Improving the value of clinical research through the use of Common Data Elements.

The use of Common Data Elements can facilitate cross-study comparisons, data aggregation, and meta-analyses; simplify training and operations; improve overall efficiency; promote interoperability between different systems; and improve the quality of data collection. A Common Data Element is a combination of a precisely defined question (variable) paired with a specified set of responses to the question that is common to multiple datasets or used across different studies. Common Data Elements, especially when they conform to accepted standards, are identified by research communities from variable sets currently in use or are newly developed to address a designated data need. There are no formal international specifications governing the construction or use of Common Data Elements. Consequently, Common Data Elements tend to be made available by research communities on an empiric basis. Some limitations of Common Data Elements are that there may still be differences across studies in the interpretation and implementation of the Common Data Elements, variable validity in different populations, and inhibition by some existing research practices and the use of legacy data systems. Current National Institutes of Health efforts to support Common Data Element use are linked to the strengthening of National Institutes of Health Data Sharing policies and the investments in data repositories. Initiatives include cross-domain and domain-specific resources, construction of a Common Data Element Portal, and establishment of trans-National Institutes of Health working groups to address technical and implementation topics. The National Institutes of Health is seeking to lower the barriers to Common Data Element use through greater awareness and encourage the culture change necessary for their uptake and use. As National Institutes of Health, other agencies, professional societies, patient registries, and advocacy groups continue efforts to develop and promote the responsible use of Common Data Elements, particularly if linked to accepted data standards and terminologies, continued engagement with and feedback from the research community will remain important.

Sizing the Problem of Improving Discovery and Access to NIH-Funded Data: A Preliminary Study.

OBJECTIVE: This study informs efforts to improve the discoverability of and access to biomedical datasets by providing a preliminary estimate of the number and type of datasets generated annually by research funded by the U.S. National Institutes of Health (NIH). It focuses on those datasets that are "invisible" or not deposited in a known repository. METHODS: We analyzed NIH-funded journal articles that were published in 2011, cited in PubMed and deposited in PubMed Central (PMC) to identify those that indicate data were submitted to a known repository. After excluding those articles, we analyzed a random sample of the remaining articles to estimate how many and what types of invisible datasets were used in each article. RESULTS: About 12% of the articles explicitly mention deposition of datasets in recognized repositories, leaving 88% that are invisible datasets. Among articles with invisible datasets, we found an average of 2.9 to 3.4 datasets, suggesting there were approximately 200,000 to 235,000 invisible datasets generated from NIH-funded research published in 2011. Approximately 87% of the invisible datasets consist of data newly collected for the research reported; 13% reflect reuse of existing data. More than 50% of the datasets were derived from live human or non-human animal subjects. CONCLUSION: In addition to providing a rough estimate of the total number of datasets produced per year by NIH-funded researchers, this study identifies additional issues that must be addressed to improve the discoverability of and access to biomedical research data: the definition of a "dataset," determination of which (if any) data are valuable for archiving and preservation, and better methods for estimating the number of datasets of interest. Lack of consensus amongst annotators about the number of datasets in a given article reinforces the need for a principled way of thinking about how to identify and characterize biomedical datasets.

The National Institutes of Health's Big Data to Knowledge (BD2K) initiative: capitalizing on biomedical big data.

Biomedical research has and will continue to generate large amounts of data (termed 'big data') in many formats and at all levels. Consequently, there is an increasing need to better understand and mine the data to further knowledge and foster new discovery. The National Institutes of Health (NIH) has initiated a Big Data to Knowledge (BD2K) initiative to maximize the use of biomedical big data. BD2K seeks to better define how to extract value from the data, both for the individual investigator and the overall research community, create the analytic tools needed to enhance utility of the data, provide the next generation of trained personnel, and develop data science concepts and tools that can be made available to all stakeholders.

Sharing heterogeneous data: the national database for autism research.

The National Database for Autism Research (NDAR) is a secure research data repository designed to promote scientific data sharing and collaboration among autism spectrum disorder investigators. The goal of the project is to accelerate scientific discovery through data sharing, data harmonization, and the reporting of research results. Data from over 25,000 research participants are available to qualified investigators through the NDAR portal. Summary information about the available data is available to everyone through that portal.

Validity of childhood adiposity classification in predicting adolescent overweight and obesity.

OBJECTIVE: Identification of children at risk for adolescent overweight can assist in targeting interventions. Uncertainty remains regarding the validity of current body mass index (BMI) reference values in predicting future risk on a population basis. This study aimed to assess the validity of current childhood adiposity classifications in predicting adolescent overweight and obesity among Israeli youth. DESIGN: Historical cohort study. SETTING: School-based childhood health studies and adolescent physical examinations. PARTICIPANTS: A total of 3 163 subjects surveyed first at age 8-15 and again at age 17-19. OBSERVATIONS: Age, sex, height, weight and BMI. OUTCOME MEASURES: Sensitivity, specificity, positive and negative predictive values, and relative risk of childhood adiposity classification. RESULTS: Childhood overweight and obesity showed low sensitivity and high specificity for predicting adolescent overweight and obesity. Positive predictive values were low and varied by age and sex, but negative predictive values were consistently high in both sexes and all ages (range 0.85-0.99). After adjusting for age and sex, both childhood overweight and obesity substantially increased the risk of adolescent overweight (relative risk [RR] 7.03 and 7.20, respectively) and adolescent obesity (RR 24.34 and 28.41, respectively). CONCLUSIONS: Childhood overweight and obesity are strong risk factors for adolescent overweight and obesity among Israeli youth. Normal weight children were at very low risk for adolescent overweight. These findings suggest that population-based health promotion aimed at maintaining normal weight among children should be given preference over risk-guided approaches targeting weight reduction among obese children.

Preventive effect of meningococcal vaccination in Israeli military recruits.

BACKGROUND: Meningococcal disease remains a major concern in populations living under crowded conditions. Following the 1995 report of several cases of meningococcal disease in Israeli soldiers, the Department of Epidemiology of the Army Health Branch, Israel Defense Forces (IDF) adopted an immunization policy for all recruits. The aim of the study was to summarize the IDF experience to date. METHODS: The study population included all compulsory and permanent personnel of both sexes serving in the IDF from 1983 to 2007. Ages ranged from 18 to 55 years, although the majority of subjects was younger than 22 years. Meningococcal disease was defined as the isolation of Neisseria meningitidis from blood or cerebrospinal fluid. RESULTS: The person-time incidence rate of vaccine-preventable meningococcal disease dropped from 1.31 cases per 100,000 person-years in 1983-1994, the period preceding the start of immunization, to 0 in 1995-2007 (P < .001). CONCLUSION: The meningococcal immunization policy of the IDF led to a dramatic drop in the incidence of vaccine-preventable meningococcal disease.

Incidence of anemia and iron deficiency in strenuously trained adolescents: results of a longitudinal follow-up study.

PURPOSE: Combat soldiers have a higher prevalence of anemia than age- and gender-matched civilians. This may be caused by hemodilution, which is typical among athletes, or by reduced body iron stores. The aim of this study was to investigate the incidence of iron-deficiency anemia in recruits to the Israel Defense Force after 6 months of training. METHODS: Blood was collected from recruits before training. After 6 months of follow-up, 153 paired blood samples were collected from the initial cohort. Total blood count and serum iron, transferrin, and ferritin were measured at both time points. Soluble transferrin receptor (sTfR) was measured in 119 of the paired samples and the sTfR/log ferritin ratio was calculated. RESULTS: At recruitment, mean hemoglobin concentration was 14.7 +/- .9 g/dl. Iron-transferrin saturation was 34.1% +/- 13.6%, and mean ferritin concentration was 53.6 +/- 33.2 ng/ml. Anemia prevalence (Hb <14 g/dl) was 17.6%, and 14.9% of participants were iron-deficient (ferritin <22 mg/dl). At 6 months, 50.3% of the cohort was anemic, and 27.3% demonstrated iron-store depletion. Paired analysis showed an average reduction of .83 g/dl in hemoglobin (p < .001), and of 9.8 mg/dl in ferritin (p < .001). sTfR increased from 1.9 to 2.1 mg/dl (p < .003) among recruits who became anemic. Half of the recruits experienced mild anemia after 6 months of training. Iron store depletion was observed among 24.5% of the cohort after training, as opposed to 15% at recruitment. Overall, these changes were not accompanied by a significant increase in sTfR, but among the subset of anemic subjects, there was a slight increase in index value. CONCLUSIONS: In half of the cases, new-onset anemia was attributable to iron deficiency, and in the remainder, to hemodilution.

[Development of an evidence-based managerial decision aid to assist in the provision of secondary medical services in the Israel Defense Forces (IDF)].

BACKGROUND: Increasing global expenditures on health, together with increased patient demand for quality and service, have created a need for health care management tools based on economic and quaLity-based criteria. Despite the recognition of this need, decision-support tools are Lacking. In the Israel Defense Forces (IDF), policy change and budgetary and quality constraints necessitated the development of an evidence-based managerial decision aid, to assist in providing medical services at acceptable quality and availability leveLs, while addressing economic concerns. OBJECTIVE: To develop a decision-support model for the IDF Medical Corps, that balances the conflicting considerations of service avaiLabiLity and cost. METHODS: The authors developed a manageriaL model to characterize regional secondary medical care, and to compare it to country-wide patterns and to historic regional patterns. Secondary care systems were then analyzed by specialty. Finally, the relative costs of medical encounters for each speciaLty were anaLyzed. RESULTS: Core specialties examined included dermatology, orthopedics and otolaryngology. Two-thirds of all referrals to core specialists were made to intra-organizational resources. Furthermore, several intra-organizationaL clinics were found to have short waiting times and low output indices. In response to the application of the model, IDF Medical Corps policy was updated and suppliers were reprioritized, yielding substantial savings of up to NIS 5.5 million in 2006 alone. This cost saving enabled budgetary reallocation and alternative investment in the emergency and primary health care systems. CONCLUSION: Applying efficient managerial tools can lead to cost savings and to increased quality and availability of services. These tools must effectively follow changes in the dynamics of the health care system. These changes are to be impLemented rapidly, in order to provide practical guidance for medical administrators and to enable them to infLuence the real-time utiLization of medical services.

Diameter-by-age reference curves for the uterine cervix by computerized tomography.

OBJECTIVE: To create diameter-by-age reference curves for the uterine cervix using computerized tomographic studies. METHODS: Measurements of the anterior-posterior (AP) and lateral diameters of nonpathological cervices were made at the level of the vaginal fornices in 499 computerized tomographic studies. Patients were grouped by 10-year age intervals. For each age group, median AP and lateral cervical diameters were calculated, as were 10th and 90th percentile values. Values for the 3 curves were smoothed across age categories using second-order polynomial regression procedures. RESULTS: The median AP diameter was 26 mm (range, 15-45 mm), and the median lateral diameter was 32 mm (range, 20-70 mm). For both measurements, the range of values between the 10th and 90th percentiles decreased with increasing age, creating funnel-shaped plots. CONCLUSIONS: Radiological measurements of cervical diameters and comparison to standard curves may contribute information in the evaluation of uterine cervical pathology or may heighten awareness of pathologies not previously identified.

Hypertension and socioeconomic status.

PURPOSE OF REVIEW: The impact of socioeconomic status on hypertension is complicated and unclear. In this article, we review the findings of recently published studies pertaining to the association between socioeconomic status and hypertension. Specifically, we focus on several potentially modifiable modes of pathogenesis involved in this association, including education, occupation, and social environment. We also review several mechanisms through which the effects of socioeconomic status on hypertension may be mediated. RECENT FINDINGS: Several modifiable socioeconomic determinants, such as education and occupation, are associated with hypertension. Additional socioeconomic status markers such as urban or rural dwelling and individual, local or national economic conditions are also associated with hypertension, although these associations are complicated and at times somewhat contradictory. Possible explanations for this impact include awareness of hypertension prevention and control and better accessibility and adherence to medical treatment among higher socioeconomic status groups, as well as low birth weight and higher job strain among lower socioeconomic status groups. SUMMARY: Low socioeconomic status is associated with higher blood pressure. There is a need to develop and test culturally appropriate interventions to reduce the prevalence of hypertension among these populations to minimize the resultant cardiovascular morbidity and mortality.

Influenza vaccine refusal in Israeli young adults.

OBJECTIVE: The purpose of this study was to identify correlates of noncompliance with influenza immunization among young adults and to determine the reasons leading to immunization refusal. METHODS: Self-administered questionnaires were distributed in 10 military bases during two consecutive annual Israel Defense Force influenza vaccination campaigns. Multivariate logistic regression was performed to identify independent correlates. RESULTS: Of 2,000 questionnaires distributed over two seasons, 942 were completed and returned. Of those, 401 respondents were not vaccinated either because of medical contraindication or for administrative reasons. The remaining 541 respondents who reported either receiving the vaccine or refusing to receive it were analyzed. Risk groups for vaccine refusal included older age (17.9% vs. 3.5% refusal rate) and officer rank (25.9% vs. 13.8% refusal rate). The main reasons for vaccine refusal differed significantly between officers and nonofficers (chi2 = 7.587, p = 0.023). Officers refused mainly (60%) because of fear of possible vaccine adverse effects, whereas nonofficers refused mainly (44.2%) because of disbelief in the vaccine's efficacy in preventing illness. CONCLUSION: Officers serve as a negative role model in this case, and efforts directed toward dissemination of evidence-based information regarding vaccine-related adverse effects should be introduced to increase vaccination rates in this group.

Relative impact of socioeconomic status on blood pressure lessons from a large-scale survey of young adults.

BACKGROUND: Although several studies reported on the association between socioeconomic status (SES) and hypertension, the results are conflicting, the quantification is problematic, only a few focused on young adults, and the effects of various key determinants of SES, such as education and job type, need further clarification. We aimed to assess the influence of SES on blood pressure in a large population of young adults. METHODS: We studied 11,053 male Israel Defense Force officers who underwent periodic medical evaluation during the years 1991 to 1999. Subjects completed a detailed medical questionnaire and underwent physical examination. We calculated mean systolic and diastolic blood pressure (SBP and DBP, respectively) by level of education, rank, and job type (as measures of SES), adjusting for demographic variables and body mass index (BMI). RESULTS: Adjusted means of SBP and DBP were highest among low-ranking officers (SBP, 119 mm Hg, compared with 117 and 115 mm Hg among intermediate and high-ranking officers, respectively, P < .001; DBP, 77 mm Hg, compared with 76 mm Hg among intermediate and high-ranking officers, P = .001). No differences were observed for level of education, but the mean SBP was higher among office workers (117 mm Hg v 116 mm Hg among physical workers, P = .038). The partial eta(2) for rank, age, and BMI was found to be 0.003, 0.008, and 0.066, respectively, for SBP, and 0.002, 0.026 and 0.054, respectively, for DBP. CONCLUSIONS: Low SES, as reflected by low rank, is associated with elevated blood pressure. However, as a whole, SES is a weak determinant of blood pressure compared with age and BMI.

A radiological study on the anatomical proximity of the ureters and the cervix.

In order to evaluate risk factors for anatomical proximity between the cervix and the ureters the distance between the ureters and the cervix was measured in 499 computerized tomography (CT) studies at the most dorsal reflection of the ureters. The relationship between the ureter-cervical distance and the presence of pelvic pathology was assessed by correlation tests and regression analysis. Of the 499 CT studies, 252 demonstrated radiographic pathologies. Among abnormal scans, 126 (50%) involved cervical pathology. At least one ureter was within 0.5 cm of the cervix in 3.6% of patients with normal CT scans and in 10.3% of patients with cervical pathology. Overall, the right ureter was significantly closer to the cervix than the left (2.0 +/- -0.8 cm vs. 2.2 +/- 1.0 cm, p < 0.05). In cases were the pathology was limited to the cervix, the right ureter was more distant than the left (2.0 +/- 0.6 cm vs. 1.7 +/- 0.6 cm, p < 0.05). The distance between the ureters and the cervix was inversely correlated with the lateral diameter of the cervix (r = 0.18, p < 0.001) and its anterior-posterior diameter (r = 0.11, p < 0.001). Age did not correlate with the distance of the ureters from the cervix (r = 0.002, p = N.S). In conclusion, approximately 10% of patients with cervical pathology can be expected to have a ureter proximate less than 5 mm from the cervix. For patients with cervical pathology undergoing a planned hysterectomy, preoperative measurement of cervical-ureteric distance may be warranted. In these circumstances intra-operative measures to protect the ureter and ascertain its integrity may be invaluable.

Appropriateness of US and international BMI-for-age reference curves in defining adiposity among Israeli school children.

Effective surveillance of trends in paediatric overweight and obesity requires the establishment of valid cutoff values to identify children at risk. In Israel, standard values for childhood BMI-for-age are currently based on growth charts published by the US Centers for Disease Control and Prevention. However, the appropriateness of using US reference values in populations outside the US is questionable, due to inherent differences in ethnicity, culture and socioeconomic status. We recorded data from 9,988 children aged 6-12 selected by random cluster sampling within the framework of school-based health surveys conducted in Israel during the years 1997 and 2000. We constructed population-specific centile BMI-for-age curves valid for Israeli children, and compared these curves to current standard US and international reference values. Curves were constructed using LMS statistical curve smoothing methods. The data set of Israeli schoolchildren produced reference centiles substantially different than those based on US children. Israeli reference values were closer to centile curves published by the International Obesity Task Force. In conclusion, local and national health planners should recognize the intrinsic limitations associated with the use of "standard" reference values in defining paediatric overweight and obesity in dissimilar populations. The results of this large population-based study highlight the need for population-specific BMI-for-age reference values, in order to accurately describe the prevalence of paediatric overweight and obesity.

Perioperative predictors of successful hysteroscopic endometrial ablation.

OBJECTIVE: To determine which perioperative factors influence the success of hysteroscopic endometrial ablation in patients with menorrhagia. STUDY DESIGN: A longitudinal study of 128 women who underwent hysteroscopic endometrial ablation or resection. Clinical data included age, uterine size, the presence of intramural or submucosal myomas and polyps, and length of follow-up from initial hysteroscopic ablation to re-ablation or hysterectomy ('failure'). Kaplan-Meier survival analysis, log-rank tests and Cox proportional hazard regression were used to evaluate the equality of survival distributions and to model the overall effects of the various predictor variables on surgical outcomes. RESULTS: Patients were followed for a median time of 44 months. Thirteen women (10.2%) underwent a second operative procedure. Multivariate analysis identified submucosal myoma as a statistically significant positive predictor of the risk of failure [hazard ratio (HR) 5.22, 95% confidence interval (CI) = 1.63, 16.73)]. Older age was associated with a marginally lower risk of subsequent surgery (HR 0.90 per additional year of age, 95% CI = 0.81, 1.00). CONCLUSIONS: The presence of submucosal myoma increases the risk of subsequent surgery in patients undergoing endometrial ablation.

Declining population immunity to mumps among Israeli military recruits.

Population-based seroepidemologic data on mumps have not been available in Israel since 1987, and the effects of mass immigration from the Commonwealth of Independent States during the 1990s have not been investigated. We conducted a seroprevalence study of mumps antibodies among 353 Israeli military recruits aged 18-19, based on a representative sample of sera collected in 1999. The overall seroprevalence rate was 83.3%, which was significantly lower than that measured in 1987 (94.1%, P<0.001). Foreign-born subjects had substantially lower seroporevalence rates than their native Israeli counterparts (68.5% versus 86.1%, P<0.001). Recent seroprevalence levels are below those required for herd immunity, and most likely contributed to an outbreak of mumps observed among young adults in Israel in 2005. Immigration appears to be a contributing factor to the decrease in population seroprevalence over time.

Prevalence of prehypertension and associated cardiovascular risk profiles among young Israeli adults.

Recently the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure introduced the term "prehypertension" for systolic blood pressure levels of 120 to 139 mm Hg and diastolic BP levels of 80 to 89 mm Hg. Little is known about the prevalence of this entity and the cardiovascular risk factors associated with it. We aimed to determine the prevalence of prehypertension and the cardiovascular risk factors associated with it in a large population-based sample of young Israeli adults. We studied 36,424 Israel Defense Forces employees during the years 1991 to 1999. Subjects completed a detailed questionnaire and underwent physical examination, and blood samples were drawn after a 14-hour fast. Prehypertension was defined as a systolic blood pressure of 120 to 139 mm Hg, and/or a diastolic blood pressure of 80 to 89 mm Hg. We calculated the age- and sex-specific prevalence of prehypertension and other cardiovascular risk factors associated with this condition. Prehypertension was observed among 50.6% of men and 35.9% of women. The prehypertensive group had higher levels of blood glucose, total cholesterol, low-density lipoprotein cholesterol, and triglycerides, higher body mass index, and lower levels of high-density lipoprotein cholesterol than did the normotensive group. Multivariate logistic regression analysis showed that body mass index was the strongest predictor of prehypertension among both males and females (odds ratio, 1.100; 95% CI, 1.078 to 1.122 and odds ratio, 1.152; 95% CI, 1.097 to 1.21, respectively, for every 1 kg/m2 increase). Our findings support the recommendation of lifestyle modification for prehypertensive patients. Further prospective studies are required to determine the role of pharmacotherapy in prehypertension.

Ten-year trends in obesity among Israeli schoolchildren: 1990-2000.

AIM: To analyze trends in childhood body mass index (BMI) in Israel between 1990 and 2000, and to determine the proportion of obese children using US and population-specific reference values. METHODS: Cross-sectional data from 13 284 second- and fifth-grade schoolchildren were collected, including age, sex, height, weight, country of birth, and time since immigration. Age- and sex-specific BMI means and centiles were calculated, and the prevalence of obesity was determined using Israeli and US reference values. RESULTS: BMI values at the 95th centile increased monotonously over time in all age and sex categories. Between 1990 and 2000, 95th centile values increased by 12.7% and 11.8% among second-grade boys and girls, respectively. Among fifth-grade children, 95th centile values increased by 10.2% and 8.4%, respectively. Among second graders in 2000, 11.4% of both boys and girls exceeded the BMI value recorded at the 95th centile in 1990. Among fifth-graders in 2000, 10.7% of boys and 11.1% of girls exceeded the 1990 BMI reference value (p for all comparisons < 0.001). The proportion of obese children increased over time using both Israeli and US reference values. CONCLUSION: This substantial increase in childhood obesity poses a serious health threat, and requires implementation of suitable public health interventions.