Hypereosinophilic syndrome: a multicenter, retrospective analysis of clinical characteristics and response to therapy

BACKGROUND: Hypereosinophilic syndrome (HES) is a heterogeneous group of rare disorders defined by persistent blood eosinophilia > or =1.5 x 10(9)/L, absence of a secondary cause, and evidence of eosinophil-associated pathology. With the exception of a recent multicenter trial of mepolizumab (anti-IL-5 mAb), published therapeutic experience has been restricted to case reports and small case series. OBJECTIVE: The purpose of the study was to collect and summarize baseline demographic, clinical, and laboratory characteristics in a large, diverse cohort of patients with HES and to review responses to treatment with conventional and novel therapies. METHODS: Clinical and laboratory data from 188 patients with HES, seen between January 2001 and December 2006 at 11 institutions in the United States and Europe, were collected retrospectively by chart review. RESULTS: Eighteen of 161 patients (11%) tested were Fip1-like 1-platelet-derived growth factor receptor alpha (FIP1L1-PDGFRA) mutation-positive, and 29 of 168 patients tested (17%) had a demonstrable aberrant or clonal T-cell population. Corticosteroid monotherapy induced complete or partial responses at 1 month in 85% (120/141) of patients with most remaining on maintenance doses (median, 10 mg prednisone equivalent daily for 2 months to 20 years). Hydroxyurea and IFN-alpha (used in 64 and 46 patients, respectively) were also effective, but their use was limited by toxicity. Imatinib (used in 68 patients) was more effective in patients with the FIP1L1-PDGFRA mutation (88%) than in those without (23%; P < .001). CONCLUSION: This study, the largest clinical analysis of patients with HES to date, not only provides useful information for clinicians but also should stimulate prospective trials to optimize treatment of HES.

A 4-year study on clinical characteristics of children hospitalized with rotavirus gastroenteritis

Rotavirus (RV) is a frequent cause of severe gastroenteritis (GE) in children. With the licensure of new RV vaccines, data on the burden of disease are important regarding immunization strategies. We reviewed the medical records of children hospitalized with RV infection in our institution between July 2002 and March 2006. Relevant data were extracted in a standardized fashion from records of hospitalized children with a positive RV antigen test in a stool sample. Severity of disease was graded by the 20-point Vesikari score. Population data were obtained from the Federal Office of Statistics. Six hundred eighty-six RVGE were identified and records of 608 hospitalizations (in 607 children) were available. In 539 (89%) cases, RVGE was the primary reason for hospitalization and 69 (11%) were nosocomial infections; yearly peaks occurred between February and May. Cumulative incidence of RVGE was 26.7/1,000 children <3 years of age. Median age of 539 children (55.6% male) with primary RVGE was 1.4 years and median stay in the hospital for both community acquired and nosocomial RVGE was 4 days (interquartile range 3-5). Thirtypercent and 94% of RV hospitalizations were in children <1 and <3 years of age, respectively. Mean Vesikari score was 15 (range 6-20; 96% >11). Intravenous fluids were administered in 378 (70%) patients, 130 (24%) patients were rehydrated via nasogastral tube, and 31 (5.7%) received rehydration by mouth. RVGE causes a substantial burden in children with an estimated risk for hospitalization due to RVGE of one in 37 children <3 years of age.

Poverty, Educational Attainment and Health Among America’s Children: Current and Future Effects of Population Diversification and Associated Socioeconomic Change

A complex of interrelated factors including minority status, poverty, education, health status, and other factors determine the general welfare of children in America, particularly in heavily diverse states such as Texas. Although racial/ethnic status is clearly only a concomitant factor in that determination it is a factor for which future projections are available and for which the relationships with the other factors in the complex can be assessed. After examining the nature of the interrelationships between these factors we utilize direct standardization techniques to examine how the future diversification of the United States and Texas will affect the number of children in poverty, the educational status of the householders in households in which children in poverty live and the health status of children in 2040 assuming that the current relationships between minority status and these socioeconomic factors continue into the future. In the results of the analyses, data are compared with the total population of the United States and Texas in 2040 assumed in the first simulation scenario, to have the race/ethnicity characteristics of 2008 and in the second those projected for 2040 by the U.S. Census Bureau for the nation and by the Texas State Data Center for Texas in 2040. The results show that the diversification of the population could increase the number of children in poverty in the United States by nearly 1.8 million more than would occur with the lower levels of diversification evident in 2008. In addition, poverty would become increasingly concentrated among minority children with minority children accounting for 76.2 percent of all children in poverty by 2040 and with Hispanic children accounting for nearly half of the children in poverty by 2040. Results for educational attainment show an increasing concentration of minority children in households with householders with very low levels of education such that by 2040, 85.2 percent of the increase in the number of children in poverty would be in households with a householder with less than a high school level of education. Finally, the results related to several health status factors show that children in poverty will have a higher prevalence of nearly all health conditions. For example, the number of children with untreated dental conditions could increase to more than 4 million in the United States and to nearly 500,000 in Texas. The results clearly show that improving the welfare of children in America will require concerted efforts to change the poverty, educational, and health status characteristics associated with minority status and particularly Hispanic status. Failing to do so will lead to a future in which America’s children are increasingly impoverished, more poorly educated, and less healthy and which, as a result, is an America with a more tentative future.

Comparison of pain-resilient working individuals to population-based case controls with/without momentary low back pain

Background: Few studies have examined the 20% of individuals who never experience an episode of low back pain (LBP). To date, no investigation has been undertaken that examines a group who claim to have never experienced LBP in their lifetime in comparison to two population-based case–control groups with and without momentary LBP. This study investigates whether LBP-resilient workers between 50 and 65 years had better general health, demonstrated more positive health behaviour and were better able to achieve routine activities compared with both case–control groups. Methods: Forty-two LBP-resilient participants completed the same pain assessment questionnaire as a population-based LBP sample from a nationwide, large-scale cross-sectional survey in Switzerland. The LBP-resilient participants were pairwise compared to the propensity score-matched case controls by exploring differences in demographic and work characteristics, and by calculating odds ratios (ORs) and effect sizes. A discriminant analysis explored group differences, while the multiple logistic regression analysis specified single indicators which accounted for group differences. Results: LBP-resilient participants were healthier than the case controls with momentary LBP and achieved routine activities more easily. Compared to controls without momentary LBP, LBP-resilient participants had a higher vitality, a lower workload, a healthier attitude towards health and behaved more healthily by drinking less alcohol. Conclusions: By demonstrating a difference between LBP-resilient participants and controls without momentary LBP, the question that arises is what additional knowledge can be attained. Three underlying traits seem to be relevant about LBP-resilient participants: personality, favourable work conditions and subjective attitudes/attributions towards health. These rationales have to be considered with respect to LBP prevention.

A pure population of lung alveolar epithelial type II cells derived from human embryonic stem cells.

Alveolar epithelial type II (ATII) cells are small, cuboidal cells that constitute approximately 60% of the pulmonary alveolar epithelium. These cells are crucial for repair of the injured alveolus by differentiating into alveolar epithelial type I cells. ATII cells derived from human ES (hES) cells are a promising source of cells that could be used therapeutically to treat distal lung diseases. We have developed a reliable transfection and culture procedure, which facilitates, via genetic selection, the differentiation of hES cells into an essentially pure (>99%) population of ATII cells (hES-ATII). Purity, as well as biological features and morphological characteristics of normal ATII cells, was demonstrated for the hES-ATII cells, including lamellar body formation, expression of surfactant proteins A, B, and C, alpha-1-antitrypsin, and the cystic fibrosis transmembrane conductance receptor, as well as the synthesis and secretion of complement proteins C3 and C5. Collectively, these data document the successful generation of a pure population of ATII cells derived from hES cells, providing a practical source of ATII cells to explore in disease models their potential in the regeneration and repair of the injured alveolus and in the therapeutic treatment of genetic diseases affecting the lung.

The effects of population density on the spread of disease

The objective of this study is to identify the relationship between population density and the initial stages of the spread of disease in a local population. This study proposes to concentrate on the question of how population density affects the distribution of the susceptible individuals in a local population and thus affects the spread of the disease, measles. Population density is measured by the average of the number of contacts with susceptible individuals by each individual in the population during a fixed-length time period. The term “contact with susceptible individuals” means sufficient contact between two people for the disease to pass from an infectious person to a susceptible person. The fixed-length time period is taken to be the average length of time an infected person is infectious without symptoms of the disease. For this study of measles, the time period will be seven days. ^ While much attention has been given to modeling the entire epidemic process of measles, attempts have not been made to study the characteristics of contact rates required to initiate an epidemic. This study explores the relationship between population density, given a specific herd immunity rate in the population, and initial rate of the spread of the disease by considering the underlying distribution of contacts with susceptibles by the individuals in the population. ^ This study does not seek to model an entire measles epidemic, but to model the above stated relationship for the local population within which the first infective person is introduced. This study describes the mathematical relationship between population density parameters and contact distribution parameters. ^ The results are displayed in graphs that show the effects of different population densities on the spread of disease. The results support the idea that the number of new infectives is strongly related to the distribution of susceptible contacts. The results also show large differences in the epidemic measures between populations with densities equal to four versus three. ^

Breast cancer in younger women in Switzerland 1996-2009: A longitudinal population-based study.

BACKGROUND Breast cancer (BC) is the most commonly diagnosed cancer and a leading cause of death in younger women. METHODS We analysed incidence, mortality and relative survival (RS) in women with BC aged 20-49 years at diagnosis, between 1996 and 2009 in Switzerland. Trends are reported as estimated annual percentage changes (EAPC). RESULTS Our findings confirm a slight increase in the incidence of BC in younger Swiss women during the period 1996-2009. The increase was largest in women aged 20-39 years (EAPC 1.8%). Mortality decreased in both age groups with similar EAPCs. Survival was lowest among women 20-39 years (10-year RS 73.4%). We observed no notable differences in stage of disease at diagnosis that might explain these differences. CONCLUSIONS The increased incidence and lower survival in younger women diagnosed with BC in Switzerland indicates possible differences in risk factors, tumour biology and treatment characteristics that require additional examination.

Warm Breze from the Starboard Bow: a new Population of neutral Helium in the Heliosphere

We investigate the signals from neutral helium atoms observed in situ from Earth orbit in 2010 by the Interstellar Boundary Explorer (IBEX). The full helium signal observed during the 2010 observation season can be explained as a superposition of pristine neutral interstellar He gas and an additional population of neutral helium that we call the Warm Breeze. The Warm Breeze is approximately 2 times slower and 2.5 times warmer than the primary interstellar He population, and its density in front of the heliosphere is ~7% that of the neutral interstellar helium. The inflow direction of the Warm Breeze differs by ~19° from the inflow direction of interstellar gas. The Warm Breeze seems to be a long-term, perhaps permanent feature of the heliospheric environment. It has not been detected earlier because it is strongly ionized inside the heliosphere. This effect brings it below the threshold of detection via pickup ion and heliospheric backscatter glow observations, as well as by the direct sampling of GAS/Ulysses. We discuss possible sources for the Warm Breeze, including (1) the secondary population of interstellar helium, created via charge exchange and perhaps elastic scattering of neutral interstellar He atoms on interstellar He+ ions in the outer heliosheath, or (2) a gust of interstellar He originating from a hypothetic wave train in the Local Interstellar Cloud. A secondary population is expected from models, but the characteristics of the Warm Breeze do not fully conform to modeling results. If, nevertheless, this is the explanation, IBEX-Lo observations of the Warm Breeze provide key insights into the physical state of plasma in the outer heliosheath. If the second hypothesis is true, the source is likely to be located within a few thousand AU from the Sun, which is the propagation range of possible gusts of interstellar neutral helium with the Warm Breeze characteristics against dissipation via elastic scattering in the Local Cloud. Whatever the nature of the Warm Breeze, its discovery exposes a critical new feature of our heliospheric environment.

About DNA databasing and investigative genetic analysis of externally visible characteristics: A public survey.

During the last decade, DNA profiling and the use of DNA databases have become two of the most employed instruments of police investigations. This very rapid establishment of forensic genetics is yet far from being complete. In the last few years novel types of analyses have been presented to describe phenotypically a possible perpetrator. We conducted the present study among German speaking Swiss residents for two main reasons: firstly, we aimed at getting an impression of the public awareness and acceptance of the Swiss DNA database and the perception of a hypothetical DNA database containing all Swiss residents. Secondly, we wanted to get a broader picture of how people that are not working in the field of forensic genetics think about legal permission to establish phenotypic descriptions of alleged criminals by genetic means. Even though a significant number of study participants did not even know about the existence of the Swiss DNA database, its acceptance appears to be very high. Generally our results suggest that the current forensic use of DNA profiling is considered highly trustworthy. However, the acceptance of a hypothetical universal database would be only as low as about 30% among the 284 respondents to our study, mostly because people are concerned about the security of their genetic data, their privacy or a possible risk of abuse of such a database. Concerning the genetic analysis of externally visible characteristics and biogeographical ancestry, we discover a high degree of acceptance. The acceptance decreases slightly when precise characteristics are presented to the participants in detail. About half of the respondents would be in favor of the moderate use of physical traits analyses only for serious crimes threatening life, health or sexual integrity. The possible risk of discrimination and reinforcement of racism, as discussed by scholars from anthropology, bioethics, law, philosophy and sociology, is mentioned less frequently by the study participants than we would have expected. A national DNA database and the widespread use of DNA analyses for police and justice have an impact on the entire society. Therefore the concerns of lay persons from the respective population should be heard and considered. The aims of this study were to draw a broader picture of the public opinion on DNA databasing and to contribute to the debate about the possible future use of genetics to reveal phenotypic characteristics. Our data might provide an additional perspective for experts involved in regulatory or legislative processes.

Anatomic characteristics and clinical implications of angiographic coronary thrombus: insights from a patient-level pooled analysis of SYNTAX, RESOLUTE, and LEADERS Trials.

BACKGROUND The distribution of thrombus-containing lesions (TCLs) in an all-comer population admitted with a heterogeneous clinical presentation (stable, ustable angina, or an acute coronary syndrome) and treated with percutaneous coronary intervention is yet unclear, and the long-term prognostic implications are still disputed. This study sought to assess the distribution and prognostic implications of coronary thrombus, detected by coronary angiography, in a population recruited in all-comer percutaneous coronary intervention trials. METHODS AND RESULTS Patient-level data from 3 contemporary coronary stent trials were pooled by an independent academic research organization (Cardialysis, Rotterdam, the Netherlands). Clinical outcomes in terms of major adverse cardiac events (major adverse cardiac events, a composite of death, myocardial infarction, and repeat revascularization), death, myocardial infarction, and repeated revascularization were compared between patients with and without angiographic TCL. Preprocedural TCL was present in 257 patients (5.8%) and absent in 4193 (94.2%) patients. At 3-year follow-up, there was no difference for major adverse cardiac events (25.3 versus 25.4%; P=0.683); all-cause death (7.4 versus 6.8%; P=0.683); myocardial infarction (5.8 versus 6.0%; P=0.962), and any revascularizations (17.5 versus 17.7%; P=0.822) between patients with and without TCL. The comparison of outcomes in groups weighing the jeopardized myocardial by TCL also did not show a significant difference. TCL were seen more often in the first 2 segments of the right (43.6%) and left anterior descending (36.8%) coronary arteries. The association of TCL and bifurcation lesions was present in 40.1% of the prespecified segments. CONCLUSIONS TCL involved mainly the proximal coronary segments and did not have any effect on clinical outcomes. A more detailed thrombus burden quantification is required to investigate its prognostic implications. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00114972, NCT01443104, NCT00617084.

The winner takes it all? Characteristics of adolescents at-risk/problem gamblers in Switzerland

Background: Gambling has and still entertains people in almost all societies throughout the world. Western societies have faced considerable changes in the amount and accessibility of gambling possibilities during the last decades, and the rates of both adolescent gamblers and problem gamblers have increased significantly. Objective: To determine the characteristics of at-risk and problem adolescent gamblers in Switzerland. Subjects: The study population consisted of 3134 students (1669 females) attending post-mandatory education in 15 randomly chosen centres. Participants were divided into non- (n=2207), non-problematic (n=754) and at-risk/ problematic gamblers (n=176). Methods: Both gambling groups were compared to non-gamblers on socio-demographic measures, substance use and Internet use. Overall, 29.6% had gambled during the past year and 5.6% had gambled in a risky or problematic way. Compared to non-gamblers and after controlling for potential confounders, non-problem gamblers were significantly more likely to be male, apprentices and to misuse alcohol. At-risk/problematic gamblers were additionally more likely to smoke cannabis, to be problematic Internet users and to be non-Swiss than non-gamblers. Conclusion: At-risk and problematic adolescent gambling is associated with other health risk behaviours. Health practitioners should include gambling in the psycho-social screening and preventive counselling of adolescents.

A multinational case-control study on childhood brain tumours, anthropogenic factors, birth characteristics and prenatal exposures: A validation of interview data.

Little is known about the aetiology of childhood brain tumours. We investigated anthropometric factors (birth weight, length, maternal age), birth characteristics (e.g. vacuum extraction, preterm delivery, birth order) and exposures during pregnancy (e.g. maternal: smoking, working, dietary supplement intake) in relation to risk of brain tumour diagnosis among 7-19 year olds. The multinational case-control study in Denmark, Sweden, Norway and Switzerland (CEFALO) included interviews with 352 (participation rate=83.2%) eligible cases and 646 (71.1%) population-based controls. Interview data were complemented with data from birth registries and validated by assessing agreement (Cohen's Kappa). We used conditional logistic regression models matched on age, sex and geographical region (adjusted for maternal age and parental education) to explore associations between birth factors and childhood brain tumour risk. Agreement between interview and birth registry data ranged from moderate (Kappa=0.54; worked during pregnancy) to almost perfect (Kappa=0.98; birth weight). Neither anthropogenic factors nor birth characteristics were associated with childhood brain tumour risk. Maternal vitamin intake during pregnancy was indicative of a protective effect (OR 0.75, 95%-CI: 0.56-1.01). No association was seen for maternal smoking during pregnancy or working during pregnancy. We found little evidence that the considered birth factors were related to brain tumour risk among children and adolescents.

The impact of nutrition intervention on glycemic control in a pediatric type 1 diabetes mellitus population

Aim: The goal of this study was to evaluate the change in hemoglobin A1C and glycemic control after nutrition intervention among a population of type 1 diabetic pediatric patients. Methods: Data was collected from all type 1 diabetic patients who were scheduled for a consultation with the diabetes/endocrine RD from January 2006 through December 2006. Two groups were compared, those who kept their RD appointment and those who did not keep their appointment. The main outcome measure was HgbA1C. An independent samples t-test compared the two groups with respect to change in HbgA1C before and after the most recent scheduled appointment with the RD. Baseline characteristics were used as covariates and analyzed and controlled for using analysis of covariance (ANCOVA). Results: There was no difference in HgbA1c after either attending an RD appointment or not having attended an RD appointment. Those who arrived for and attended their RD appointment and those who did not arrive for and attend their RD appointment, had statistically different HgbA1C's before their scheduled appointment as well as after the RD appointment. However, the two groups were not equal at the beginning of the study period. Discussion: A study design with inclusion criteria of a specified range of HgbA1C values within which the study subjects needed to fall, would have potentially eliminated the difference between the two groups at the beginning of the study period. Conducting either another retrospective study that controlled for the initial HgbA1C value or conducting a prospective study that designated a range of HgbA1C values would be worth investigating to evaluate the impact of medical nutrition therapy intervention and the role of the RD in diabetes management. It is an interesting finding that there was a significant difference in the initial HgbA1c for those who came to the RD appointment compared to those who did not come. The fact that in this study those who did not arrive for their RD appointment had worse control of their diabetes suggests that this is a high-risk group. Targeting diabetes education toward this group of patients may prove to be beneficial. ^

Psychosocial job characteristics as predictors of overall health: Results from a community-based cross-sectional study conducted in southeast Texas in 2001 and 2002

Stress at the workplace exposes people to increased risk for poor physical and/or mental health. Recently psychological and social disadvantages have been proven to place the worker at risk for mental or physical health outcomes. The overall purpose of this study was to study full time employed study subjects and (1) describe the various psychosocial job characteristics in a population of low income individuals stratified by race/ethnicity residing in Houston and Brownsville, Texas and (2) examine the associations between psychosocial job characteristics and physical, mental, and self rated health. It was observed that having a low level of education is associated with having very little or no control, security, and social support at the workplace. Being Mexican American was associated with having good job control, job security, job social support and having a less demanding job. Furthermore, the psychosocial job characteristics were associated with mental health outcomes but not with physical and self rated health. ^

The association of internet use and depression among spinal cord injury population

The purpose of this study was to exam the relationship between internet use and depression among a population of individuals who have sustained spinal cord injury. This was cross-sectional survey design conducted among spinal cord injury (SCI) patients in the Model Spinal Cord Injury System. We included a total of 1,011 SCI-patients who were interviewed face-to-face or by telephone interview over approximately a three year time period (2004–2006). All data were collected through a telephone survey which included the Patient Health Questionnaire-9 (PHQ-9) to assess depression. We examined various scales of this survey, included a reduced 3-item scale (items 1, 2 and 6) to avoid the presence of somatic symptoms among SCI patients from influencing classification of depression. The frequency of internet usage was grouped as daily/weekly/monthly/non user. Covariates examined as possible confounders included demographic characteristics, occupational status, educational level, injury type, daily function of living, pain level, self-perceived health status and satisfaction with life. We observed a negative association between the frequency of internet use and the level of depression. Daily use of internet was associated with lower PHQ-9 score and depression; however this association did not reach statistical significance after for the mentioned covariates. In conclusion, the factors related to lower depression in SCI patients who use the internet are complicated. Daily internet usage was associated with lower levels of depression. The accuracy of 3-item scale needs further validation and investigation. Further study of internet usage pattern in SCI patient is recommended. ^