Self management for patients with chronic obstructive pulmonary disease.

BACKGROUND: Self management interventions help patients with chronic obstructive pulmonary disease (COPD) acquire and practise the skills they need to carry out disease-specific medical regimens, guide changes in health behaviour and provide emotional support to enable patients to control their disease. Since the first update of this review in 2007, several studies have been published. The results of the second update are reported here. OBJECTIVES: 1. To evaluate whether self management interventions in COPD lead to improved health outcomes.2. To evaluate whether self management interventions in COPD lead to reduced healthcare utilisation. SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register of trials (current to August 2011). SELECTION CRITERIA: Controlled trials (randomised and non-randomised) published after 1994, assessing the efficacy of self management interventions for individuals with COPD, were included. Interventions with fewer than two contact moments between study participants and healthcare providers were excluded. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. Investigators were contacted to ask for additional information. When appropriate, study results were pooled using a random-effects model. The primary outcomes of the review were health-related quality of life (HRQoL) and number of hospital admissions. MAIN RESULTS: Twenty-nine studies were included. Twenty-three studies on 3189 participants compared self management versus usual care; six studies on 499 participants compared different components of self management on a head-to-head basis. Although we included non-randomised controlled clinical trials as well as RCTs in this review, we restricted the primary analysis to RCTs only and reported these trials in the abstract.In the 23 studies with a usual care control group, follow-up time ranged from two to 24 months. The content of the interventions was diverse. A statistically relevant effect of self management on HRQoL was found (St George's Respiratory Questionnaire (SGRQ) total score, mean difference (MD) -3.51, 95% confidence interval (CI) -5.37 to -1.65, 10 studies, 1413 participants, moderate-quality evidence). Self management also led to a lower probability of respiratory-related hospitalisation (odds ratio (OR) 0.57, 95% CI 0.43 to 0.75, nine studies, 1749 participants, moderate-quality evidence). Over one year of follow-up, eight (95% CI 5 to 14) participants with a high baseline risk of respiratory-related hospital admission needed to be treated to prevent one participant with at least one hospital admission, and 20 (95% CI 15 to 35) participants with a low baseline risk of hospitalisation needed to be treated to prevent one participant with at least one respiratory-related hospital admission.No statistically significant effect of self management on all-cause hospitalisation (OR 0.77, 95% CI 0.45 to 1.30, 6 studies, 1365 participants, low-quality evidence) or mortality (OR 0.79, 95% CI 0.58 to 1.07, 8 studies, 2134 participants, very low-quality evidence) was detected. Also, dyspnoea measured by the (modified) Medical Research Council Scale ((m)MRC) was reduced in individuals who participated in self management (MD -0.83, 95% CI -1.36 to -0.30, 3 studies, 119 participants, low-quality evidence). The difference in exercise capacity as measured by the six-minute walking test was not statistically significant (MD 33.69 m, 95% CI -9.12 to 76.50, 6 studies, 570 participants, very low-quality evidence). Subgroup analyses depending on the use of an exercise programme as part of the intervention revealed no statistically significant differences between studies with and without exercise programmes in our primary outcomes of HRQoL and respiratory-related hospital admissions.We were unable to pool head-to-head trials because of heterogeneity among interventions and controls; thus results are presented narratively within the review. AUTHORS' CONCLUSIONS: Self management interventions in patients with COPD are associated with improved health-related quality of life as measured by the SGRQ, a reduction in respiratory-related hospital admissions, and improvement in dyspnoea as measured by the (m)MRC. No statistically significant differences were found in other outcome parameters. However, heterogeneity among interventions, study populations, follow-up time and outcome measures makes it difficult to formulate clear recommendations regarding the most effective form and content of self management in COPD.

Rationale and design of the PRegnancy and Infant DEvelopment (PRIDE) Study.

BACKGROUND: To optimise the health of pregnant women and their children by evidence-based primary and secondary prevention, more scientific knowledge is needed. To overcome the methodological limitations of many studies on pregnancy and child health, which often use a retrospective design, we established the PRIDE (PRegnancy and Infant DEvelopment) Study. METHODS AND RESULTS: The PRIDE Study is a large prospective cohort study that aims at including 150 000-200 000 women in early pregnancy to study a broad range of research questions pertaining to pregnancy complications, maternal and child health, and adverse developmental effects in offspring. Women are invited to participate by their prenatal care provider before or at their first prenatal care visit and are asked to fill out web-based questionnaires in gestational weeks 8-10, 17, and 34, as well as biannually throughout childhood. In addition, a food frequency questionnaire and a paternal questionnaire are administered and medical records are consulted. Multiple validation studies will be conducted and paper-and-pencil questionnaires are available for women who cannot or do not want to participate through the Internet. For subgroups of participants, blood and saliva samples for genetic and biochemical analyses are being collected. The pilot phase, which started in July 2011, showed a response rate of 47%. Recruitment will eventually cover all of the Netherlands. CONCLUSIONS: We expect that this study, which will be the largest birth cohort in the world so far, will provide new insights in the aetiology of disorders and diseases that originate in pregnancy. The PRIDE Study is open for collaboration.

Cancer in adolescents and young adults (15-29 years): a population-based study in the Netherlands 1989-2009.

BACKGROUND: Cancer among adolescents and young adults (AYAs; 15-29 years old) is relatively rare but its incidence is increasing worldwide. To define the extent and nature of the AYA patients, this population-based study was performed to explore trends in cancer incidence, survival and risk of second primary cancers in AYAs. MATERIAL AND METHODS: Data from all AYAs diagnosed with cancer between 1989 and 2009 were obtained from the Netherlands Cancer Registry. Age-standardized incidence rates with estimated annual percentage of change (EAPC) and five-year relative survival rates were calculated. Relative survival was used as a good approximation of cause-specific survival. All analyses were stratified by gender, five-year age group and calendar period. In addition, Standardized Incidence Ratios were determined to evaluate the risk of second primary cancers. RESULTS: 23 161 AYAs were diagnosed with cancer between 1989 and 2009. Since 1989 the cancer incidence has increased significantly from 28 to 43 per 100 000 person years in males (EAPC: 1.9) and from 30 to 40 per 100 000 person years in females (EAPC: 1.4). The most frequently diagnosed cancers in male AYAs included testicular cancer, melanoma and Hodgkin's disease, whereas in females melanoma, breast cancer and Hodgkin's disease were the most frequently occurring cancers. Five-year relative survival rates were 80% and 82% for males and females, respectively. Over time, the five-year relative survival increased from 74% to 86% and from 79% to 86% in males and females, respectively. The risk of developing a second primary cancer was increased three to six times in males and two to five times in females, depending on rules for counting second primary cancers. CONCLUSIONS: Although the overall survival has improved over time, the progress made in AYAs for specific cancers is still less compared to improvements made in children and adults. This and the increasing incidence and high risk of second primary cancers warrants further research.

Hypospadias: risk factor patterns and different phenotypes.

OBJECTIVE: To obtain more insight into the origin of hypospadias by exploring a wide range of potential risk factors in a case-referent study in which a distinction was made between different phenotypes. PATIENTS AND METHODS: Cases and referents were 305 boys with hypospadias and 629 boys with middle ear effusion whose parents completed postal questionnaires. Hypospadias phenotype was classified as distal (195 boys), middle (67), and proximal (43). Adjusted odds ratios (OR) with 95% confidence intervals (CI) were estimated using logistic regression. RESULTS: Low birth weight, being a twin or triplet, mother being a diethylstilbestrol-daughter, fertility treatments, paternal subfertility, obesity, prescriptive drug use, and familial occurrence of hypospadias or testicular cancer were associated with hypospadias in general. For familial occurrence of hypospadias, there were high risk estimates for the distal and middle phenotypes with an OR (95%CI) of 10.4 (4.5-24.1) and 9.0 (3.1-26.0), but not for the proximal type at 1.8 (0.2-14.9). By contrast, the association with low birth weight (a proxy for placental dysfunction) seemed much stronger for proximal hypospadias with an OR (95%CI) of 9.1 (3.4-24.2) compared with distal and middle hypospadias at 2.6 (1.4-5.0) and 2.3 (0.8-6.5). There were similar estimates for pre-eclampsia. CONCLUSION: These findings indicate aetiological heterogeneity of hypospadias and provide indications for the possible mechanisms through which specific risk factors may interfere with penile development.

Fatigue and chronic fatigue syndrome-like complaints in the general population.

BACKGROUND: Most knowledge on chronic fatigue (CF) and chronic fatigue syndrome (CFS) is based on clinical studies, not representative of the general population. This study aimed to assess the prevalence of fatigue in an adult general population and to identify associations with lifestyle factors. METHODS: Total 22,500 residents of Nijmegen were selected at random and interviewed by questionnaire. Data on 9062 respondents (43% response) were analysed, taken into account age, gender and concomitant disease. Subjects were classified into four groups: not fatigued (NF, reference group), short-term fatigue (SF, <6 months), chronic fatigue (CF, >or=6 months) and CFS-like fatigue (in accordance with the Center for Disease Control criteria for CFS, without clinical confirmation). RESULTS: Our study population showed the following breakdown: NF 64.4% (95% CI 63.6-65.6%), SF 4.9% (95% CI 4.5-5.4%), CF 30.5% (95% CI 29.5-31.4%) and CFS-like fatigue 1.0% (95% CI 0.8-1.2%). Compared with the NF group, more of the CFS respondents were female [odds ratio (OR) = 1.9], obese (OR = 4.1), using analgesics (OR = 7.8), had a low alcohol intake (OR = 0.4), were eating less healthy food (OR = 0.5) and were physically less active (OR = 0.1). These associations largely applied to the SF and CF group. The fatigue could have been due to a concomitant disease in 34 and 55.5% of the SF and CF cases, respectively. CONCLUSION: The prevalence of CF in the general population appears to be much higher than previously indicated. Even with strict criteria for CFS, it is estimated that approximately 1% of the adult population experiences this condition. Interestingly, a large part of this group remains unrecognized by the general practitioner. A striking similarity in lifestyle pattern between SF, CF and CFS calls for further research.

Striking trends in the incidence of health problems in The Netherlands (2002-05). Findings from a new strategy for surveillance in general practice.

BACKGROUND: This study aimed to detect striking trends based on a new strategy for monitoring public health. METHODS: We used data over 4 years from electronic medical records of a large, nationally representative network of general practices. Episodes were either directly recorded by general practitioners (GPs) or were constructed using a new record linkage method (EPICON). The episodes were used to estimate raw morbidity rates for all codes of the International Classification of Primary Care (ICPC). Multilevel Poisson regression models were used to analyse the trend over time for 15 health problems that showed an obvious change over time. Based on these models, we calculated adjusted incidence rates corrected for clustering, sex and age. RESULTS: During 2002-05, both men and women increasingly consulted the GP because of concern about a drug reaction, a change in faeces/bowel movements and urination problems. Men showed an increase in consultations for prostate problems and venereal diseases. The incidence of chronic internal knee derangement decreased for both sexes. Women consulted their GP less frequently about sterilization and fear of being pregnant. CONCLUSION: The strategy developed proved to be useful to detect trends across a short period of time. Changes in the health care market, such as the increasing availability of over-the-counter drugs and various large advertising campaigns for medications may explain some of the findings. The increasing incidence of health problems in the urogenital area deserves attention as it could reflect increases in the incidence of sexually transmitted diseases (STDs) and urinary tract infections.

The Dutch Parelsnoer Institute Cerebrovascular Disease Initiative: a retrospective study of the effects of integrating clinical care and research on costs and quality of care in patients with ischaemic stroke.

INTRODUCTION: The Dutch Parelsnoer Institute (PSI) is a collaboration between all university medical centres in which clinical data, imaging and biomaterials are prospectively and uniformly collected for research purposes. The PSI has the ambition to integrate data collected in the context of clinical care with data collected primarily for research purposes. We aimed to evaluate the effects of such integrated registration on costs, efficiency and quality of care. METHODS: We retrospectively included patients with cerebral ischaemia of the PSI Cerebrovascular Disease Consortium at two participating centres, one applying an integrated approach on registration of clinical and research data and another with a separate method of registration. We determined the effect of integrated registration on (1) costs and time efficiency using a comparative matched cohort study in 40 patients and (2) quality of the discharge letter in a retrospective cohort study of 400 patients. RESULTS: A shorter registration time (mean difference of -4.6 min, SD 4.7, p=0.001) and a higher quality score of discharge letters (mean difference of 856 points, SD 40.8, p<0.001) was shown for integrated registration compared with separate registration. Integrated registration of data of 300 patients per year would save around €700 salary costs per year. CONCLUSION: Integrated registration of clinical and research data in patients with cerebral ischaemia is associated with some decrease in salary costs, while at the same time, increased time efficiency and quality of the discharge letter are accomplished. Thus, we recommend integrated registration of clinical and research data in centres with high-volume registration only, due to the initial investments needed to adopt the registration software.

Objective and perspective determine the choice of composite endpoint.

The most important consideration in the choice of study design and endpoint is that these two features match and represent the objective and the perspective of the trial as closely as possible. The mechanism may also be helpful, but arguments based on the mechanism, structure or levels of the variables, or based on practical considerations, such as (statistical) efficiency, must always be secondary considerations.

External validation of EPICON: a grouping system for estimating morbidity rates using electronic medical records.

OBJECTIVE: To externally validate EPICON, a computerized system for grouping diagnoses from EMRs in general practice into episodes of care. These episodes can be used for estimating morbidity rates. DESIGN: Comparative observational study. MEASUREMENTS: Morbidity rates from an independent dataset, based on episode-oriented EMRs, were used as the gold standard. The EMRs in this dataset contained diagnoses which were manually grouped by GPs. The authors ungrouped these diagnoses and regrouped them automatically into episodes using EPICON. The authors then used these episodes to estimate morbidity rates that were compared to the gold standard. The differences between the two sets of morbidity rates were calculated and the authors analyzed large as well as structural differences to establish possible causes. RESULTS: In general, the morbidity rates based on EPICON deviate only slightly from the gold standard. Out of 675 diagnoses, 36 (5%) were considered to be deviating diagnoses. The deviating diagnoses showed differences for two main reasons: "differences in rules between the two methods of episode construction" and "inadequate performance of EPICON." CONCLUSION: The EPICON system performs well for the large majority of the morbidity rates. We can therefore conclude that EPICON is useful for grouping episodes to estimate morbidity rates using EMRs from general practices. Morbidity rates of diseases with a broad range of symptoms should, however, be interpreted cautiously.

Reproductive disorders among male and female greenhouse workers.

The aim of this study was to evaluate reproductive disorders in male and female greenhouse workers. In 2002, data were collected from 4872 Dutch greenhouse workers and 8133 referents through postal questionnaires with detailed questions on reproductive disorders of the most recent pregnancy, lifestyle habits, and occupational exposures (e.g. pesticides) prior to conception. Different reproductive outcome measures were compared between 957 male and 101 female greenhouse workers and 1408 referents by means of logistic regression analyses. The analyses of primigravidous couples showed a slightly elevated risk of prolonged TTP (OR(women)=1.9; 95% CI: 0.8-4.4) and an increased risk of spontaneous abortion among female greenhouse workers (OR(women)=4.0; 95% CI: 1.1-14.0). A decreased risk of preterm birth was found among male greenhouse workers (OR(men)=0.1; 95% CI: 0.03-0.5). This study may offer some evidence for the hypothesis that pesticide exposure affects human reproduction leading to spontaneous abortion and possibly to prolonged time-to-pregnancy.

Results of sonotubometry in testing eustachian tube ventilatory function in children with cleft palate.

OBJECTIVES: In previous studies, an updated sonotubometry setup was tested in healthy adults and children to test its validity and reproducibility in the assessment of the ventilatory function of the eustachian tube (ET). The results were promising, but further investigations were needed to confirm the discriminative potential of this sonotubometry setup. Our objective in the present study was to test the discriminative potential of an updated sonotubometry setup in children with cleft palate. METHODS: The ET ventilatory function was tested in 56 children with cleft palate, ie, children with impaired ET function, and compared to the outcomes in 61 healthy children who served as a control group. All of the children were between 5 and 9 years of age. To test the reproducibility, we performed the sonotubometric testing in 2 sessions of 10 acts of swallowing each. Spearman's coefficient was used to test the correlation between the 2 sets of measurements. The results of measurements in the cleft palate group were compared with those in the otologically healthy control group and analyzed by means of a Mann-Whitney U test. RESULTS: Opening of the ET was recorded in at least 1 of the 2 measurement sessions in 57% of the children with cleft palate, as compared to 82% in the control group. The mean number of openings was lower in the cleft palate group than in the control group (respectively, 2.3 versus 3.7 out of 10; p < .01). The first and second sessions were highly correlated in both the cleft palate group and the control group, with Spearman's coefficients of, respectively, 0.96 and 0.89. CONCLUSIONS: The results of this study show that this updated sonotubometry setup has the potential to discriminate between these groups of children with various states of ET ventilatory function. Furthermore, the results of this study once again show that this updated sonotubometry setup is capable of assessing ET ventilatory function in both healthy children and children with cleft palate and that the measurements are highly reproducible. A persistent disadvantage remains that in 18% of the 61 healthy children there was no ET opening that could be registered, which still prohibits a definite assessment at the individual level.

The FAIR guiding principles for data stewardship: fair enough?

The FAIR guiding principles for research data stewardship (findability, accessibility, interoperability, and reusability) look set to become a cornerstone of research in the life sciences. A critical appraisal of these principles in light of ongoing discussions and developments about data sharing is in order. The FAIR principles point the way forward for facilitating data sharing more systematically-provided that a number of ethical, methodological, and organisational challenges are addressed as well.

Patients to learn from: on the need for systematic integration of research and care in academic health care.

Patients suffering from rare, extreme or extremely complex sets of symptoms have something to expect from efforts to improve care through research. Biomedical research and care have often been approached as distinct worlds which are and should be only loosely connected. For observational research focusing on data drawn from real-world settings, however, that approach is found wanting. Integrating research and care responsibly is the main challenge instead. Integrated IT infrastructures facilitating Personalized medicine and Big Data are crucial components of a learning health care system, in which patients regularly play a double role: as individuals to be treated and as cases to learn from. Drawing on the example of the Dutch Parelsnoer Institute (PSI), a national biobanking and IT infrastructure integrated with clinical care procedures, this article outlines the reforms that are needed. Systematic integration of research and care offers a promising avenue, provided that a number of conditions are met: data and IT infrastructures will require overhauls in order to facilitate secure, high-quality data integration between research and care; institutional focus is needed to bring patient populations and expertise together; ethical frameworks and approaches for integrating research and care responsibly require further elaboration; clinical procedures and professional responsibilities may need to be adapted in order to accommodate research requirements in clinical processes; and involvement of patients and other stakeholders in design and research priority setting is needed to further the goals of real-world and patient relevance. RELEVANCE FOR PATIENTS: Integrating research and care in academic medicine in a more systematic fashion offers a promising perspective to current and future patients. In order to live up to these promises, research and care should be integrated more systematically in academic health science, with patients being included as research participants by default. Data and tissue infrastructures and facilities can provide a platform for doing so. At the same time, many issues remain to be settled. New ethical ways and means for protecting and respecting patient-participants in such a double role are also needed in this respect. In this way a deeper transformation is at stake as well: a change towards a setting in which patients fully take center stage in debate and action on the future of biomedicine.

A Stepwise Procedure to Define a Data Collection Framework for a Clinical Biobank.

INTRODUCTION: Current guidelines for clinical biobanking have a strong focus on obtaining, handling, and storage of biospecimens. However, to allow for research tying biomarker analysis to clinical decision making, there should be more focus on collection of data on donor characteristics. Therefore, our aim was to develop a stepwise procedure to define a framework as a tool to help start the data collection process in clinical biobanking. MATERIALS AND METHODS: The Radboud Biobank (RB) is a central clinical biobanking facility designed in accordance with the standards set by the Parelsnoer Institute, a Dutch national biobank originally initiated with eight different disease cohorts. To organize the information of these cohorts, we used our experience and knowledge in the field of biobanking and translational research to identify research domains and information categories to classify data. We extended this classification system to a stepwise procedure for defining a data collection framework and examined its utility for existing RB biobanks. RESULTS: Our approach resulted in the definition of a three-step procedure: (1) Identification of research domains and relevant questions within the field that may benefit from biobank samples. (2) Identification of information categories and accompanying subcategories that are relevant for answering questions in identified research domains. (3) Reduction to an efficient framework based on essentiality and quality criteria. We showed the utility of the procedure for three existing RB biobanks. DISCUSSION: We developed guidelines for the definition of a framework that supports the standardization of the biobank data collection process. Connecting the biobank database to pertinent information collected from the electronic health record will improve data quality and efficiency for both care and research. This is crucial when using the corresponding biospecimens for scientific research. Further, it also facilitates the combination of different clinical biobanks for a specific disease.

A generalized concept of power helped to choose optimal endpoints in clinical trials.

OBJECTIVES: A clinical trial may have multiple objectives. Sometimes the results for several parameters may need to be significant or meet certain other criteria. In such cases, it is important to evaluate the probability that all these objectives will be met, rather than the probability that each will be met. The purpose of this article is to introduce a definition of power that is tailored to handle this situation and that is helpful for the design of such trials. STUDY DESIGN AND SETTING: We introduce a generalized concept of power. It can handle complex situations, for example, in which there is a logical combination of partial objectives. These may be formulated not only in terms of statistical tests and of confidence intervals, but also in nonstatistical terms, such as "selecting the optimal by dose." RESULTS: The power of a trial was calculated for various objectives and combinations of objectives. CONCLUSION: The generalized concept of power may lead to power calculations that closely match the objectives of the trial and contribute to choosing more efficient endpoints and designs.

Sonotubometry: a useful tool to measure intra-individual changes in eustachian tube ventilatory function.

OBJECTIVE: To determine whether intra-individual changes in eustachian tube (ET) function induced by local application of a histamine phosphate solution can be detected using an improved sonotubometer. DESIGN: The function of the ET was measured with a revised sonotubometer before and after histamine was applied to the nasopharyngeal ostium of the ET. SETTING: Tertiary referral hospital. PATIENTS: Twenty-five otologically healthy adults. INTERVENTIONS: A histamine phosphate solution with a concentration of 16 mg/mL was applied to the nasopharyngeal ostium of the ET using a pressure nebulizer. MAIN OUTCOME MEASURES: The number of openings during 10 acts of swallowing. This outcome value could range from 0 to 10. The number of ET openings before and after histamine application was compared. RESULTS: The mean number of ET openings dropped dramatically: from 8.4 before application of histamine to 2.7 after application. This difference was statistically significant; there was a mean difference of 5.6 (95% confidence interval, 4.4-6.9; P < .001). CONCLUSION: Sonotubometry is capable of detecting intra-individual changes in ET function and may therefore be a very useful tool in monitoring and/or clinical research of ET dysfunction or function.

Reproducibility of sonotubometry as Eustachian tube ventilatory function test in healthy children.

OBJECTIVES: To devise a simple and reliable diagnostic procedure to test Eustachian tube function routinely in an ENT outpatient setting. One method to measure ET ventilatory function is sonotubometry. The reproducibility of a recently updated sonotubometry set-up was tested in healthy children. METHODS: The test population comprised 61 school children aged from 6 to 8 years. Only otologically healthy children were included. Health state was established by means of a 12-item questionnaire. To test reproducibility, sonotubometric testing took place in two sessions of 10 acts of swallowing each. Spearman's coefficient was used to test the correlation between the two sets of measurements. All testing took place at a primary school in a nearby village. RESULTS: Opening of the ET was recorded in at least one of the two measurement sessions in 82% of the children. The first and second sessions were highly correlated, with a Spearman's coefficient of 0.89. CONCLUSIONS: In otologically healthy children, opening of the ET was recorded frequently using the updated sonotubometry set-up. Measurement results had high reproducibility. Therefore, the test forms a useful method to assess ET ventilatory function in otologically healthy children. The performance of this updated version needs to be established in children with otological diseases.

An investigation of clinical studies suggests those with multiple objectives should have at least 90% power for each endpoint.

BACKGROUND AND OBJECTIVES: Many clinical studies have more than one objective, either formally or informally, but this is not usually taken into account in the determination of the sample size. We investigated the overall power of a study, that is, the probability that all the objectives will be met. METHODS: We calculated the overall power in the case that the study has two primary outcome variables and in the case that one outcome variable is evaluated on two subsets, in particular, the Per Protocol group and the Intention to Treat group. RESULTS: A power of 80% for each of the two end points leads to poor power for the end points combined. However, a power of 90% preserves better the overall power. The power of the Per Protocol analysis can be higher or lower than the power of the Intention to Treat analysis. CONCLUSION: Power should be calculated for all end points combined, and it should be at least 90% for each primary end point. If the sample size for the intention-to-treat analysis is determined by adding a percentage of "nonevaluable subjects" to the sample size required for the per protocol analysis, then this may lead to an underpowered study.

Prediction of asthma in young adults using childhood characteristics: Development of a prediction rule.

OBJECTIVE: To develop an easily applicable prediction rule for asthma in young adulthood using childhood characteristics. METHODS: A total of 1,055 out of 1,328 members of a Dutch birth cohort were followed from 2 to 21 years of age. Univariate and multivariate logistic regression analyses were used to evaluate the predictive value of childhood characteristics on asthma at 21 years of age. A prognostic function was developed, and the area under the receiving operating characteristic (ROC) curve was used to estimate the predictive ability of the prognostic models. RESULTS: Of the 693 responding subjects, 86 (12%) were diagnosed with asthma. Independent prognostic factors at ages 2 and 4 years were female gender (odds ratios (OR) 1.9 and 2.1; 95% confidence intervals (CI) 1.2-3.2 and 1.3-2.5), smoking mother (OR 1.6 and 1.6; CI 1.0-2.7 and 1.0-2.6), lower respiratory tract illness (OR 1.9 and 2.4; CI 1.0-3.6 and 1.4-4.0), and atopic parents (OR 2.1 and 1.9; CI 1.3-3.4 and 1.2-3.1). The predictive power of both models was poor; area under ROC curve was 0.66 and 0.68, respectively. CONCLUSION: Asthma in young adulthood could not be predicted satisfactorily based on childhood characteristics. Nevertheless, we propose that this method is further tested as a tool to predict development of asthma.

Pesticide exposure: the hormonal function of the female reproductive system disrupted?

Some pesticides may interfere with the female hormonal function, which may lead to negative effects on the reproductive system through disruption of the hormonal balance necessary for proper functioning. Previous studies primarily focused on interference with the estrogen and/or androgen receptor, but the hormonal function may be disrupted in many more ways through pesticide exposure. The aim of this review is to give an overview of the various ways in which pesticides may disrupt the hormonal function of the female reproductive system and in particular the ovarian cycle. Disruption can occur in all stages of hormonal regulation: 1. hormone synthesis; 2. hormone release and storage; 3. hormone transport and clearance; 4. hormone receptor recognition and binding; 5. hormone postreceptor activation; 6. the thyroid function; and 7. the central nervous system. These mechanisms are described for effects of pesticide exposure in vitro and on experimental animals in vivo. For the latter, potential effects of endocrine disrupting pesticides on the female reproductive system, i.e. modulation of hormone concentrations, ovarian cycle irregularities, and impaired fertility, are also reviewed. In epidemiological studies, exposure to pesticides has been associated with menstrual cycle disturbances, reduced fertility, prolonged time-to-pregnancy, spontaneous abortion, stillbirths, and developmental defects, which may or may not be due to disruption of the female hormonal function. Because pesticides comprise a large number of distinct substances with dissimilar structures and diverse toxicity, it is most likely that several of the above-mentioned mechanisms are involved in the pathophysiological pathways explaining the role of pesticide exposure in ovarian cycle disturbances, ultimately leading to fertility problems and other reproductive effects. In future research, information on the ways in which pesticides may disrupt the hormonal function as described in this review, can be used to generate specific hypotheses for studies on the effects of pesticides on the ovarian cycle, both in toxicological and epidemiological settings.