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OBJECTIVES: To determine the effect of fall-related concerns on physical, mental, and social function. DESIGN: Community-based prospective cohort study (secondary analysis using control group data from a randomized controlled trial). SETTING: Two municipalities in the south of the Netherlands. PARTICIPANTS: Community-dwellingolderadults(N =260). MEASUREMENTS: Two groups were created using Modified Falls Efficacy Scale scores (high and low levels of fallrelated concerns). Five outcome measures representing physical, mental, and social function were included: activities of daily living (ADLs), symptoms of depression, feelings of anxiety, social participation, and social support interactions. Outcomes were measured at baseline and at 2, 8, and 14 months. Data were analyzed using analysis of covariance and mixed-effect regression models for longitudinal data, adjusting for age, sex, living status (alone or with another person), educational level, cognitive status, self-perceived health, and falls history at baseline. RESULTS: At baseline, significantly more limitations in ADLs and social participation were found for older persons with high levels of fall-related concerns than for those with low levels of concern. These differences persisted over 14 months of follow-up and were consistent over time. No significant differences were found for symptoms of depression, feelings of anxiety, or social support interactions, except for feelings of anxiety at 14 months. CONCLUSION: Older persons with higher levels of fallrelated concerns reported up to 14 months poorer ADL and social participation for up to 14 months than those with lower levels of fall-related concerns. From a clinical point of view, the clear relationship between fall-related concerns and ADL dysfunction and social participation may help to target groups who are at risk of developing adverse consequences of concerns about falls. J Am Geriatr Soc 62:2333–2338, 2014.

Objective To assess the impact of obesity on the likelihood of remaining in midwife-led care throughout pregnancy and childbirth. Design Secondary analysis of data from a prospective cohort study. Setting Dutch midwife-led practices. Population A cohort of 1369 women eligible for midwife-led care after their first antenatal visit. Methods First-trimester body mass index (BMI) was calculated as weight measured at booking divided by height squared. Obstetric data were retrieved from medical records. Multiple logistic regressions were performed to examine the effects of BMI classification on midwife-led pregnancies and childbirths. Main outcome measures Percentages of women remaining in midwife-led care throughout pregnancy and throughout childbirth. Results Of women in obesity classes II and III, 55% remained in midwife-led care throughout pregnancy and 30% remained in midwife-led care throughout birth. Compared with women of normal weight, women in obesity classes II and III had fewer midwife-led pregnancies (OR 0.38, 95% CI 0.21–0.69), and women who were overweight or in obesity class I had fewer midwife-led childbirths (OR 0.63, 95% CI 0.44–0.90; OR 0.49, 95% CI 0.29–0.84, respectively). Compared with women of normal weight, women who were obese had higher referral rates for hypertensive disorders (4 versus 14%), prolonged labour (4.6 versus 10.4%), and intrapartum pain relief (4 versus 10.4%). The women who were eligible for midwife-led birth and who were overweight or obese, had no more urgent referrals than women of normal weight. Women who were obese and who completed a midwife-led birth had no more adverse outcomes than women of normal weight, with the exception of higher rates of large for gestational age (LGA) babies (>97.7 centile; 12.1%, versus 1.9% in normal weight and versus 3.3% in overweight women). Conclusions Although fewer women who were obese remain in midwife-led care during pregnancy and childbirth, there was no increased risk of unfavourable birth outcomes for women who were obese and eligible for a midwife-led birth when compared with women of normal weight. This indicates that when primary care midwives use a risk assessment tool throughout pregnancy and childbirth they are able to safely assign women who are obese to either midwife-led or obstetrician-led care.

Smoking cessation interventions for cardiac patients need improvement given their weak effects on long-term abstinence rates and low compliance by nurses to implementation. This study tested the effectiveness of two smoking cessation interventions against usual care in cardiac patients, and conditional effects for patients' motivation to quit and socio-economic status (SES). An experimental study was conducted from 2009 to 2012 for which Dutch cardiac patient smokers were assigned to: usual care (UC; n = 245), telephone counseling (TC; n = 223) or face-to-face counseling (FC; n = 157). The three groups were comparable at baseline and had smoked on average 21 cigarettes a day before hospitalization. After six months, interviews occurred to assess self-reported smoking status. Patients in the TC and FC group had significantly higher smoking abstinence rates than patients in the UC group (p a parts per thousand currency sign 0.05 at all times). Regression analysis further revealed significant conditional effects of the interventions on smoking abstinence in patients with lower SES, with a larger effect for TC than FC when compared to UC. These findings suggest that intensive counseling is effective in increasing short-term abstinence rates, particularly in patients with lower SES. Future studies need to investigate how patients with higher SES can profit equally from these type of interventions.

Diet composition may affect blood pressure (BP), but the mechanisms are unclear. The aim of the present study was to compare postprandial BP-related responses to the ingestion of pea protein, milk protein and egg-white protein. In addition, postprandial BP-related responses to the ingestion of maltodextrin were compared with those to the ingestion of sucrose and a protein mix. We hypothesised that lower postprandial total peripheral resistance (TPR) and BP levels would be accompanied by higher plasma concentrations of nitric oxide, insulin, glucagon-like peptide 1 (GLP-1) and glucagon. On separate occasions, six meals were tested in a randomised order in forty-eight overweight or obese adults with untreated elevated BP. Postprandial responses of TPR, BP and plasma concentrations of insulin, glucagon, GLP-1 and nitrite, nitroso compounds (RXNO) and S-nitrosothiols (NOx) were measured for 4 h. No differences were observed in TPR responses. Postprandial BP levels were higher after the ingestion of the egg-white-protein meal than after that of meals containing the other two proteins (P≤ 0·01). The ingestion of the pea-protein meal induced the highest NOxresponse (P≤ 0·006). Insulin and glucagon concentrations were lowest after the ingestion of the egg-white-protein meal (P≤ 0·009). Postprandial BP levels were lower after the ingestion of the maltodextrin meal than after that of the protein mix and sucrose meals (P≤ 0·004), while postprandial insulin concentrations were higher after the ingestion of the maltodextrin meal than after that of the sucrose and protein mix meals after 1–2 h (P≤ 0·0001). Postprandial NOx, GLP-1 and glucagon concentrations were lower after the ingestion of the maltodextrin meal than after that of the protein mix meal (P≤ 0·008). In conclusion, different protein and carbohydrate sources induce different postprandial BP-related responses, which may be important for BP management. Lower postprandial BP levels are not necessarily accompanied by higher NOx, insulin, glucagon or GLP-1 responses.

Objectives: To investigate the malnutrition prevalence in Dutch care home residents with dementia over the years. Secondly, to examine the relationship of malnutrition and dementia and the role of care dependency and co-morbidity within this relationship. Design: This study is a secondary analysis of data of the annual independent Dutch National Prevalence Measurement of Care Problems of Maastricht University. The design involves a cross-sectional, multicenter point prevalence measurement. Setting: Care homes. Participants: 75399 residents older than 65 years (4523 resident with dementia) participated over 5 years (2006-2010). Sixty organizations measured 4 times, 31 organizations 3 times, 68 organizations 2 times, 511 organizations 1 time. Measurements: A standardized questionnaire was used to register amongst others data of weight, height, nutritional intake, undesired weight loss, comorbidity, dementia, and care dependency. Results: The study was able to show that there is a significant decline in malnutrition prevalence in the group of non-demented residents over the years (Non-demented group p

Vision loss is highly prevalent in old age and has a substantial impact on different aspects of quality of life including depressive symptoms. Our objective was to examine the mediating role of disability and social support in the association between low vision and depressive symptoms.Differences in disability, social support, and depressive symptoms between 148 persons with low vision and a reference population (N = 4,792) all a parts per thousand yen57 years were compared. The association between low vision and depressive symptoms and the mediating role of disability and social support was examined by the means of regression.A significant effect of low vision on depressive symptoms was identified even after the adjustment for disability and social support (standardized beta 0.053, P Prevention of disability and the increase in social support may help to reduce symptoms of depression in older adults with low vision. By taking such information into account in their intervention work, health professionals working in this area may improve their care quality.

BackgroundPreventing smoking initiation among adolescents is crucial to reducing tobacco-caused death and disease. This study focuses on the effectiveness of a Web-based computer-tailored smoking prevention intervention aimed at adolescents. ObjectiveThe intent of the study was to describe the intervention characteristics and to show the effectiveness and results of a randomized controlled trial. We hypothesized that the intervention would prevent smoking initiation among Dutch secondary school students aged 10-20 years and would have the largest smoking prevention effect among the age cohort of 14-16 years, as smoking uptake in that period is highest. MethodsThe intervention consisted of a questionnaire and fully automated computer-tailored feedback on intention to start smoking and motivational determinants. A total of 89 secondary schools were recruited via postal mail and randomized into either the computer-tailored intervention condition or the control condition. Participants had to complete a Web-based questionnaire at baseline and at 6-month follow-up. Data on smoking initiation were collected from 897 students from these schools. To identify intervention effects, multilevel logistic regression analyses were conducted using multiple imputation. ResultsSmoking initiation among students aged 10-20 years was borderline significantly lower in the experimental condition as compared to the control condition 6 months after baseline (OR 0.25, 95% CI 0.05-1.21, P=.09). Additional analyses of the data for the 14-16 year age group showed a significant effect, with 11.5% (24/209) of the students in the control condition reporting initiation compared to 5.7% (10/176) in the experimental condition (OR 0.22, 95% CI 0.05-1.02, P=.05). No moderation effects were found regarding gender and educational level. ConclusionsThe findings of this study suggest that computer-tailored smoking prevention programs are a promising way of preventing smoking initiation among adolescents for at least 6 months, in particular among the age cohort of 14-16 years. Further research is needed to focus on long-term effects. Trial RegistrationInternational Standard Randomized Controlled Trial Number (ISRCTN): 77864351; http://www.controlled-trials.com/ISRCTN77864351 (Archived by WebCite at http://www.webcitation.org/6BSLKSTm5).

Arm activities are required for maintenance of self-care and independent living. This study aimed to investigate whether and to what extent arm activities of daily living (ADL) in chronic obstructive pulmonary disease (COPD) patients differ compared to healthy controls and the extent to which they perform arm ADL at a relatively higher upper limb muscle effort.Daily arm and leg activities were assessed using accelerometers in the home environment (COPD: n = 21, healthy: n = 24; part 1). The relative efforts of the trapezius, deltoid and biceps muscles were studied using electromyography during domestic arm ADL in a laboratory setting (COPD: n = 17, healthy: n = 15; part 2).After correction for walking time, the time spent on arm ADL was similar between COPD patients and healthy control subjects (p = 0.52), while the intensity of arm activities was lower in COPD patients (p = 0.041). In the laboratory setting, arm ADL were performed at a lower intensity by COPD patients, while the trapezius muscle effort was significantly higher during several arm ADL compared to healthy control subjects (p

In this paper, the optimal sample sizes at the cluster and person levels for each of two treatment arms are obtained for cluster randomized trials where the cost-effectiveness of treatments on a continuous scale is studied. The optimal sample sizes maximize the efficiency or power for a given budget or minimize the budget for a given efficiency or power. Optimal sample sizes require information on the intra-cluster correlations (ICCs) for effects and costs, the correlations between costs and effects at individual and cluster levels, the ratio of the variance of effects translated into costs to the variance of the costs (the variance ratio), sampling and measuring costs, and the budget. When planning, a study information on the model parameters usually is not available. To overcome this local optimality problem, the current paper also presents maximin sample sizes. The maximin sample sizes turn out to be rather robust against misspecifying the correlation between costs and effects at the cluster and individual levels but may lose much efficiency when misspecifying the variance ratio. The robustness of the maximin sample sizes against misspecifying the ICCs depends on the variance ratio. The maximin sample sizes are robust under misspecification of the ICC for costs for realistic values of the variance ratio greater than one but not robust under misspecification of the ICC for effects. Finally, we show how to calculate optimal or maximin sample sizes that yield sufficient power for a test on the cost-effectiveness of an intervention.

This study describes the swallowing function of patients with myotonic dystrophy type 1 (DM1) and the effect of bolus consistency on swallowing in this group. The aim of the study is twofold: (a) to identify which (and to what extent) swallowing variables change for DM1 patients relative to healthy control subjects and (b) to examine whether the degree of oropharyngeal dysphagia is associated with disease severity. Forty-five consecutive DM1 patients and ten healthy subjects underwent a swallowing assessment, at Maastricht University medical Center in the Netherlands. The assessment included a standardized fiberoptic endoscopic evaluation of swallowing (FEES) protocol using different bolus consistencies. Clinical severity of the disease was assessed using the muscular impairment rating scale (MIRS). Significant differences were found between patients and controls for all FEES variables. The magnitude of these differences depended on the bolus consistency. The odds of a more pathological swallowing outcome increased significantly with higher MIRS levels. In conclusion, swallowing function is found to be significantly altered in DM1 patients. The results emphasize the importance of conducting a detailed swallowing assessment in all patients, even those with mild muscle weakness. (C) 2014 Elsevier B.V. All rights reserved.

Aim : To compare the health related quality of life (HRQOL) of long-term breast cancer survivors with and without breast cancer related lymphedema (BCRL) treated in the sentinel lymph node biopsy (SLNB) era. Methods : HRQOL was assessed as subject of a secondary analysis of data gathered for a study evaluating the prevalence of BCRL in long-term breast cancer survivors. The 145 women in this study cohort had undergone SLNB and or axillary, lymph node dissection (ALND) according to Dutch Breast cancer treatment guidelines. HRQOL was assessed using two questionnaires : the European Organization for Research and Treatment of Cancer Quality (QLQ-C30) and the Breast Cancer-specific Quality of life questionnaire (QLQ-BR23). Results : Twenty-six women, of whom 5 only underwent SLNB, were identified with objectively measured lymphedema and/or self-perceived arm swelling. Patients with BCRL scored significantly lower on the social (p = 0.000) functioning scale after adjustment for BMI and age compared to women without BCRL. Compared to normative data, women with BCRL scored significantly lower on social- (p

summary To date, no information is available about the effect of structural and process factors of nutritional care on the prevalence of malnutrition over time in the long-term care sector. This study analyzes the trend of malnutrition prevalence rates between 2007 and 2011 in the long-term care sector, and the related effects of 1 process indicators such as nutritional screening and treatment and 2) structural indicators (guideline, protocol or nutritional screening policy). From 2007 to 2011, the Dutch National Prevalence Measurement of Care Problems (LPZ) was performed in Dutch long-term care organizations using a standardized questionnaire involving measurements at institutional, ward and resident level. The data were analyzed by mixed-linear regression for longitudinal data. Presence of malnutrition was assessed by BMI, undesired weight loss and nutritional intake. Seventy-four care homes were included (26,101 residents). The malnutrition prevalence trend significantly decreased (P < 0.001) from 26% to 18% from 2007 to 2011. In the final model of the mixed effects analysis only the interacted process indicators nutritional screening and oral nutritional supplementation (ONS) were significant in influencing malnutrition prevalence rates over time. Structural indicators had no impact on the malnutrition prevalence over time. In conclusion, over time a lower prevalence of malnutrition is associated with a higher degree of nutritional screening. As might be expected, a higher prevalence of malnutrition is associated with higher use of ONS. Structural nutritional screening is an important intervention to tackle the problem of malnutrition in the long term care sector.

Women delivering with EA (EA group) were matched on parity with 453 women with deliveries without EA (non-EA group). Significantly more neonates born in the EA-group had fever ≥ 38.0°C (11.6% vs 1.8%, p < 0.001) at birth. The overall incidence of neonatal sepsis, based on clinical symptoms and defined as proven (by a positive blood culture) or suspected (no positive blood culture), was significantly higher in the EA group (6.0% vs 2.2%; p = 0.002), but the incidence of proven neonatal sepsis alone was not (0.4% vs 0%; p = 0.250). EA turned out to be an independent risk factor for neonatal sepsis (adjusted OR 2.43, 95% CI 1.15-5.13; p = 0.020). However, in the EA group as well as the non-EA group, the incidence of neonatal sepsis was significantly higher in mothers with intrapartum fever compared with afebrile mothers (11.0% vs 2.9% in the EA group; p = 0.004; 8.2% vs 1.3% in the non-EA group; p = 0.006). Therefore we conclude, that the positive association between neonatal sepsis and labour EA is possibly mediated by maternal intrapartum fever.

Summary The histopathology of premalignant laryngeal lesions does not provide reliable information on the risk of malignant transformation, hence we examined new molecular markers which can easily be implemented in clinical practice. Dual-target fluorescence in situ hybridisation (FISH) for chromosome 1 and 7 centromeres was performed on tissue sections of laryngeal premalignancies in 69 patients. Chromosome instability was indicated by numerical imbalances and/or polysomy for chromosomes 1 and 7. Additionally immuno-stainings for p53, Cyclin D1 and (p)FADD expression were evaluated. Malignant progression was recorded. Eighteen patients with carcinoma in situ (CIS) were treated after diagnosis and excluded from follow-up. Chromosome instability was strongly associated with a high risk of malignant transformation, especially in lower grade lesions (hyperplasia, mild and moderate dysplasia; odds ratio = 8.4, p = 0.004). Patients with lesions containing chromosome instability showed a significantly worse 5-year progression-free survival than those with premalignancies without chromosome instability ( p = 0.002). Neither histopathology nor the protein markers predicted progression in univariate analysis, although histo-pathological diagnosis, p53 and FADD contributed positively to chromosome instability in multivariate analysis. Chromosome instability is associated with malignant progression of laryngeal premalignancies, especially in lower grade lesions. These results may contribute to better risk counselling, provided that they can be validated in a larger patient set.

In medicine and health sciences mixed effects models are often used to study time-structured data. Optimal designs for such studies have been shown useful to improve the precision of the estimators of the parameters. However, optimal designs for such studies are often derived under the assumption of a zero autocorrelation between the errors, especially for binary data. Ignoring or misspecifying the autocorrelation in the design stage can result in loss of efficiency. This paper addresses robustness of Bayesian D-optimal designs for the logistic mixed effects model for longitudinal data with a linear or quadratic time effect against incorrect specification of the autocorrelation. To find the Bayesian D-optimal allocations of time points for different values of the autocorrelation, under different priors for the fixed effects and different covariance structures of the random effects, a scalar function of the approximate variance---covariance matrix of the fixed effects is optimized. Two approximations are compared; one based on a first order penalized quasi likelihood (PQL1) and one based on an extended version of the generalized estimating equations (GEE). The results show that Bayesian D-optimal allocations of time points are robust against misspecification of the autocorrelation and are approximately equally spaced. Moreover, PQL1 and extended GEE give essentially the same Bayesian D-optimal allocation of time points for a given subject-to-measurement cost ratio. Furthermore, Bayesian optimal designs are hardly affected either by the choice of a covariance structure or by the choice of a prior distribution.

Background Chest complaints presented to a general practitioner (GP) are frequently caused by diseases which have advantageous outcomes. However, in some cases, acute coronary syndrome (ACS) is present (1.5-22% of cases). The patient’s signs, symptoms and electrocardiography results are insufficient diagnostic tools to distinguish mild disease from ACS. Therefore, most patients presenting chest complaints are referred to secondary care facilities where ACS is then ruled out in a majority of patients (78%). Recently, a point of care test for heart-type fatty acid-binding protein (H-FABP) using a low cut-off value between positive and negative of 4 ng/ml has become available. We aim to study the role of this point of care device in triage of patients presenting chest complaints possibly due to ACS, in primary care. Our research protocol is presented in this article. Results are expected in 2015. Methods/Design Participating GPs will register signs and symptoms in all patients presenting chest complaints possibly due to ACS. Point of care H-FABP testing will also be performed. Our study will be a derivation study to identify signs and symptoms that, combined with point of care H-FABP testing, can be part of an algorithm to either confirm or rule out ACS. The diagnostic value for ACS of this algorithm in general practice will be determined. Discussion A safe diagnostic elimination of ACS by application of the algorithm can be of significant clinical relevance. Improved triage and thus reduction of the number of patients with chest complaints without underlying ACS, that are referred to secondary care facilities, could lead to a substantial cost reduction. Trial registration ClinicalTrials.gov, NCT01826994, accepted April 8th 2013.

Background22q11 deletion syndrome (22q11DS) is associated with mild or borderline intellectual disability (ID). There are hardly any reports on subjects with 22q11DS with moderate or severe ID, and therefore its behavioural and psychiatric characteristics are unknown. MethodWe describe behavioural and psychiatric characteristics of 33 adults with 22q11DS and a Full-Scale IQ (FSIQ) below 55. Participants were divided into two groups: one group having a FSIQ55 caused by intellectual decline (n=21) and one group with a FSIQ55 who had always functioned at this level (n=12). ResultsHigh scores on psychopathology sub-scales were found for both subgroups. 22q11DS patients with intellectual decline showed higher rates of co-morbid psychopathology, particularly psychosis. Furthermore, psychosis and intellectual decline were positive correlated. ConclusionThis is the first report addressing adult patients with 22q11DS and moderate to severe ID. Overall we found high levels of psychopathology with higher scores of psychopathology in the intellectual decline group. Life time psychosis seems to be related to deterioration.

Background: In Southeast Asia, the process of obtaining informed consent is influenced by both culture and policy at the hospital and national level. Both physicians and nurses play vital roles in this process, but physicians influence the roles of nurses. Objectives: Since the physicians and nurses often have different perspectives, it is important to investigate their views about the informed consent process and nurses’ roles therein and whether there is a difference between ideal and experienced practice (reality), and whether this differs across hospitals. Methods: A questionnaire was developed and a survey was conducted among physicians and nurses. Using exploratory factor analysis a three factor structure was determined: ‘nurses’ roles’, ‘barriers in informed consent’, and ‘adequacy of information’. Non-parametric tests were applied to compare nurses and physicians, and hospital setting. Participants and research context: Responses were obtained from 129 physicians and 616 nurses from two Indonesian hospitals. Those hospitals differ in ownership, location, and size. Ethical consideration: The study was reviewed by the hospital ethical committee. Participation was voluntary and confidentiality was ensured by keeping the responses anonymous. Findings: Physicians and nurses differ significantly on all three factors. The scores reflecting disparity between ideal and reality regarding nurses’ roles varied across professions, while barriers in informed consent differed between hospitals. Discussion: The differences between ideal and reality indicated that improvement in the informed consent process and nurses’ roles therein is called for. Varying views between physicians and nurses on nurses’ roles may hinder collaboration. The differences between hospital settings showed interventions may have to be customized for different settings. Conclusion: Views on nurses’ roles vary across professions. Views on barriers in informed consent vary across hospitals. Therefore interprofessional education is needed to promote interprofessional collaboration and intervention to improve informed consent practice should be tailored to the hospital context.

Background Chronic Obstructive Pulmonary Disease (COPD) is a growing worldwide problem that imposes a great burden on the daily life of patients. Since there is no cure, the goal of treating COPD is to maintain or improve quality of life. We have developed a new tool, the Assessment of Burden of COPD (ABC) tool, to assess and visualize the integrated health status of patients with COPD, and to provide patients and healthcare providers with a treatment algorithm. This tool may be used during consultations to monitor the burden of COPD and to adjust treatment if necessary. The aim of the current study is to analyse the effectiveness of the ABC tool compared with usual care on health related quality of life among COPD patients over a period of 18 months. Methods/Design A cluster randomised controlled trial will be conducted in COPD patients in both primary and secondary care throughout the Netherlands. An intervention group, receiving care based on the ABC tool, will be compared with a control group receiving usual care. The primary outcome will be the change in score on a disease-specific-quality-of-life questionnaire, the Saint George Respiratory Questionnaire. Secondary outcomes will be a different questionnaire (the COPD Assessment Test), lung function and number of exacerbations. During the 18 months follow-up, seven measurements will be conducted, including a baseline and final measurement. Patients will receive questionnaires to be completed at home. Additional data, such as number of exacerbations, will be recorded by the patients’ healthcare providers. A total of 360 patients will be recruited by 40 general practitioners and 20 pulmonologists. Additionally, a process evaluation will be performed among patients and healthcare providers. Discussion The new ABC tool complies with the 2014 Global Initiative for Chronic Obstructive Lung Disease guidelines, which describe the necessity to classify patients on both their airway obstruction and a comprehensive symptom assessment. It has been developed to classify patients, but also to provide visual insight into the burden of COPD and to provide treatment advice. Trial registration Netherlands Trial Register, NTR3788.

Background and Aims Nicotine vaccination has been proposed as a possible treatment to aid smoking cessation. First efficacy results of the nicotine vaccine 3'-AmNic-rEPA (NicVAX) showed that only a subgroup of the top 30% antibody responders achieved higher abstinence rates than placebo. The present study examined the efficacy of adding NicVAX versus placebo to varenicline and behavioural support as an aid in smoking cessation and relapse prevention. Design Randomized placebo-controlled trial. Setting Two research centres (Maastricht University Medical Centre and Slotervaart Hospital) in the Netherlands. Participants A total of 558 smokers were assigned randomly to six injections with NicVAX (n = 278) or placebo (n = 280) both co-administered with open label varenicline and behavioural support. Measures Outcomes were prolonged carbon monoxide-validated abstinence from weeks 9 to 52 (primary) and weeks 37 to 52 (secondary). We also performed a pre-planned subgroup analysis in the top 30% antibody responders. Findings There was no difference in abstinence rates between NicVAX and placebo from weeks 9 to 52 [27.7 versus 30.0%, odds ratio (OR) = 0.89, 95% confidence interval (CI) = 0.62-1.29] or weeks 37 to 52 (33.8 versus 33.2%, OR = 1.03, 95% CI = 0.73-1.46). The top 30% antibody responders, compared to the placebo group, showed a non-significant tendency towards higher abstinence rates from weeks 37 to 52 (42.2 versus 33.2%, OR = 1.47, 95% CI = 0.89-2.42). Conclusion The nicotine vaccine, NicVAX, does not appear to improve the chances of stopping smoking when given in addition to varenicline and behavioural support.

Cigarette smoking continues to be the leading cause of preventable death and is the main risk factor of major diseases such as chronic obstructive pulmonary disease (COPD). The best treatment to help smokers quit is a combination of behavioural support with pharmacotherapy. Varenicline is the newest drug on the market and has been shown to be effective in the general smoking population and in smokers with COPD. The safety profile of varenicline was initially established using standard approaches to pharmacovigilance, but postmarketing reports have raised concerns about a possible association between the use of varenicline and cardiovascular and neuropsychiatric events. Although recent studies have not confirmed such an association, further research is needed given the large number of smokers who are being prescribed varenicline, including important subgroups such as smokers with COPD who may be particularly vulnerable to side effects of drugs. The aim of this study is to assess the cardiovascular and neuropsychiatric safety of varenicline using data from the QResearch general practice (GP) database.We will conduct a retrospective cohort study in the QResearch GP database. Patients will be categorised into three exposure groups: prescription of (1) varenicline, (2) bupropion or (3) nicotine replacement therapy (NRT Rx; =reference group). We will separately consider major incident neuropsychiatric and cardiovascular outcomes that occur during 6?months of follow-up using Cox proportional hazards models, adjusted for confounders. Furthermore, propensity score analysis will be used as an analytical approach to account for potential confounding by indication.This work involves analysis of anonymised, routinely collected data. The protocol has been independently peer-reviewed by the QResearch Scientific Board and meets the requirements of the Trent research ethics committee. We plan to disseminate the results from this study via articles in international peer-reviewed journals and presentations at relevant national and international health conferences.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.

Item does not contain fulltext BACKGROUND AND STUDY AIMS: Sessile serrated adenomas/polyps (SSA/Ps) are precursors of colorectal cancer (CRC), but their endoscopic detection can be difficult. We therefore examined the endoscopic characteristics of SSA/Ps with and without dysplasia in a cross-sectional study. PATIENTS AND METHODS: We reviewed clinical, endoscopic, and histopathologic data from patients undergoing colonoscopy between February 2008 and February 2012. We categorized colorectal polyps according to anatomic site, size, and shape, and classified serrated polyps using the World Health Organization (WHO) classification. Multiple logistic regression analyses examined potential differences regarding site, size, and shape between SSA/Ps and colorectal adenomas (overall and advanced only). RESULTS: We examined 7433 patients (mean age 59 years, 45.9 % men) with 5968 colorectal polyps. In total, we found 170 SSA/Ps (170/5968, 2.9 %), including 63 SSA/Ps with dysplasia (1.1 %) and 107 SSA/Ps without dysplasia (1.8 %). Compared with SSA/Ps with dysplasia, SSA/Ps without dysplasia were more often proximally located (odds ratio [OR] 3.3, 95 % confidence interval [95 %CI] 1.7 - 6.4), but less often < 6 mm in size (OR 0.6, 95 %CI 0.3 - 1.1). No significant differences were found regarding location between SSA/Ps with dysplasia and advanced adenomas (proximal colon, 47.6 % vs. 40.1 %). However, SSA/Ps with dysplasia were more often < 6 mm in size than advanced adenomas (OR 0.3, 95 %CI 0.2 - 0.5). Of the 63 dysplastic SSA/Ps, 6 (9.5 %) contained high grade dysplasia, but none invasive carcinoma. CONCLUSIONS: SSA/Ps with dysplasia are frequently < 6 mm in size, located throughout the colon and 9.5 % of them contain high grade dysplasia. These findings underscore the importance of high quality colonoscopic examination to maximize protection against CRC.

Smoking prevalence is higher among low socio-economic status (LSES) groups, and this difference may originate from a higher intention to smoke in childhood. This study aims to identify factors that explain differences in intention to smoke between children living in high socio-economic status (HSES) and LSES neighbourhoods. Cross-sectional data were derived from the baseline assessment of a smoking prevention intervention study. Dutch primary school children, aged 10 – 11 years (N = 2,612), completed a web-based questionnaire about their attitude, subjective norm, self-efficacy expectations, modelling and intention to smoke. Linear and logistic regression analyses were performed to assess potential individual cognitive (attitude, subjective norm and self-efficacy) and social environmental (modelling) mediators between SES and intention to smoke. Multiple mediation models indicated that modelling mediated the association between SES (B = -0.09 (p

From a corporate social responsibility perspective, there are many reasons to promote teleconference use as an alternative to business travel. The present study examines psychosocial and organizational factors relevant to teleconference use. We tested an extended Theory of Planned Behavior model of teleconference use among office workers of four organizations. Results indicate that intention was the strongest direct predictor of teleconference use. Habit and perceived norm, in turn, were the strongest predictors of intention to use teleconference. In contrast, attitude was only weakly predictive and perceived control not predictive at all of intention to use teleconference. We also examined how this model was influenced by the organizational context by comparing organizations from two different regions, and organizations from the private vs . the public sector. Most teleconference-related beliefs differed between regions and organizational sectors. The relevance of specific attitudinal and normative beliefs to the overall attitude and perceived norm also differed between organizational sectors. Implications for practice and future research are discussed.

Background: Corresponding with the T helper cell type 1/T helper cell type 2 hypothesis, autoimmune and allergic diseases are considered pathologically distinct and mutually exclusive conditions. Co-occurrence of autoimmune disorders and allergy within patients, however, has been reported. Transgenerational co-occurrence of autoimmune and allergic disease has been less often described and may differ from the intra-patient results..Aims: To test the hypothesis that autoimmune disorders in parents are a risk factor for the development of an allergic disease in their offspring.Methods: Prospectively registered (by academic general practitioners) International Classifications of Primary Care (ICPC) for diagnoses of autoimmune disorders and allergy within families were evaluated (n=5,604 families) by performing multiple logistic regression analyses.Results: The presence of any ICPC-encoded autoimmune disorder in fathers appeared to be associated with an increased risk in their eldest children of developing an allergy (odds ratio (OR) 1.4, 95% Cl 1.042 to 1.794). Psoriasis in fathers was particularly shown to be of influence (OR 1.5, 95% CI 1.061 to 2.117) and, although any ICPC-encoded autoimmune disease in mothers was found not to be of significance, the combined international code for registering rheumatoid arthritis/ankylosing spondylitis in mothers was OR 1.7 (95% Cl 1.031 to 2.852).Conclusions: The occurrence of ICPC-encoded autoimmune disorders in parents, especially psoriasis and rheumatoid arthritis/ankylosing spondylitis, significantly increases the occurrence of allergic disease in their children. After validation in follow-up research in a larger sample, these results may lead to the inclusion of 'parental autoimmune condition' as a risk factor in the general practitioner's diagnostics of allergic disease. (C) 2013 Primary Care Respiratory Society UK. All rights reserved.

Background:Small-scale, home-like care environments are increasingly implemented in institutional nursing care as a model to promote resident-directed care, although evidence on its effects is sparse. This study focuses on the effects of small-scale living facilities on the behavior of residents with dementia and use of physical restraints and psychotropic drugs.Methods:A quasi-experimental study was conducted comparing residents in two types of long-term institutional nursing care (i.e. small-scale living facilities and traditional psychogeriatric wards) on three time points: at baseline and follow-ups after six and 12 months. Residents were matched at baseline on cognitive and functional status to increase comparability of groups at baseline. Nurses assessed neuropsychiatric and depressive symptoms, agitation, social engagement, and use of physical restraints using questionnaires. Psychotropic drug use was derived from residents’ medical records.Results:In total, 259 residents were included: 124 in small-scale living facilities and 135 controls. Significantly fewer physical restraints and psychotropic drugs were used in small-scale living facilities compared with traditional wards. Residents in small-scale living facilities were significantly more socially engaged, at baseline and after six months follow-up, and displayed more physically non-aggressive behavior after 12 months than residents in traditional wards. No other differences were found.Conclusions:This study suggests positive effects of small-scale living facilities on the use of physical restraints and psychotropic drugs. However, the results for behavior were mixed. More research is needed to gain an insight on the relationship between dementia care environment and other residents’ outcomes.

Objectives The goal of this study was to test the unverified assumption that chronically elevated cardiac troponin T (cTnT) levels fluctuate randomly around a homeostatic set point. Background The introduction of high-sensitivity cardiac troponin (cTn) assays has improved sensitivity for acute myocardial infarction (AMI). However, many patients with a single positive cTn test result do not have AMI. Therefore, the diagnosis of AMI relies strongly on serial testing and interpretation of cTn kinetics. Essential in this regard is a profound understanding of the biological variation of cTn. Methods Two studies were conducted to assess biological cTnT variation and to investigate the presence of a diurnal rhythm of cTnT. Study 1 comprised 23 male subjects with type 2 diabetes, with no acute cardiovascular disease. Serial venous blood samples were drawn over an 11-h period (8:30 AM to 7:30 PM). In study 2, the presence of a diurnal cTnT rhythm was investigated by hourly sampling of 7 subjects from study 1 over 25 h. Results In study 1, we observed a gradual decrease in cTnT concentrations during the day (24 2%). This decrease was present in all participants and was most prominent in subjects with the highest baseline cTnT values (Pearson’s R 0.93). Diurnal variation of cTnT, as assessed in study 2, was characterized by peak concentrations during morning hours (8:30 AM, 17.1 2.9 ng/l), gradually decreasing values during daytime (8:30 PM, 11.9 1.6 ng/l), and rising concentrations during nighttime (8:30 AM the next day, 16.9 2.8 ng/l). Conclusions A diurnal cTnT rhythm substantiates the recommendation that all dynamic changes in cTnT should be interpreted in relation to the clinical presentation. Epidemiological studies and risk-stratification protocols with the use of cTnT may benefit from standardized sampling times. (Exercise and Glycemic Control in Type 2 Diabetes; NCT00945165) (J Am Coll Cardiol 2014;63:1788–95) ª 2014 by the American College of Cardiology Foundation Ca

Background Medication reviews are considered to be important to maintain a high quality of pharmacotherapy. However, there is a large variation in the quality of these reviews. Aim To evaluate the covariates that may lead to high-quality medication reviews and to establish their relative importance. Design Healthcare professionals, including community pharmacists, hospital pharmacists, nursing home physicians, general practitioners and geriatricians, were recruited in the province of Limburg, The Netherlands. Method A research group, selected for their expertise in the field of medication reviews, established covariates that could possibly affect the quality of medication reviews. An electronic questionnaire, including these covariates, was developed and was subsequently sent to the participants who rated the covariates using a 10-point scale. Finally, the research group classified the scores. Physicians and pharmacists were evaluated jointly and separately to account for possible differences. Results 29 out of 49 participants completed the study. 13 covariates were evaluated and their medians and ranges were calculated. The five most important covariates were, from most to less important, knowledge of the indication for the drug, use of guidelines, reviewer's professional field, knowledge of the medical history, and use of laboratory values. Both groups found the indication for the drug the most important covariate. Conclusions We found that the most relevant covariates that may lead to a high-quality medication review are the drug's indication, use of patients' medical history, use of guidelines, reviewer's professional field, and use of laboratory values.

Objective: To evaluate the effectiveness of a stroke-specific follow-up care model on quality of life for stroke patients, being discharged home, and their caregivers. Design: A non-randomized, controlled trial, comparing an intervention group with a control group (usual care). Subjects: Stroke patients and their caregivers. Methods: Intervention involved 5 home visits by a stroke care coordinator over a period of 18 months, using a structured assessment tool. Outcome measures were conducted at baseline (T0) and every 6 months thereafter (T6, T12 and T18) in the domains of quality of life (primary), activities of daily living, social activities, depression, anxiety and caregiver strain. Results: The intervention group (n = 62) had significantly increased its social activities after 18 months, whereas the control group (n = 55) showed significantly decreased levels of social activities. In the first 6 months, levels of depression decreased significantly in caregivers of the intervention group. No differences were found for quality of life and the other outcome measures. Conclusion: The intervention was not effective in improving quality of life, but was effective in improving levels of social activities. The intervention may have focussed too much on screening for stroke-related problems and not as much on adequate follow-up care and referral.

Background Asthma remains poorly controlled in children. Home monitoring of asthma control may help to improve the level of asthma control. Objectives To compare 2 methods to assess asthma control: (1) prospective home monitoring, based on daily assessment of forced expiratory volume in 1 second (FEV 1 ) and electronic symptom score, and (2) Asthma Control Questionnaire (ACQ) with retrospective assessment of symptoms and FEV 1 . Methods Ninety-six children with asthma were prospectively followed up during 1 year. Asthma control was assessed by home monitoring, including an electronic symptom score based on Global Initiative for Asthma (GINA) criteria and FEV 1 measurements. In the hospital, the ACQ was completed and FEV 1 was measured. Kappa analysis was performed to assess levels of agreement between the 2 methods. Results Agreement between the 2 methods was low (κ coefficient of 0.393). In 29 children (37%), prospective home monitoring was less optimistic than the retrospective assessment of asthma control by the ACQ. Conclusion This study found low agreement between asthma control based on GINA criteria by means of prospective home monitoring and the hospital ACQ. The prospective home monitor detected more cases of less well-controlled asthma than the ACQ. However, optimization of adherence to home monitor use is necessary. Trial Registration clinicaltrials.gov Identifier: NCT01239238.

Several studies have shown a positive association between maternal fish intake in pregnancy and pregnancy duration and child birth weight (BW), probably due to fish n-3 (ω-3) long-chain polyunsaturated fatty acids (LC-PUFAs). n-3 LC-PUFAs can also be synthesized endogenously, and their synthesis depends on single nucleotide polymorphisms (SNPs) in the fatty acid desaturase (FADS) gene encoding for FADS. We assessed the associations of maternal docosahexaenoic acid (DHA) intake in pregnancy with pregnancy duration and BW and investigated whether these associations are modified by maternal or fetal FADS SNP genotypes. We hypothesized that we would find stronger associations in minor allele homozygous mothers or fetuses due to their lower n-3 LC-PUFA endogenous synthesis and hence higher dependence on dietary supply. Data on maternal diet, pregnancy duration, and BW were available for 2622 mother-child pairs from the KOALA (Kind, Ouders en gezondheid: Aandacht voor Leefstijl en Aanleg) Birth Cohort Study. The rs174556 FADS SNP was genotyped in 1516 mothers and 1515 children. Associations and gene-diet interactions were tested with linear regression adjusting for potential confounders, including intake of other PUFAs. Women at the 75th percentile of DHA intake had 0.7-d longer pregnancies (P = 0.016) and 28-g heavier infants (P = 0.039) than did women at the 25th percentile of intake. Associations with arachidonic acid intake were of the same order but in the opposite direction. Mothers who were homozygous for the minor allele had 2-d shorter pregnancies (P = 0.035) and infants who were nearly 140 g lighter (P = 0.006) than did mothers who were major allele homozygotes. Post hoc analyses revealed that they had higher prepregnancy BMI (P = 0.020). Among the women homozygous for the minor allele, those at the 75th percentile of DHA intake had 226-g heavier infants than those at the 25th percentile of intake (P = 0.030), whereas DHA intake was not significantly associated with BW in major allele carriers. These findings suggest that maternal and fetal fatty acid requirements during pregnancy depend on maternal genetic variation in LC-PUFA synthesis.

The reach, retention and costs of four strategies aimed to recruit smokers for participation in a computer-tailored smoking cessation intervention was explored. The study was part of a randomized controlled trial whereby 832 respondents were randomized to three conditions. Smokers were invited by general practitioners (GPs), newspapers, Internet and other strategies (i.e. mailing organizations) to take part. ANOVA's/Chi-square tests explored sample differences. Logistic regression analyses investigated differences between the samples regarding retention and smoking behaviour. Smokers recruited via GPs (N = 144) had a lower educational level and suffered more from chronic obstructive pulmonary disease compared with respondents recruited via Internet (N = 307) (chi(2) = 11.554, df = 3, P = 0.009). Less motivated respondents recruited by GPs were more likely to return to study compared with the less motivated respondents recruited by 'other recruitment' strategies (chi(2) = 6.416, df = 3, P = 0.093). Highly addicted respondents recruited from newspapers (N = 213) were less likely to make a quit attempt compared with highly addicted respondents recruited by GPs (OR = 0.334, P = 0.035). Females from newspapers were less likely to remain abstinent compared with the GP sample (OR = 0.337, P = 0.005). Recruitment via GPs showed highest costs. Recruitment strategy influenced the type of smokers. Group differences were associated with different patterns of quitting.

Expert opinion plays an important role when selecting promising clusters of chemical compounds in the drug discovery process. We propose a method to quantify these qualitative assessments using hierarchical models. However, with the most commonly available computing resources, the high dimensionality of the vectors of fixed effects and correlated responses renders maximum likelihood unfeasible in this scenario. We devise a reliable procedure to tackle this problem and show, using theoretical arguments and simulations, that the new methodology compares favorably with maximum likelihood, when the latter option is available. The approach was motivated by a case study, which we present and analyze., Published in at http://dx.doi.org/10.1214/14-AOAS772 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org)

The increasing cost of drug development has raised the demand on the use of biomarkers as surrogate endpoints for the evaluation of new drugs in clinical trials. However, failed past attempts to use surrogate endpoints made it clear that, before deciding on the use of a candidate surrogate endpoint, it is of the utmost importance to investigate its validity. Such validation process has proven challenging for conceptual and practical reasons. In the present chapter, some of the statistical methods introduced for the evaluation of surrogate markers will be discussed. Emphasis will be made on the so-called meta-analytic approach and its information-theoretic version, where information from several units is combined to carry out the validation exercise. The methods will be illustrated using a case study in ophthalmology.

Background: A fracture liaison service model of care is widely recommended and applied, but data on its effectiveness are scarce. Therefore, the risk of subsequent nonvertebral fractures and mortality within two years after a nonvertebral fracture was analyzed in patients who presented to a hospital with a fracture liaison service and a hospital without a fracture liaison service. Methods: In 2005 to 2006, all consecutive patients with an age of fifty years or older presenting with a nonvertebral fracture were included. In the group that presented to a hospital without a fracture liaison service (the no-FLS group), only standard fracture care procedures were followed to address proper fracture-healing. In the group that presented to a hospital with a fracture liaison service (the FLS group), dual x-ray absorptiometry scans and laboratory testing were performed, and if applicable, patients were treated according to the Dutch guideline for osteoporosis. The risk for subsequent nonvertebral fracture and mortality were analyzed using multivariable Cox regression models with adjustments for age, sex, and baseline fracture location. Results: In total, 1412 patients presented to the fracture liaison service (73.2% were women, and the mean age was 71.1 years), and 1910 underwent standard fracture care (69.8% were women, and the mean age was 69.5 years). After adjustment for age, sex, and baseline fracture location, patients who attended the fracture liaison service had a significantly lower mortality risk (hazard ratio: 0.65; 95% confidence interval [CI]: 0.53 to 0.79) over two years of follow-up. The subsequent nonvertebral fracture risk was also significantly lower in the patients in the FLS group, but this effect was time-dependent, with a hazard ratio of 0.84 (95% CI: 0.64 to 1.10) at twelve months and 0.44 (95% CI: 0.25 to 0.79) at twenty-four months. Conclusions: Patients seen at the fracture liaison service had a significantly lower mortality and subsequently a lower risk of nonvertebral fracture than those not seen at the fracture liaison service, with a reduction of 35% and 56%, respectively, over two years of follow-up. A fracture liaison service appears to be a successful approach to reduce the number of subsequent fractures and premature mortality in this cohort of patients. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

BackgroundEffective interventions are needed to reduce neurobehavioral impairments in children due to maternal alcohol use during pregnancy. Currently, health-counseling interventions have shown inconsistent results to reduce prenatal alcohol use. Thus, more research using health counseling is needed to gain more knowledge about the effectiveness of this type of intervention on reducing alcohol use during pregnancy. An alternative and promising strategy is computer tailoring. However, to date, no study has shown the effectiveness of this intervention mode. ObjectiveThe aim was to test the effectiveness of health counseling and computer tailoring on stopping and reducing maternal alcohol use during pregnancy in a Dutch sample of pregnant women using alcohol. MethodsA total of 60 Dutch midwifery practices, randomly assigned to 1 of 3 conditions, recruited 135 health counseling, 116 computer tailoring, and 142 usual care respondents from February to September 2011. Health-counseling respondents received counseling from their midwife according to a health-counseling protocol, which consisted of 7 steps addressed in 3 feedback sessions. Computer-tailoring respondents received usual care from their midwife and 3 computer-tailored feedback letters via the Internet. Usual care respondents received routine alcohol care from their midwife. After 3 and 6 months, we assessed the effect of the interventions on alcohol use. ResultsMultilevel multiple logistic regression analyses showed that computer-tailoring respondents stopped using alcohol more often compared to usual care respondents 6 months after baseline (53/68, 78% vs 51/93, 55%; P=.04). Multilevel multiple linear regression analyses showed that computer-tailoring respondents (mean 0.35, SD 0.31 units per week) with average (P=.007) or lower (P

Bayesian optimal designs for binary longitudinal responses analyzed with mixed logistic regression describing a linear time effect are considered. In order to find the optimal number and allocations of time points, for different priors, cost constraints and covariance structures of the random effects, a scalar function of the approximate information matrix based on the first order penalized quasi likelihood (PQL1) is optimized. To overcome the problem of dependence of Bayesian designs on the choice of prior distributions, maximin Bayesian D -optimal designs are proposed. The results show that the optimal number of time points depends on the subject-to-measurement cost ratio and increases with the cost ratio. Furthermore, maximin Bayesian D -optimal designs are highly efficient and robust under changes in priors. Locally D -optimal designs are also investigated and maximin locally D -optimal designs are found to have much lower minimum relative efficiency and fewer time points than maximin Bayesian D -optimal designs. When comparing the efficiencies of designs with equidistant time points with the Bayesian D -optimal designs, it was found that three or four equidistant time points are advisable for small cost ratios and five or six equidistant time points for large cost ratios.

BackgroundA wide range of effective smoking cessation interventions have been developed to help smokers to quit. Smoking rates remain high, especially among people with a lower level of education. Multiple tailoring adapted to the individual’s readiness to quit and the use of visual messaging may increase smoking cessation. ObjectiveThe results of video and text computer tailoring were compared with the results of a control condition. Main effects and differential effects for subgroups with different educational levels and different levels of readiness to quit were assessed. MethodsDuring a blind randomized controlled trial, smokers willing to quit within 6 months were assigned to a video computer tailoring group with video messages (n=670), a text computer tailoring group with text messages (n=708), or to a control condition with short generic text advice (n=721). After 6 months, effects on 7-day point prevalence abstinence and prolonged abstinence were assessed using logistic regression analyses. Analyses were conducted in 2 samples: (1) respondents (as randomly assigned) who filled in the baseline questionnaire and completed the first session of the program, and (2) a subsample of sample 1, excluding respondents who did not adhere to at least one further intervention session. In primary analyses, we used a negative scenario in which respondents lost to follow-up were classified as smokers. Complete case analysis and multiple imputation analyses were considered as secondary analyses. ResultsIn sample 1, the negative scenario analyses revealed that video computer tailoring was more effective in increasing 7-day point prevalence abstinence than the control condition (OR 1.45, 95% CI 1.09-1.94, P=.01). Video computer tailoring also resulted in significantly higher prolonged abstinence rates than controls among smokers with a low (ready to quit within 4-6 months) readiness to quit (OR 5.13, 95% CI 1.76-14.92, P=.003). Analyses of sample 2 showed similar results, although text computer tailoring was also more effective than control in realizing 7-day point prevalence abstinence. No differential effects were found for level of education. Complete case analyses and multiple imputation yielded similar results. ConclusionsIn all analyses, video computer tailoring was effective in realizing smoking cessation. Furthermore, video computer tailoring was especially successful for smokers with a low readiness to quit smoking. Text computer tailoring was only effective for sample 2. Results suggest that video-based messages with personalized feedback adapted to the smoker’s motivation to quit might be effective in increasing abstinence rates for smokers with diverse educational levels. Trial RegistrationNetherlands Trial Register: NTR3102; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=3102 (Archived by WebCite at http://www.webcitation.org/6NS8xhzUV).

Objective The quality of colonoscopy is key for ensuring protection against colorectal cancer (CRC). We therefore aimed to elucidate the aetiology of postcolonoscopy CRCs (PCCRCs), and especially to identify preventable factors. Methods We conducted a population-based study of all patients diagnosed with CRC in South-Limburg from 2001 to 2010 using colonoscopy and histopathology records and data from the Netherlands Cancer Registry. PCCRCs were defined as cancers diagnosed within 5 years after an index colonoscopy. According to location, CRCs were categorised into proximal or distal from the splenic flexure and, according to macroscopic aspect, into flat or protruded. Aetiological factors for PCCRCs were subdivided into procedure-related (missed lesions, inadequate examination/surveillance, incomplete resection) and biology-related (new cancers). Results We included a total of 5107 patients with CRC, of whom 147 (2.9% of all patients, mean age 72.8 years, 55.1% men) had PCCRCs diagnosed on average 26 months after an index colonoscopy. Logistic regression analysis, adjusted for age and gender, showed that PCCRCs were significantly more often proximally located (OR 3.92, 95% CI 2.71 to 5.69), smaller in size (OR 0.78, 95% CI 0.70 to 0.87) and more often flat (OR 1.70, 95% CI 1.18 to 2.43) than prevalent CRCs. Of the PCCRCs, 57.8% were attributed to missed lesions, 19.8% to inadequate examination/surveillance and 8.8% to incomplete resection, while 13.6% were newly developed cancers. Conclusions In our experience, 86.4% of all PCCRCs could be explained by procedural factors, especially missed lesions. Quality improvements in performance of colonoscopy, with special attention to the detection and resection of proximally located flat precursors, have the potential to prevent PCCRCs.

Few randomized controlled trials (RCTs) have been performed in patients undergoing pancreaticoduodenectomy (PD). An important factor contributing to this is the large number of patients needed to adequately power RCTs for relevant clinical single endpoints. A PD-specific composite endpoint (CEP) could solve this problem. The aim of the present study was to develop a PD-specific CEP, consisting of complications related to PD, allowing reduction in sample sizes and improving the ability to compare outcomes. PD-specific CEP components were selected after a systematic review of the literature and consensus between 25 international pancreatic surgeons. Ultimately, prospective cohorts of patients who underwent PD in two high-volume HPB centers (London, UK, and Maastricht, NL) were used to assess the event rate and effect of implementing a PD-specific CEP. From a total of 18 single-component endpoints, intra-abdominal abscess, sepsis, post-PD hemorrhage, bile leakage, gastrojejunostomy leakage, leakage of the pancreatic anastomosis, delayed gastric emptying, and operative mortality within 90 days were selected to be included the PD-specific CEP. All eight components had consensus definitions and a Dindo–Clavien classification of 3 or more. The incidence of the PD-specific CEP was 24.7 % in the Maastricht cohort and 23.3 % in the London cohort. These incidence rates led to a twofold reduction in the theoretical calculated sample size for an adequately powered RCT on PD using this CEP as a primary endpoint. The proposed PD-specific CEP enables clinical investigators to adequately power RCTs on PD and increases the feasibility, comparability, and utility in meta-analysis.

There is increasing interest in the earlier detection of, and intervention in, patients at highest risk of developing chronic obstructive pulmonary disease (COPD). The objective of this research was to develop and validate a risk prediction model for general practitioner (GP)-recorded diagnosis of COPD. We used data from 239 Scottish GP practices; two-thirds were randomly allocated to a derivation cohort and the other third to a validation cohort. We included patients aged 35–74 years at the cohort entry date, and excluded patients with a recorded diagnosis of COPD prior to the entry date and with missing data on smoking status. There were 480,903 patients in the derivation cohort and 247,755 in the validation cohort. The incidence of COPD in the total cohort was 5.53/1,000 patient-years of follow-up (95% confidence interval (CI), 5.46–5.60). In the derivation cohort, the COPD risk for ever- versus never-smokers was substantially higher in women (hazard ratio (HR)=9.61, 95% CI, 8.92–10.34) than in men (HR=6.72, 95% CI, 6.19–7.30). Other risk factors for both sexes were level of deprivation and a previously recorded asthma diagnosis. In the validation cohort, the model discriminated well between patients who did and those who did not develop COPD: area under the receiver operating characteristics curve=0.845 (95% CI, 0.840–0.850) for females and 0.832 (95% CI, 0.827–0.837) for males. We have developed and validated the first risk prediction model for COPD, which has the major advantage of being populated entirely by routinely collected data and consequently may be used for clinical practice. A model to assess the risk of developing chronic obstructive pulmonary disease (COPD) has been developed. Lung diseases such as emphysema and chronic bronchitis, collectively known as COPD, are responsible for 6% of all deaths annually worldwide. Smoking is a key risk factor but there is no tool available to doctors that accurately predicts who will develop the disease. Now, Daniel Kotz at Maastricht University Medical Centre, together with an international team of researchers, has developed the first prediction model for assessing COPD risk in patients. Using data from 10 years' worth of general practice records following 728,658 patients in Scotland, the model determined those most likely to develop COPD with 85% accuracy. Female smokers were most at risk, with social deprivation and a history of asthma also important risk factors.

KEY MESSAGE: • Statistical significance testing alone is not the most adequate manner to evaluate if there is indeed a clinically relevant effect • Effect sizes should be added to significance testing • Effect sizes facilitate the decision whether a clinically relevant effect is found, helps determining the sample size for future studies, and facilitates comparison between scientific studies

BackgroundWeb-based computer-tailored interventions for multiple health behaviors can have a significant public health impact. Yet, few randomized controlled trials have tested this assumption. ObjectiveThe objective of this paper was to test the effects of a sequential and simultaneous Web-based tailored intervention on multiple lifestyle behaviors. MethodsA randomized controlled trial was conducted with 3 tailoring conditions (ie, sequential, simultaneous, and control conditions) in the Netherlands in 2009-2012. Follow-up measurements took place after 12 and 24 months. The intervention content was based on the I-Change model. In a health risk appraisal, all respondents (N=5055) received feedback on their lifestyle behaviors that indicated whether they complied with the Dutch guidelines for physical activity, vegetable consumption, fruit consumption, alcohol intake, and smoking. Participants in the sequential (n=1736) and simultaneous (n=1638) conditions received tailored motivational feedback to change unhealthy behaviors one at a time (sequential) or all at the same time (simultaneous). Mixed model analyses were performed as primary analyses; regression analyses were done as sensitivity analyses. An overall risk score was used as outcome measure, then effects on the 5 individual lifestyle behaviors were assessed and a process evaluation was performed regarding exposure to and appreciation of the intervention. ResultsBoth tailoring strategies were associated with small self-reported behavioral changes. The sequential condition had the most significant effects compared to the control condition after 12 months (T1, effect size=0.28). After 24 months (T2), the simultaneous condition was most effective (effect size=0.18). All 5 individual lifestyle behaviors changed over time, but few effects differed significantly between the conditions. At both follow-ups, the sequential condition had significant changes in smoking abstinence compared to the simultaneous condition (T1 effect size=0.31; T2 effect size=0.41). The sequential condition was more effective in decreasing alcohol consumption than the control condition at 24 months (effect size=0.27). Change was predicted by the amount of exposure to the intervention (total visiting time: beta=–.06; P=.01; total number of visits: beta=–.11; P

Background There is increasing interest in utilising novel markers of cardiovascular disease risk in patients with chronic heart failure (HF). Recently, it was shown that alpha-1-antichymotrypsin (ACT), an acute-phase protein and major inhibitor of cathpesin G, plays a role in the pathophysiology of HF and may serve as a marker for myocardial distress. Objective To assess whether ACT is independently associated with long-term mortality in chronic HF patients. Methods ACT plasma levels were categorised into quartiles. Survival times were analysed using Kaplan-Meier curves and Cox proportional hazards regression, without and with correction for clinically relevant risk factors, including sex, age, duration of HF, kidney function (MDRD), ischaemic HF aetiology and NT-proBNP. Results Twenty healthy individuals and 224 patients (mean age 71 years, 72 % male, median HF duration 1.6 years) with chronic HF were included. In total, 159 (71 %) patients died. The median survival time was 5.3 (95 % CI 4.5–6.1) years. ACT was significantly elevated in patients (median 433 μg/ml, IQR 279–680) in comparison with controls (median 214 μg/ml, IQR 166–271; p

Objective To present and describe a non-invasive method to study the origin and development of bladder filling sensation and to evaluate the repeatability of the method. Method Eighteen volunteers participated in the study and were given a water loading protocol consisting of 1,000ml water intake 1hr before the session and 200ml every 10min during the session. Protocol 1: To evaluate diuresis rate, seven participants were asked to void every 15min and the voided volume was measured. Protocol 2: Eleven volunteers graded bladder sensation on regular time points, on an empty graph with time on the X-axis and intensity of sensation on the Y-axis. The protocol ended at absolute need to void (maximal intensity) and voided volumes were measured. This protocol was conducted three times with a 10 days interval. Results Protocol 1: The diuresis rate was not different during the sessions and showed no variation over the studied time period (P=0.2). Protocol 2: For an individual, the diuresis rate was not different between the sessions. The curves in all patients showed a continuously increasing bladder intensity. In seven participants the curve was convex, in the other four, the curve was sigmoidal. For each individual the pattern was constant during the three sessions. Conclusion A strict water loading protocol induces a constant diuresis. This allows individuals to draw an introspection bladder sensation curve with a specific shape, which can be used as a method to study the development of bladder sensation non-invasively. Neurourol. Urodynam. 33:502-506, 2014. (c) 2013 Wiley Periodicals, Inc.