Psychometric analysis of the Patient Assessment of Own Functioning Inventory in women with breast cancer.

BACKGROUND AND PURPOSE: The purpose of this secondary analysis was to examine the reliability and validity of the Patient Assessment of Own Functioning Inventory (PAOFI) in postmenopausal women with early-stage breast cancer before adjuvant therapy. METHODS: Data from 259 postmenopausal women with early-stage breast cancer before adjuvant therapy were analyzed. Exploratory factor analysis was used to uncover the PAOFI's underlying factor structure and reliability coefficients were computed for each subscale. RESULTS: 5 factors measuring perceived cognitive functioning had eigenvalues > 1 and accounted for 54% of the extracted variance. Subscale reliability coefficients ranged from .572 to .883. CONCLUSIONS: Psychometric evaluation of the PAOFI provided evidence of reliability and construct validity in this population. Additional studies are needed to confirm the 5-factor structure.

If we know so much about preeclampsia, why haven't we cured the disease?

Preeclampsia has been recognized for at least 100 years. In the last 20 years, the consideration of the disorder as more than simply hypertension in pregnancy has led to an explosion in knowledge about preeclampsia pathophysiology. It is now evident that for most cases of preeclampsia, the root cause is the placenta. Relatively reduced placental perfusion leads to inflammation, oxidative stress, and endoplasmic reticulum stress, which converge to modify maternal physiology, with endothelium an important target. Although preeclampsia is characteristically diagnosed in the last third of pregnancy, it is evident that many of these pathophysiological changes can be detected long before clinically evident disease. Furthermore, it is evident that the "maternal constitution," including genetic, behavioral, and metabolic factors, influences the maternal response to the abnormal placentation of preeclampsia. These insights would seem to provide a guide for the prediction of the disorder in early pregnancy, along with targets for intervention. However, this has not been the case. Predictive tests guided by this knowledge do not predict well and several interventions guided by the expanded understanding of pathophysiology do not prevent the disease. We propose that these failures are secondary to the fact that preeclampsia is more than one disorder. Further, we suggest that future progress toward prediction and prevention will require research guided by this concept.

Variation in endoglin pathway genes is associated with preeclampsia: a case-control candidate gene association study.

BACKGROUND: Preeclampsia is a hypertensive, multi-system pregnancy disorder whose pathophysiology remains unclear. Elevations in circulating soluble endoglin (sENG) and placental/blood ENG mRNA expression antedate the clinical onset of preeclampsia. This study investigated if endoglin (ENG) pathway genetic variation was also associated with the development of preeclampsia. METHODS: We used a case-control candidate gene association design. Data from 355 white (181 preeclampsia cases/174 controls) and 60 black (30 preeclampsia cases/30 controls) women matched on ancestry, age, and parity were analyzed. Tagging single nucleotide polymorphisms (tSNPs) and potentially functional SNPs in ENG, TGFß1, TGFßR1, ALK1, and TGFßR2 were genotyped with iPLEX® and TaqMan®. Chi-square or Fisher's exact tests were used to conduct allele/genotype/haplotype tests in white/black subgroups separately. Odds ratios were computed with binary logistic regression for tSNPs with significant genotype tests. RESULTS: Of the 49 SNPs evaluated, variation in two ENG tSNPs (rs11792480, rs10121110) and one TGFßR2 tSNP (rs6550005) was associated with preeclampsia in white women (P <0.05, each). In black women, variation in two TGFß1 tSNPs (rs4803455, rs4803457), one TGFßR1 tSNP (rs10739778), and three TGFßR2 tSNPs (rs6550005, rs1346907, rs877572) was associated with preeclampsia (P <0.05, each). Further evaluation of ENG tSNP rs10121110 revealed that white women inheriting the AA genotype were 2.29 times more likely to develop preeclampsia compared to the GG genotype (P = 0.008, [99% CI: 1.02 to 5.13]). For black women, similar evaluation of TGFß1 tSNP rs4803457 revealed women inheriting the CT genotype were 7.44 times more likely to develop preeclampsia than those with the CC genotype (P = 0.005, [99% CI: 1.19 to 46.41]). CONCLUSIONS: ENG pathway genetic variation is associated with preeclampsia. Different ENG pathway genes may be involved in preeclampsia development among white and black women. Additional studies are needed to validate these findings and to determine if genetic variation in ENG pathway genes impacts ENG and sENG levels in preeclampsia.

A systematic review of endoglin gene expression in preeclampsia.

OBJECTIVE: To synthesize scientific literature that addresses the role of endoglin (ENG) gene expression in preeclampsia (PE). DATA SOURCES: A literature search of PubMed and Ovid MEDLINE was conducted using the keywords endoglin, gene, and preeclampsia. Restrictions included English language and humans. Additional articles were identified/selected for evaluation via PubMed e-mail updates (keywords: endoglin and preeclampsia) and review of article reference lists obtained from the search. STUDY SELECTION: The initial 14 abstracts retrieved from the literature search were reviewed and 9 studies were selected for evaluation. Review articles and studies not addressing ENG expression (messenger RNA [mRNA] level) in the context of PE were excluded. An additional six articles were selected from PubMed e-mail updates and reference lists. DATA EXTRACTION: Data related to study objective, design, setting, subject information, phenotype, tissue type, data collection method, statistics, and results were extracted. DATA SYNTHESIS: Regardless of PE definition, ancestral background, gene expression analysis method, tissue type, and time of specimen collection, endoglin appears to play a role in PE development. Moreover, results suggest that a variety of biological mechanisms have the ability to modulate ENG expression in PE, demonstrating the potential complexity associated with endoglin's role in PE. CONCLUSIONS: This review article is the first to systematically synthesize evidence related to ENG expression in PE. Findings can be utilized to design future studies that (a) address methodological limitations observed in the reviewed studies and (b) specifically examine why ENG expression levels are altered and address mechanisms explaining how these alterations are involved in PE development.

A historical overview of preeclampsia-eclampsia.

Preeclampsia is a hypertensive, multisystem disorder of pregnancy whose etiology remains unknown. Although management is evidence-based, preventative measures/screening tools are lacking, treatment remains symptomatic, and delivery remains the only cure. Past hypotheses/scientific contributions have influenced current understanding of preeclampsia pathophysiology and guided management strategies and classification criteria. To provide insight into how past hypotheses/scientific contributions have shaped current practice trends, this article provides a historical overview of preeclampsia-eclampsia.