.
Methods: The 46 PCPs enrolled at 4 medical centers in the active intervention arm were asked to complete a post-intervention survey. 41/46 (89%) of these PCPs responded to the survey: 16 MDs, 24 NPs, and 1 PA. PCPs rated their experience in terms of the usefulness of the information provided, ease of understanding the information presented, and ease of using the system. Response options for survey questions were of 3 types: (1) Very Useful, Useful, Not Useful, Don't Know/No Opinion; (2) Excellent, Good, Fair, Poor; or (3) Very Often, Often, Not Often.
Results: Many PCPs reported that they found ATHENA-HTN to be Useful or Very Useful as a reminder to manage hypertension (34/41(83%)); to intensify treatment when the patient's BP was above target (34/41(83%)); and to consider thiazides as part of a multi-drug regimen (27/41(66%)). They reported that Often or Very Often information ATHENA-HTN presented was useful (29/40(73%)) and had an impact on their choice of treatment (18/39(46%)). The system was rated as having Excellent or Good readability (30/41(73%)), ease of navigation (27/41(66%)), and integration with overall clinical workflow (21/41 (51%)). PCPs also found the BP prescription graphs (21/37 (57%)) and the ability to enter in a new BP and update the advisory (19/39 (54%)) to be useful.
Discussion/Conclusions: CDS such as ATHENA-HTN can assist PCPs with providing evidence-based care to patients.
140st APHA Annual Meeting and Exposition 2012; 10/2012
[Show abstract][Hide abstract] ABSTRACT: In spite of widespread anecdotal and scientific evidence much remains to be understood about the long-suspected connection between psychological factors and susceptibility to cancer. The skin is the most common site of cancer, accounting for nearly half of all cancers in the US, with approximately 2-3 million cases of non-melanoma cancers occurring each year worldwide. We hypothesized that a high-anxious, stress-prone behavioral phenotype would result in a higher chronic stress burden, lower protective-immunity, and increased progression of the immuno-responsive skin cancer, squamous cell carcinoma. SKH1 mice were phenotyped as high- or low-anxious at baseline, and subsequently exposed to ultraviolet-B light (1 minimal erythemal dose (MED), 3 times/week, 10-weeks). The significant strengths of this cancer model are that it uses a normal, immunocompetent, outbred strain, without surgery/injection of exogenous tumor cells/cell lines, and produces lesions that resemble human tumors. Tumors were counted weekly (primary outcome), and tissues collected during early and late phases of tumor development. Chemokine/cytokine gene-expression was quantified by PCR, tumor-infiltrating helper (Th), cytolytic (CTL), and regulatory (Treg) T cells by immunohistochemistry, lymph node T and B cells by flow cytometry, adrenal and plasma corticosterone and tissue vascular-endothelial-growth-factor (VEGF) by ELISA. High-anxious mice showed a higher tumor burden during all phases of tumor development. They also showed: higher corticosterone levels (indicating greater chronic stress burden), increased CCL22 expression and Treg infiltration (increased tumor-recruited immuno-suppression), lower CTACK/CCL27, IL-12, and IFN-γ gene-expression and lower numbers of tumor infiltrating Th and CTLs (suppressed protective immunity), and higher VEGF concentrations (increased tumor angiogenesis/invasion/metastasis). These results suggest that the deleterious effects of high trait anxiety could be: exacerbated by life-stressors, accentuated by the stress of cancer diagnosis/treatment, and mediate increased tumor progression and/or metastasis. Therefore, it may be beneficial to investigate the use of chemotherapy-compatible anxiolytic treatments immediately following cancer diagnosis, and during cancer treatment/survivorship.
PLoS ONE 04/2012; 7(4):e33069. DOI:10.1371/journal.pone.0033069 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: For any particular psychological instrument, published normative distributions have been derived in one to at most a few specific "reference" populations. Here a method is provided for estimating a normative distribution pertinent to the specific population being evaluated in a randomized clinical trial. Normative quantiles are obtained using quantile regression, a method chosen for its flexibility in that no assumptions are made about the parametric form (e.g., Gaussian) of the normative distribution to be estimated. Outcome is regressed on disease severity for the τth quantile using that sample of consented participants who were not randomized because they fell below the trial's disease severity entry criterion. The τth quantile of the normative distribution is then estimated by the intercept of this fitted regression function, which corresponds to severity of zero. Additional covariates that explain variation in outcome may be included to permit adjustment for shifts in their distributions between the randomized and non-randomized samples. The method is illustrated using data on a depression instrument (GRID Hamilton Rating Scale for Depression) and a neurocognitive instrument (CogScreen Pathfinder Number) from a multicenter clinical trial in sleep apnea patients.