ipw: An R Package for Inverse Probability Weighting

We describe the R package ipw for estimating inverse probability weights. We show how to use the package to fit marginal structural models through inverse probability weighting, to estimate causal effects. Our package can be used with data from a point treatment situation as well as with a time-varying exposure and time-varying confounders. It can be used with binomial, categorical, ordinal and continuous exposure variables

Prediction and treatment of asthma in preschool children at risk: study design and baseline data of a prospective cohort study in general practice (ARCADE)

Background: Asthma is a difficult diagnosis to establish in preschool children. A few years ago, our group presented a prediction rule for young children at risk for asthma in general practice. Before this prediction rule can safely be used in practice, cross-validation is required. In addition, general practitioners face many therapeutic management decisions in children at risk for asthma. The objectives of the study are: (1) identification of predictors for asthma in preschool children at risk for asthma with the aim of cross-validating an earlier derived prediction rule; (2) compare the effects of different treatment strategies in preschool children. Design: In this prospective cohort study one to five year old children at risk of developing asthma were selected from general practices. At risk was defined as 'visited the general practitioner with recurrent coughing (≥ 2 visits), wheezing (≥ 1) or shortness of breath (≥ 1) in the previous 12 months'. All children in this prospective cohort study will be followed until the age of six. For our prediction rule, demographic data, data with respect to clinical history and additional tests (specific immunoglobulin E (IgE), fractional exhaled nitric oxide (FENO), peak expiratory flow (PEF)) are collected. History of airway specific medication use, symptom severity and health-related quality of life (QoL) are collected to estimate the effect of different treatment intensities (as expressed in GINA levels) using recently developed statistical techniques. In total, 1,938 children at risk of asthma were selected from general practice and 771 children (40%) were enrolled. At the time of writing, follow-up for all 5-year olds and the majority of the 4-year olds is complete. The total and specific IgE measurements at baseline were carried out by 87% of the children. Response rates to the repeated questionnaires varied from 93% at baseline to 73% after 18 months follow-up; 89% and 87% performed PEF and FENO measurements, respectively. Discussion: In this study a prediction rule for asthma inyoung children, to be used in (general) practice, will be cross-validated. Our study will also provide more insight in the effect of treatment of asthma in preschool children

ICE COLD ERIC – International collaborative effort on chronic obstructive lung disease: exacerbation risk index cohorts – Study protocol for an international COPD cohort study

<p>Abstract</p> <p>Background</p> <p>Chronic Obstructive Pulmonary Disease (COPD) is a systemic disease; morbidity and mortality due to COPD are on the increase, and it has great impact on patients' lives. Most COPD patients are managed by general practitioners (GP). Too often, GPs base their initial assessment of patient's disease severity mainly on lung function. However, lung function correlates poorly with COPD-specific health-related quality of life and exacerbation frequency. A validated COPD disease risk index that better represents the clinical manifestations of COPD and is feasible in primary care seems to be useful. The objective of this study is to develop and validate a practical COPD disease risk index that predicts the clinical course of COPD in primary care patients with GOLD stages 2–4.</p> <p>Methods/Design</p> <p>We will conduct 2 linked prospective cohort studies with COPD patients from GPs in Switzerland and the Netherlands. We will perform a baseline assessment including detailed patient history, questionnaires, lung function, history of exacerbations, measurement of exercise capacity and blood sampling. During the follow-up of at least 2 years, we will update the patients' profile by registering exacerbations, health-related quality of life and any changes in the use of medication. The primary outcome will be health-related quality of life. Secondary outcomes will be exacerbation frequency and mortality. Using multivariable regression analysis, we will identify the best combination of variables predicting these outcomes over one and two years and, depending on funding, even more years.</p> <p>Discussion</p> <p>Despite the diversity of clinical manifestations and available treatments, assessment and management today do not reflect the multifaceted character of the disease. This is in contrast to preventive cardiology where, nowadays, the treatment in primary care is based on patient-specific and fairly refined cardiovascular risk profile corresponding to differences in prognosis. After completion of this study, we will have a practical COPD-disease risk index that predicts the clinical course of COPD in primary care patients with GOLD stages 2–4. In a second step we will incorporate evidence-based treatment effects into this model, such that the instrument may guide physicians in selecting treatment based on the individual patients' prognosis.</p> <p>Trial registration</p> <p>ClinicalTrials.gov Archive NCT00706602</p

Physical risk factors for neck pain

To identify physical risk factors for neck pain, a systematic review of the literature was carried out. Based on methodological quality and study design, 4 levels of evidence were defined to establish the strength of evidence for the relationship between risk factors and neck pain. Altogether, 22 cross-sectional studies, 2 prospective cohort studies, and 1 case-referent study were eligible for determining the level of evidence. The results showed some evidence for a positive relationship between neck pain and the duration of sitting and twisting or bending of the trunk. A sensitivity analysis was carried out excluding 3 items of the quality list, the importance of which seemed doubtful. On the basis of this sensitivity analysis, it was concluded that there is some evidence for a positive relationship between neck pain and the following work-related risk factors: neck flexion, arm force, arm posture, duration of sitting, twisting or bending of the trunk, hand-arm vibration, and workplace design

Clinical relevance of gallbladder polyps; is cholecystectomy always necessary?

Background: Gallbladder polyps are common incidental findings during abdominal ultrasonography. Cholecystectomy is recommended for polyps equal or greater than 10 mm on ultrasound due to their malignant potential. However, the majority of lesions appear to be pseudopolyps with no malignant potential. Our aim was to determine the correlation between ultrasonographic findings and histopathological findings after cholecystectomy for gallbladder polyps in two institutions. Method: A retrospective analysis was performed at two Dutch institutions of patients who underwent cholecystectomy. All cholecystectomies for suspected gallbladder polyps between January 2010 and August 2017 were included. Ultrasonographic and histopathological reports were analyzed. Results: A total of 108 patients underwent cholecystectomy for gallbladder polyps. At abdominal ultrasound sixty-five patients (60.2%) were diagnosed with multiple gallbladder polyps. The mean diameter of the polyps was 11 mm. On pathological examination after cholecystectomy, only three specimens harbored true polyps. No anomalies were found in 48 (44%) patients and 51 (47%) had cholesterolosis. Conclusion: The prevalence of true gallbladder polyps was much lower in this study than reported in literature. After cholecystectomy for gallbladder polyps diagnosed by ultrasound, 97% of patients had non-neoplastic or not identifiable lesions in the gallbladder. These findings question the usefulness of current guidelines for management of suspected gallbladder polyps

Intraleaflet hemorrhages are a common finding in symptomatic aortic and mitral valves

Introduction: Intraleaflet hemorrhage (ILH) has been reported to occur in calcified degenerated aortic valves. At present, no such information is available for mitral valves or for other types of valvular disease. We examined the prevalence, age, and potential source of ILH in a consecutive series of surgically removed aortic and mitral valves, and related the findings to specific types of heart valve pathology. Methods: A total of 105 aortic (n=85) and mitral (n=20) valves were retrieved from 100 symptomatic patients. Pathological diagnosis was made on photographic images and histology. Presence, extent, and age of ILH; its possible association with calcification; microvessels; and microvascular leakage were assessed with conventional and immunohistochemical staining methods and related to the type of underlying valvular disease. Results: Pathological diagnosis revealed degenerative aortic valve disease (n=70), postinflammatory disease (n=16), endocarditis (n=12), myxoid degenerative mitral valve disease (n=6), and one normal valve. ILH was found in 86% of aortic and 75% ofmitral valves. Microvessels were present in 91% of all valves. Microvascular leakagewas noted in 70% of aortic and 84% of mitral valves; in both groups, colocalization with ILH was found in 48%. Most aortic valves (91%) contained calciumdeposits, of which 54% showed colocalization with ILH. In 66% of valves with ILH, a combination of recent hemorrhage and iron deposits was seen, indicating an ongoing process of episodic hemorrhages. Conclusion: The prevalence of ILH is very high in resected heart valves. Both aortic and mitral valves showed an association of ILH with microvessels, microvascular leakage, and calcifications. We speculate that repetitive microvascular-leakage-related ILH may contribute to valve dysfunction on the (very) long term. (C) 2017 The Authors. Published by Elsevier In

Treatment of somatosensory tinnitus : a randomized controlled trial studying the effect of orofacial treatment as part of a multidisciplinary program

Background: Tinnitus, or ringing in the ears, is a perception of sound in the absence of overt acoustic stimulation. In some cases, tinnitus can be influenced by temporomandibular somatosensory input, then called temporomandibular somatosensory tinnitus (TST). It is, however, not entirely known if orofacial treatment can decrease tinnitus severity. The purpose of this study was to evaluate the effect of orofacial treatment on tinnitus complaints in patients with TST. Methods: Adult patients with TST were included, and all patients received information and advice about tinnitus and conservative orofacial treatment consisting of physical therapy, and, in case of grinding, occlusal splints were applied. Included patients were randomly assigned to an early start group and a delayed start group according to our delayed treatment design. Results: In total, 40 patients were included in each group. The treatment effect on tinnitus severity was investigated using the tinnitus questionnaire (TQ) and Tinnitus Functional Index (TFI). Regarding the TQ score, no clinically relevant reductions were observed, and no significant differences in the decrease were observed between the early start group and delayed start group. Contrarily, a significantly higher percentage of patients showed a decrease in the TQ degree in the early start group compared to the delayed start group (30.0% versus 2.8%, p = 0.006). The TFI score did show a significantly greater and clinically relevant reduction in the early start group compared to the delayed start group (p = 0.042). Conclusion: A multidisciplinary non‐invasive orofacial treatment was able to reduce tinnitus severity in patients with temporomandibular related somatosensory tinnitus

Fibrotic aortic valve disease after radiotherapy: an immunohistochemical study in breast cancer and lymphoma patients

Background: Radiation-associated aortic valve (AV) stenosis is frequently seen as a late sequela after thoracic radiotherapy (RT). Although the clinical relationship between thoracic radiotherapy and valvular dysfunction has been established, the process leading to accelerated aortic valve stenosis remains unclear. The aim of this study was to determine whether increased inflammatory cell infiltration, fibrosis, and calcification is present in aortic valves after radiotherapy at the time of aortic valve replacement. Methods: Stenotic aortic valve specimens from 43 patients were obtained after surgical aortic valve replacement. A total 28 patients had previously undergone radiotherapy for breast cancer or malignant lymphoma. A total 15 patients were included as control. The valve leaflets were assessed by (immuno)histochemistry for inflammatory cell composition (CD3, CD20, CD68, and CD163) and extracellular matrix changes (collagen and calcification). Results: Aortic valve cell density after radiotherapy for lymphoma was markedly decreased when compared with other groups. Irradiated aortic valve show similar (low) degrees of late T and B lymphocyte infiltration as control valves, whereas macrophage marker CD68 was decreased after radiotherapy for breast cancer. Collagen content was increased following radiotherapy. Aortic valves of patients with lymphoma contained significantly less calcified tissue when compared with the other groups. Conclusion: High-dose radiation at a young age (patients with lymphoma) results in cell loss and premature fibrotic aortic valve stenosis as opposed to the degenerative calcific stenosis observed in patients with breast cancer. Our findings suggest a possible dose-dependent effect of radiotherapy on aortic valve fibrosis. The active presence of inflammatory cells may be limited to the acute phase after radiotherapy