The Internet is a frequently used source of health information. Adolescents in particular seem to be receptive to online health information (OHI) and often incorporate such information in their decision-making processes. Yet, OHI is often incomplete, inaccurate, or unreliable. This study assessed the quality of Hebrew online (non-user-generated) content on oral contraceptives (OC), with regard to accuracy/completeness, credibility, and usability.Twenty-nine websites in Hebrew, including those of the four Israeli HMOs, were identified and evaluated. The websites were categorized as: HMO, health portal, contraception-specific, promotional-commercial, and life style and women’s health. A set of established content parameters was selected by a family planning expert to assess accuracy/completeness. The Health on the Net Foundation Code of Conduct (HONcode) principles were used to assess the websites’ reliability. Usability was assessed by applying items selected from the Minervation Validation and the University of Michigan’s ′Website Evaluation checklist′ scale. Mean scores, standard deviations (SD), and ranges were calculated for all websites and for category-specific websites. Correlation between dimensions and Inter-rater reliability were also examined.The mean score for accuracy/completeness was 50.9% for all websites . Many websites failed to provide complete information, or provided inaccurate information regarding what to do when a pill is missed and when to use back–up methods. The average credibility score for all websites was 70.6% . The credibility parameters that were most commonly absent were funding source, authoring, date of content creation and last modification, explicit reference to evidence-based information, and references and citations. The average usability score for all websites was 94.5% . A weak correlation was found between the three quality parameters assessed.Wide variation was noted in the quality of Hebrew-language OC websites. HMOs’ websites scored highest on credibility and usability, and contraceptive-specific websites exhibited the greatest accuracy/completeness. The findings highlight the need to establish quality guidelines for health website content, train health care providers in assisting their patients to seek high quality OHI, and strengthen e-health literacy skills among online-information seekers, including perhaps health professionals. Despite the sometimes questionable quality of online health information (OHI) -3, milliOftentimes, OHI influences an individual’s knowledge, attitudes, and behaviors, and modifies the doctor-patient relationship -14. For Online sources and types of OHI vary greatly and range from peer-reviewed medical journals’ websites to websites that promote risky behaviors , and widWebsites may attempt to conceal the origin of the information   or preseHealth websites also vary in their complexity, design, and aesthetics. These factors affect the user’s perceptions of website credibility (or “believability” ) and theConcerns regarding the quality of OHI are not new, and various solutions aiming to control or evaluate aspects of health information quality have been developed. These range from codes of conduct to user guides, filters, and third party certification -34. For Accuracy and completeness of OHI can be assessed by subject matter experts or by assessing the extent to which the OHI meets evidence-based practice protocols or guidelines. However, some health topics are too broad or lack formal, widely-accepted guidelines. In the dynamically changing fields of medicine, health, and science, up-to-date guidelines are often difficult to maintain.A recent Israeli survey of a nationally representative sample of just over 7,000 7th–12th graders in 158 Ministry of Education schools found that among the 98.7% of adolescents who have Internet access, 52% had searched for health-related information online in the 12 months prior to the survey. While many information-seeking adolescents access OHI by going directly to specific health websites and portals, a much greater proportion (70%) seek information using search engines, primarily Google.co.il, Finder, and Kafe . About oWhile the majority of adolescent Internet users in Israel seek OHI, there has been little, if any, assessment of the quality of Hebrew-language OHI, particularly on topics relevant to this population group . The proThe selected websites were chosen based on the results of a national survey that identified web-sources commonly used by Israeli school adolescents when seeking OHI . AccordiWe gathered the first 100 search results for each search term  on 6 search engines. The seventh search engine–Nana10, produced fewer than 30 results per search term and therefore all of Nana10’s results were added to the list. To increase the number of possible websites to be assessed and in order to avoid duplicates, the results were organized into four groups based on the type of search engine: 1) Google and Google-powered search engines–Finder and Kafe, 2) Yahoo-powered search engines–Yahoo and Walla, 3) Bing, and 4) Nana10. For each search term, we compared the results from the four search engine groups and excluded overlapping items. A list of 158 websites was compiled, after combining the results of the search of the six search-terms and excluding non-Hebrew websites. Of these, 27 were unique , accessible, active, and provided (non-user-generated) OC information on at least one webpage. This list contained the websites of two of the four major Israeli HMOs , so the websites of the other two HMOs were added in order to assess the quality of all four HMOs. Thus, 29 websites were selected for evaluation. Within each website, text searches were conducted to identify all the pages included in the same domain name with at least one title and one paragraph with information on OC use. When available, non-OC related pages of the website  were also evaluated to assess parameters of credibility  and usability .The quality of each website was assessed on three key parameters: accuracy/completeness, credibility, and usability.Accuracy/completeness of the OC content was assessed based on 13 established content items selected by a family planning expert from contraception guidelines . Items tThe HONcode principles were developed to assess the credibility of OHI . The eigBasic aspects of the websites’ usability were also assessed by applying an 11-item instrument selected from the Minervation Validation instrument   and/or tThe websites were classified as belonging to one of the following 5 categories: a) HMOs , b) health portals , c) contraception-specific , d) promotional and commercial , e) life style and women’s websites .All websites were evaluated by one of us (LF). Following analyses of the data and in response to a reviewer’s suggestion on a previous version of this report, six randomly selected websites  were independently assessed by YN and RS, and reassessed by LF. Some inter-rater variation was observed for accuracy/completeness and usability , ranges, and percentages were calculated for all websites and for category-specific websites. Pearson correlation coefficients of the three parameters assessed were estimated for all, and for category-specific websites.Statistical analyses were performed using SPSS 17.0.Evaluation of individual scale items indicates that more than half  of the websites evaluated provided information regarding the efficacy, safety, reversibility, side effects, and general use , but many failed to provide complete information, or provided inaccurate instructions regarding what to do when a pill is missed and when to use back-up methods (Table The mean score for accuracy/completeness was 50.9% (SD=30.1%) for all websites evaluated. Contraception-specific websites contained the most accurate and complete information (mean=66.7%) compared with a mean of 62.2% for health portals, 50.0% for HMOs and life style and women’s health websites, and 40.4% for promotional websites.As seen in Figure Two-thirds  of the websites stated that the health information they contained should not replace the advice of a health professional, and provided information about the organization that owns the website. Just over half  of the websites mentioned their content author’s qualifications and expertise, stated that information presented reflects only the opinion of the author, and presented their privacy policy. About three-quarters  of the websites contained information as to their intended audience and purpose, and provided information about different contraception methods. Nearly all websites had a contact e-mail address . Credibility parameters that were commonly missed included sources of funding, webmaster contact information, date of content creation and last modification, explicit reference to scientific evidence-based information, and references and citations (Table The mean score for credibility was 70.6% (SD=15.1%) for all websites evaluated. The HMOs’ websites contained the most credible information (80.0%), while contraception-specific websites had the lowest credibility score (65.0%). Health portals’ credibility (76.2%) was similar to that of the HMOs’ websites and higher than that of the promotional websites (67.1%) and life style and women’s health websites (67.3%).For all websites, the lowest mean credibility score was 38% and the highest was 98%. Promotional websites  and life style and women’s health websites  exhibited the greatest variability followed by HMO websites (SD=15.5% range=62–98%). Health portals  and contraception-specific websites  showed the least variation in their credibility scores , usability items were commonly presented or addressed .Overall, low correlation coefficients were noted between credibility and accuracy/completeness (0.08), between credibility and usability (0.10), and between accuracy/completeness and usability 0.25); however, these varied across website categories. Among HMO websites, there was a strong positive correlation between credibility and accuracy/completeness (0.88), a weak positive correlation between usability and credibility (0.26), and an intermediate positive correlation between accuracy/completeness and usability (0.48). Among health portals, on the other hand, a strong negative correlation was noted between credibility and accuracy/completeness (−0.59), and weak correlations between credibility and usability (0.08), and accuracy/completeness and usability (0.16). Among the contraception-specific websites there was a weak negative correlation between credibility and accuracy/completeness (−0.24), a weak positive correlation between credibility and usability (0.17), and a strong positive correlation between accuracy/completeness and usability (0.92). Promotional websites revealed very weak correlations between credibility and accuracy/completeness (−0.08) and credibility and usability (−0.17), and accuracy/completeness and usability (0.05). Life style and women’s health websites showed little correlation between credibility and accuracy/completeness (0.08), a weak correlation between credibility and usability (0.29), a moderate positive correlation between accuracy/completeness and usability (0.50) .Regardless of website category, all websites showed mid-scale accuracy/completeness scores, with the majority primarily failing to provide complete information. The commonly missing items included instructions on what to do if a pill is missed and when to use backup methods. Providing this information is relevant for OC users of all ages, but particularly for adolescent users, who frequently find it difficult to remember to take a pill every day. Poor dosage compliance constitutes one of the main reasons of method failure and teenage pregnancy among OC users .As expected, subject-specific websites  yield better results in terms of accuracy/completeness, while promotional websites exhibited the lowest mean score. However, the mean score of accuracy/completeness was generally about 50% across websites of all categories. Notably, accuracy/completeness scores of the HMOs’ websites showed important variations. The low mean score for accuracy/completeness of the HMOs’ websites, coupled with a high standard deviation and a strong correlation (0.88) between credibility and accuracy/completeness scores, reflect a division between two sub-groups within the HMO website category. Two of the HMOs’ websites presented accurate, complete, and credible OC information, in sharp contrast with the information presented on the websites of the other two HMOs. While HMO websites with low OC quality information were added by the authors to the list of websites evaluated, HMO websites with the high OC quality information were explicitly mentioned by respondents in a national school survey  as onlinCredibility parameters that were commonly absent included sources of funding, authorship disclosure, date of content creation and last modification, explicit reference to scientific evidence-based information, and references and citations. These parameters are anchors for contextualizing and comparing information; therefore, their appearance on the website is imperative. Knowing that the information retrieved is current is particularly important given the dynamic nature of medical practice and scientific knowledge. Furthermore, presenting the scientific and financial sources of information helps the reader identify the forces and interests influencing the content provided, and to act accordingly. In fact, websites that explicitly aim to promote health information, that is, health portals and the HMO websites, earned the highest credibility scores, in contrast to promotional websites and life style and women’s health websites, which earned lower scores. The low credibility of contraception-specific websites may prevent contraception information-seekers from fully benefitting from the highly accurate information they provide.Usability scores were relatively homogeneous across websites. Standard guidelines and “pre-formatted” platforms facilitate designers’ compliance with existing usability scales. In contrast with the HMOs’ websites–the most usable websites, contraception-specific websites earned the lowest score for usability. This suggests that usability should not be relied upon as a sole indicator of the quality of information.Overall, the correlation of the dimensions evaluated was very weak; however when assessed independently by website category, the HMO websites showed a strong correlation between accuracy/completeness and credibility (0.88). In contrast, health portals revealed a moderately strong negative correlation between accuracy/completeness and credibility (−0.59). The low correlation coefficients observed in the health portals category possibly reflects limited knowledge or expertise of health information providers in addressing the three quality dimensions evaluated, and suggest the need to advocate for regulating the design of online health content. At the same time, the discrepancy in the correlations emphasizes the need for providing adolescents with the skills necessary to assess the quality of the information retrieved, even from certified websites.The four HMOs’ websites differ in their approach to adolescent health-information seekers. HMO-A’s website targets adolescents directly by dedicating a forum (one of nearly 40 forums) entirely to the adolescent audience. The forum’s specific information compensates to some extent for the insufficient and rather general scope of the editorial content for adolescents. Other than the forum, relevant information for youth, such as OC information, appears in the different website sections. No section, however, is designed specifically for adolescents or brings together information on health issues that are of greatest concern to young adults. At the time this review was conducted, HMO-A’s forums were only compatible with Internet Explorer and not with other popular browsers such as Mozilla, Firefox, and Google Chrome.HMO-B’s website structure is guided by a concern for providing information about health topics  and situations requiring medical assistance , rather than for directly addressing specific populations and audiences, such as adolescents. HMO-B’s website has a “Youth” section that features articles on topics such as smoking cessation, drug abuse, and medical screening checkups, although these articles seem to have in mind adults and parents more than adolescents.HMO-C has a well-developed youth section on its website, featuring articles on a variety of topics, including drugs, mental health, nutrition, and teenage pregnancy. Yet, as with HMO-B, the articles seem to be written primarily for an adult audience, perhaps for concerned parents, and to a much lesser extent for teenagers seeking information on health issues. For example, in their youth section, there is a call to parents to provide adolescents with proper health information on sex, but no such information is actually provided.HMO-D’s website approaches adolescent health information seekers by offering adolescents the option of asking a physician health questions through its website. Very few answers are published on the website, and interestingly, some of the questions were from parents, indicating that the online Q&A service is not exclusively for adolescents. Since the answers are not published, there is very little information on the website that addresses adolescents directly or even indirectly.The effect of each particular approach on the process of health information seeking and health seeking behaviors requires further study. Interpretation and application of results of this website-evaluation study warrant a certain degree of caution. Although a comprehensive standard electronic evaluation form was designed and approved by the research team, the relatively low inter-rater reliability score for credibility suggests that credibility parameters might fluctuate from one page to another within a single website, or that the interpretation of these parameters is sensitive to the evaluators’ knowledge and beliefs. Second, the large number of websites and the great amount of online information on a seemingly infinite number of health-related subjects make it nearly impossible to generate a sample of websites that could be considered representative. To compensate, the evaluated websites were selected in such a way so as to resemble the array of OC websites that would be retrieved by an average Israeli adolescent health-information seeker. Finally, this evaluation was restricted to content posted by the website developers and excluded user-generated content  that would require a different set of assessment tools .By implementing a systematic approach for the evaluation of online health information, our study identifies gaps between evidence-based information and the information available online regarding OC. Furthermore, the findings highlight, for the first time, the varied quality of Hebrew-language online information available about OC from different category websites, with generally low to medium scores in credibility and accuracy/completeness, and higher scores in usability. The weak correlation observed between the three quality dimensions assessed, particularly for promotional websites, suggests that quality guidelines should be established and promoted in order to improve the quality of OHI in general, and OC online information in particular. The findings also emphasize the need to strengthen the e-health literacy skills among online-information seekers. Adolescents should be provided with the skills needed to assess the quality of the online information available. Such skills would allow the information seeker to more effectively sort and understand the information retrieved, incorporate this information into their decision-making processes and consequently improve their health status. In addition, health care providers should be encouraged to support their patients in the process of selecting accurate and reliable health-related online resources.OC: Oral contraceptives; OHI: Online Health Information.The authors declare that they have no competing interests.YN and CL-Q designed the study. LF, CL-Q, and RS designed the instrument. LF collected the data and analyzed the websites. CL-Q performed the statistical analysis. LF, YN, and RS evaluated the websites. LF, CL-Q, and YN wrote the first drafts of the manuscript. All authors read and approved the final version of the manuscript.Yehuda Neumark, PhD, MPH, is an Associate Professor of Epidemiology at the Braun School of Public Health & Community Medicine of Hebrew University-Hadassah in Jerusalem, Israel, where he teaches courses in epidemiology, research methods, and community-oriented health care, and directs the International Master of Public Health Program. His research focuses primarily on social, economic, and genetic variations in the epidemiology of alcohol and drug use and misuse, and the application of information and communication technologies for health promotion. He is the father of four and grandfather of six.Lior Flum earned his master’s degree in Sociology and Anthropology at the Hebrew University of Jerusalem, Israel. Currently, he is a graduate student at the School of Education and Human Development at the University of Colorado – Denver, where he is completing a master’s degree in Information and Learning Technologies. His areas of interest include: e-Learning, social interactions and the web, e-Literacy, and online communication.Catalina Lopez-Quintero earned her PhD in Public Health at the Braun School of Public Health & Community Medicine in the Hebrew University of Jerusalem, Israel, and is currently a post-doctoral fellow in the Department of Epidemiology and Biostatistics at Michigan State University. Her research focuses on identifying and understanding factors associated with drug use involvement and addiction, with the aim to translate her findings into health policy. Her other research interests include: e-health literacy, mental health, and HIV/AIDS among minority populations, children, and adolescents.Ronny A. Shtarkshall holds a PhD in Physiology; a Diploma in Family Marriage and Sex Therapy (University of Pennsylvania); and is a registered social worker. He is a tenured faculty member at the Braun School of Public Health and Community Medicine of the Hebrew University and Hadassah, Jerusalem, Israel. His research interests include culture and sexuality, sexuality education, adolescents’ sexuality, immigrants’ health, multiple orgasms in women, and perceptions of sexual misconduct and violence.Inter-rater reliability estimates for analysis of accuracy/completeness, credibility, and usability parameters of Hebrew-language websites on oral contraceptives (Cronbach's Alpha if item deleted). (DOC 53 kb)Click here for file


Epidemiological studies suggest an association between obesity and asthma in adults and children. Asthma diagnosis criteria are different among studies. The aim of this study was to test the influence of asthma definition on the asthma-obesity relationship.In a cross-sectional analysis of 1922 men and women, subjects completed a translated questionnaire from the European Community Respiratory Health Survey and underwent spirometry and a bronchial challenge test. Weight, height and waist circumference were measured. Multiple logistic regression analysis was carried out to assess the association of variables related to obesity and asthma. Asthma was defined either by the presence of symptoms with bronchial hyperresponsiveness (BHR) or by a self-report of a physician-made diagnosis. The following variables were separately tested for associations with asthma: socioeconomic characteristics, schooling, physical activity, smoking status, anthropometry and spirometry.2; OR = 1.02 (0.74 - 1.40) for obesity assessed by abnormal waist-to-height ratio; and, OR = 0.96 (0.69 - 1.33) for abnormal waist circumference. On the contrary, a previous diagnosis of asthma was associated with obesity, OR = 1.48 (1.01 - 2.16) for body mass index ≥ 30 kg/m2; OR = 1.48 (1.13 - 1.93) for abnormal waist-to-height ratio; and, OR = 1.32 (1.00 – 1.75) for abnormal waist circumference. Female gender, schooling ≥ 12 years and smoking were associated with BHR-confirmed asthma. Physically inactive subjects were associated with a previous diagnosis of asthma.No association was detected between asthma confirmed by BHR and obesity indicators, odds ratio (OR) = 1.08  for obesity assessed by body mass index ≥ 30 kg/mOur findings indicate that the relationship between asthma and obesity in epidemiological studies depends on the definition adopted. Certain components of asthma, for instance, symptoms may be more prone to the obesity influence than other ones, like bronchial hyperresponsiveness. Overweight and obesity are major causes of morbidity and mortality. The prevalence of asthma has experienced an increase, with rates that are greater today than they were 30 years ago ,2. DiffeSeveral cross-sectional studies have found an increase in the prevalence of asthma among obese patients. These studies included a large number of patients and have provided significant epidemiological data on both disorders. However, in most studies, asthma was diagnosed and classified solely on the basis of a compatible clinical history, acceptance of a previous diagnosis, or based on the use of anti-asthma drugs -11. Few The bronchial challenge test with methacholine to measure bronchial hyperresponsiveness is considered one of the best approaches to identify asthma in clinical practice. In the last decade, the assessment of bronchial hyperresponsiveness as a tool for asthma diagnosis has become common practice in epidemiological studies, for example, European Community Respiratory Health Survey (ECRHS), the International Study on Allergy and Asthma in Childhood (ISAAC) and Study on Occupational Allergy Risks (SOLAR II) . ApproveIn a previous study, we showed that asthma prevalence and asthma risk factors may depend on the asthma definition. Prevalence varied from 3.5% when asthma was defined by asthma attacks in the last 12 months to 19.4% when asthma was defined by wheezing. In that study, maternal asthma and perceived food allergy were related to asthma defined by a score based on 8 questions, but they were not related to the other asthma definitions. Atopy, smoking and rhinitis were risk factors for asthma regardless of the asthma definition . The infWe hypothesized that the relationship between asthma and obesity may be under the influence of the fact that obesity leads to a set of clinical and physiological perturbations that mimics asthma. In this case, the use of questionnaires to define asthma could induce an association between asthma and obesity due to symptoms that are not asthma-dependent. Therefore, the criteria for asthma detection could have impact on the putative association. We aimed to test the influence of asthma definition on the asthma-obesity relationship by evaluating two asthma definitions, one based on methacholine challenge test and the other one based on a previous physician-made diagnosis of asthma.This is a cross-sectional analysis of a Brazilian population sample. We interviewed 2063 men and women aged 23 to 25 years randomly selected from a cohort of 6827 singleton babies born during the years of 1978 and 1979 in the city of Ribeirão Preto, a regional center in the Northeastern region of São Paulo State, Southeastern Brazil. The main economic activities are sugar cane industry, trading, services, and financing. The number of inhabitants in the city of Ribeirão Preto was approximately 550.000 when data were collected between 2002 and 2004.The potential participants in the evaluation were identified on the basis of the charts of the liveborns of the original cohort. For the location of the participants the following sources were used: the system of electronic scheduling of visits for users of the public medical services, lists of users of private health plans, charts of evaluation of schoolchildren of the cohort performed in 1987 to 1989, and charts of evaluation of the military recruits belonging to the original cohort. A total of 5665 individuals were located, with the initial contact being made with those who had a fixed or mobile phone, in view of the high distribution of telephones per inhabitant. In addition, letters containing explanations about the objectives of the study and a telephone number reserved for the project were mailed. Other means of dissemination of the information were used, such as television, radio and newspapers, as well as the distribution of explanatory posters to public health services. Based on the geo-economic characterization of the city which is composed of four geographic regions defined by the income of the head of the family and classified as “poor”, “middle-poor”, “middle-rich” and ”rich”, one of the each three individuals belonging to the same geographic area was contacted. In the case of refusal or of the impossibility to participate  or the inability to locate an individual, contact was made with the next name on the list.In this process, 705 individuals had to be excluded because of refusal (209 cases), imprisonment (31 cases), death after 20 years of age (34 cases), and failure to appear for the interview (431 cases). Thus, 2063 adults effectively participated in the study, corresponding to 31.8% of the original sample. We considered original sample as 6827 singleton babies minus 343 deaths before 20 years of age. Of these 2063 subjects, 1922 underwent the bronchial challenge test. We compared those 2063 subjects with our sample of 1922 subjects regarding gender, body mass index (BMI), waist circumference, waist-to-height ratio, physical activity, smoking, schooling and BHR. We did not find significant differences.The ECRHS  questionWe also asked about physical activity status, smoking status and educational level of the subjects. Physical activity status was defined as active if the subject regularly practiced physical activity, including activity at work and inactive when the reply was negative. Regarding smoking status, the subject was asked if he/she had been smoking at least one month before the interview. Those who responded positively were defined as smokers and those who responded negatively as non-smokers. Finally, socioeconomic level was evaluated on the basis of educational level, determined by asking about the numbers of years of schooling and divided into three groups: 8 years or less, 9 to 11 years or 12 years or more. Gender was obtained from the medical interview chart.2), the subjects were divided into three groups: normal (BMI ≤ 24.9 kg/m2), overweight (BMI between 25.0 and 29.9 kg/m2) and obese (BMI ≥ 30 kg/m2) . The statistical significance level was set at 0.05.Comparisons between genders were performed using xOf the 1922 volunteers who completed all tests, 427 (22.2%) had BHR. The prevalence of asthma confirmed by BHR and symptoms was 10.4% and the prevalence of a previous diagnosis of asthma was 14.8%. The prevalence of obesity ranged from 12.1% considering BMI to 34.0% considering waist-to-height ratio  symptoms associated with a positive methacholine challenge test; and 2) self-report of physician-diagnosed asthma. We found that the relationship between asthma and obesity in epidemiological studies depends on the criteria adopted. An association was detected between physician-made diagnosis of asthma and obesity, but not between BHR-confirmed asthma and obesity. These findings did not change for any of the variables used to evaluate obesity. In addition, female gender, schooling and smoking were associated with asthma defined by BHR.One probable interpretation of this observation is the overdiagnosis of asthma in obese people. Because people who are obese are more likely than nonobese people to report dyspnea  or asthmAaron et al.  conducteOur results could also be interpreted as a consequence of the time interval between past symptoms and study measurements. Natural history of asthma shows variations of asthma severity in a same individual. Data on this subject indicate that a high proportion (up to 50%) of asthmatics experience a clinically defined remission from childhood to adulthood -36. SomeIf the obesity influence on asthma is really dependent on the asthma definition, the evaluation of asthma components separately will reveal different associations with obesity. In fact, respiratory symptoms are clearly affected by obesity in most published studies ,26,40, w1 and FVC  increased in obese women who lost a significant amount of weight and did not improve in those who failed to lose weight. Findings did not demonstrate any significant effect of weight loss on bronchial responsiveness. The authors suggested that improvements in FEV1 and FVC occur due to a reduction in massloading on the respiratory system, rather than improvements in asthma per se [th percentile) was associated with an increased prevalence of wheezing and atopy, but it was not associated with augmented bronchial responsiveness, except among girls [Schachter et al. reported an analysis of cross sectional data in 1971 Australian adults. Despite the fact that severe obesity was associated with a higher prevalence of wheeze, obese subjects did not have any increase in bronchial responsiveness to histamine . Aaron ea per se . A recenng girls . An incrng girls -49. Thenng girls . Severalng girls -57.Airway inflammation is another defining characteristic of asthma . The effThere is little information about the trends of asthma in Latin America, although the prevalence of asthma symptoms has been shown to be high. Obesity has markedly increased in Latin America . A recenBHR and respiratory symptoms, used herein to define asthma, may be found in other diseases than asthma, like chronic obstructive pulmonary disease (COPD). However, since the subjects in our study were young (ranging from 23 to 25 years old) and smoking prevalence was low in this cohort , COPD doThe increasing prevalence of asthma is still a matter of preoccupation worldwide . The neeThis study added evidence to the asthma-obesity relationship because we tested this association with both definitions: BHR-confirmed asthma and physician-diagnosed asthma. We do not confirm a positive association between obesity and asthma defined by BHR with symptoms. However, the association exists when asthma is defined by a previous diagnosis made by a physician. Further studies are necessary to establish the real diagnosis of asthma that is associated with obesity, as well as to rule out that the association is dependent on the respiratory symptoms caused by obesity.1: Forced expiratory volume in the first second; IgE: Immunoglobulin E; ISAAC: the International Study on Allergy and Asthma in Childhood; OR: Odds ratio; PC20: the provocative concentration causing a 20% fall in FEV1; SOLAR II: Study on Occupational Allergy Risks.BHR: Bronchial hyperresponsiveness; BMI: Body mass index; COPD: Chronic obstructive pulmonary disease; ECRHS: European Community Respiratory Health Survey; FVC: Forced vital capacity; FEVThe authors declare no competing interests.AAC: performed data organization, analysis and interpretation of data, and drafted the manuscript. MRG: performed the statistical analysis, the interpretation and organization of data. HB: participated in the conceiving and designing of the study and data collection MAB: participated in the conceiving and designing of the study and data collection. EOV: participated in the conceiving, planning and structuring of the pulmonary function laboratory and skin tests routine (prick test), interpretation of data and drafted the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/12/844/prepub


Adolescence is the period of stress and strain. Researchers have shown that adolescents without strong social supports would have tendency towards smoking and drug abuse.This study aimed to evaluate the relationship between low self-esteem and illegal drug abuse.Participants were 943 grades nine to 12 high school students, from Sarakhs during 2010 - 2011. Adolescents participated in the study, completed two self-report questionnaires. The first questionnaire included questions about individual and family information, smoking and illegal drug abuse history, and the second was the Rosenberg's self-esteem scale.53.8% of participants were male . The mean Rosenberg self-esteem score was 19.8 + 5.2, and the most frequent obtained scores were from 22 to 30. The difference of Rosenberg self-esteem score test between students who did not use any substance and those who had a history of smoking or drug abuse like heroin, pills, alcohols, betel nut (Nas) and other drugs (such as Pan and Hookah) was significant (P < 0.001). But this difference was not significant for marijuana (hashish) and opium. The difference of mean self-esteem scores between adolescents who lived with both or one of the parents, and those who did not live with any of parents, was significant (P = 0.04). There was also a significant association between the number of children in the family and self-esteem score.The current study showed significant association between the Rosenberg self-esteem test results and smoking, and illegal drug abuse like heroin, pills, alcohol, Nas, and other substances. Therefore, increasing self-esteem is essential for preventing the adolescents’ emotional and behavioral disorders. This fact could guide us to the new approaches for smoking and drug-abuse prevention in adolescents. Adolescence is the period of stress and strain. Researchers have shown that adolescents lacking strong social supports,would have tendency towards smoking and drug abuse . Recent The most common description for self-esteem is the Rosenberg definition: a stable sense of personal worth or unworthy towards oneself. Feeling worthy influences all aspects of one’s life including the person’s view towards his or her abilities . Many stIn the last few decades, efforts for reducing illegal drug abuse have drawn their attention from risk factors towards protecting factors . On the This study aimed to evaluate the relationship between low self-esteem and illegal drug abuse.A cross sectional study was performed on high school and technical school students, grades nine to 12, from Sarakhs, Iran (41 schools with 5243 students) during 2010-2011. Sarakhs County is located in North East of Iran, neighboring Turkmenistan and Afghanistan. Ethnical diversity of this county is unique in Iran. This region is religiously  and ethnically  diverse. Calculated study size based on the estimation of proportion in population (α = 0.05 and d = 1.4p) was 325. The number was multiplied by three for cluster sampling (975). Thirty-two students were excluded from the study due to being absent in the day of filling the questionnaire, refusal of responding, and incomplete questionnaires. So the overall response rate was 96.7% with 975 participants and the final sampling number was 943. The study samples were divided into clusters with appropriate proportion to their population. In the next step, four schools were randomly selected from each cluster. The calculated study samples for each cluster were divided between schools appropriate to their population. In each school, students were selected with simple sampling method. They were justified by a team including researchers, consolers, teachers, and education experts. Two self-administrated questionnaires were completed by students. Totally, all data were considered confidential. Data were collected and recorded without names, just by code. The first questionnaire including demographic questions and questions about individual and family information, smoking and illegal drug abuse history , and other substances) personally and in the family was filled. Any use of these substances was sufficient for that individual to be classified as being a drug user. No report was classified as never being a drug user.We assessed self-esteem by the Persian version of the Rosenberg self-esteem questionnaire , 20-22, Ethical approval was obtained from Mashhad University of Medical Sciences (MUMS) Research Ethics Committee. Permission was also received from MUMS for application of the data collection tools. Ethical issues  have been completely observed by the authors. The respondents were anonymous and participated willingly and voluntarily in this study. In addition, all of the responses were treated confidentially.Among all the questionnaires, 943 met the criteria to enter the study (3% missing). 55% were male, and the mean age of the students was 16.4 ± 1.1 years . Demographic and school information of participants are shown in The mean of Rosenberg questionnaire self-esteem score in students who lived with both parents was 19.8 + 5.22. The mean of self-esteem score for students who lived with their single father was 20.43 + 3.87, in those who lived with single mother was 19.97 + 4.9, and in students who lived with other relatives was 15 + 7.32. The differences of self-esteem scores between student groups based on people they lived with, were not significant. The differences of self-esteem scores between students who lived with other relatives and other groups (those who lived with one or both parents) were significant (P = 0.04). We found positive correlation between self-esteem scores with the number of family members, and also with the number of sisters . There was not any significant correlation between the number of brothers and self-esteem score. Some variables such as age, sex, history of grade failure, family situation (who they live with) could be considered as confounding factors in our study, but we did not find any association between them and self-esteem. There were 16 underlying causes of drug usage in abuser students, of which having fun, impact of peer and curiosity were the three most frequent ones. 68.7% of students were aware of drug usage disadvantages by Media (TV and radio), family and books respectively.The prevalence of substance abuse in this study was consistent with some previous national surveys , 20, 23.There is a strong association between the adolescent age and substance abuse . In the Self-esteem is one of the human behavior stablishment factors. A person’s self-view and judgment determines his or her interactions with various issues. A person’s low self-esteem and self-respect, might lead to family and friends isolation as well as aggressive and antisocial behaviors. Self-esteem can be described as a collection of thoughts, feelings, emotions and experiences which are shaped through social life process. Considering thousands of personal experiences and self-assessments, a stable sense of worth or unworthiness gets built in the person . AdolescOur results showed a low prevalence of substance abuse in Iranian adolescents, and also determined some of its associated factors. By considering the high prevalence of addiction in the Iranian adult population , longituIncreasing self-esteem is essential to prevent problems arising from low self-esteem in adolescents . ConsideThis cross-sectional study had some limitations. First, the underlying causes such as psychosocial factors, smoking, alcohol, drugs access and friends and family attitudes were not fully investigated. Second, the limited number of schools, as well as ethical, social and legal limitations for assessment of sexual and other risk behaviors restricted the study. Fewer reported drug usage in such studies is common, because it is a social evil and may be a threat for the participants. In addition, the current study did not include students fired from school, in which the prevalence of substance abuse has been shown more than other students by numerous studies , 48. The


Severe illness can disrupt family life, cause family dysfunction, strain resources, and cause caregiver burden. The family's ability to cope with crises depends on their resources. This study sought to assess families of children with cancer in terms of family function-dysfunction, family caregiver strain and the adequacy of family resources using a new family resources assessment instrument.This is a cross-sectional study involving 90 Filipino family caregivers of children undergoing cancer treatment. This used a self-administered questionnaire composed of a new 12-item family resources questionnaire (SCREEM-RES) based on the SCREEM method of analysis, Family APGAR to assess family function-dysfunction; and Modified Caregiver Strain Index to assess strain in caring for the patient.More than half of families were either moderately or severely dysfunctional. Close to half of caregivers were either predisposed to strain or experienced severe strain, majority disclosed that their families have inadequate economic resources; many also report inaccessibility to medical help in the community and insufficient educational resources to understand and care for their patients. Resources most often reported as adequate were: family's faith and religion; help from within the family and from health providers. SCREEM-RES showed to be reliable with Cronbach's alpha of 0.80. There is good inter-item correlation between items in each domain: 0.24-0.70. Internal consistency reliability for each domain was also good: 0.40-0.92. Using 2-point scoring system, Cronbach's alpha were slightly lower: full scale (0.70) and for each domain 0.26-.82. Results showed evidence of association between family resources and family function based on the family APGAR but none between family resources and caregiver strain and between family function and caregiver strain.Many Filipino families of children with cancer have inadequate resources, especially economic; and are moderately or severely dysfunctional. Many caregivers are predisposed to caregiver strain or are already experiencing severe strain. To provide appropriate care for these families, physicians should regularly assess family function, resources and strain experienced by caregivers. The SCREEM-RES questionnaire used in this study is a helpful and reliable instrument to assess adequacy of family resources. Approximately 144 per 1 million Filipino children and adolescents are diagnosed with cancer each year in Philippines . This tool was formulated by the authors to create a valid and reliable measure of family resources that would be useful in clinical practice and research. It was based on the: 1) SCREEM method of analysis by Smilkstein ,13 whichDescriptive statistics was done using means for continuous variables; frequencies using categorical variables. For continuous variables, tests of differences between means and independent groups were done to determine difference. Reliability analysis was done by measuring inter-item correlation, item-total correlation, and Cronbach's alpha.For preliminary test for association, the study used simple dichotomous categories for the SCREEM Questionnaire. Each item was scored on a 0 - 3 basis using the following key: Strongly Disagree = 0, Disagree = 1, Agree = 2, and Strongly Agree = 3. The scores for all of the items, domains and entire SCREEM-RES were summed resulting to scores of 0-3 for each item, 0-6 for each domain and 0-36 for the entire SCREEM-RES. The scores were further grouped to determine inadequacy or adequacy of resources. Inadequate resources for each item have scores of 0 to 1, for each domain 0 to 3 and for the total SCREEM-RES 0-18. On the other hand, adequate resources are signified by the following scores, 2 to 3 for each item, 4 to 6 for each domain and 19 to 36 for the whole SCREEM-RES.Chi-square test was used to determine association between family resources, family function and caregiver strain. Exact tests were used when indicated, such as when expected frequencies were lower than 5. Cramer's V was used to determine the strength of association; and it increases from 0 to 1 as the strength of association increases.An exploratory factor analysis was also done to examine the structure of relationships between the items of the family resources questionnaire. All statistical analysis in the study was done using SPSS. For the study, level of significance was set at 0.05.A total of 90 Filipino family caregivers of Filipino children with cancer took part in the study. Table Table Based on the results of the Family APGAR, illustrated in Figure It is shown in Figure Table Cronbach's alpha (α) for the entire scale was 0.80, using the original scores from 0 to 3 for each item, indicating good internal consistency reliability. There is a wide range of values in the inter-item correlation matrix (-0.13 to 0.69) for all the items which is consistent with the highly multidimensional nature of the scale. However, there is good inter-item correlation between items in each domain: social (0.27), cultural (0.51), religious (0.35), economic (0.70), educational (0.67), and medical (0.24). Internal consistency reliability, α, for each domain were: social (0.61), cultural (0.77), religious (0.60), economic (0.92), educational (0.78), and medical (0.40).In preparation for the planned tests for independence and association, further analysis was done using a simplified dichotomous scoring system. Item scores were grouped into two . Using this scoring system, item analysis and reliability results were lower compared to analysis using the original (0 to 3) scores. Internal consistency remained good (α = 0.70). Internal consistency reliability, α. for each domain were: social (0.38), cultural (0.67), religious (0.39), economic (0.82), educational (0.80), and medical (0.26). Inter-tem correlations for each domain and for the entire instrument remained unchanged.Tests for independence and association were done using dichotomous categories for family resources and standard categories recommended for the Family APGAR (3 categories) and the MCSI (3 categories). Significant associations were found between family function based on the Family APGAR and the adequacy of the following domains of family resources: social (chi square (2) = 18.440, exact p < 0.001; p = 0.001, Fisher's Exact Test, FET), cultural (chi square (2) = 13.127, exact p = 0.002; p = 0.003, FET), and medical (chi square (2) = 8.291, exact p = 0.015; p = 0.017, FET). Computed values for Cramer's V showed moderate to strong associations of these domains with family function: social (0.453), cultural (0.382), and medical (0.304). Results also showed a significant association between the over-all adequacy of family resources based on the entire SCREEM-RES and family function based on the Family APGAR (chi square (2) = 16.157, exact p = 0.001; p = .002, FET). Cramer's V was 0.426 which indicates a strong association. For the analysis, all contingency tables had at least 80% of expected frequencies that were 5 or larger. There was no significant association found between family resources and caregiver strain based on MCSI, and between family function and caregiver strain.The study did not find evidence for significant associations between caregiver strain and other demographic variables in the sample studied including: caregiver's age group , caregiver's educational attainment , caregiver's gender , relationship to the patient , the patient's age group  and patient's gender . There was also no significant association found between the family caregiver's educational attainment and the reported adequacy of educational resources based on the subscale for educational resources.Exploratory factor analysis of the 12 item family resources instrument was done using the simplified 2-point scoring system for each item. The sample size of this study was inadequate (Kaiser-Meyer-Olkin Measure of Sampling Adequacy at 0.640) for an actual factor analysis, but an exploratory factor analysis was done to examine the structure of relationships between the items of the family resources questionnaire. Varimax with Kaiser Normalization was used. Initial analysis showed that the scale is composed of 4 domains which accounted for 63.3% of variance. All items under the original social, cultural and religious domains formed the first factor. The remaining items in the economic, educational and medical domains formed the other three factors which directly corresponded to the original domains.According to Smilkstein's cycle of family function , familieBased on the results of the Family APGAR and Modified Caregiver Strain Index (MCSI) many Filipino families and family caregivers experience significant psychosocial distress following the diagnosis of childhood cancer. These families need appropriate psychosocial care and support to help them cope with the illness.The study used a newly developed instrument, SCREEM-RES to assess family resources which was based on Smilkstein's SCREEM method of analysis of family resources ,13. The The Philippine government has low budget for health; a local television news program aired last August 12, 2011 that the administration only allocates Php 300.00 or USD 7.14 of its budget per annum for every Filipino's medical services. Most of the country's hospitals are privately-owned; moreover, its social insurance arm, the Philippine Health Insurance Corporation  only gives health benefits to regular paying members. Thus, the nation's healthcare system could hardly help its sick people and their caregivers and this is much felt by cancer victims who shoulder much if not all of their treatments.Many Filipino families, who are living in the Philippines, have limited economic or financial resources. Based on data from the National Statistics Office 2000), 70% of Filipino families can only afford to spend less than Php 2,200 (approximately 45 USD) for healthcare-related expenses every year .The majority of the family caregivers in the study were young mothers who are more prone to experience significant stress and caregiver strain -29. HoweThis study focused on family resources, family function and family caregiver strain; and the relationships between these factors. A better understanding of these factors and their relationships is important in the development of ways to determine the family's risk of going into severe crisis. It is also important in the development of appropriate and effective family interventions to help families who are at risk and families who are already in severe crisis. Moreover, this study provided initial evidences that the family resources instrument used in this study is a helpful, reliable and valid tool in the assessment of the adequacy of family resources, especially in times of severe stress and crisis.The relative cost and time that has required the researchers to carry out this investigation was small using convenience sampling; it also enabled them to gather useful information that would have not been possible using probability sampling techniques. However, the subjects they used in this study may not have wholly represented the population of pediatric cancer caregivers; hence, it limited the ability of this paper to make generalizations about the entire population. It is therefore recommended that a randomized population be generated in a follow-up study so as to avoid under or over representation of this particular group of caregivers.The cross-sectional study design used in this study found significant associations between family resources and family function, but the study design also limited the ability to establish causality. Future longitudinal studies may better describe the roles of family resources, family functioning and caregiver strain during the illness trajectory. Also, this survey is based on self-report, and may be prone to social desirability bias. Social desirability bias is a tendency of the respondents to reply in a manner that will be viewed favorably by others which leads to over reporting of good caregiver and family characteristics and under reporting of bad characteristics. Though most of the family caregivers were mothers, other relatives were also included in the study. Reliance on different family members may be a limitation considering that they may have different interactions with the child and possibly different emotional reactions to the child's illness.The study was also limited by the availability of appropriate Filipino data collection tools and instruments. The lack of readily available Filipino psychosocial tools to assess the family was a significant limitation of the study. Future studies are warranted once more Filipino family assessment instruments become available. The family resources questionnaire used in this research, like the original SCREEM Method of Analysis by Smilkstein from which it is based, is only meant to do a general assessment of family resources. It is planned to be a generic instrument that can be used in different populations and settings. Assessment tools which are more caregiver focused, or more disease specific are also needed. For example, a more caregiver-specific tool can be developed by including variables that are more directly related to caregiver strain such as personal or internal resources, severity of patient's illness, and the patient's caregiving needs. Future studies should assess the relations between these variables to family resources and family function-dysfunction in order to comprehensively evaluate all possible family resources that could help families cope with crisis. A more intensive evaluation of the SCREEM-RES was done, and will be presented in a succeeding study .A follow up study using a bigger and more heterogeneous population is also recommended. These studies can further evaluate the reliability and validity of the SCREEM-RES. Furthermore, studies are needed to better determine cut off values for adequacy of family resources. Results of this study described the psychosocial needs of families and caregivers. These results support the use of family interventions to improve family resources, support family function, and ease caregiver strain.Many Filipino families of children with cancer have inadequate family resources, especially economic resources, to deal with medical crises; and many families are moderately or severely dysfunctional.Many adult family caregivers are predisposed to caregiver strain or are already experiencing severe strain. Majority of Filipino family caregivers of children with cancer disclosed that they have inadequate economic resources. Many families also report inaccessibility to medical help in the community and insufficient education to understand and care for their patients. Most families acknowledged that their family's faith and religion is helpful; they also felt that help from within the family and health providers were adequate. In order to be able to provide appropriate care for families of patients with severe illnesses such as childhood cancer, physicians should regularly assess family function, family resources and the strain experienced by family caregivers. The SCREEM-RES questionnaire, which was used in this study, is a helpful and reliable instrument to assess the adequacy of family resources.Permission on the use of family resources questionnaire utilized in this study must be obtained from Manuel F. Medina, Jr. M.D. and the Section of Supportive Palliative and Hospice Medicine, Department of Family and Community Medicine, University of the Philippines - Philippine General Hospital, Manila. The content and format of this family resources questionnaire must not be modified or altered without the permission of the tool developer.APGAR: is an acronym for Adaptability, Partnership, Growth, Affection, Resolve while; MCSI: stands for Modified Caregiver Strain Index; SCREEM-RES: stands for Social, Cultural, Religious, Economic, Educational, Medical Resources; SPHM: is an abbreviation for Supportive Palliative and Hospice Medicine.The authors declare that they have no competing interests.This document is based on a previous report for a research entitled "Testing the association of family resources with caregiver strain and family function among pediatric cancer patients using a novel SCREEM questionnaire" which was presented at the Annual Resident's Research Forum of the Department of Family and Community Medicine, University of the Philippines -Philippine General Hospital, October, 2010.AC with the supervision of MM, was responsible for the overall preparation of the original research manuscript, including the analysis and write-up of the findings and discussion. The family resources questionnaire was developed by MM who also provided critical review of the original manuscript. The original manuscript was further edited, data analysis was checked and additional analysis was done by MM, resulting in the current manuscript. Both AC and MM read and approved the final manuscript.MM is a family medicine consultant at University of the Philippines-Philippine General Hospital and is the current head of the Section of Supportive Hospice and Palliative Medicine which provides palliative care to both adult and pediatric cancer patients in this institution. He has written various manuscripts on palliative care and has been active in teaching his residents and fellows in addressing psychosocial issues of patients.AC is a newly certified family and community medicine specialist trained at the University of the Philippines-Philippine General Hospital. At the time of the conceptualization of her research as a requirement for graduation in residency training, she was inspired by the works of Dr. MM for children with cancer as she was rotating at the section of Supportive Palliative and Hospice Medicine where the latter is head thus both collaborated for the fulfillment of this study.


Various pharmacokinetic parameters including AUCt0–, AUC0–∞, Cmax, Tmax, T1/2, and elimination rate constant (Kel) were determined from the plasma concentration of both formulations of test (dexibuprofen 300 mg) and reference (dexibuprofen 300 mg tablets). The merits of PK-PD in the development of dosage forms and how PK-PD model development necessitates the development of new drugs and bio analytical method development and validation are discussed. The objectives of the present study, namely, to develop and validate the methods to estimate the selected drugs in the biological fluids by HPLC, the development of in vitro dissolution methods, and PK-PD model development have been described.Pharmacokinetic-pharmacodynamic (PK-PD) modeling has emerged as a major tool in clinical pharmacology to optimize drug use by designing rational dosage forms and dosage regimes. Quantitative representation of the dose-concentration-response relationship should provide information for the prediction of the level of response to a certain level of drug dose. This paper describes the experimental details of the preformulation study, tablet manufacture, optimization, and bioanalytical methods for the estimation of dexibuprofen in human plasma. The hydrophilic matrix was prepared with xanthen gum with additives Avicel PH 102. The effect of the concentration of the polymer and different filler, on the  Dexibuprofen, S(+)-ibuprofen, is a pharmacologically active form and is more potent than ibuprofen, which has equal quantities of R(−)- and S(+)-enantiomers . IbuprofMathematical models can be considered as the simplifications of a phenomenon described in terms of an algebraic or differential equation. In the case of PK-PD modeling, it is expected to not only describe, but also predict distinct situations, such as scaling between preclinical to clinical trials, multiple dosing schemes, or different routes of administration , 13. To Because of the multiple factors intervening in a PK-PD study, it then appears adequate to divide the modeling project into the following two basic blocks such as concerning the clinical or experimental design by itself and the data analysis. Diverse models have been suggested to describe the PK-PD relationship depending upon the nature of drug administration scheme  and the time dependency of PD parameters. Thus, when the system is kinetically at steady state, the concentrations of the active moiety at the active site are constant (after long-term infusions or multiple doses); relatively simple models are needed to characterize the PK-PD relationship. Otherwise, after single doses (nonsteady-state condition) and when time variant PD parameters are present, more complex models are needed to account for phenomena involved in the PK-PD relationship. Approaches such as disequilibrium between biophase and plasma compartment , the appThe development and validation of a PK/PD is based on the ability of the fraction of the drug absorbed versus the fraction of the drug-dissolved relationship of various formulations. For the estimation of the drugs present in the biological fluids, HPLC method –28 is coAcetonitrile, methanol, orthophosphoric acid, sodium acetate, perchloric acid, and triethylamine were supplied by Qualigens Fine Chemicals and S.D. Fine Chemicals. Water (HPLC grade) was obtained from Milli-Q system. All the reagents and chemicals used were of HPLC or analytical grade.Working standards of dexibuprofen was purchased from Noven Life Sciences  HPMC ; xanthen and starch 1500 were gift samples from Colorcon Asia Pvt Ltd . Polyvinyl pyrrolidine (PVP-K-30) was a gift sample from Anshul Agencies . Aerosil was purchased from Degussa India Pvt Ltd .in vitro dissolution methods, in vitro data analysis, in vivo data analysis, statistical analysis of pharmacokinetic data, and development of pharmacokinetic-pharmacodynamic model.This chapter describes the experimental details of the preformulation study, tablet manufacture, bio availability study design and data handling, optimization and validation of the bio analytical methods for the estimation of dexibuprofen in human plasma samples, preparation of standard and sample solutions, development of in vitro dissolution method, and the compatibility between the drug and the selected polymer were determined.Preformulation in the broadest sense encompasses all the activities and studies that are required to convert an active pharmacological substance into a suitable dosage form. It can be defined as an investigation of the physical and chemical properties of a drug substance alone and also when combined with the excipients. In the present study, therefore, the evaluation of granulations, development of in vitro drug release.Dexibuprofen SR tablets were prepared by the wet granulation method. All the composition, with the exception of magnesium stearate and aerosol, were thoroughly mixed in a tumbling mixer for 5 min and wetted in a mortar with isopropyl alcohol. The wet mass was sieved (16 mesh) and granules were dried at 40°C for 16 h. The dried granules were sieved (22 mesh) and these granules were lubricated with a mixture of magnesium stearate and aerosil (2 : 1). The dexibuprofen tablets were prepared using an electrically operated punching machine. Compression was performed after granulation process with a single punch press applying a compression force of a 9 KN (preliminary work) or 12 KN , equipped with a 12 mm flat-faced punch. For the preliminary work, batches of 100 tablets were prepared. Each batch of experimental design consisted of 100 tablets (drug content in the tablet was 300 mg). Three batches were prepared for each formulation and the compositions of different batches of dexibuprofen SR tablets are given in Cmax, Tmax, t1/2, kel, AUCt0–, and AUC0–∞ were estimated.Bioavailability studies of the optimized formulations were carried out in crossover design in healthy human volunteers between the developed formulations and the conventional dosage form. The protocol of the study was submitted to the Institutional Human Ethical Committee and the approval for conducting the same was obtained and a prior consent of the volunteers participated in the study was taken. Randomized, two-treatment, two-period, two-sequence, single-dose, crossover bioavailability studies were carried out in healthy human volunteers between the developed sustained release (SR) formulation and the marketed conventional immediate release (IR) formulation to prove the safety and efficacy of the developed SR formulation. A reproducible analytical technique was developed for the estimation of the drugs in the plasma samples. Various pharmacokinetic parameters such as A visual analogue scale (VAS) is a measurement instrument that tries to measure a characteristic or attitude that is believed to range across a continuum of values and cannot easily be directly measured. For example, the amount of pain that a patient feels ranges across a continuum from none to an extreme amount of pain. From the patient's perspective, this spectrum appears continuous ±; their pain does not take discrete jumps, as a categorization of none, mild, moderate, and severe would suggest. It was to capture this idea of an underlying continuum that the VAS was devised. Operationally a VAS is usually a horizontal line, 100 mm in length, anchored by word descriptors at each end see . The patients mark on the line the point that they feel it represents their perception of their current state. The VAS score is determined by measuring in millimetres from the left hand end of the line to the point that the patient marks. There are many other ways in which VAS has been presented, including vertical lines and lines with extra descriptors. Wewers and Lowe  provide in vitro dissolution method, determination of pharmacokinetic parameters, statistical evaluation, in vivo and in vitro data analysis, and pharmacodynamic model.This section describes the experimental results obtained in the present investigation in the form of tables and figures along with a detailed analysis on the results of preformulation study, tablet manufacture, bioavailability study design, data handling, optimization and validation of the bio analytical methods for theestimationofdexibuprofen in human plasma samples, amount of the selected drugs present in plasma samples, The physical properties of different batches of developed tablets are given in A single-dose, randomized, complete, two-treatment crossover study was conducted in healthy human subjects for the selected drug formulations. Six volunteers aged between 20 and 30 years were selected. Seven days prior to the commencement of the study, volunteers were subjected to preliminary screening and standard clinical and biochemical investigations.After overnight fasting, the volunteers were given code numbers and allocated to the treatment in accordance with the randomized code. The order of treatment administration was randomized in two sequences (AB and BA) in blocks of two. In each dosing session, volunteers received reference product A (immediate release formulations) and Test B (sustained release formulations). A wash-out period of seven days was allowed between dose administrations. Blood samples (4 mL) were collected at 0 (before drug administration), 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 18.0, and 24.0 h after dosing. The samples were centrifuged and plasma was separated. There were no serious adverse effects observed during the entire study .Cmax), time to peak concentration (tmax), area under the plasma concentration-time curve (AUCt0– and AUC0–∞), elimination rate constant (kel), and elimination half-life (t1/2) were calculated separately and the blood level data of selected formulations were compared.Pharmacokinetic parameters such as peak plasma concentration  using SPSS version 16.0. The results indicated by the pain scale  of the dBased on these observations, it is concluded that the formulated matrix tablets containing dexibuprofen are capable of exhibiting sustained release properties, stable and feasible for industrial scale production. Thus they are capable of reducing the dose intake, minimize the blood level oscillations, dose-related adverse effects and cost, and ultimately improve the patient compliance in the therapeutic management of pain and hypertension. It is also concluded that the present PK/PD studies have demonstrated that pain and blood pressure management were found to be effective in developed SR formulations of dexibuprofen as compared with marketed immediate release formulations. Further studies involving their suitability for long-time application, shelf life determination, bioavailability, and clinical investigations in large populations may, however, be necessary to further establish its potential and therapeutic efficacy.


Emphysematous cystitis (EC) is a comparatively rare urinary tract infection characterized by air within the bladder wall and lumen and is usually associated with immunosuppression or poorly controlled diabetes mellitus.We report a case of EC in a 70-year-old man who recently underwent transrectal ultrasound needle-guided prostate biopsy, after which he underwent pylorogastrectomy. He did not have any history of diabetes mellitus or any immunosuppressive disease. The patient developed severe sepsis, requiring intravenous antibiotics and urinary catheterization. Despite therapy, the patient developed disseminated intravascular coagulopathy and acute respiratory distress syndrome. Therefore, he was admitted to the intensive care unit, antibiotic coverage was broadened, and danaparoid sodium and sivelestat sodium hydrate was administered. After 20 days, the patient’s condition improved, and on the 28th day, the patient was discharged to home in a good condition without any sequelae.Prompt diagnosis and treatment are warranted to prevent potential morbidity of and mortality in cases of EC. Emphysematous cystitis (EC) is the presence of intramural gas along with or without luminal gas within the bladder caused by primary infection of the lower urinary tract in a gas-producing organism. The disease is most common among middle-aged diabetic women and is relatively rare in patients who do not have immunosuppressive disease.A 70-year-old man, who did not have any history of diabetes mellitus, long-term steroid use, abnormalities in the immune system, or long-term urinary catheter use and a normal digital rectal examination result, had elevated serum prostatic specific antigen (PSA) level of 13.3 ng/mL. Because of the elevated serum PSA level and stomach cancer, the patient underwent a transrectal ultrasound needle-guided prostate biopsy and a pylorogastrectomy on the same day. Before the procedures, the patient received a rectal enema and an oral fluoroquinolone antibiotic.3, a hemoglobin level of 9.7 g/dL, a platelet count of 17.8 × 104/mm3, and a C-reactive protein level of 14.8 mg/dL. The urinalysis result demonstrated more than 50 white blood cells/h.p.f. Urine and blood culture specimens were obtained. On a bladder scan, a post-void residual urine volume of 350 mL was noted. Acute prostatitis was diagnosed, and intravenous meropenem therapy was initiated. Despite the administration of the antibiotic, the patient’s body temperature was still 104°F. Subsequently, a plain radiograph of the abdomen and a computed tomography (CT) image of the abdomen and pelvis (with and without intravenous contrast) were obtained. The plain radiograph of the abdomen revealed a nonspecific gas pattern and a small amount of air in the true pelvis in the shape of the bladder  associated with gross hematuria. The patient was noted to have a white blood cell count of 10500 cells/mmThe diagnosis of EC was confirmed on the CT image, which revealed the presence of extensive gas within the wall of the urinary bladder Figure .Escherichia coli. A urinary catheter was then inserted for draining the bladder. Despite these maneuvers, the patient developed disseminated intravascular coagulopathy (DIC) and acute respiratory distress syndrome, requiring transfer and monitoring in the intensive care unit. The patient’s antibiotic treatment was changed from ciprofloxacin to vancomycin. In addition to the standard supportive procedures, patient therapeutic regimen of danaparoid sodium and sivelestat sodium hydrate was initiated. After 20 days of conservative management, the patient’s condition improved, and on hospital day 28, the patient was discharged to home in a stable condition. After 1 year, the patient did not report any sequelae from the EC.The blood and urine cultures were positive for pan-sensitive EC is a relatively uncommon condition. Of the cases of EC, 60% are associated with diabetes mellitus,2. KelesIn the present case, EC developed secondarily after major surgery and prostate biopsy. Kimura et al. reportedPatients with EC might have varied clinical presentations, ranging from incidental diagnosis on abdominal imaging to severe sepsis. SymptomE. coli, followed by Klebsiella pneumoniae, accounting for approximately 18–21% of the cases[Proteus, Staphylococcus, and Clostridium. It is thought that these organisms can ferment glucose present in urine, producing acid and CO2. The transportation of accumulated CO2 away from the tissue is disrupted by local inflammation or obstructive uropathy. The accumulation of gas further increases the local pressure and may lead to infarction of the adjacent tissues, augmenting the barrier to gas transportation and thus creating a vicious cycle[The mechanism of aerosis in EC is still unknown. The bacterium responsible for approximately 58–60% of the reported EC cases is he cases. The othTreatment of EC consists of broad-spectrum antibiotics and placement of a urinary catheter to drain the bladder. In our case, we hesitated to insert the urethral catheter because acute prostatitis is believed to lead to EC and insertion of a urethral catheter was generally not preferred for acute prostatitis. Furthermore, we were also uncertain whether a cystostomy should be performed, as it might not be suitable in cases with an infectious bladder. With ingravescent course, the patient needed to undergo urine drainage because of residual urine. We, then, decided to insert a urethral catheter because he rejected cystostomy. If a patient has diabetes mellitus, then immediate blood glucose control should be warranted. In severe cases, septicemia may lead to DIC, which occurred in our patient. The death rate from EC is reported to be approximately 7–10%, illustrating the need for rapid diagnosis and early treatment,9.We report a case of EC occurring after a transrectal needle-guided biopsy of the prostate. The patient did not have any history of diabetes mellitus and urinary tract infection. However, in addition to the transrectal biopsy, stress by pylorogastrectomy was thought to cause the adverse event. Successful management of EC depends on its early diagnosis, with correction of the underlying causes and administration of the appropriate antibiotics. Early detection and prompt treatment are encouraged.Written informed consent for publication of this case report and any accompanying images was obtained from the parents. A copy of the written consent is available for review by the editor-in-chief of this Journal.DIC: Disseminated intravascular coagulopathy; EC: Emphysematous cystitis; CT: Computed tomography; PSA: Prostatic specific antigen.The authors declare that they have no financial or non-financial competing interests.TH and KN drafted the manuscript. TH, KN, AT, KS and TG were the attending physicians throughout the disease course. MT is the Chairman and the Professor of Department of Urology. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2334/12/322/prepub


To evaluate whether teicoplanin could be an alternative to vancomycin for treatment of MRSA infection in Chinese population using a meta-analysis in randomized controlled trials.The following databases were searched: Chinese Biomedical Literature database (CBM), Chinese Journal Full-text database (CNKI), Wanfang database, Medline database, Ovid database and Cochrane Library. Articles published from 2002 to 2013 that studied teicoplanin in comparison to vancomycin in the treatment of MRSA infected patients were collected. Overall effects, publishing bias analysis and sensitivity analysis on clinical cure rate, microbiologic eradication rate and adverse events rate were performed by using Review Manager 5.2 and Stata 11.0 softwares.Twelve articles met entry criteria. There was no statistically significant difference between the two groups regarding the clinical cure rate , microbiological cure rate  and adverse event rate .The meta-analysis results indicate that the two therapies are similar in both efficacy and safety, thus teicoplanin can act as an effective alternative to vancomycin for treating patients infected by MRSA. Staphylococcus aureus (MRSA) has spread all over the world. It has caused serious health consequences since it was first identified in 1961 Staphylococcus aureus(S.aureus), which occupies the largest proportion of the overall gram-positive bacteria Methicillin-resistant S. aureus (VISA), first described in a Japanese child who was clinically unresponsive to vancomycin S. aureus (VRSA), first reported in an American patient who was naturally resistant to vancomycin Vancomycin, one of the most common glycopeptides, has been used as a golden standard for the treatment of patients with MRSA infection, especially for those with life-threatening disease The meta-analysis followed the PRISMA guidelines To be included in this Meta-analysis, studies must meet the following criteria: (a) RCTs; (b) the subjects were proven MRSA-infected Chinese patients; (c) the two parallel groups were treated with vancomycin and teicoplanin, respectively; (d) the outcome indicators included at least one of the followings: clinical cure rate, microbiological eradication rate and adverse event rate. Studies were excluded when they were: (a) missing baseline information, or a lack of medical information or statistical differences of baseline information were detected; (b) duplicate of previous publications; (c) reviews, letters, editorial articles or meta-analyses; (d) changing antibiotics during treatments.Data from the published studies were extracted independently by two reviewers. For each study, the following characteristics were collected: the first author, year of publication, location, number of subjects, age, gender ratio, and outcome of indicators were also included. In case of conflicting evaluations, the disagreements were resolved by discussion among the whole group members.Two reviewers independently assessed the quality of included studies according to the Jadad standards 2 test (ranges from 0 to 100%). A significant Chi-square based Q test with P<0.1 or I2>50% Statistical heterogeneities, included clinical cure rate, microbiological rate and adverse events rate, were estimated using Chi-square based Q statistic with a P-value <0.1 as statistically significant heterogeneity The process of selecting studies for the meta-analysis is shown in 2 = 0%), so the fixed effect model was applied. The meta-analysis results showed that there was no difference of clinical cure rate between teicoplanin and vancomycin treatment groups .Eight studies containing the comparison of clinical cure rate . The het2 = 0%), so the fixed effect model was used. The meta-analysis results indicated that the clinical cure rate of teicoplanin was not apparently different from that of vancomycin .Nine studies involved the comparison of microbiological eradication rate . The het2 = 0%), hence the fixed effect model was employed. The meta-analysis results showed that the overall adverse event rate of teicoplanin is not much distinct from that of vancomycin . Specifically, several adverse effects were reported in teicoplanin or vancomycin group: liver dysfuncton, leucopenia, nephrotoxicity, red man syndrome, neurologic abnormality, rash and diarrhea. In the vancomycin group, there were three cases of liver dysfunction, one case of leucopenia, five cases of nephrotoxicity, two cases of red man syndrome and one case of rash. However, in the teicoplanin group, there were two cases of liver dysfunction, one case of leucopenia, four cases of nephrotoxity, one case of diarrhea and one case with neurologic abnormality.Eight studies have performed the comparison of overall clinical cure rate . The hetp values of Begger’s test and Egger’s test were above 0.1  to 0.973 (0.752∼1.258) for clinical cure rate, 0.975 (0.895∼1.062) to 0.996 (0.917∼1.082) for microbiological eradication rate, and 0.654(0.257∼1.664) to 1.018(0.456∼2.276) for overall adverse events rate, respectively, suggesting that the results were consistent .Teicoplanin and vancomycin, both belong to glycopeptides class, share similar mechanism of antimicrobial activity by binding to the D-alanyl-D-alanine residue of murein monomer and then blocking the biosynthesis of bacterial cell wall. While an experiment of a VSSA strain conducted by Hanaki et al. demonstrated that the over-expression of PBP2’ (penicillin-binding protein 2′) does lead to slightly rise of vancomycin MIC (from 1 to 2 mg/L), whereas that of teicoplanin increased significantly (from 2 to 8 mg/L) The results of the meta-analysis indicate that the efficacy of teicoplanin is as effective as that of vancomycin for the treatment of Chinese patients with MRSA infections. The conclusion is based on both the comparison of clinical cure rate as well as microbiological eradication rate. Similarly, teicoplanin has a similar rate of overall adverse events as with vancomycin. We did not compare each single type of adverse event due to the limited sample size. We calculated the Q statistic in order to assess the heterogeneity, and the results are satisfactory for the little implication of heterogeneity. Therefore, any stratified assessments on the source of heterogeneity couldn’t be conducted. Furthermore, the reliability and stability of the studies were tested by the sensitivity analysis, and the results have proved to be stable and reliable in that the effect estimates did not change significantly after in turn removing each single study. To the best of our knowledge, our meta-analysis is the first study to comprehensively evaluate the efficacy and safety of teicoplanin and vancomycin used for treatment of Chinese MRSA patients. A meta- analysis had compared the mortality and adverse events of teicoplanin and vancomycin among MRSA patients, and the results also showed that teicoplanin was as effective as vancomycin with less adverse events The meta-analysis has some merits. Firstly, all of the included studies are RCTs that have provided comparable and adequate baseline information between the two groups. Secondly, all the subjects are Chinese patients, thus ruling out the impact of ethnicity, which was thought to be a major potential cofounder. Thirdly, the studies are published between 2002 and 2013, which are representative of the safety and efficacy of vancomycin vs teicoplanin in these years. Fourthly, the heterogeneity between the studies is quite small and there was no strong evidence of publication bias and unstable results, thus demonstrating that the outcomes were both reliable and stable. Finally, the included studies were dispersed in ten cities of eight provinces, four cities lie in North China and six cities lie in South China, which can comprehensively represent the population distribution of the whole country.Nevertheless, our meta-analysis also bears some limitations and drawbacks. Firstly, the number of the participate subjects and articles are small. This may decrease the power of our analysis. Secondly, the qualities of the included studies are relatively poor because the Jadad scores of them are between 2 and 3. Thirdly, we cannot take account of the influence of other factors such as the original health situations of the patients, the quality care of the doctors and hospitals for the authors of the included articles failed to offer such information. Finally, we are ineligible to collect the data from unpublished articles, therefore we cannot speculate whether there are similar results or not.In conclusion, our study demonstrates that teicoplanin and vancomycin showed similar efficacy and safety in the treatments of MRSA in Chinese patients. Teicoplanin could be used as an alternative antibiotic for vancomycin when vancomycin is not effective. More high-quality RCTs are needed to evaluate the two antibiotics in a more accurate way.Checklist S1PRISMA checklist of this meta-analysis.(DOC)Click here for additional data file.


There is an ongoing debate concerning the risk benefit ratio of psychopharmacologic compounds. With respect to the benefit, recent reports and meta-analyses note only small effect sizes with comparably high placebo response rates in the psychiatric field. These reports together with others lead to a wider, general critique on psychotropic drugs in the scientific community and in the lay press. In a recently published article, Leucht and his colleagues compare the efficacy of psychotropic drugs with the efficacy of common general medicine drugs in different indications according to results from reviewed meta-analyses. The authors conclude that, overall, the psychiatric drugs were generally not less effective than most other medical drugs. This article will highlight some of the results of this systematic review and discuss the limitations and the impact of this important approach on the above mentioned debate. Psychiatry, psychiatric patients and psychiatric medication are still highly stigmatized. Psychiatry itself often promotes stigmatisation via close collaborations with the pharmaceutical industry and the disregard of psychotherapy, often overemphasizing the impact of psychopharmacology. A different line of criticism arises from recent meta-analyses questioning the efficacy of psychopharmacologic compounds. Examples are meta-analyses that have questioned the effectiveness  and safeThe British Journal of Psychiatry recently published a systematic review, planned and conducted by a psychiatrist who is an experienced member of the Cochrane collaboration and familiar with the pitfalls of meta-analyses - this article is a milestone in destigmatizing psychiatry and its pharmacological treatments .et al., the authors compared the efficacy of psychiatric medications with general medicine medication by comparing effect sizes of meta-analyses [In the review by Stefan Leucht analyses . For thaanalyses .For example, in patients with hepatitis C infection, the number of patients with no detectable virus at treatment end was increased from 1% to 38%, which corresponds to a standardized mean difference (SMD) of 2.27. Other impressive examples are proton pump inhibitors for the indication of reflux oesophagitis showing an increase of remitters from 28.3% with the placebo up to 83.2% (SMD: 1.39).On the other hand, there are well established, but less effective first-line, options such as aspirin for the secondary prevention of cardiovascular diseases resulting in 8.2% participants per year with cardiovascular events taking placebo as compared to 6.7% with aspirin (SMD: 0.12). Statins for the same indication are somewhat in between those two ends. They reduce the event rate from 17.8% with placebo to 14.1% (SMD: 0.15). Other drugs for multifactorial diseases, such as, for example, metformin for the indication of diabetes, show a mortality rate of 14.6% against 21.7% with placebo (SMD: 0.27), and a mean fasting blood glucose level reduction of 1.84 mmol/l (SMD: 0.87). The use of angiotensin converting enzyme inhibitors in primary blood pressure reduces the cardiovascular events and mortality from 18.1% to 14.1% (SMD: 0.11).These data are contrasted by psychiatric medications, such as, for example, lithium in relapse prevention for bipolar disorder resulting in 81.4% relapses with placebo and 36.2% with lithium maintenance treatment (SMD: 1.2). A substantial reduction of relapse rates can also be found in schizophrenia patients with a reduction from 57% relapse with placebo to 22% with an antipsychotic (SMD: 0.92). Less pronounced are effects that can be seen with cholinesterase inhibitors for dementia with 16.8% of patients without a cognitive decline taking placebo compared to 24.4% with an active drug (SMD: 0.26). In between are, for example, second generation antipsychotics or haloperidol for the indication of acute mania in bipolar disorder increasing the response rate from 30.8% with placebo up to 49.9% with an active drug (SMD: 0.44). Overall, sample sizes were smaller in psychiatric indications but still sufficient due to the robust effect sizes. In general, larger sample sizes were necessary in medical indications in order to find significant differences for smaller effects.However, there are numerous limitations for this approach, (most of which are openly discussed by the authors themselves), which should be mentioned. For example, the translation of dichotomous variables into SMDs is only a rough estimate, which on the other hand was necessary in order to get a comparable measure across the diverse outcomes. A second important limitation is that different outcomes, such as the reduction of psychopathological symptoms assessed with rating scales and mortality outcomes are not easily comparable. However, untreated psychiatric disorders not only can lead to suicide but also may lead to negligence of, for example, severe comorbid somatic conditions, which also implies considerable health risks. In other words, psychopharmacologic compounds may also have effects which, according to Stefan Leucht, "could accumulate over time".Another limitation of the study is the selection of the reviewed medical conditions. It was consensus based and not complete and this selection might have been biased. When reviewing meta-analyses, the publication bias must also be considered and side effects, as well as psychotherapy, should be considered. Furthermore, efficacy trials rarely allow conclusions regarding the effectiveness in day-to-day practice. Thus, as the authors truly acknowledge, this review is observational and qualitative by nature. Despite these limitations, this work raises some interesting and important implications and conclusions for both fields.From a naïve point of view one might have expected that in psychiatry, since it covers "psychic disorders", the placebo effect  might be higher and, as a consequence, the resulting true "pharmacologic" effect would be lower than in general medicine. One could also argue that in general medicine the pathophysiology and the mechanism of action of an active compound are somewhat clearer than in psychiatry and, therefore, the efficacy should be higher. But obviously neither seems to be universally valid. The astonishing similar efficacy of psychopharmacological medications and general medicine medications reminds us that many general medical conditions are, just like psychiatric conditions, of a "multifactorial" nature.Therefore, it is not a surprise that in many medical and psychiatric conditions placebo response rates are relatively high. This may be especially true for idiopathic and functional medical conditions such as migraine, neurological disorders (such as Parkinson's disease), autoimmune disorders and asthma . In otheet al. is an important contribution to overcoming the stigma against psychiatric medication and in putting its efficacy into a wider perspective.In a survey on 1,088 healthy subjects in Germany from 1995, 70% of all respondents answered that medications for cardiovascular conditions are effective, while only 18% believed the medication might be effective in psychiatric conditions [et al. only reviews pharmacological interventions which cover a part of all available medical treatment options. In psychiatry, for example, next to psychopharmacology and psychotherapy, there are other highly effective somatic treatments available, such as electro convulsion therapy (ECT) and transcranial magnetic stimulation (TMS). In general medicine, there are, of course, more and more minimally-invasive interventions available complementing the pharmacologic treatments, such as percutane transluminal coronary angioplasty (PTCA).On the other hand, it should be kept in mind that the paper by Stefan Leucht This review is remarkable in two respects. Firstly, it gives the clinician an overview over effectsizes of diverse pharmacological treatments for medical and psychiatric conditions Secondly the effectsizes of psychiatric and medical conditions are compared with each other. Within its field it allows the clinician to align his clinical experience with the efficacy of treatments in day-to-day practice with the results from meta-analyses. In comparison to a second and different medical field, it shows us the limitations of pharmacological interventions in a holistic way. It thus, also, calls for more integrating research across the field borders. A good example of this is major depression, which is an independent risk factor for coronary artery disease , and myoECT: Electro Convulsion Therapy; PTCA: Percutane Transluminal Coronary Angioplasty; SMD: standardized mean difference; TMS: Transcranial Magnetic StimulationFS received grants and research support from Lilly, Astra Zeneca and Glaxo-Smith Kline. He received honoraria from Lundbeck, Bristol-Meyers Squibb, Lilly and Astra Zeneca. HJM has received grants/research support from Lundbeck, Pfizer, Sanofi Aventis and Servier. He received Honoraria from Servier, Pfizer, Lilly, Jansen, Astra-Zeneca, Wyeth, Lundbeck and Sanofi Aventis. Prof Möller is a speaker or a member of advisory boards for Servier, Pfizer, Lilly, Jansen, Astra-Zeneca, Lundbeck, Sanofi Aventis and Wyeth. RM has received research support from AstraZeneca and Janssen-Cilag. SD declares that she has no competing interest.FS wrote all manuscript drafts. RM carried out the literature search and helped to draft the manuscript. HJM and SD read and critically revised all manuscript drafts. All authors read and approved the final manuscript.FS is specialized in the treatment of and research on affective disorders. FS and RM are consultants for psychiatry at the Department of Psychiatry at the Ludwig-Maximilians-University Munich. SD is senior psychologist at the Department of Psychiatry at the Ludwig-Maximilians-University Munich. HJM is the head of the Department of Psychiatry at the Ludwig-Maximilians-University Munich.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1741-7015/10/17/prepub