Characterization of Cytomegalovirus Disease in Solid Organ Transplant Recipients by Markers of Inflammation in Plasma

Background

While several studies have examined the general inflammatory responses in relation to cytomegalovirus infection, the identification of the various inflammatory mediators as well as their relative importance is far from clear.

Patients and Methods

Solid organ recipients enrolled in an international multicenter trial of cytomegalovirus disease treatment (the VICTOR study) were analyzed (n = 289) (ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00431353","term_id":"NCT00431353"}}NCT00431353). Plasma markers of inflammation and endothelial cell activation were assessed at baseline by enzyme immunoassays.

Results

The major findings were: (i) Plasma levels of the CXC-chemokine interferon-inducible protein-10 (P<0.001) and C-reactive protein (P = 0.046) were independently associated with the presence of cytomegalovirus DNAemia above lower level of quantification. (ii) High levels of CC-chemokine ligand 21 (P = 0.027) and pentraxin 3 (P = 0.033) were independently associated with tissue invasive cytomegalovirus disease as opposed to cytomegalovirus syndrome.

Conclusion

Our findings illustrate the complex interaction between cytomegalovirus and the immune system, involving a wide range of inflammatory mediators that could be associated to disease manifestations in cytomegalovirus related disease.     

Cognitive Training Improves Sleep Quality and Cognitive Function among Older Adults with Insomnia

Study Objectives

To investigate the effect of an eight-week, home-based, personalized, computerized cognitive training program on sleep quality and cognitive performance among older adults with insomnia.

Design

Participants (n = 51) were randomly allocated to a cognitive training group (n = 34) or to an active control group (n = 17). The participants in the cognitive training group completed an eight-week, home-based, personalized, computerized cognitive training program, while the participants in the active control group completed an eight-week, home-based program involving computerized tasks that do not engage high-level cognitive functioning. Before and after training, all participants'' sleep was monitored for one week by an actigraph and their cognitive performance was evaluated.

Setting

Community setting: residential sleep/performance testing facility.

Participants

Fifty-one older adults with insomnia (aged 65–85).

Interventions

Eight weeks of computerized cognitive training for older adults with insomnia.

Results

Mixed models for repeated measures analysis showed between-group improvements for the cognitive training group on both sleep quality (sleep onset latency and sleep efficiency) and cognitive performance (avoiding distractions, working memory, visual memory, general memory and naming). Hierarchical linear regressions analysis in the cognitive training group indicated that improved visual scanning is associated with earlier advent of sleep, while improved naming is associated with the reduction in wake after sleep onset and with the reduction in number of awakenings. Likewise the results indicate that improved “avoiding distractions” is associated with an increase in the duration of sleep. Moreover, the results indicate that in the active control group cognitive decline observed in working memory is associated with an increase in the time required to fall asleep.

Conclusions

New learning is instrumental in promoting initiation and maintenance of sleep in older adults with insomnia. Lasting and personalized cognitive training is particularly indicated to generate the type of learning necessary for combined cognitive and sleep enhancements in this population.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00901641","term_id":"NCT00901641"}}NCT00901641http://clinicaltrials.gov/ct2/show/NCT00901641     

Routine Opt-Out HIV Testing Strategies in a Female Jail Setting: A Prospective Controlled Trial

Background

Ten million Americans enter jails annually. The objective was to evaluate new CDC guidelines for routine opt-out HIV testing and examine the optimal time to implement routine opt-out HIV testing among newly incarcerated jail detainees.

Methods

This prospective, controlled trial of routine opt-out HIV testing was conducted among 323 newly incarcerated female inmates in Connecticut''s only women''s jail. 323 sequential entrants to the women''s jail over a five week period in August and September 2007 were assigned to be offered routine opt-out HIV testing at one of three points after incarceration: immediate (same day, n = 108), early (next day, n = 108), or delayed (7 days, n = 107). The primary outcome was the proportion of women in each group consenting to testing.

Results

Routine opt-out HIV testing was significantly highest (73%) among the early testing group compared to 55% for immediate and 50% for 7 days post-entry groups. Other factors significantly (p = 0.01) associated with being HIV tested were younger age and low likelihood of early release from jail based on bond value or type of charge for which women were arrested.

Conclusions

In this correctional facility, routine opt-out HIV testing in a jail setting was feasible, with highest rates of testing if performed the day after incarceration. Lower testing rates were seen with immediate testing, where there is a high prevalence of inability or unwillingness to test, and with delayed testing, where attrition from jail increases with each passing day.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00624247","term_id":"NCT00624247"}}NCT00624247     

Genetic Variants of the α-Synuclein Gene SNCA Are Associated with Multiple System Atrophy

Background

Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterized by parkinsonism, cerebellar ataxia and autonomic dysfunction. Pathogenic mechanisms remain obscure but the neuropathological hallmark is the presence of α-synuclein-immunoreactive glial cytoplasmic inclusions. Genetic variants of the α-synuclein gene, SNCA, are thus strong candidates for genetic association with MSA. One follow-up to a genome-wide association of Parkinson''s disease has identified association of a SNP in SNCA with MSA.

Methodology/Findings

We evaluated 32 SNPs in the SNCA gene in a European population of 239 cases and 617 controls recruited as part of the Neuroprotection and Natural History in Parkinson Plus Syndromes (NNIPPS) study. We used 161 independently collected samples for replication. Two SNCA SNPs showed association with MSA: rs3822086 (P = 0.0044), and rs3775444 (P = 0.012), although only the first survived correction for multiple testing. In the MSA-C subgroup the association strengthened despite more than halving the number of cases: rs3822086 P = 0.0024, OR 2.153, (95% CI 1.3–3.6); rs3775444 P = 0.0017, OR 4.386 (95% CI 1.6–11.7). A 7-SNP haplotype incorporating three SNPs either side of rs3822086 strengthened the association with MSA-C further (best haplotype, P = 8.7×10⁻⁴). The association with rs3822086 was replicated in the independent samples (P = 0.035).

Conclusions/Significance

We report a genetic association between MSA and α-synuclein which has replicated in independent samples. The strongest association is with the cerebellar subtype of MSA.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00211224","term_id":"NCT00211224"}}NCT00211224. [{"type":"clinical-trial","attrs":{"text":"NCT00211224","term_id":"NCT00211224"}}NCT00211224]     

Levels of Cholesterol in Small LDL Particles Predict Atherosclerosis Progression and Incident CHD in the HDL-Atherosclerosis Treatment Study (HATS)

Objective

Test whether angiographically-documented changes in percent stenosis and clinical endpoints (coronary-related deaths, myocardial infarctions, stroke, revascularization for worsening ischemia) in the HDL-Atherosclerosis Treatment Study (HATS) were attributable to specific LDL-subclasses.

Methods

Gradient gel electrophoresis of on-study LDL-subclass cholesterol concentrations were measured in 32 placebo, 33 simvastatin-niacin, 38 antioxidant, and 39 simvastatin-niacin & antioxidant treated participants. The prespecified primary end point was the mean change per patient from the initial arteriogram to the final arteriogram in the percent stenosis caused by the most severe lesion in each of the nine proximal coronary segments.

Results

The change in the percent stenosis of the most severe proximal lesions increased in association with higher concentrations of the small LDL subfractions LDL-IIIb (24.2–24.6 nm) and LDL-IVa (23.3–24.1 nm) before (both P = 0.002) and after (P = 0.01 and P = 0.03 respectively) adjustment for treatment group and on-study HDL-cholesterol, LDL-cholesterol, and triglyceride concentrations. The associations appeared specific to lesions with <30% baseline stenosis. When adjusted for age, sex, baseline BMI and cigarette use, the odds for primary clinical endpoints (death from coronary causes, nonfatal myocardial infarction, stroke, or revascularization for worsening ischemia) were significantly greater in subjects with higher on-study LDL-IIIb levels both before (P = 0.01) and after (P = 0.03) adjustment for treatment group and the standard lipid values.

Conclusions

Plasma LDL-IIIb cholesterol concentrations were related to changes in coronary artery stenosis and cardiovascular events in patients with coronary artery disease and low HDL-cholesterol.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00000553","term_id":"NCT00000553"}}NCT00000553     

Effectiveness of a Randomized School-Based Intervention Involving Families and Teachers to Prevent Excessive Weight Gain among Adolescents in Brazil

Objective

To evaluate the effectiveness of a school-based intervention involving the families and teachers that aimed to promote healthy eating habits in adolescents; the ultimate aim of the intervention was to reduce the increase in body mass index (BMI) of the students.

Design

Paired cluster randomized school-based trial conducted with a sample of fifth graders.

Setting

Twenty classes were randomly assigned into either an intervention group or a control group.

Participants

From a total of 574 eligible students, 559 students participated in the study (intervention: 10 classes with 277 participants; control: 10 classes with 282 participants). The mean age of students was 11 years.

Intervention

Students attended 9 nutritional education sessions during the 2010 academic year. Parents/guardians and teachers received information on the same subjects.

Main Outcome Measurement

Changes in BMI and percentage of body fat.

Results

Intention-to-treat analysis showed that changes in BMI were not significantly different between the 2 groups (β = 0.003; p = 0.75). There was a major reduction in the consumption of sugar-sweetened beverages and cookies in the intervention group; students in this group also consumed more fruits.

Conclusion

Encouraging the adoption of healthy eating habits promoted important changes in the adolescent diet, but this did not lead to a reduction in BMI gain. Strategies based exclusively on the quality of diet may not reduce weight gain among adolescents.

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01046474","term_id":"NCT01046474"}}NCT01046474.     

Effect of Alpha Linolenic Acid Supplementation on Serum Prostate Specific Antigen (PSA): Results from the Alpha Omega Trial

Background

Alpha linolenic acid (ALA) is the major omega-3 fatty acid in the diet. Evidence on health effects of ALA is not conclusive, but some observational studies found an increased risk of prostate cancer with higher intake of ALA. We examined the effect of ALA supplementation on serum concentrations of prostate-specific antigen (PSA), a biomarker for prostate cancer.

Methods

The Alpha Omega Trial (ClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT00127452","term_id":"NCT00127452"}}NCT00127452) was a double-blind, placebo-controlled trial of ALA and the fish fatty acids eicosapentanoic acid (EPA) and docosahexanoic acid (DHA) on the recurrence of cardiovascular disease, using a 2×2 factorial design. Blood was collected at the start and the end of the intervention period. The present analysis included 1622 patients with a history of a myocardial infarction, aged 60–80 years with an initial PSA concentration <4 ng/mL. They received either 2 g per day of ALA or placebo in margarine spreads for 40 months. T-tests and logistic regression were used to assess the effects of ALA supplementation on changes in serum PSA (both continuously and as a dichotomous outcome, cut-off point: >4 ng/mL).

Findings

Mean serum PSA increased by 0.42 ng/mL on placebo (n = 815) and by 0.52 ng/mL on ALA (n = 807), a difference of 0.10 (95% confidence interval: −0.02 to 0.22) ng/mL (P = 0·12). The odds ratio for PSA rising above 4 ng/mL on ALA versus placebo was 1.15 (95% CI: 0.84–1.58).

Interpretation

An additional amount of 2 g of ALA per day increased PSA by 0.10 ng/mL, but the confidence interval ranged from −0.02 to 0.22 ng/mL and included no effect. Therefore, more studies are needed to establish whether or not ALA intake has a clinically significant effect on PSA or prostate cancer.

Trial registration information

ClinicalTrials.gov; Identifier: {"type":"clinical-trial","attrs":{"text":"NCT00127452","term_id":"NCT00127452"}}NCT00127452. URL: http://www.clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT00127452","term_id":"NCT00127452"}}NCT00127452.     

Electroacupuncture for Moderate and Severe Benign Prostatic Hyperplasia: A Randomized Controlled Trial

Purpose

To evaluate the effects of electroacupuncture (EA) on the International Prostate Symptom Score (IPSS), postvoid residual urine (PVR), and maximum urinary flow rate (Qmax), and explore the difference between EA at acupoints and non-acupoints in patients with moderate to severe benign prostate hyperplasia (BPH).

Subjects and Methods

Men with BPH and IPSS ≥8 were enrolled. Participants were randomly allocated to receive EA at acupoint (treatment group, n = 50) and EA at non-acupoint (control group, n = 50). The primary outcome measure includes the change of IPSS at the 6th week and the secondary outcome measures include changes of PVR and Qmax at the 6th week and change of IPSS at the 18th week.

Results

100/192 patients were included. At the 6th week, treatment group patients had a 4.51 (p<0.001) and 4.12 (p<0.001) points greater decline in IPSS than the control group in the intention to treat (ITT) and per-protocol (PP) populations. At the 18th week, a 3.2 points (p = 0.001) greater decline was found in IPSS for the treatment. No significant differences were found between the two groups in Qmax at the 6th week (p = 0.819). No significant difference was observed in PVR (P = 0.35).

Conclusion

Acupoint EA at BL 33 had better effects on IPSS, but no difference on PVR and Qmax as compared with non-acupoint EA. The results indicate that EA is effective in improving patient''s quality of life and acupoint may have better therapeutic effects than non-acupoints in acupuncture treatments of BPH.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01218243","term_id":"NCT01218243"}}NCT01218243.     

Sleep Extension Improves Neurocognitive Functions in Chronically Sleep-Deprived Obese Individuals

Background

Sleep deprivation and obesity, are associated with neurocognitive impairments. Effects of sleep deprivation and obesity on cognition are unknown, and the cognitive long-term effects of improvement of sleep have not been prospectively assessed in short sleeping, obese individuals.

Objective

To characterize neurocognitive functions and assess its reversibility.

Design

Prospective cohort study.

Setting

Tertiary Referral Research Clinical Center.

Patients

A cohort of 121 short-sleeping (<6.5 h/night) obese (BMI 30–55 kg/m²) men and pre-menopausal women.

Intervention

Sleep extension (468±88 days) with life-style modifications.

Measurements

Neurocognitive functions, sleep quality and sleep duration.

Results

At baseline, 44% of the individuals had an impaired global deficit score (t-score 0–39). Impaired global deficit score was associated with worse subjective sleep quality (p = 0.02), and lower urinary dopamine levels (p = 0.001). Memory was impaired in 33%; attention in 35%; motor skills in 42%; and executive function in 51% of individuals. At the final evaluation (N = 74), subjective sleep quality improved by 24% (p<0.001), self-reported sleep duration increased by 11% by questionnaires (p<0.001) and by 4% by diaries (p = 0.04), and daytime sleepiness tended to improve (p = 0.10). Global cognitive function and attention improved by 7% and 10%, respectively (both p = 0.001), and memory and executive functions tended to improve (p = 0.07 and p = 0.06). Serum cortisol increased by 17% (p = 0.02). In a multivariate mixed model, subjective sleep quality and sleep efficiency, urinary free cortisol and dopamine and plasma total ghrelin accounted for 1/5 of the variability in global cognitive function.

Limitations

Drop-out rate.

Conclusions

Chronically sleep-deprived obese individuals exhibit substantial neurocognitive deficits that are partially reversible upon improvement of sleep in a non-pharmacological way. These findings have clinical implications for large segments of the US population.

Trail registration

www.ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00261898","term_id":"NCT00261898"}}NCT00261898. NIDDK protocol 06-DK-0036     

Harnessing Naturally Occurring Tumor Immunity: A Clinical Vaccine Trial in Prostate Cancer

Background

Studies of patients with paraneoplastic neurologic disorders (PND) have revealed that apoptotic tumor serves as a potential potent trigger for the initiation of naturally occurring tumor immunity. The purpose of this study was to assess the feasibility, safety, and immunogenicity of an apoptotic tumor-autologous dendritic cell (DC) vaccine.

Methods and Findings

We have modeled PND tumor immunity in a clinical trial in which apoptotic allogeneic prostate tumor cells were used to generate an apoptotic tumor-autologous dendritic cell vaccine. Twenty-four prostate cancer patients were immunized in a Phase I, randomized, single-blind, placebo-controlled study to assess the safety and immunogenicity of this vaccine. Vaccinations were safe and well tolerated. Importantly, we also found that the vaccine was immunogenic, inducing delayed type hypersensitivity (DTH) responses and CD4+ and CD8+ T cell proliferation, with no effect on FoxP3+ regulatory T cells. A statistically significant increase in T cell proliferation responses to prostate tumor cells in vitro (p = 0.002), decrease in prostate specific antigen (PSA) slope (p = 0.016), and a two-fold increase in PSA doubling time (p = 0.003) were identified when we compared data before and after vaccination.

Conclusions

An apoptotic cancer cell vaccine modeled on naturally occurring tumor immune responses in PND patients provides a safe and immunogenic tumor vaccine. (ClinicalTrials.gov number {"type":"clinical-trial","attrs":{"text":"NCT00289341","term_id":"NCT00289341"}}NCT00289341).

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00289341","term_id":"NCT00289341"}}NCT00289341     

The Effect of Ginseng (The Genus Panax) on Glycemic Control: A Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials

Importance

Despite the widespread use of ginseng in the management of diabetes, supporting evidence of its anti-hyperglycemic efficacy is limited, necessitating the need for evidence-based recommendations for the potential inclusion of ginseng in diabetes management.

Objective

To elucidate the effect of ginseng on glycemic control in a systematic review and meta-analysis of randomized controlled trials in people with and without diabetes.

Data sources

MEDLINE, EMBASE, CINAHL and the Cochrane Library (through July 3, 2013).

Study selection

Randomized controlled trials ≥30 days assessing the glycemic effects of ginseng in people with and without diabetes.

Data extraction

Relevant data were extracted by 2 independent reviewers. Discrepancies were resolved by consensus. The Heyland Methodological Quality Score and the Cochrane risk of bias tool were used to assess study quality and risk of bias respectively.

Data synthesis

Sixteen trials were included, in which 16 fasting blood glucose (n = 770), 10 fasting plasma insulin (n = 349), 9 glycated hemoglobin (n = 264), and 7 homeostasis model assessment of insulin resistance (n = 305) comparisons were reported. Ginseng significantly reduced fasting blood glucose compared to control (MD =  −0.31 mmol/L [95% CI: −0.59 to −0.03], P = 0.03). Although there was no significant effect on fasting plasma insulin, glycated hemoglobin, or homeostasis model assessment of insulin resistance, a priori subgroup analyses did show significant reductions in glycated hemoglobin in parallel compared to crossover trials (MD = 0.22% [95%CI: 0.06 to 0.37], P = 0.01).

Limitations

Most trials were of short duration (67% trials<12wks), and included participants with a relatively good glycemic control (median HbA1c non-diabetes = 5.4% [2 trials]; median HbA1c diabetes = 7.1% [7 trials]).

Conclusions

Ginseng modestly yet significantly improved fasting blood glucose in people with and without diabetes. In order to address the uncertainty in our effect estimates and provide better assessments of ginseng''s anti-diabetic efficacy, larger and longer randomized controlled trials using standardized ginseng preparations are warranted.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01841229","term_id":"NCT01841229"}}NCT01841229     

IV t-PA Influences Infarct Volume in Minor Stroke: A Pilot Study

Background

There is an ongoing debate whether stroke patients presenting with minor or moderate symptoms benefit from thrombolysis. Up until now, stroke severity on admission is typically measured with the NIHSS, and subsequently used for treatment decision.

Hypothesis

Acute MRI lesion volume assessment can aid in therapy decision for iv-tPA in minor stroke.

Methods

We analysed 164 patients with NIHSS 0–7 from a prospective stroke MRI registry, the 1000+ study (clinicaltrials.org {"type":"clinical-trial","attrs":{"text":"NCT00715533","term_id":"NCT00715533"}}NCT00715533). Patients were examined in a 3 T MRI scanner and either received (n = 62) or did not receive thrombolysis (n = 102). DWI (diffusion weighted imaging) and PI (perfusion imaging) at admission were evaluated for diffusion - perfusion mismatch. Our primary outcome parameter was final lesion volume, defined by lesion volume on day 6 FLAIR images.

Results

The association between t-PA and FLAIR lesion volume on day 6 was significantly different for patients with smaller DWI volume compared to patients with larger DWI volume (interaction between DWI and t-PA: p = 0.021). Baseline DWI lesion volume was dichotomized at the median (0.7 ml): final lesion volume at day 6 was larger in patients with large baseline DWI volumes without t-PA treatment (median difference 3, IQR −0.4–9.3 ml). Conversely, in patients with larger baseline DWI volumes final lesion volumes were smaller after t-PA treatment (median difference 0, IQR −4.1–5 ml). However, this did not translate into a significant difference in the mRS at day 90 (p = 0.577).

Conclusion

Though this study is only hypothesis generating considering the number of cases, we believe that the size of DWI lesion volume may support therapy decision in patients with minor stroke.

Trial Registration

Clinicaltrials.org {"type":"clinical-trial","attrs":{"text":"NCT00715533","term_id":"NCT00715533"}}NCT00715533     

Effects of High Doses of Cholecalciferol in Normal Subjects: A Randomized Double-Blinded,Placebo-Controlled Trial

Background

Vitamin D repletion with high doses of vitamin D is often recommended to patients and healthy subjects. The safety, especially concerning changes in urinary calcium excretion is of great importance.

Methods

In a double-blinded, placebo-controlled study in 40 healthy volunteers, we examined the changes in mineral metabolism during supplementation with 3000 IU of oral cholecalciferol daily during 4 months.

Results

Both 25(OH)vitamin D and 1,25(OH)₂vitamin D increased significantly in the active treated group as compared to the placebo group (186% versus 14% (P<0.001) and 28% versus – 8% (P<0.001)). No change was observed in urinary calcium excretion in the active group compared to the placebo group (P = 0.891). Fibroblast growth factor 23 increased significantly by 10% (P<0.018) in the active group. However, there was no difference in changes in FGF23 between treatment groups (P = 0.457).

Conclusion

High dose cholecalciferol significantly increases 25(OH)vitamin D and 1,25(OH)₂vitamin D levels compared to placebo. No changes in urinary calcium excretion or other measured components of the mineral metabolism were found between groups.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00952562","term_id":"NCT00952562"}}NCT00952562.     

Effect of an Educational Toolkit on Quality of Care: A Pragmatic Cluster Randomized Trial

Background

Printed educational materials for clinician education are one of the most commonly used approaches for quality improvement. The objective of this pragmatic cluster randomized trial was to evaluate the effectiveness of an educational toolkit focusing on cardiovascular disease screening and risk reduction in people with diabetes.

Methods and Findings

All 933,789 people aged ≥40 years with diagnosed diabetes in Ontario, Canada were studied using population-level administrative databases, with additional clinical outcome data collected from a random sample of 1,592 high risk patients. Family practices were randomly assigned to receive the educational toolkit in June 2009 (intervention group) or May 2010 (control group). The primary outcome in the administrative data study, death or non-fatal myocardial infarction, occurred in 11,736 (2.5%) patients in the intervention group and 11,536 (2.5%) in the control group (p = 0.77). The primary outcome in the clinical data study, use of a statin, occurred in 700 (88.1%) patients in the intervention group and 725 (90.1%) in the control group (p = 0.26). Pre-specified secondary outcomes, including other clinical events, processes of care, and measures of risk factor control, were also not improved by the intervention. A limitation is the high baseline rate of statin prescribing in this population.

Conclusions

The educational toolkit did not improve quality of care or cardiovascular outcomes in a population with diabetes. Despite being relatively easy and inexpensive to implement, printed educational materials were not effective. The study highlights the need for a rigorous and scientifically based approach to the development, dissemination, and evaluation of quality improvement interventions.

Trial Registration

http://www.ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01411865","term_id":"NCT01411865"}}NCT01411865 and {"type":"clinical-trial","attrs":{"text":"NCT01026688","term_id":"NCT01026688"}}NCT01026688 Please see later in the article for the Editors'' Summary     

CXCL13 predicts disease activity in early rheumatoid arthritis and could be an indicator of the therapeutic ‘window of opportunity’

Introduction

A key phenomenon in rheumatoid arthritis is the formation of lymphoid follicles in the inflamed synovial membrane. C-X-C motif chemokine 13 (CXCL13) is central in this process as it attracts C-X-C chemokine receptor type 5 (CXCR5)-expressing B cells and T follicular helper cells to the follicle. We here examine the role of CXCL13 and its association with disease in patients with treatment-naïve early rheumatoid arthritis.

Methods

Plasma samples from patients in the OPERA trial were examined for CXCL13 at treatment initiation and after 6 months of treatment with either methotrexate plus placebo (DMARD) (n = 37) or methotrexate plus adalimumab (DMARD + ADA) (n = 39). Treatment outcome was evaluated after 1 and 2 years. CXCL13 plasma levels in healthy volunteers (n = 38) were also examined.

Results

Baseline CXCL13 plasma levels were increased in early rheumatoid arthritis patients in comparison with healthy volunteers. Also, plasma CXCL13 correlated positively with disease activity parameters; swollen joint count 28 (rho = 0.34) and 40 (rho = 0.39), visual analog score (rho = 0.38) and simplified disease activity index (rho = 0.25) (all P <0.05). CXCL13 levels decreased a significantly twofold more in the DMARD + ADA group than in the DMARD group. Baseline CXCL13 plasma levels in the DMARD group correlated inversely with disease activity parameters; disease activity score in 28 joints, four variables, C-reactive protein based (DAS28CRP) (rho = 0.58, P <0.05) at 12 months. High baseline CXCL13 was associated with remission (DAS28CRP less than 2.6) after 2 years.

Conclusions

In treatment-naïve early rheumatoid arthritis patients, plasma CXCL13 levels were associated with joint inflammation. Furthermore, patients with high baseline plasma CXCL13 levels had an improved chance of remission after 2 years. We propose that high CXCL13 concentrations indicate recent onset of inflammation that may respond better to early aggressive treatment. Thus, high levels of CXCL13 could reflect the ‘the window of opportunity’ for optimal treatment effect.

Trial registration

Clinicaltrial.gov {"type":"clinical-trial","attrs":{"text":"NCT00660647","term_id":"NCT00660647"}}NCT00660647. Registered 10 April 2008     

Effect of Tree Nuts on Glycemic Control in Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Dietary Trials

Background

Tree nut consumption has been associated with reduced diabetes risk, however, results from randomized trials on glycemic control have been inconsistent.

Objective

To provide better evidence for diabetes guidelines development, we conducted a systematic review and meta-analysis of randomized controlled trials to assess the effects of tree nuts on markers of glycemic control in individuals with diabetes.

Data Sources

MEDLINE, EMBASE, CINAHL, and Cochrane databases through 6 April 2014.

Study Selection

Randomized controlled trials ≥3 weeks conducted in individuals with diabetes that compare the effect of diets emphasizing tree nuts to isocaloric diets without tree nuts on HbA1c, fasting glucose, fasting insulin, and HOMA-IR.

Data Extraction and Synthesis

Two independent reviewer’s extracted relevant data and assessed study quality and risk of bias. Data were pooled by the generic inverse variance method and expressed as mean differences (MD) with 95% CI’s. Heterogeneity was assessed (Cochran Q-statistic) and quantified (I²).

Results

Twelve trials (n = 450) were included. Diets emphasizing tree nuts at a median dose of 56 g/d significantly lowered HbA1c (MD = −0.07% [95% CI:−0.10, −0.03%]; P = 0.0003) and fasting glucose (MD = −0.15 mmol/L [95% CI: −0.27, −0.02 mmol/L]; P = 0.03) compared with control diets. No significant treatment effects were observed for fasting insulin and HOMA-IR, however the direction of effect favoured tree nuts.

Limitations

Majority of trials were of short duration and poor quality.

Conclusions

Pooled analyses show that tree nuts improve glycemic control in individuals with type 2 diabetes, supporting their inclusion in a healthy diet. Owing to the uncertainties in our analyses there is a need for longer, higher quality trials with a focus on using nuts to displace high-glycemic index carbohydrates.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01630980","term_id":"NCT01630980"}}NCT01630980     

The Effect of a Physical Activity Program on the Total Number of Primary Care Visits in Inactive Patients: A 15-Month Randomized Controlled Trial

Background

Effective promotion of exercise could result in substantial savings in healthcare cost expenses in terms of direct medical costs, such as the number of medical appointments. However, this is hampered by our limited knowledge of how to achieve sustained increases in physical activity.

Objectives

To assess the effectiveness of a Primary Health Care (PHC) based physical activity program in reducing the total number of visits to the healthcare center among inactive patients, over a 15-month period.

Research Design

Randomized controlled trial.

Subjects

Three hundred and sixty-two (n = 362) inactive patients suffering from at least one chronic condition were included. One hundred and eighty-three patients (n = 183; mean (SD); 68.3 (8.8) years; 118 women) were randomly allocated to the physical activity program (IG). One hundred and seventy-nine patients (n = 179; 67.2 (9.1) years; 106 women) were allocated to the control group (CG). The IG went through a three-month standardized physical activity program led by physical activity specialists and linked to community resources.

Measures

The total number of medical appointments to the PHC, during twelve months before and after the program, was registered. Self-reported health status (SF-12 version 2) was assessed at baseline (month 0), at the end of the intervention (month 3), and at 12 months follow-up after the end of the intervention (month 15).

Results

The IG had a significantly reduced number of visits during the 12 months after the intervention: 14.8 (8.5). The CG remained about the same: 18.2 (11.1) (P = .002).

Conclusions

Our findings indicate that a 3-month physical activity program linked to community resources is a short-duration, effective and sustainable intervention in inactive patients to decrease rates of PHC visits.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00714831","term_id":"NCT00714831"}}NCT00714831     

Intravenous Amantadine for Freezing of Gait Resistant to Dopaminergic Therapy: A Randomized,Double-Blind,Placebo-Controlled,Cross-Over Clinical Trial

Background

Freezing of gait (FOG) is one of the most disabling symptoms in Parkinsonism. Open-label studies have suggested that intravenous (IV) amantadine is effective against FOG resistant to dopaminergic therapy in Parkinson''s disease (PD). We evaluated the efficacy of IV amantadine on FOG resistant to dopaminergic therapy.

Methodology/Principal Findings

This was a randomized, double-blind, placebo-controlled, cross-over study on IV amantadine. The placebo (normal saline) and amantadine (400 mg/day) were injected for 2 days with a 52-hour washout period. The instruments for the outcome measures were the Freezing of Gait Questionnaire (FOGQ), Unified Parkinson''s disease rating Scale (UPDRS), and the duration of the 4×10 m walking test. The placebo arm was compared to the amantadine arm. Ten patients were enrolled but two patients withdrew, one from each arm. The FOGQ and UPDRS scores and the duration of the 4×10 m walking test improved in both arms compared to the baseline (P<0.05 in all). However, there were no differences in these values between the amantadine arm and placebo arm (P = 0.368, P = 0.583, P = 0.206, respectively). Follow-up measures 2weeks after discharge in an open-label study showed the beneficial effects of an amantadine tablet on FOG (FOGQ, P = 0.018; UPDRS, P = 0.012 respectively).

Conclusions/Significance

This double blind, placebo-controlled study did not show the efficacy of IV amantadine on FOG when compared with the placebo. This study provides Class II evidence due to small sample size for the lack of benefit of IV amantadine on FOG resistant to dopaminergic therapy

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01313819","term_id":"NCT01313819"}}NCT01313819     

An Adaptive Physical Activity Intervention for Overweight Adults: A Randomized Controlled Trial

Background

Physical activity (PA) interventions typically include components or doses that are static across participants. Adaptive interventions are dynamic; components or doses change in response to short-term variations in participant''s performance. Emerging theory and technologies make adaptive goal setting and feedback interventions feasible.

Objective

To test an adaptive intervention for PA based on Operant and Behavior Economic principles and a percentile-based algorithm. The adaptive intervention was hypothesized to result in greater increases in steps per day than the static intervention.

Methods

Participants (N = 20) were randomized to one of two 6-month treatments: 1) static intervention (SI) or 2) adaptive intervention (AI). Inactive overweight adults (85% women, M = 36.9±9.2 years, 35% non-white) in both groups received a pedometer, email and text message communication, brief health information, and biweekly motivational prompts. The AI group received daily step goals that adjusted up and down based on the percentile-rank algorithm and micro-incentives for goal attainment. This algorithm adjusted goals based on a moving window; an approach that responded to each individual''s performance and ensured goals were always challenging but within participants'' abilities. The SI group received a static 10,000 steps/day goal with incentives linked to uploading the pedometer''s data.

Results

A random-effects repeated-measures model accounted for 180 repeated measures and autocorrelation. After adjusting for covariates, the treatment phase showed greater steps/day relative to the baseline phase (p<.001) and a group by study phase interaction was observed (p = .017). The SI group increased by 1,598 steps/day on average between baseline and treatment while the AI group increased by 2,728 steps/day on average between baseline and treatment; a significant between-group difference of 1,130 steps/day (Cohen''s d = .74).

Conclusions

The adaptive intervention outperformed the static intervention for increasing PA. The adaptive goal and feedback algorithm is a “behavior change technology” that could be incorporated into mHealth technologies and scaled to reach large populations.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01793064","term_id":"NCT01793064"}}NCT01793064