Effect of Nurse Home Visits vs. Usual Care on Reducing Intimate Partner Violence in Young High-Risk Pregnant Women: A Randomized Controlled Trial

Background

Expectant mothers and mothers of young children are especially vulnerable to intimate partner violence (IPV). The nurse-family partnership (NFP) is a home visitation program in the United States effective for the prevention of adverse child health outcomes. Evidence regarding the effect of nurse home visiting on IPV is inconsistent. This study aims to study the effect of VoorZorg, the Dutch NFP, on IPV.

Methods

A random sample of 460 eligible disadvantaged women <26 years, with no previous live births, was randomized. Women in the control group (C; n=223) received usual care; women in the intervention group (I; n=237) received usual care plus nurse home visits periodically during pregnancy and until the child’s second birthday.

Results

At 32 weeks of pregnancy, women in the intervention group self-reported significantly less IPV victimization than women in the control group in: level 2 psychological aggression (C: 56% vs. I: 39%), physical assault level 1 (C: 58% vs. I: 40%) and level 2 (C: 31% vs. I: 20%), and level 1 sexual coercion (C: 16% vs. I: 8%). Furthermore, women in the intervention group reported significantly less IPV perpetration in: level 2 psychological aggression (C: 60% vs. I: 46%), level 1 physical assault (C: 65% vs. I: 52%), and level 1 injury (C: 27% vs. I: 17%). At 24 months after birth, IPV victimization was significantly lower in the intervention group for level 1 physical assault (C: 44% vs. I: 26%), and IPV perpetration was significantly lower for level 1 sexual assault (C: 18% vs. I: 3%). Multilevel analyses showed a significant improvement in IPV victimization and perpetration among women in the intervention group at 24 months after birth.

Conclusion

VoorZorg, compared with the usual care, is effective in reducing IPV during pregnancy and in the two years after birth among young high-risk women.

Trial Registration

Dutch Trial Register NTR854 http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=854     

Using Ecological Momentary Assessment in Testing the Effectiveness of an Alcohol Intervention: A Two-Arm Parallel Group Randomized Controlled Trial

Background

Alcohol consumption of college students has a fluctuating nature, which might impact the measurement of intervention effects. By using 25 follow-up time-points, this study tested whether intervention effects are robust or might vary over time.

Methods

Data were used from a two-arm parallel group randomized controlled trial applying ecological momentary assessment (EMA) with 30 data time-points in total. Students between 18 and 24 years old who reported heavy drinking in the past six months and who were ready to change their alcohol consumption were randomly assigned to the experimental (n = 456: web-based brief alcohol intervention) and control condition (n = 451: no intervention). Outcome measures were weekly alcohol consumption, frequency of binge drinking, and heavy drinking status.

Results

According to the intention-to-treat principle, regression analyses revealed that intervention effects on alcohol consumption varied when exploring multiple follow-up time-points. Intervention effects were found for a) weekly alcohol consumption at 1, 2, 3, 4, and 7 weeks follow-up, b) frequency of binge drinking at 1, 2, 7, and 12 weeks follow-up, and c) heavy drinking status at 1, 2, 7, and 16 weeks follow-up.

Conclusions

This research showed that the commonly used one and six month follow-up time-points are relatively arbitrary and not using EMA might bring forth erroneous conclusions on the effectiveness of interventions. Therefore, future trials in alcohol prevention research and beyond are encouraged to apply EMA when assessing outcome measures and intervention effectiveness.

Trial registration

Netherlands Trial Register NTR2665     

The Effect of Souvenaid on Functional Brain Network Organisation in Patients with Mild Alzheimer’s Disease: A Randomised Controlled Study

Background

Synaptic loss is a major hallmark of Alzheimer’s disease (AD). Disturbed organisation of large-scale functional brain networks in AD might reflect synaptic loss and disrupted neuronal communication. The medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect, is designed to enhance synapse formation and function and has been shown to improve memory performance in patients with mild AD in two randomised controlled trials.

Objective

To explore the effect of Souvenaid compared to control product on brain activity-based networks, as a derivative of underlying synaptic function, in patients with mild AD.

Design

A 24-week randomised, controlled, double-blind, parallel-group, multi-country study.

Participants

179 drug-naïve mild AD patients who participated in the Souvenir II study.

Intervention

Patients were randomised 1∶1 to receive Souvenaid or an iso-caloric control product once daily for 24 weeks.

Outcome

In a secondary analysis of the Souvenir II study, electroencephalography (EEG) brain networks were constructed and graph theory was used to quantify complex brain structure. Local brain network connectivity (normalised clustering coefficient gamma) and global network integration (normalised characteristic path length lambda) were compared between study groups, and related to memory performance.

Results

The network measures in the beta band were significantly different between groups: they decreased in the control group, but remained relatively unchanged in the active group. No consistent relationship was found between these network measures and memory performance.

Conclusions

The current results suggest that Souvenaid preserves the organisation of brain networks in patients with mild AD within 24 weeks, hypothetically counteracting the progressive network disruption over time in AD. The results strengthen the hypothesis that Souvenaid affects synaptic integrity and function. Secondly, we conclude that advanced EEG analysis, using the mathematical framework of graph theory, is useful and feasible for assessing the effects of interventions.

Trial registration

Dutch Trial Register NTR1975.     

Immune responses to stress after stress management training in patients with rheumatoid arthritis

Introduction

Psychological stress may alter immune function by activating physiological stress pathways. Building on our previous study, in which we report that stress management training led to an altered self-reported and cortisol response to psychological stress in patients with rheumatoid arthritis (RA), we explored the effects of this stress management intervention on the immune response to a psychological stress task in patients with RA.

Methods

In this study, 74 patients with RA, who were randomly assigned to either a control group or a group that received short stress management training, performed the Trier Social Stress Test (TSST) 1 week after the intervention and at a 9-week follow-up. Stress-induced changes in levels of key cytokines involved in stress and inflammatory processes (for example, interleukin (IL)-6 and IL-8) were assessed.

Results

Basal and stress-induced cytokine levels were not significantly different in patients in the intervention and control groups one week after treatment, but stress-induced IL-8 levels were lower in patients in the intervention group than in the control group at the follow-up assessment.

Conclusions

In line with our previous findings of lower stress-induced cortisol levels at the follow-up of stress management intervention, this is the first study to show that relatively short stress management training might also alter stress-induced IL-8 levels in patients with RA. These results might help to determine the role of immunological mediators in stress and disease.

Trial registration

The Netherlands National Trial Register (NTR1193)     

Feasibility of a Combined Aerobic and Strength Training Program and Its Effects on Cognitive and Physical Function in Institutionalized Dementia Patients. A Pilot Study

Objectives

We examined the feasibility of a combined aerobic and strength training program in institutionalized dementia patients and studied the effects on cognitive and physical function.

Methods

Thirty-three patients with dementia, recruited from one nursing home, participated in this non-randomized pilot study (25 women; age = 85.2±4.9 years; Mini Mental State Examination = 16.8±4.0). In phase 1 of the study, seventeen patients in the Exercise group (EG) received a combined aerobic and strength training program for six weeks, five times per week, 30 minutes per session, in an individually supervised format and successfully concluded the pre and posttests. In phase 2 of the study, sixteen patients in the Social group (SG) received social visits at the same frequency, duration, and format and successfully concluded the pre and posttests.

Results

Indices of feasibility showed that the recruitment and adherence rate, respectively were 46.2% and 86.3%. All EG patients completed the exercise program according to protocol without adverse events. After the six-week program, no significant differences on cognitive function tests were found between the EG and SG. There was a moderate effect size in favor for the EG for the Visual Memory Span Forward; a visual attention test. There were significant differences between groups in favor for the EG with moderate to large effects for the physical tests Walking Speed (p = .003), Six-Minute Walk Test (p = .031), and isometric quadriceps strength (p = .012).

Conclusions

The present pilot study showed that it is feasible to conduct a combined aerobic and strength training program in institutionalized patients with dementia. The selective cognitive visual attention improvements and more robust changes in motor function in favor of EG vs. SG could serve as a basis for large randomized clinical trials.

Trial Registration

trialregister.nl 1230     

Adalimumab serum levels and antidrug antibodies towards adalimumab in peripheral spondyloarthritis: no association with clinical response to treatment or with disease relapse upon treatment discontinuation

Introduction

In this study, we evaluated the clinical relevance of serum drug levels and antidrug antibodies (ADAbs) with regard to response to treatment, as well as to relapse upon treatment discontinuation, in peripheral spondyloarthritis (pSpA) patients treated with adalimumab.

Methods

The study included 26 pSpA patients treated with adalimumab for either 12 weeks (n = 12) or 24 weeks (n = 14) in a randomized controlled trial. Patients achieving inactive disease measured by Ankylosing Spondylitis Disease Activity Score (ASDAS) at the end of the treatment period were classified as responders. Clinical characteristics, serum trough adalimumab levels and ADAbs were assessed at the end of the treatment period and at follow-up (upon relapse or, in absence of relapse, at 16 weeks after discontinuation).

Results

Serum adalimumab levels measured 2 weeks after the last adalimumab administration ranged from <0.002 to 23.0 μg/ml, with a median of 11.5 μg/ml. These levels were associated with neither response to treatment or disease activity measurements at the end of treatment nor with the occurrence of relapse and time to relapse after discontinuation of treatment. Antiadalimumab ADAbs were present in 23% of the patients at end of treatment and in 35% at follow-up after treatment discontinuation, indicating that ADAbs were masked by the presence of the drug in some patients. However, ADAbs at the end of treatment and at follow-up were not different between responders and nonresponders and were not associated with relapse upon discontinuation of treatment.

Conclusions

There is no clear association between adalimumab serum levels or antiadalimumab ADAbs with clinical response to treatment or with relapse upon treatment discontinuation in pSpA.

Trial registration

Netherlands Trial Register ID: NTR1806 (registered 7 May 2009)     

The Efficacy of Mindfulness-Based Cognitive Therapy as a Public Mental Health Intervention for Adults with Mild to Moderate Depressive Symptomatology: A Randomized Controlled Trial

Objective

Although there has been growing evidence for the efficacy of mindfulness-based cognitive therapy (MBCT) for different clinical populations, its effectiveness as a public mental health intervention has not been studied. The present study evaluates a community-based MBCT intervention for adults with mild to moderate depressive symptomatology in a large multi-site, pragmatic randomized controlled trial.

Method

The participants with mild to moderate depressive symptomatology were recruited from the general population and randomized to the MBCT intervention (n = 76) or to a waiting list control group (n = 75). Participants completed measures before and after the intervention. Participants in the experimental condition also completed these measures at a 3-month follow-up.

Results

In the experimental condition significant reductions in depression, anxiety, and experiential avoidance, and improvements in mindfulness and emotional- and psychological mental health were found, compared to the waiting list (effect sizes Cohen''s d = 0.31–0.56). These effects were sustained at the 3-month follow-up. The likelihood of a clinically significant change in depressive symptoms was significantly higher for the MBCT group [odds ratio (OR) 3.026, p<0.01 at post-treatment; NNT = 5.10].

Discussion

MBCT as a public mental health intervention for adults with mild to moderate depressive symptoms seems effective and applicable in a natural setting.

Trial Registration

Nederlands Trial Register NTR2096     

Improving Executive Functioning in Children with ADHD: Training Multiple Executive Functions within the Context of a Computer Game. A Randomized Double-Blind Placebo Controlled Trial

Introduction

Executive functions (EFs) training interventions aimed at ADHD-symptom reduction have yielded mixed results. Generally, these interventions focus on training a single cognitive domain (e.g., working memory [WM], inhibition, or cognitive-flexibility). However, evidence suggests that most children with ADHD show deficits on multiple EFs, and that these EFs are largely related to different brain regions. Therefore, training multiple EFs might be a potentially more effective strategy to reduce EF-related ADHD symptoms.

Methods

Eighty-nine children with a clinical diagnosis of ADHD (aged 8–12) were randomized to either a full-active-condition where visuospatial WM, inhibition and cognitive-flexibility were trained, a partially-active-condition where inhibition and cognitive-flexibility were trained and the WM-training task was presented in placebo-mode, or to a full placebo-condition. Short-term and long-term (3-months) effects of this gamified, 25-session, home-based computer-training were evaluated on multiple outcome domains.

Results

During training compliance was high (only 3% failed to meet compliance criteria). After training, only children in the full-active condition showed improvement on measures of visuospatial short-term-memory (STM) and WM. Inhibitory performance and interference control only improved in the full-active- and the partially-active condition. No Treatment-condition x Time interactions were found for cognitive-flexibility, verbal WM, complex-reasoning, nor for any parent-, teacher-, or child-rated ADHD behaviors, EF-behaviors, motivational behaviors, or general problem behaviors. Nonetheless, almost all measures showed main Time-effects, including the teacher-ratings.

Conclusions

Improvements on inhibition and visuospatial STM and WM were specifically related to the type of treatment received. However, transfer to untrained EFs and behaviors was mostly nonspecific (i.e., only interference control improved exclusively in the two EF training conditions). As such, in this multiple EF-training, mainly nonspecific treatment factors – as opposed to the specific effects of training EFs—seem related to far transfer effects found on EF and behavior.

Trial Registration

trialregister.nl NTR2728. Registry name: improving executive functioning in children with ADHD: training executive functions within the context of a computer game; registry number: NTR2728.     

Can Multiple Lifestyle Behaviours Be Improved in People with Familial Hypercholesterolemia? Results of a Parallel Randomised Controlled Trial

Objective

To evaluate the efficacy of an individualised tailored lifestyle intervention on physical activity, dietary intake, smoking and compliance to statin therapy in people with Familial Hypercholesterolemia (FH).

Methods

Adults with FH (n = 340) were randomly assigned to a usual care control group or an intervention group. The intervention consisted of web-based tailored lifestyle advice and face-to-face counselling. Physical activity, fat, fruit and vegetable intake, smoking and compliance to statin therapy were self-reported at baseline and after 12 months. Regression analyses were conducted to examine between-group differences. Intervention reach, dose and fidelity were assessed.

Results

In both groups, non-significant improvements in all lifestyle behaviours were found. Post-hoc analyses showed a significant decrease in saturated fat intake among women in the intervention group (β = −1.03; CI −1.98/−0.03). In the intervention group, 95% received a log on account, of which 49% logged on and completed one module. Nearly all participants received face-to-face counselling and on average, 4.2 telephone booster calls. Intervention fidelity was low.

Conclusions

Individually tailored feedback is not superior to no intervention regarding changes in multiple lifestyle behaviours in people with FH. A higher received dose of computer-tailored interventions should be achieved by uplifting the website and reducing the burden of screening questionnaires. Counsellor training should be more extensive.

Trial Registration

Dutch Trial Register NTR1899     

Pharmacological Activation of the Bile Acid Nuclear Farnesoid X Receptor Is Feasible in Patients with Quiescent Crohn's Colitis

Background

The bile acid-activated nuclear receptor Farnesoid X Receptor (FXR) is critical in maintaining intestinal barrier integrity and preventing bacterial overgrowth. Patients with Crohn''s colitis (CC) exhibit reduced ileal FXR target gene expression. FXR agonists have been shown to ameliorate inflammation in murine colitis models. We here explore the feasibility of pharmacological FXR activation in CC.

Methods

Nine patients with quiescent CC and 12 disease controls were treated with the FXR ligand chenodeoxycholic acid (CDCA; 15 mg/kg/day) for 8 days. Ileal FXR activation was assessed in the fasting state during 6 hrs after the first CDCA dose and on day 8, by quantification of serum levels of fibroblast growth factor (FGF) 19. Since FGF19 induces gallbladder (GB) refilling in murine models, we also determined concurrent GB volumes by ultrasound. On day 8 ileal and cecal biopsies were obtained and FXR target gene expression was determined.

Results

At baseline, FGF19 levels were not different between CC and disease controls. After the first CDCA dose, there were progressive increases of FGF19 levels and GB volumes during the next 6 hours in CC patients and disease controls (FGF19: 576 resp. 537% of basal; GB volumes: 190 resp. 178% of basal) without differences between both groups, and a further increase at day 8. In comparison with a separate untreated control group, CDCA affected FXR target gene expression in both CC and disease controls, without differences between both groups.

Conclusions

Pharmacological activation of FXR is feasible in patients with CC. These data provide a rationale to explore the anti-inflammatory properties of pharmacological activation of FXR in these patients.

Trial Registration

TrialRegister.nl NTR2009     

Exercise as an Intervention to Reduce Study-Related Fatigue among University Students: A Two-Arm Parallel Randomized Controlled Trial

Background

Many university students experience high levels of study-related fatigue. This high prevalence, and the negative impact of fatigue on health and academic performance, call for prevention and reduction of these symptoms. The primary aim of the current study was to investigate to what extent an exercise intervention is effective in reducing three indicators of study-related fatigue (emotional exhaustion, overall fatigue, and need for recovery). Effects of exercise on secondary outcomes (sleep quality, self-efficacy, physical fitness, and cognitive functioning) were also investigated.

Methods

Participants were students with high levels of study-related fatigue, currently not exercising or receiving other psychological or pharmacological treatments, and with no medical cause of fatigue. They were randomly assigned to either a six-week exercise intervention (low-intensity running three times a week, n = 49) or wait list (no intervention, n = 48). All participants were measured before the intervention (T0), and immediately after the intervention (T1). Exercisers were also investigated 4 weeks (T2) and 12 weeks (T3) after the intervention.

Results

Participants in the exercise condition showed a larger decrease in two of the three indicators of study-related fatigue (i.e., overall fatigue and need for recovery) as compared to controls. Additionally, sleep quality and some indicators of cognitive functioning improved more among exercisers than among controls. No effects were found for self-efficacy, and physical fitness. The initial effects of the exercise intervention lasted at follow-up (T2 and T3). At 12-week follow up (T3), 80% of participants in the exercise condition still engaged in regular exercise, and further enhancements were seen for emotional exhaustion, overall fatigue, and sleep quality.

Conclusions

These results underline the value of low-intensity exercise for university students with high levels of study-related fatigue. The follow-up effects that were found in this study imply that the intervention has the potential to promote regular exercise and accompanying beneficial effects in the longer run.

Trial Registration

Netherlands Trial Register NTR4412     

Experience Sampling-Based Personalized Feedback and Positive Affect: A Randomized Controlled Trial in Depressed Patients

Objectives

Positive affect (PA) plays a crucial role in the development, course, and recovery of depression. Recently, we showed that a therapeutic application of the experience sampling method (ESM), consisting of feedback focusing on PA in daily life, was associated with a decrease in depressive symptoms. The present study investigated whether the experience of PA increased during the course of this intervention.

Design

Multicentre parallel randomized controlled trial. An electronic random sequence generator was used to allocate treatments.

Settings

University, two local mental health care institutions, one local hospital.

Participants

102 pharmacologically treated outpatients with a DSM-IV diagnosis of major depressive disorder, randomized over three treatment arms.

Intervention

Six weeks of ESM self-monitoring combined with weekly PA-focused feedback sessions (experimental group); six weeks of ESM self-monitoring combined with six weekly sessions without feedback (pseudo-experimental group); or treatment as usual (control group).

Main outcome

The interaction between treatment allocation and time in predicting positive and negative affect (NA) was investigated in multilevel regression models.

Results

102 patients were randomized (mean age 48.0, SD 10.2) of which 81 finished the entire study protocol. All 102 patients were included in the analyses. The experimental group did not show a significant larger increase in momentary PA during or shortly after the intervention compared to the pseudo-experimental or control groups (χ² (2) =0.33, p=.846). The pseudo-experimental group showed a larger decrease in NA compared to the control group (χ² (1) =6.29, p=.012).

Conclusion

PA-focused feedback did not significantly impact daily life PA during or shortly after the intervention. As the previously reported reduction in depressive symptoms associated with the feedback unveiled itself only after weeks, it is conceivable that the effects on daily life PA also evolve slowly and therefore were not captured by the experience sampling procedure immediately after treatment.

Trial Registration

Trialregister.nl/trialreg/index.asp. NTR1974     

Airway inflammation and mannitol challenge test in COPD

Background

Eosinophilic airway inflammation has successfully been used to tailor anti-inflammatory therapy in chronic obstructive pulmonary disease (COPD). Airway hyperresponsiveness (AHR) by indirect challenges is associated with airway inflammation. We hypothesized that AHR to inhaled mannitol captures eosinophilia in induced sputum in COPD.

Methods

Twenty-eight patients (age 58 ± 7.8 yr, packyears 40 ± 15.5, post-bronchodilator FEV₁ 77 ± 14.0%predicted, no inhaled steroids ≥4 wks) with mild-moderate COPD (GOLD I-II) completed two randomized visits with hypertonic saline-induced sputum and mannitol challenge (including sputum collection). AHR to mannitol was expressed as response-dose-ratio (RDR) and related to cell counts, ECP, MPO and IL-8 levels in sputum.

Results

There was a positive correlation between RDR to mannitol and eosinophil numbers (r = 0.47, p = 0.03) and level of IL-8 (r = 0.46, p = 0.04) in hypertonic saline-induced sputum. Furthermore, significant correlations were found between RDR and eosinophil numbers (r = 0.71, p = 0.001), level of ECP (r = 0.72, p = 0.001), IL-8 (r = 0.57, p = 0.015) and MPO (r = 0.64, p = 0.007) in sputum collected after mannitol challenge. ROC-curves showed 60% sensitivity and 100% specificity of RDR for >2.5% eosinophils in mannitol-induced sputum.

Conclusions

In mild-moderate COPD mannitol hyperresponsiveness is associated with biomarkers of airway inflammation. The high specificity of mannitol challenge suggests that the test is particularly suitable to exclude eosinophilic airways inflammation, which may facilitate individualized treatment in COPD.

Trial registration

Netherlands Trial Register (NTR): NTR1283     

Intensive Lifestyle Intervention in General Practice to Prevent Type 2 Diabetes among 18 to 60-Year-Old South Asians: 1-Year Effects on the Weight Status and Metabolic Profile of Participants in a Randomized Controlled Trial

Aim

To study 1-year effectiveness of an intensive, culturally targeted lifestyle intervention in general practice for weight status and metabolic profile of South-Asians at risk of type 2 diabetes.

Methods

536 South-Asians at risk of type 2 diabetes were randomized to an intervention (n = 283) or control (n = 253) group. The intervention, which was targeted culturally to the South-Asian population, consisted of individual lifestyle counselling, a family session, cooking classes, and supervised physical activity programme. All components of the intervention were carried out by professionals as part of their daily clinical practice. The control group received generic lifestyle advice. Change in weight status and metabolic profile were assessed after 1 year.

Results

After 1 year, 201 participants were lost to follow-up. Remaining participants in intervention (n = 177) and control (n = 158) group had similar baseline characteristics. Weight loss in the intervention group was 0.2±3.3 kg, weight gain in the control group was 0.4±3.1 kg (p = 0.08). Changes in other weight-related measurements did not differ significantly between groups. Furthermore, there were no differences between groups in changes of metabolic profile. All results remained similar after repeating analyses in a multiple imputed dataset.

Discussion

An intensive, culturally targeted, lifestyle intervention of 1 year did not improve weight status and metabolic profile of South-Asians at risk of type 2 diabetes. The laborious recruitment, high drop-out, and lack of effectiveness emphasise the difficulty of realising health benefits in practice and suggest that this strategy might not be the optimal approach for this population.

Trial Registration

Nederlands Trial Register NTR1499     

Effectiveness of Educational Poster on Knowledge of Emergency Management of Dental Trauma - Part 2: Cluster Randomised Controlled Trial for Secondary School Students

Objective

To investigate the effectiveness of educational poster on improving secondary school students'' knowledge of emergency management of dental trauma.

Methods

A cluster randomised controlled trial was conducted. 16 schools with total 671 secondary students who can read Chinese or English were randomised into intervention (poster, 8 schools, 364 students) and control groups (8 schools, 305 students) at the school level. Baseline knowledge of dental trauma was obtained by a questionnaire. Poster containing information of dental trauma management was displayed in a classroom for 2 weeks in each school in the intervention group whereas in the control group there was no display of such posters. Students of both groups completed the same questionnarie after 2 weeks.

Results

Two-week display of posters improved the knowledge score by 1.25 (p-value = 0.0407) on average.

Conclusion

Educational poster on dental trauma management significantly improved the level of knowledge of secondary school students in Hong Kong.

Trial Registration

HKClinicalTrial.com HKCTR-1343 ClinicalTrials.gov NCT01809457     

Evaluation of coagulation activation after Rhinovirus infection in patients with asthma and healthy control subjects: an observational study

Background

Asthma exacerbations are frequently triggered by rhinovirus infections. Both asthma and respiratory tract infection can activate haemostasis. Therefore we hypothesized that experimental rhinovirus-16 infection and asthmatic airway inflammation act in synergy on the haemostatic balance.

Methods

28 patients (14 patients with mild allergic asthma and 14 healthy non-allergic controls) were infected with low-dose rhinovirus type 16. Venous plasma and bronchoalveolar lavage fluid (BAL fluid) were obtained before and 6 days after infection to evaluate markers of coagulation activation, thrombin-antithrombin complexes, von Willebrand factor, plasmin-antiplasmin complexes, plasminogen activator inhibitor type-1, endogenous thrombin potential and tissue factor-exposing microparticles by fibrin generation test, in plasma and/or BAL fluid. Data were analysed by nonparametric tests (Wilcoxon, Mann Whitney and Spearman correlation).

Results

13 patients with mild asthma (6 females, 19-29 y) and 11 healthy controls (10 females, 19-31 y) had a documented Rhinovirus-16 infection. Rhinovirus-16 challenge resulted in a shortening of the fibrin generation test in BAL fluid of asthma patients (t = -1: 706 s vs. t = 6: 498 s; p = 0.02), but not of controls (t = -1: 693 s vs. t = 6: 636 s; p = 0.65). The fold change in tissue factor-exposing microparticles in BAL fluid inversely correlated with the fold changes in eosinophil cationic protein and myeloperoxidase in BAL fluid after virus infection (r = -0.517 and -0.528 resp., both p = 0.01).Rhinovirus-16 challenge led to increased plasminogen activator inhibitor type-1 levels in plasma in patients with asthma (26.0 ng/mL vs. 11.5 ng/mL in healthy controls, p = 0.04). Rhinovirus-16 load in BAL showed a linear correlation with the fold change in endogenous thrombin potential, plasmin-antiplasmin complexes and plasminogen activator inhibitor type-1.

Conclusions

Experimental rhinovirus infection induces procoagulant changes in the airways of patients with asthma through increased activity of tissue factor-exposing microparticles. These microparticle-associated procoagulant changes are associated with both neutrophilic and eosinophilic inflammation. Systemic activation of haemostasis increases with Rhinoviral load.

Trial registration

This trial was registered at the Dutch trial registry (http://www.trialregister.nl): NTR1677.     

The Effect of VoorZorg,the Dutch Nurse-Family Partnership,on Child Maltreatment and Development: A Randomized Controlled Trial

Background

Child maltreatment is a great public health concern that has long-term mental and physical health consequences and can result in death. We studied the effect of a nurse home visiting program on child maltreatment among young disadvantaged families in the Netherlands. This study is the first to investigate the effects of this program outside of the United States.

Methods

We conducted a single blind, parallel-group, randomized controlled trial that compared usual care with the nurse home visitation program, which began during pregnancy and continued until the children’s second birthdays, in 460 disadvantaged women who were pregnant for the first time and <26 years of age. The primary outcome was the existence of a report about the child from a child protecting services agency (CPS reports). Secondary outcome measures included home environment and child behavior.

Results

Two hundred twenty-three participants were assigned to the control group, and 237 were assigned to the intervention group. Three years after birth, 19% of the children in the control group had a CPS report. The 11 percent of children in the intervention group with CPS files was significantly lower (relative risk 0.91, p-value 0.04). At 24 months, the intervention group scored significantly better on the IT-HOME. At 24 months after birth, the children in the intervention group exhibited a significant improvement in internalizing behavior (relative risk 0.56, p-value 0.04) but no evidence of a difference from the control group in externalizing behavior (relative risk 0.71, p-value 0.12).

Conclusion

The number of CPS reports for the intervention group was significantly lower than that of the control group. Additionally, the long-term home environments were improved and internalizing behaviors of the children were lower in the intervention group.

Trial Registration

Dutch Trial Register NTR854     

ACE Inhibitors Potently Reduce Vascular Inflammation,Results of an Open Proof-Of-Concept Study in the Abdominal Aortic Aneurysm

Background

Independent of their blood pressure lowering effect, ACE inhibitors are thought to reduce vascular inflammation. The clinical relevance of this effect is unclear with the current knowledge. Abdominal aortic aneurysms (AAA) are characterized by a broad, non-specific inflammatory response, and thus provide a clinical platform to evaluate the anti-inflammatory potential of ACE inhibitors.

Methods and Results

Eleven patients scheduled for open AAA repair received ramipril (5 mg/day) during 2–4 weeks preceding surgery. Aortic wall samples were collected during surgery, and compared to matched samples obtained from a biobank. An anti-inflammatory potential was evaluated in a comprehensive analysis that included immunohistochemistry, mRNA and protein analysis. A putative effect of ACE inhibitors on AAA growth was tested separately by comparing 18-month growth rate of patients on ACE inhibitors (n = 82) and those not taking ACE inhibitors (n = 204). Ramipril reduces mRNA expression of multiple pro-inflammatory cytokines such as IL-1β, IL-6, IL-8, TNF -α, Interferon-, and MCP-1, as well as aortic wall IL-8 and MCP-1 (P = 0.017 and 0.008, respectively) protein content. The is followed by clear effects on cell activation that included a shift towards anti-inflammatory macrophage (M2) subtype. Evaluation of data from the PHAST cohort did not indicate an effect of ACE inhibitors on 18-month aneurysm progression (mean difference at 18 months: −0.24 mm (95% CI: −0.90–0.45, P = NS).

Conclusions

ACE inhibition quenches multiple aspects of vascular inflammation in AAA. However, this does not translate into reduced aneurysm growth.

Trial Registration

Nederlands Trial Register 1345.     

Randomised Trial of Planned Caesarean Section Prior to Versus after 39 Weeks: Unscheduled Deliveries and Facility Logistics - A Secondary Analysis

Objectives

To compare the impact of scheduling caesarean section prior to versus after 39 completed weeks of gestation on the occurrence of unscheduled caesarean section and rescheduling of the procedure.

Methods

Secondary analysis from a multicentre randomised open-label trial including singleton pregnant women with a healthy foetus and a reliable due date. Women were allocated by computerized telephone randomisation to planned caesarean section at 38 weeks and three days or 39 weeks and three days. The outcomes were unscheduled deliveries with provided reasons, such as spontaneous labour onset or supervening complications, and any changes in the scheduled delivery date. Statistical analyses were according to intention-to-treat using Fisher’s exact test.

Results

From March 2009 to June 2011 1,274 women were included. Median difference in gestational age at delivery was six days. Compared to the 38 weeks group, the women in the 39 weeks group were more likely to have an unscheduled caesarean section (15.2% vs. 9.3%; RR 1.64, 95% CI 1.21; 2.22), to deliver between 6 pm and 8 am (10 % vs. 6%; RR 1.68, 95% CI 1.14; 2.47), or to have the procedure rescheduled (36.7% vs. 23%; RR 1.6, 95% CI 1.34;1.90).

Conclusions

Scheduling caesarean section after 39 weeks leads to a 60% increase in unscheduled caesarean sections and a 70% increase in delivery outside regular work hours as compared to scheduling of the procedure prior to 39 weeks.

Trial Registration

www.clinicaltrials.gov NCT00835003 http://www.clinicaltrials.gov/ct2/show/NCT00835003?term=NCT00835003&rank=1     

Effects of internet-based guided self-help problem-solving therapy for adolescents with depression and anxiety: a randomized controlled trial

Background

Symptoms of depression and anxiety are highly prevalent in adolescence and they are the cause of considerable suffering. Even so, adolescents are not inclined to seek professional help for emotional problems. Internet-based preventive interventions have been suggested as a feasible method of providing appropriate care to adolescents with internalizing symptoms. The objective of this study was to evaluate the effects of preventive Internet-based (guided) self-help problem-solving therapy (PST) for adolescents reporting mild to moderate symptoms of depression and/or anxiety as compared to a waiting list control group (WL).

Methodology/Principal Findings

A total of 45 participants were randomized to the 2 conditions. PST consisted of 5 weekly lessons. Participants were supported by e-mail. Self-report measures of depression and anxiety were filled in at baseline and after 3 weeks, 5 weeks, and 4 months. Of the 45 participants, 28 (62.2%) completed questionnaires after 3 weeks, 28 (62.2%) after 5 weeks, and 27 (60%) after 4 months. Hierarchical linear modeling analyses revealed overall improvement over time for both groups on depressive and anxiety symptoms. However, no significant group x time interactions were found. No differences were found between completers and non-completers.

Conclusions/Significance

Results show that depressive and anxiety symptoms declined in both groups. No support was found, however, for the assumption that Internet-based PST was efficacious in reducing depression and anxiety in comparison to the waiting list control group. This finding could represent lack of power.

Trial Registration

Netherlands Trial Register NTR1322