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author:("menten, made")
1.  Assessment of malignancy risk in patients with multiple sclerosis treated with intramuscular interferon beta-1a: retrospective evaluation using a health insurance claims database and postmarketing surveillance data 
Background
Intramuscular interferon beta-1a (IFNβ-1a), a multiple sclerosis (MS) therapy that has been commercially available for over a decade, provides a unique opportunity to retrospectively assess postmarketing data for evidence of malignancy risk, compared with relatively limited data available for more recently approved therapies. Postmarketing and claims data were analyzed to determine the risk of malignancy in MS patients treated with intramuscular IFNβ-1a.
Materials and methods
The cumulative reporting rates of suspected adverse drug reactions coded to malignancy in the intramuscular IFNβ-1a global safety database were compared with malignancy incidence rates in the World Health Organization GLOBOCAN database. In addition, using data from a large US claims database, the cumulative prevalence of malignancy in MS patients treated with intramuscular IFNβ-1a was compared with non-MS population controls, MS patients without intramuscular IFNβ-1a use, and untreated MS patients. Mean follow-up was approximately 3 years for all groups, ie, 3.1 years for the intramuscular IFNβ-1a group (range 0.02–6.0 years), 2.6 years for non-MS population controls (range 0–6.0 years), 2.6 years for the intramuscular IFNβ-1a nonuse group (range 0.01–6.0 years), and 2.4 years for the untreated MS group (range 0.01–6.0 years).
Results
An estimated 402,250 patients received intramuscular IFNβ-1a during the postmarketing period. Cumulative reporting rates of malignancy in this population were consistent with GLOBOCAN incidence rates observed within the general population. The claims database included 12,894 MS patients who received intramuscular IFNβ-1a. No significant difference in malignancy prevalence was observed in intramuscular IFNβ-1a users compared with other groups.
Conclusion
Results from this evaluation provide no evidence of an increased risk of malignancy with intramuscular IFNβ-1a use.
doi:10.2147/TCRM.S31347
PMCID: PMC3387830  PMID: 22767995
multiple sclerosis; malignancy; safety; intramuscular interferon beta-1a; postmarketing surveillance; claims
2.  Functional Variants in the Catalase and Myeloperoxidase Genes, Ambient Air Pollution, and Respiratory-related School Absences: An Example of Epistasis in Gene-Environment Interactions 
American Journal of Epidemiology  2009;170(12):1494-1501.
The individual effect of functional single nucleotide polymorphisms within the catalase and myeloperoxidase genes (CAT and MPO) has been studied in relation to asthma; however, their interrelationship with ambient air pollution exposures has yet to be determined. The authors investigated the interrelationships between variants in CAT and MPO, ambient air pollutants, and acute respiratory illness. Health information, air pollution, and incident respiratory-related school absences were ascertained in January–June 1996 for 1,136 Hispanic and non-Hispanic white US elementary schoolchildren as part of the prospective Children's Health Study. Functional and tagging single nucleotide polymorphisms for the CAT and MPO loci were genotyped. The authors found epistasis between functional polymorphisms in the CAT/MPO loci, which differed by levels of oxidant-stress-producing air pollutants. Risk of respiratory-related school absences was elevated for children with the CAT (G/G) and MPO (G/A or A/A) genes (relative risk = 1.35, 95% confidence interval: 1.03, 1.77; P-interaction = 0.005). The epistatic effect of CAT and MPO variants was most evident in communities exhibiting high ambient ozone levels (P-interaction = 0.03). The association of respiratory-illness absences with functional variants in CAT and MPO that differ by air pollution levels illustrates the need to consider genetic epistasis in assessing gene-environment interactions.
doi:10.1093/aje/kwp310
PMCID: PMC2800273  PMID: 19897513
air pollution; catalase; epistasis, genetic; peroxidase; respiratory tract infections
3.  Effects of In Utero and Childhood Tobacco Smoke Exposure and β2-Adrenergic Receptor Genotype on Childhood Asthma and Wheezing 
Pediatrics  2008;122(1):e107-e114.
Objective
Associations between single-nucleotide polymorphisms in the β2-adrenergic receptor gene and asthma and wheeze have been inconsistent. Recent studies indicated that tobacco smoke affects β2-adrenergic receptor gene expression and associations of β2-adrenergic receptor gene variants with asthma in adults. We aimed to investigate the joint effects of in utero and childhood secondhand tobacco smoke exposure and 2 well-characterized functional single-nucleotide polymorphisms (Arg16Gly and Glu27Gln) of β2-adrenergic receptor gene on asthma and wheezing in 3128 non-Hispanic and Hispanic white children of the Children's Health Study.
Methods
We fitted logistic regression models to estimate odds ratios and 95% confidence intervals for the independent and joint effects of these single-nucleotide polymorphisms and in utero and secondhand tobacco smoke exposure on asthma and wheeze outcomes.
Results
Exposures to in utero maternal smoking and secondhand tobacco smoke were associated with wheezing. Children who were homozygous for the Arg16 allele and were exposed to maternal smoking in utero were at a threefold increased risk for lifetime wheeze compared with children who were unexposed and had at least 1 Gly16 allele. We found similar joint effects of secondhand tobacco smoke and Arg16Gly with wheezing. The risk for lifetime, current, and nocturnal wheeze increased with the number of smokers at home among Arg16 homozygous children. The results were consistent in 2 cohorts of children recruited in 1993 and 1996. Diplotype-based analyses were consistent with the single-nucleotide polymorphism–specific results. No associations were found for Glu27Gln.
Conclusions
Both in utero and childhood exposure to tobacco smoke were associated with an increased risk for wheeze in children, and the risks were greater for children with the Arg16Arg genotype or 2 copies of the Arg16–Gln27 diplotype. Exposures to smoking need to be taken into account when evaluating the effects of β2-adrenergic receptor gene variants on respiratory health outcomes.
doi:10.1542/peds.2007-3370
PMCID: PMC2748980  PMID: 18558635
β-2 adrenergic receptor; prenatal exposure; secondhand-smoke exposure; asthma; wheeze
4.  Turnover intention in new graduate nurses: a multivariate analysis 
Journal of Advanced Nursing  2008;62(1):41-52.
Title
Turnover intention in new graduate nurses: a multivariate analysis
Aim
This paper is a report of a study to determine the relationship of new nurse turnover intent with individual characteristics, work environment variables and organizational factors and to compare new nurse turnover with actual turnover in the 18 months of employment following completion of a residency.
Background
Because of their influence on patient safety and health outcomes nurse turnover and turnover intent have received considerable attention worldwide. When nurse staffing is inadequate, especially during nursing shortages, unfavourable clinical outcomes have been documented.
Method
Prospective data collection took place from 1999 to 2006 with 889 new paediatric nurses who completed the same residency. Scores on study instruments were related to likelihood of turnover intent using logistic regression analysis models. Relationships between turnover intent and actual turnover were compared using Kaplan–Meier survivorship.
Results
The final model demonstrated that older respondents were more likely to have turnover intent if they did not get their ward choice. Also higher scores on work environment and organizational characteristics contributed to likelihood that the new nurse would not be in the turnover intent group. These factors distinguish a new nurse with turnover intent from one without 79% of the time. Increased seeking of social support was related to turnover intent and older new graduates were more likely to be in the turnover intent group if they did not get their ward choice.
Conclusion
When new graduate nurses are satisfied with their jobs and pay and feel committed to the organization, the odds against turnover intent decrease.
What is already known about this topicThere is concern in many countries about nurse turnover and the resulting effects on patient safety and quality of care.Decreasing ability to recruit experienced nurses has increased the emphasis on recruitment of new graduate nurses, particularly in the United States of America.Historically, new graduate nurses have a high turnover rate within the first year of employment.What this paper addsWhen new graduate nurses are satisfied with their jobs and pay and feel committed to the organization, the odds of turnover intent decrease.Increased seeking social support to cope with the transition from student to competent Registered Nurse is related to turnover intent.Older graduates (>30) are 4·5 times more likely to have turnover intent if they do not get their ward of choice.
doi:10.1111/j.1365-2648.2007.04570.x
PMCID: PMC2440489  PMID: 18352963
longitudinal study; nursing; paediatric nurses; personnel turnover; support; work environment
5.  TNF-308 Modifies the Effect of Second-Hand Smoke on Respiratory Illness–related School Absences 
Rationale: Exposure to second-hand smoke (SHS) has been associated with increased risk of respiratory illness in children including respiratory illness–related school absences. The role of genetic susceptibility in risk for adverse effects from SHS has not been extensively investigated in children.
Objective: To determine whether the tumor necrosis factor (TNF) G-308A genotype influences the risk for respiratory illness–related school absences associated with SHS exposure.
Methods: Incident school absences were collected, using an active surveillance system, between January and June 1996, as part of the Air Pollution and Absence Study, a prospective cohort study nested in the Children's Health Study. Buccal cells and absence reports were collected on 1,351 students from 27 elementary schools in California.
Measurements and Main Results: Illness-related school absences were classified as nonrespiratory and respiratory illness–related, which were further categorized into upper or lower respiratory illness–related absences based on symptoms. The effect of SHS exposure on respiratory illness–related absences differed by TNF genotype (p interaction, 0.02). In children possessing at least one copy of the TNF-308 A variant, exposure to two or more household smokers was associated with a twofold risk of a school absence due to respiratory illness (relative risk, 2.13; 95% confidence interval, 1.34, 3.40) and a fourfold risk of lower respiratory illness–related school absence (relative risk, 4.15; 95% confidence interval, 2.57, 6.71) compared with unexposed children homozygous for the common TNF-308 G allele.
Conclusions: These results indicate that a subgroup of genetically susceptible children are at substantially greater risk of respiratory illness if exposed to SHS.
doi:10.1164/rccm.200503-490OC
PMCID: PMC2718456  PMID: 16166621
epidemiology; school absence; second-hand smoke; TNF

Results 1-5 (5)