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Background It remains unclear as to whether neglecting residential mobility during pregnancy introduces bias in studies investigating air pollution and adverse perinatal outcomes, as most studies assess exposure based on residence at birth. The aim of this study was to ascertain whether such bias can be observed in a study on the effects of PM 10 on risk of preterm birth and fetal growth restriction. Methods This was a retrospective study using four pregnancy cohorts of women recruited in Connecticut, USA (N=10,025). We ascertained associations with PM 10 exposure calculated using first recorded maternal address, last recorded address, and full address histories. We used a discrete time-to-event model for preterm birth, and logistic regression to investigate associations with small for gestational age (SGA) and term low birth weight (LBW). Results Pregnant women tended to move to areas with lower levels of PM 10 . For all outcomes, there was negligible difference between effect sizes corresponding to exposures calculated with first, last and full address histories. For LBW, associations were observed for exposure in second trimester (OR 1.09; 95% CI: 1.04–1.14 per 1 μg/m 3 PM 10 ) and whole pregnancy (OR 1.08; 95% CI: 1.02–1.14). For SGA, associations were observed for elevated exposure in second trimester (OR 1.02; 95% CI: 1.00–1.04) and whole pregnancy (OR 1.03; 95% CI: 1.01–1.05). There was insufficient evidence for association with preterm birth. Conclusion PM 10 was associated with both SGA and term LBW. However, there was negligible benefit in accounting for residential mobility in pregnancy in this study. [ABSTRACT FROM AUTHOR]

Objective: To assess whether folic acid intake during the first trimester of pregnancy is related to pregnancy outcomes preeclampsia, low birth weight or preterm birth.Study Design: Prospective cohort study of 3647 women who were followed from the first trimester of pregnancy. Detailed information on quantity of folic acid intake before and during the first three months of pregnancy was recorded. Pregnancy outcome data were abstracted from obstetric records.Results: Lean mothers who used folic acid supplementation the month before pregnancy had a 40% reduced risk of developing preeclampsia. The adjusted odds ratio (OR) with 95% confidence intervals (95%CI) for preeclampsia in lean mothers (BMI<25) who used folic acid supplements the month before pregnancy was 0.6 (95% CI 0.4-1.0). Obese mothers who used folic acid supplementation in the first trimester had an increased, but not statistically significant risk for preterm birth (adjusted OR 1.9 with 95% CI 0.9-4.0). There were no significant associations between folic acid supplementation and low birth weight.Conclusion: Our study supports a possible protective effect of folate intake in early pregnancy on preeclampsia in lean mothers. There was no support for any beneficial effect of folic acid use on preterm birth or low birth weight, and we found no evidence of any harmful effects of folate use for the outcomes included in our study. [ABSTRACT FROM AUTHOR]

Background: Overweight and obesity are associated with breast cancer mortality. However, the relationship between postdiagnosis weight gain and mortality is unclear. We conducted a systematic review and meta-analysis of weight gain after breast cancer diagnosis and breast cancer-specific, all-cause mortality and recurrence outcomes.Methods: Electronic databases identified articles up through December 2014, including: PubMed (1966-present), EMBASE (1974-present), CINAHL (1982-present), and Web of Science. Language and publication status were unrestricted. Cohort studies and clinical trials measuring weight change after diagnosis and all-cause/breast cancer-specific mortality or recurrence were considered. Participants were women age 18 years or older with stage I-IIIC breast cancer. Fixed effects analysis summarized the association between weight gain (≥5.0% body weight) and all-cause mortality; all tests were two-sided.Results: Twelve studies (n = 23 832) were included. Weight gain (≥5.0%) compared with maintenance (<±5.0%) was associated with increased all-cause mortality (hazard ratio [HR] = 1.12, 95% confidence interval [CI] = 1.03 to 1.22, P = .01, I(2) = 55.0%). Higher risk of mortality was apparent for weight gain ≥10.0% (HR = 1.23, 95% CI = 1.09 to 1.39, P < .001); 5% to 10.0% weight gain was not associated with all-cause mortality (P = .40). The association was not statistically significant for those with a prediagnosis body mass index (BMI) of less than 25 kg/m(2) (HR = 1.14, 95% CI = 0.99 to 1.31, P = .07) or with a BMI of 25 kg/m(2) or higher (HR = 1.00, 95% CI = 0.86 to 1.16, P = .19). Weight gain of 10.0% or more was not associated with hazard of breast cancer-specific mortality (HR = 1.17, 95% CI = 1.00 to 1.38, P = .05).Conclusions: Weight gain after diagnosis of breast cancer is associated with higher all-cause mortality rates compared with maintaining body weight. Adverse effects are greater for weight gains of 10.0% or higher. [ABSTRACT FROM AUTHOR]

Triple-crossover randomized controlled intervention trial to test whether reduced exposure to household NO2 or fine particles results in reduced symptoms among children with persistent asthma. Children (n = 126) aged 5–11 years with persistent asthma living in homes with gas stoves and levels of NO2 15 ppb or greater recruited in Connecticut and Massachusetts (2015–2019) participated in an intervention involving three air cleaners configured for: (1) NO2 reduction: sham particle filtration and real NO2 scrubbing; (2) particle filtration: HEPA filter and sham NO2 scrubbing; (3) control: sham particle filtration and sham NO2 scrubbing. Air cleaners were randomly assigned for 5-week treatment periods using a three-arm crossover design. Outcome was number of asthma symptom-days during final 14 days of treatment. Treatment effects were assessed using repeated measures, linear mixed models. Measured NO2 was lower (by 4 ppb, p <.0001) for NO2-reducing compared to control or particle-reducing treatments. NO2-reducing treatment did not reduce asthma morbidity compared to control. In analysis controlling for measured NO2, there were 1.8 (95% CI −0.3 to 3.9, p =.10) fewer symptom days out of 14 in the particle-reducing treatment compared to control. It remains unknown if using an air cleaner alone can achieve levels of NO2 reduction large enough to observe reductions in asthma symptoms. We observed that in small, urban homes with gas stoves, modest reductions in asthma symptoms occurred using air cleaners that remove fine particles. An intervention targeting exposures to both NO2 and fine particles is complicated and further research is warranted. NCT02258893. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study examines the effect of preinjury depressive symptoms on outcomes 3 mos after complicated and uncomplicated cases of mild traumatic brain injury. DESIGN: Preinjury depressive symptoms, experienced in the 30 days before injury, as measured by retrospective self-report, were assessed within the first 2 wks after injury. The outcome measures assessed at 3 mos after injury included affective/behavioral, cognitive, and physical problems and health-related quality-of-life. RESULTS: There were 177 patients who completed both the baseline and 3-mo follow-up interviews. The sample was categorized by severity of depressive symptoms in the month before injury as normal, mild, or moderate-severe. Compared with those reporting no preinjury depressive symptoms, persons reporting moderate-severe depressive symptoms had significantly worse outcomes on the Affective and Behavioral and the Cognitive subscales of the Head Injury-Family Interview Problem Checklist and on the 36-item Short-Form Health Survey Mental Component Summary score. The group reporting mild preinjury depressive symptoms scored worse on a measure of cognitive symptoms compared with those with no preinjury depressive symptoms. There was no interaction between preinjury depressive symptoms and severity of the mild traumatic brain injury (complicated or uncomplicated) for any of the outcomes. CONCLUSION: Moderate to severe depressive symptoms in the month before injury seems to be a possible risk factor for poor affective/behavioral, cognitive, and mental health-related quality-of-life outcomes at 3 mos after mild traumatic brain injury. Clinicians and researchers should consider the impact of preinjury depression on the recovery process to provide at-risk patients adequate treatment soon after injury. [ABSTRACT FROM AUTHOR]

On June 20, 2013, the American Journal of Epidemiology sponsored a symposium at the Society for Epidemiologic Research's 46th Annual Meeting in Boston, Massachusetts, entitled, “What Is the Role of Epidemiology in the Era of Molecular Biology and Genomics?” The future of epidemiology depends on innovation in generating interesting and important testable hypotheses that are relevant to population health. These new strategies will depend on new technology, both in measurement of agents and environment and in the fields of pathophysiology and outcomes, such as cellular epidemiology and molecular pathology. The populations to be studied, sample sizes, and study designs should be selected based on the hypotheses to be tested and include case-control, cohort, and clinical trials. Developing large mega cohorts without attention to specific hypotheses is inefficient, will fail to address many associations with high-quality data, and may well produce spurious results. [ABSTRACT FROM PUBLISHER]

A genome-wide association study was undertaken to identify maternal single nucleotide polymorphisms (SNPs) and copy-number variants (CNVs) associated with pre-eclampsia. Case-control analysis was performed on 1070 Afro-Caribbean (n = 21 cases and 1049 controls) and 723 Hispanic (n = 62 cases and 661 controls) mothers and 1257 mothers of European ancestry (n = 50 cases and 1207 controls) from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study. European ancestry subjects were genotyped on Illumina Human610-Quad and Afro-Caribbean and Hispanic subjects were genotyped on Illumina HumanlM-Duo BeadChip microarrays. Genome-wide SNP data were analyzed using PLINK. CNVs were called using three detection algorithms (GNOSIS, PennCNV, and QuantiSNP), merged using CNVision, and then screened using stringent criteria. SNP and CNV findings were compared to those of the Study of Pregnancy Hypertension in Iowa (SOPHIA), an independent pre-eclampsia case-control dataset of Caucasian mothers (n = 177 cases and 116 controls). A list of top SNPs were identified for each of the HAPO ethnic groups, but none reached Bonferroni-corrected significance. Novel candidate CNVs showing enrichment among pre-eclampsia cases were also identified in each of the three ethnic groups. Several variants were suggestively replicated in SOPHIA. The discovered SNPs and copy-number variable regions present interesting candidate genetic variants for pre-eclampsia that warrant further replication and investigation. [ABSTRACT FROM AUTHOR]

Manolio et al. (Am J Epidemiol. 2012;175:859–866) proposed that large cohort studies adopt novel models using “temporary assessment centers” to enroll up to a million participants to answer research questions about rare diseases and “harmonize” clinical endpoints collected from administrative records. Extreme selection bias, we are told, will not harm internal validity, and “process expertise to maximize efficiency of high-throughput operations is as important as scientific rigor” (p. 861). In this article, we describe serious deficiencies in this model as applied to the United States. Key points include: 1) the need for more, not less, specification of disease endpoints; 2) the limited utility of data collected from existing administrative and clinical databases; and 3) the value of university-based centers in providing scientific expertise and achieving high recruitment and retention rates through community and healthcare provider engagement. Careful definition of sampling frames and high response rates are crucial to avoid bias and ensure inclusion of important subpopulations, especially the medically underserved. Prospective hypotheses are essential to refine study design, determine sample size, develop pertinent data collection protocols, and achieve alliances with participants and communities. It is premature to reject the strengths of large national cohort studies in favor of a new model for which evidence of efficiency is insufficient. [ABSTRACT FROM PUBLISHER]

Background: The x-ray cross complementing group 1 gene (XRCC1) is crucial to proper repair of DNA damage such as single-strand DNA breaks. A non-synonymous polymorphism in XRCC1, 399 G?A, has been shown to reduce effectiveness of such DNA repair and has been associated with the risk of certain cancers. The known risk for glioma from high dose ionizing radiation makes associations between this polymorphism and glioma of particular interest. Methods: A systematic literature review and meta-analysis was conducted to explore the association between XRCC1 399 G→A and glioma. Subgroup analyses by grade, gender, genotyping method, country in which study was conducted, and study size were conducted when data were available and validity of the results were assessed by influence analyses and exploration of potential publication bias. Results: Six studies were eligible for meta-analysis including data on 2,362 Caucasian glioma cases and 3,085 Caucasian controls. Pooled analysis yielded a significant association between the variant of interest and risk of glioma (OR = 1.17, 95% CI: 1.05-1.30) which was found to be disproportionately driven by a single study. Exclusion of this study, in an influence analysis, produced no statistically significant evidence of association with glioma (OR = 1.10, 95% CI: 0.98-1.23), and no evidence of publication bias. Conclusions: This meta-analysis does not suggest a major role of the XRCC1 399 G→A polymorphism in influencing risk of glioma among Caucasians. Future studies should report data separately for glioma subtypes to permit stratified analyses for Grade III and Grade IV glioma and examine other polymorphisms in this gene. [ABSTRACT FROM AUTHOR]

Background: Asthma is a phenotypically diverse disease with genetic susceptibility. A single nucleotide polymorphism (SNP) in the CD14 gene at position -260 (also known as -159) C>T has been inconsistently associated with asthma. The aim of this study was to estimate the combined likelihood of developing asthma given the CD14 -260C>T genotype. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic search and meta-analysis of the literature was conducted to estimate the association between this SNP and asthma. Planned subgroup analyses were performed to detect potential sources of heterogeneity from selected study characteristics. Post-hoc sensitivity analysis was performed to identify studies exerting excessive influence on among-study heterogeneity and combined effects. Results: Meta-analysis of 23 studies yielded a non-significant overall association with high heterogeneity across studies. After restricting analysis to studies using atopic asthma and non-atopic non-asthma case-control phenotypes and excluding studies influencing heterogeneity, the genotype-specific odds ratios (ORs) suggested a codominant model. Carriers of the TT and CT genotypes were about 33% less likely (OR = 0.67, 95% CI: 0.54-0.84) and about 20% less likely (OR = 0.80, 95% CI: 0.66-0.95), respectively, to have atopic asthma compared to carriers of the CC genotype. Among-study heterogeneity may be explained by overly broad asthma phenotype definitions, gene-environment interactions, and gene-gene interactions. Conclusions: A protective dose-response relationship between the CD14 -260T allele and atopic asthma susceptibility was observed. These results demonstrate the importance of precisely specified case-control groups as well as the need to assess interactions in the investigation of complex diseases such as asthma. [ABSTRACT FROM AUTHOR]

Abstract: Asthma is a chronic inflammatory disease of the lungs which affects more than 6.5 million American children. A family-based genome-wide association study of copy-number variation identified an association between decreased copy-number at TCRγ and childhood allergic asthma. TCRγ encodes the T-cell receptor gamma glycoprotein, a cell-surface protein found on T-cells and involved in cell-mediated immunity. Using quantitative real-time PCR, we sought to determine if copy-number variation at TCRα, TCRβ or TCRγ was associated with childhood allergic asthma in an independent cohort of 94 cases and 455 controls using DNA from buccal swabs. Copy-number variation at these loci is well-known, but appears to be dominated by somatic mutations. Genotyping results indicated that copy-number variants at these genes are largely somatic mutations, as inheritance did not show Mendelian consistency. In these mosaic cell populations, copy-number was significantly reduced among asthmatic children at TCRγ (p =0.0199), but was not associated at TCRα or TCRβ (p =0.7972 and 0.8585, respectively). These findings support the association between reduced copy-number at TCRγ and childhood allergic asthma. Further work is needed to resolve whether reduced copy-number at TCRγ predisposes individuals to asthma, or whether deletion of this gene is a somatic response to the disease. [ABSTRACT FROM AUTHOR]

Abstract: Given the potential impact of age on mortality, neurological outcomes and the extent of post-traumatic neural degeneration, we examined these issues using a large, prospectively accrued clinical database (n =485) supplemented by analysis of postmortem spinal cord tissue (n =12) to compare axonal survival and white matter degeneration in younger versus elderly individuals with spinal cord injury (SCI). Elderly individuals (≥65 years) had significantly greater mortality rates than younger individuals at 30 days, at 6 months and at 1 year following SCI (46.88% versus 4.86%, respectively; p <0.0001). However, among survivors, age was not significantly associated with motor and sensory outcomes at 6 weeks, 6 months and 1 year post-SCI in univariate and multivariate analyses. Correspondingly, neuroanatomical analysis of postmortem spinal cord tissue revealed no significant age-related differences for extent of myelin degeneration or number of intact axons within sensory, motor and autonomic spinal cord tracts post-SCI. Treatment protocols for SCI need to identify preventable predictors of mortality in the elderly post-SCI, recognizing that the potential for neurological recovery among elderly survivors of SCI is similar to that of younger individuals. [Copyright &y& Elsevier]

A letter to the editor is presented in response to the article "The Risk of Major Cardiac Malformations Associated With Paroxetine Use During the First Trimester of Pregnancy: A Systematic Review and Meta-Analysis," that was published in the previous issue.

In the clinical management of early-stage cutaneous melanoma, it is critical to determine which patients are cured by surgery alone and which should be treated with adjuvant therapy. To assist in this decision, many groups have made an effort to use molecular information. However, although there are hundreds of studies that have sought to assess the potential prognostic value of molecular markers in predicting the course of cutaneous melanoma, at this time, no molecular method to improve risk stratification is part of recommended clinical practice. To help understand this disconnect, we conducted a systematic review and meta-analysis of the published literature that reported immunohistochemistry-based protein biomarkers of melanoma out- come. Three parallel search strategies were applied to the PubMed database through January 15, 2008, to identify cohort stud- ies that reported associations between immunohistochemical expression and survival outcomes in melanoma that conformed to the REMARK criteria. Of the 102 cohort studies, we identified only 37 manuscripts, collectively describing 87 assays on 62 distinct proteins, which met all inclusion criteria. Promising markers that emerged included melanoma cell adhesion molecule (MCAM)/MUC18 (all-cause mortality [ACM] hazard ratio [HR] = 16.34; 95% confidence interval [Cl] = 3.80 to 70.28), matrix met- alloproteinase-2 (melanoma-specific mortality [MSM] HR = 2.6; 95% Cl = 1.32 to 5.07), Ki-67 (combined ACM HR = 2.66; 95% Cl = 1.41 to 5.01), proliferating cell nuclear antigen (ACM HR = 2.27; 95% Cl = 1.56 to 3.31), and p16/INK4A (ACM HR = 0.29; 95% Cl = 0.10 to 0.83, MSM HR = 0.4; 95% Cl = 0.24 to 0.67). We further noted incomplete adherence to the REMARK guidelines: 14 of 27 cohort studies that failed to adequately report their methods and nine studies that failed to either perform multivariable analyses or report their risk estimates were published since 2005. [ABSTRACT FROM AUTHOR]

There is growing concern among epidemiologists that most discovered associations are either inflated or false. The reasons for this concern have focused on methodological issues in the conduct and publication of epidemiologic research. This commentary suggests that another reason for discrepant findings may be that animal research is producing implausible hypotheses. Many animal studies are methodologically weak, and the animal literature is not systematically reviewed and synthesized. Moreover, most bodies of animal literature may be so heterogeneous that they can be used selectively to support the plausibility of almost any epidemiology study result. Epidemiologists themselves also do not consistently conduct systematic reviews of bodies of biological evidence which might point to sources of bias in an evidence base. Animal research will likely continue to provide the biological basis for epidemiological investigation, but substantial improvement is needed in how it is conducted and synthesized to improve the predictability of animal studies for the human condition. [Copyright &y& Elsevier]

Objective: Assess the screening efficiency of the caretaker-report CBCL and SDQ in community and clinical samples using published data. Methods: PyschInfo, Medline, and EMBASE were systematically searched to identify studies with appropriate efficiency data. Estimates of sensitivity and specificity were extracted from identified studies and used to generate summary likelihood ratio estimates on which the scales were compared. Summary estimates of sensitivity and specificity were calculated with respect to a ‘true’ diagnosis to compare scales. Results: A total of 29 and 3 studies met inclusion criteria for CBCL and SDQ respectively. Summary estimates of the likelihood ratios for domains assessed by CBCL ranged from 3.86 (2.23, 6.69) to 4.87 (2.90, 8.18); and for SDQ from 5.02 (1.61, 15.63) to 8.32 (2.72, 25.48). Heterogeneity was low. For total problems, the SDQ caretaker-report was found to be most specific (0.93, 95% CI 0.92, 0.94) and the CBCL caretaker-report to be most sensitive (0.66, 95%CI 0.60, 0.73). Conclusions: This meta-analysis supports continued use of the CBCL and SDQ via caretaker-report in clinical and community samples. Additional research is required to determine if there is a true difference in efficiency between the two scales. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular disease," by S.E. Nissen and K. Wolski.

The discovery of strong associations of the His402 variant of complement factor H (CFH) and the change in the promoter region of HtrA serine peptidase 1 (HTRA1) with age-related macular degeneration (AMD) have altered our conception of the pathophysiology of this disease. The complement system has been placed at the center of a flurry of research interest, and a similar growth in attention to the serine proteases is not far behind. The specific role of these variants in causing AMD is unknown, but they will undoubtedly lead to a deeper understanding of the biological mechanisms and will point to new avenues for pharmacologic management. Furthermore, these variants will enable clinicians and investigators to identify people at high risk for this condition, thereby establishing the preconditions for preventing the disease. [Copyright &y& Elsevier]

The article presents a study of published evidence regarding duration of intrapartum antibiotic prophylaxis (IAP) administration to pregnant women with group B Streptococcus (GBS). It has been found that there are no well-designed studies examining the length of IAP for prevention of early-onset GBS disease of the newborn. Continuation of IAP treatment is recommended according to the American College of Obstetricians and Gynecologists guidelines.

Purpose: To review the methodologic issues complicating caffeine exposure assessment during pregnancy; to discuss maternal and fetal caffeine metabolism, including genetic polymorphisms affecting caffeine metabolism; and to discuss the endogenous and exogenous risk factors known to influence caffeine metabolism. Methods: A review of the relevant literature. Results: There is wide inter-individual variation in caffeine metabolism, primarily due to variations in CYP1A2 enzyme activity. Some variability in CYP1A2 activity is due to genetic polymorphisms in the CYP1A2 gene which can cause increased or decreased inducibility of the enzyme. Considerable evidence exists that maternal caffeine metabolism is influenced by a variety of endogenous and exogenous factors and studying the genetic polymorphisms may improve understanding of the potential effects of caffeine and its metabolites on perinatal outcomes. There is substantial evidence that measurement of maternal, fetal, and neonatal caffeine metabolites may allow for a more precise measure of fetal caffeine exposure. Conclusions: Research on the genetic polymorphisms affecting caffeine metabolism may further explain the potential effects of caffeine and its metabolites on perinatal outcomes. [Copyright &y& Elsevier]

: ObjectiveTo prospectively examine in pregnant women whether asthma or asthma therapy influenced preterm delivery, intrauterine grown restriction (IUGR), or birthweight.: MethodsWe enrolled 873 pregnant women with a history of asthma, of whom 778 experienced asthma symptoms or took medication, and 1333 women with no asthma history, including 884 women with neither asthma diagnosis nor symptoms and 449 with symptoms but no diagnosis. Asthma symptoms, medication, and severity were classified according to 2002 Global Initiative for Asthma guidelines.: ResultsPreterm delivery was not associated with asthma diagnosis, severity, or symptoms but was associated with use of controller medications, independent of symptoms, specifically oral steroids and theophylline. Gestation was reduced by 2.22 weeks in women using oral steroids daily (P = .001) and 1.11 weeks after theophylline (P = .002). We observed a 24% (5–47%) increased risk for IUGR with each increased symptom step, which increased further in symptomatic women with no asthma diagnosis (31%, 4–65%) compared with women with neither asthma nor symptoms.: ConclusionWe found no effect of asthma symptoms or severity on preterm delivery but observed increased risks associated with use of oral steroid and theophylline. Intrauterine growth restriction was associated with asthma severity, which possibly reflects a hypoxic fetal effect. Women with asthma symptoms but no diagnosis were at particular risk of undermedication and delivering IUGR infants. These observations support guidelines that advocate active management of pregnant patients with mild or moderate asthma with β2 agonists, with oral steroids added only if severity increases. Symptomatic patients without an asthma diagnosis might need to be equally managed. [Copyright &y& Elsevier]

The National Hospital Discharge Survey records for medical-legal, spontaneous, and "other" abortions (ICDA-8 640-641, 643, and 644 respectively) for 1970-77 were analyzed to investigate the impact of liberalized access to abortion on abortion-related morbidity in the United States. The analysis suggests that in census regions where an increase in medical-legal abortions performed in hospitals occurred over the study period there was an associated decreased likelihood of a "spontaneous" or "other" abortion. The spontaneous and "other" abortion codes appear to have been used synonymously and a small number of each used to classify complications of both illegal and legal abortions performed outside hospitals. There was a significant reduction in length of slay for spontaneous and other abortions between 1970 and 1977. This is suggestive of decreasingly severe presenting symptomatology for complicated abortion. The study further suggests that: during 1970-77 illegal abortions were largely replaced by legal procedures: increases in legal abortion beyond those replacing illegal have not resulted in increased rates of hospitalization for complicated abortion; and, the case morbidity rate for legal abortion appears to have declined. [ABSTRACT FROM AUTHOR]

The relationship between abortion experience and contraceptive practice is examined among women having a first or repeat induced abortion at the same clinic(n=443 in each group). A previous abortion was the single most important predictor of past contraceptive practices and of contraception at the conception of the pregnancy being terminated. A previous abortion was associated with greater use of all methods of contraception among women not on welfare (P < 0·001). During the 18–month study the proportion of patients who had had previous abortions rose from 13·3% to 21·1%, and those undergoing repeat abortions appeared increasingly likely to be on welfare. Contraceptive practies did not change over time except for women on welfare having repeat abortions who became less likely to have used contraception at the time of conception (p < 0·05). While the experience of abortion is generally associated with improved contraceptive practice, many women in this population, particularly those on welfare, appear to remain exposed to unprotected coitus and subsequent repeat abortion. [ABSTRACT FROM PUBLISHER]

In a sample of 345 women aborting at a New York clinic, women having a repeat abortion had delayed significantly less in seeking abortion than had women aborting for the first time. Those having a repeat abortion were more likely to anticipate, suspect and acknowledge pregnancy, and to have located the abortion clinic more rapidly, once the decision to have an abortion was made. Psychological reactions to the decision did not differ between women having first and repeat abortions. The complex interactions of many of the factors involved in the decision-making process were examined by path analysis. Variables entering the path analysis explained 36·0 and 52·4% of the variance in delay for first and repeat abortions, respectively. The analyses suggest that women having repeat abortions come from at least three groups: (1) those whose contraceptive method failed because of technical failure; (2) those experiencing contraceptor failure due to social and personal interactions with the method not conducive to optimal contraceptive practice, and (3) those women who are not practising contraception and for whom repeated unwanted pregnancies may be a response to neurotic needs. [ABSTRACT FROM PUBLISHER]

Discusses the international standards for neurological and functional classification of spinal cord injury, as of May 1997. Description of the spinal cord; Recommended neurological examination, both sensory and motor components; American Spinal Injury Association's impairment scale used in grading the degree of impairment.

Presents a study comparing the efficacy of methylprednisolone administered for 24 hours with methylprednisolone administered for 48 hours tirilazad mesylate administered for 48 hours to patients with acute spinal cord injury. Objectives; Design; Setting; Patients; Intervention; Main Outcome Measures; Results; Conclusions.

Opinion. Offers the article by T. Bhuta and D.J. Henderson-Smart in the November 1997 issue of `Pediatrics,' concerning ventilation preterm infants with acute pulmonary dysfunctions, as an example of an important neonatal systematic review. Reasons for doing systematic reviews of research; Uses of systematic reviews; Production of neonatal systemic reviews.

Abstract: Calls by Lilienfeld, Fraser, and others some three decades ago to introduce epidemiology into undergraduate college education remain largely unfulfilled. Consideration of epidemiology as a “liberal art” has also led to exploring possibilities for introducing epidemiology into early education: to high and even middle schools. Adding epidemiology to school curricula should help educate the public to understand science-based evidence concerning the causes and treatments of disease, help inoculate them against a tsunami of biased and fraudulent media messaging, and permit advancing postgraduate education in epidemiology to even higher levels of scholarship. [Copyright &y& Elsevier]

The author discusses the worthiness of random sampling in the U.S. The author states that a sampling design will result in a sample that is more represented than a convenience sample is initiated. The author cites that random sampling will allow analysis to have an external validity. The author also mentions that sampling avoids bias due to under selecting high or low exposed children by disease status.

Opinion. Comments on the quality of data based on neonatal randomized trials collected by randomized trial networks. Insights into iatrogenic and other institutional and environmental influences on neonatal mortality; Example of networks; Susceptibility of network data to inappropriate generalization and overinterpretation.

The author comments on research which compared the random-effects meta-analysis and fixed-effect models and mentions the conclusion on the preference for the random-effects approach in clinical trials and its fundamental problems.

A response from the authors of the article "Weight Gain After Breast Cancer Diagnosis and All-Cause Mortality: Systematic Review and Meta-Analysis" is presented.

The article observes that several systematic analyses of pre-clinical animal experiments have uncovered serious flaws in the methodology of these studies, which thereby limit any clinical benefits these studies supposedly offer to patients and also undermine the moral justification for using animals in pre-clinical testing. In addition, the biomedical research community is increasingly questioning the reliability of animal-based models in predicting human responses to drugs and diseases.

Objective: The Follow-Up Study of patients previously enrolled in Exubera controlled clinical trials (FUSE) was designed to evaluate whether patients previously treated with Exubera (EXU; insulin human [rDNA origin], inhaled powder) in controlled clinical trials died because of incident primary lung cancer at a substantially higher rate than patients treated with a comparator.Research Design and Methods: FUSE is a hybrid, randomized, controlled trial/cohort study including participants of 17 prior EXU clinical trials. Pooled patient data from these trials were used, and the subset of patients enrolled in the follow-up cohort study was followed prospectively for 2 years in order to evaluate the incidence of fatal and nonfatal primary lung cancers and all-cause mortality.Results: There were 24,409 person-years (PY) of observation among 7,439 trial patients, with 4,017 PY (16.5%) from the period after the trials but before the prospective follow-up and 5,299 PY (21.7%) from the prospective follow-up. Just over half of the 2,631 patients (51.6%) in the prospective follow-up were randomized to EXU in the original trial. The incidence density ratio was 2.8 (95% CI 0.5, 28.5) for lung cancer-related mortality and 3.7 (95% CI 1.0, 20.7) for incident primary lung cancer. The hazard ratio for all-cause mortality was 0.81 (95% CI 0.60, 1.10).Conclusions: These data cannot exclude an increased risk of lung cancer-related mortality associated with EXU use. If real, the absolute increased risk of lung cancer-related mortality was small (0.48 cases per 1,000 PY). For all-cause mortality-the most reliably measured end point with the clearest interpretation-EXU users did not experience an excess all-cause death rate (relative or absolute) compared with users of other diabetes treatments over the study period. [ABSTRACT FROM AUTHOR]

A response by Kari R. Risnes and Michael B. Bracken to a letter to the editor about their article "Antibiotic exposure by 6 months and asthma and allergy at 6 years: findings in a cohort of 1,401 US children" in the February 2011 issue is presented.

Presents a letter to the editor regarding the occurrence of asthma symptoms during pregnancy.

The author comments on the article "Maternal caffeine intake during pregnancy is associated with risk of low birth weight: a systematic review and dose-response meta-analysis" by L.W. Chen and colleagues which appeared in the 2014 issue of the periodical "BMC Medicine." Topics include association of maternal caffeine intake with pregnancy outcomes such as low birth weight, fetal growth restriction and preterm delivery, association between caffeine use & smoking and risks of low birth weight.

Examines dispensability of clinical trials and acceptance of uncertainty in medical practice. Importance of Lugano report on highlighting problems affecting attitude toward clinical trials; Concern om randomized clinical trial violating doctor-patient relationship; Perception on dilemma on balancing unnecessary risk of current patient against risk of future patients.

A letter to the editor is presented on spinal cord injury of football player Dennis Byrd.

Therapy for childhood acute lymphoblastic leukemia (ALL) is associated with 5-year survival rates of ∼90% even after largely eliminating cranial radiation. This meta-analysis assesses the long-term neurocognitive functioning after chemotherapy-only regimens among survivors of childhood ALL. We conducted a systematic review to identify studies that evaluated long-term neurocognitive functioning following treatment of ALL by searching MEDLINE/PubMed, Database of Abstracts of Reviews of Effects, and secondary sources. Studies were included if ALL survivors were in continuous first remission, did not receive any radiation, were at least ≥2 years off therapy or ≥5 years since diagnosis, and were compared with a healthy control group. Weighted mean differences with 95% confidence intervals (CIs) were calculated. Ten nonexperimental studies met all eligibility criteria and included 509 patients and 555 controls. Meta-analysis demonstrated statistically significant moderate impairment across multiple neurocognitive domains evaluated, with intelligence most affected. Significant differences in standard deviation (SD) scores were found for Full Scale intelligence quotient (IQ) (-0.52 SD; 95% CI, -0.68 to -0.37), Verbal IQ (-0.54 SD; 95% CI, -0.69 to -0.40), and Performance IQ (-0.41 SD; 95% CI, -0.56 to -0.27); these SD scores correspond to changes in IQ of 6 to 8 points. Working memory, information processing speed, and fine motor domains were moderately, but statistically significantly, impaired. Meta-analysis of ALL survivors treated without cranial radiation demonstrated significant impairment in IQ and other neurocognitive domains. Patients and their families should be informed about these potential negative effects to encourage surveillance and educational planning. Both preventive and intervention strategies are needed. [ABSTRACT FROM AUTHOR]

Objective: Systematic review and meta-analysis to investigate the association between maternal AGTR1 gene single nucleotide polymorphisms (SNPs) and preeclampsia (PE). Methods: A systematic literature search was performed using PubMed, EMBASE, Scopus, and HuGE Literature Finder databases. The review was conducted according to PRISMA guidelines. Summary odds ratios (ORs) for the allelic and genotypic contrasts were calculated and compared to indicate the most appropriate genetic model for the polymorphism of interest. Among-study heterogeneity was assessed using the I2 statistic and publication bias was evaluated visually using funnel plots. Results: Seven maternal SNPs investigated with PE were found, but only AGTR1 +1166A>C accumulated sufficient evidence for meta-analysis. Summary ORs calculated from eight studies (10 populations involving 845 PE cases and 1150 controls) did not reveal an association between the +1166A>C polymorphism and PE (allelic OR = 1.19, 95% CI: 0.96-1.47). No evidence of publication bias and among-study heterogeneity was detected. Conclusions: meta-analysis findings did not support AGTR1 +1166A>C as a susceptibility locus for PE. Other AGTR1 SNPs require more study. [ABSTRACT FROM AUTHOR]

CONTEXT: The increasing prevalence of childhood asthma has been associated with low microbial exposure as described by the hygiene hypothesis. OBJECTIVE: We sought to evaluate the evidence of association between antibiotic exposure during pregnancy or in the first year of life and risk of childhood asthma. METHODS: PubMed was systematically searched for studies published between 1950 and July 1, 2010. Those that assessed associations between antibiotic exposure during pregnancy or in the first year of life and asthma at ages 0 to 18 years (for pregnancy exposures) or ages 3 to 18 years (for first-year-of-life exposures) were included. Validity was assessed according to study design, age at asthma diagnosis, adjustment for respiratory infections, and consultation rates. RESULTS: For exposure in the first year of life, the pooled odds ratio (OR) for all studies (N = 20) was 1.52 (95% confidence interval [CI]: 1.30-1.77). Retrospective studies had the highest pooled risk estimate for asthma (OR: 2.04 [95% CI: 1.83-2.27]; n = 8) compared with database and prospective studies (OR: 1.25 [95% CI: 1.08-1.45]; n = 12). Risk estimates for studies that adjusted for respiratory infections (pooled OR: 1.16 [95% CI: 1.08-1.25]; n = 5) or later asthma onset (pooled OR for asthma at or after 2 years: OR: 1.16 [95% CI: 1.06-1.25]; n = 3) were weaker but remained significant. For exposure during pregnancy (n = 3 studies), the pooled OR was 1.24 (95% CI: 1.02-1.50). CONCLUSIONS: Antibiotics seem to slightly increase the risk of childhood asthma. Reverse causality and protopathic bias seem to be possible confounders for this relationship. [ABSTRACT FROM AUTHOR]

We investigated if clinicians were altering their care of group B streptococcus (GBS)-positive women in labor to achieve 4 hours of intrapartum antibiotic prophylaxis based on their interpretation of the 2002 Centers for Disease Control (CDC) guidelines on prevention of perinatal GBS disease. We surveyed all clinicians with privileges on the labor floor at our institution about their interpretation and clinical application of the 2002 CDC guidelines. Seventy of 96 eligible clinicians (72.9%) completed our survey. In our survey, only 22.9% of clinicians reported not altering their management of labor in GBS-positive pregnancies that achieved less than 4 hours of prophylaxis. These alterations included ''laboring down'' or delaying pushing; turning off or decrease an oxytocin infusion; or delaying or avoiding artificial rupture of membranes. Clinicians are altering their management of labor to attempt to achieve 4 hours of intrapartum prophylaxis. The 2002 CDC guidelines do not specifically recommend prolonging labor and are being interpreted differently in the clinical setting than the authors may have intended. The effects and consequences of this interpretation are unknown. [ABSTRACT FROM AUTHOR]

Background and Purpose: Of the 795,000 strokes occurring in the USA each year, over 20% are recurrent events. Little is known about how the rates of recurrent stroke in the country have changed over time. Our objective was to determine national trends in 1-year recurrent ischemic stroke rates by US county among the elderly from 1994 to 2002. Methods: One-year recurrent stroke rates following incident ischemic stroke (ICD-9 433, 434, 436) among all fee-for-service Medicare beneficiaries were determined by US county for 1994-1996, 1997-1999, and 2000-2002. Bayesian spatiotemporal Poisson modeling was used to determine county-specific trends in recurrent stroke rates over time with risk adjustment for demographics, medical history and comorbid conditions. Results: The analysis included more than 2.5 million beneficiaries (56% women; mean age: 78 years; 87% white; n = 957,933 for 1994-1996; n = 838,330 for 1996-1999; n = 895,916 for 2000-2002) aggregated to all 3,118 US counties. After adjustment for changing patient demographics and comorbidities, there was a 4.5% decrease in recurrent stroke rates from 1994-1996 (13.2%) to 2000-2002 (12.6%; p for trend <0.0001). The geographic and temporal patterns were not uniform; the recurrent stroke rates decreased within sections of the Southeast (the 'stroke belt'), but increased in counties in the middle and western sections of the USA. Conclusions: The overall recurrent ischemic stroke rates declined by almost 5% from 1994 to 2002, but temporal patterns varied markedly by region. Additional research is needed to identify the reasons for this geographic disparity. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives: We estimated the prevalence of renal impairment in heart failure (HF) patients and the magnitude of associated mortality risk using a systematic review of published studies. Background: Renal impairment in HF patients is associated with excess mortality, although precise risk estimates are unclear. Methods: A systematic search of MEDLINE (through May 2005) identified 16 studies characterizing the association between renal impairment and mortality in 80,098 hospitalized and non-hospitalized HF patients. All-cause mortality risks associated with any renal impairment (creatinine >1.0 mg/dl, creatinine clearance [CrCl] or estimated glomerular filtration rate [eGFR] <90 ml/min, or cystatin-C >1.03 mg/dl) and moderate to severe impairment (creatinine ≥1.5, CrCl or eGFR <53, or cystatin-C ≥1.56) were estimated using fixed-effects meta-analysis. Results: A total of 63% of patients had any renal impairment, and 29% had moderate to severe impairment. After follow-up ≥1 year, 38% of patients with any renal impairment and 51% with moderate to severe impairment died versus 24% without impairment. Adjusted all-cause mortality was increased for patients with any impairment (hazard ratio [HR] = 1.56; 95% confidence interval [CI] 1.53 to 1.60, p < 0.001) and moderate to severe impairment (HR = 2.31; 95% CI 2.18 to 2.44, p < 0.001). Mortality worsened incrementally across the range of renal function, with 15% (95% CI 14% to 17%) increased risk for every 0.5 mg/dl increase in creatinine and 7% (95% CI 4% to 10%) increased risk for every 10 ml/min decrease in eGFR. Conclusions: Renal impairment is common among HF patients and confers excess mortality. Renal function should be considered in risk stratification and evaluation of therapeutic strategies for HF patients. [Copyright &y& Elsevier]

PURPOSE: Asthma is a major complication of pregnancy, but there are currently no reliable national estimates for the United States of asthma prevalence in pregnancy or in the childbearing years.METHODS: The prevalence of asthma among pregnant women and all childbearing-aged women was estimated and examined by age group using the National Health Interview Survey (NHIS), 1997–2000, the Behavioral Risk Factor Surveillance System (BRFSS), 2000–2001, and the Third National Health and Nutrition Examination Survey (NHANES III), 1988–1994. Time trends were explored using NHANES II (1976–1980) and NHANES III (1988–1994).RESULTS: Asthma was estimated to affect from 88,573 to 190,650 pregnant women between 1997 and 2001, or approximately 3.7% to 8.4% of pregnant women in the United States. A slightly lower estimate of 3.2% was obtained for the period between 1988 and 1994. Among adult women of childbearing age, a two-fold increase in asthma from 2.9% to 5.8% occurred between 1976–1980 and 1988–1994. Among women aged 18 to 24, the increase was three-fold, from 1.8% to 6.0%.CONCLUSION: The prevalence of asthma during pregnancy may be higher than previously estimated and appears to be continuing to increase. [Copyright &y& Elsevier]

Background: Inferior vena cava (IVC) filters are widely used for prevention of pulmonary embolism (PE). However, uncertainty persists about their efficacy and safety.Objectives: The authors conducted a systematic review and meta-analysis of the published reports on the efficacy and safety of IVC filters.Methods: The authors searched PubMed, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov through October 3, 2016, for randomized controlled trials (RCTs) or prospective controlled observational studies of IVC filters versus none in patients at risk of PE. Inverse variance fixed-effects models with odds ratio (OR) as the effect measure were used for primary analyses. Main outcomes included subsequent PE, PE-related mortality, all-cause mortality, and subsequent deep vein thrombosis (DVT).Results: The authors' search retrieved 1,986 studies, of which 11 met criteria for inclusion (6 RCTs and 5 prospective observational studies). Quality of evidence for RCTs was low to moderate. Overall, patients receiving IVC filters had lower risk for subsequent PE (OR: 0.50; 95% confidence interval [CI]: 0.33 to 0.75); increased risk for DVT (OR: 1.70; 95% CI: 1.17 to 2.48); nonsignificantly lower PE-related mortality (OR: 0.51; 95% CI: 0.25 to 1.05); and no change in all-cause mortality (OR: 0.91; 95% CI: 0.70 to 1.19). Limiting the results to RCTs showed similar results. Findings were substantively similar across a wide range of sensitivity analyses.Conclusions: Very few prospective controlled studies, with limited quality of evidence, exist regarding the efficacy and safety of IVC filters. Overall, filters appear to reduce the risk of subsequent PE, increase the risk for DVT, and have no significant effect on overall mortality. [ABSTRACT FROM AUTHOR]