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Study Objectives: Approximately 85% of insomnia co-occurs with other disorders. Whereas insomnia was once considered "secondary" to these disorders, it is now widely recognized as an independent condition warranting treatment. While it is clear that insomnia can affect the course of other medical conditions, there is scant literature on the economic impact of comorbid insomnia among patients with common medical conditions. The aim of this study was to determine the economic burden of comorbid insomnia in 5 medical diseases commonly associated with insomnia: type 2 diabetes mellitus (T2DM), cancer undergoing treatment, menopause undergoing hormone replacement therapy, osteoporosis, and Alzheimer's disease and related dementias (ADRDs)., Methods: This retrospective cohort study used claims data from the IBM MarketScan Commercial and Medicare Supplemental Databases from January 1, 2014, through December 31, 2019. Insomnia and comorbid disease groups were defined using physician-assigned International Classification of Diseases diagnostic codes. Insomnia medication treatment was defined based on ≥1 prescription fills for the most commonly prescribed insomnia medications (zolpidem, low-dose trazodone, and benzodiazepines [as a class]). For each comorbid disease subgroup, 4 cohorts were created: (1) patients with either treated or untreated insomnia, (2) non-sleep-disordered controls, (3) patients with untreated insomnia, and (4) patients with treated insomnia., Results: Sample sizes for individuals with comorbid insomnia ranged from 23,168 (T2DM) to 3,015 (ADRDs). Within each disease subgroup and relative to non-sleep-disordered controls, patients with comorbid insomnia demonstrated greater adjusted health care resource utilization and costs across most points of service. Likewise, relative to individuals with untreated insomnia, those with treated insomnia generally demonstrated greater adjusted health care resource utilization and costs., Conclusions: In this national analysis, both untreated comorbid insomnia and comorbid insomnia treated with commonly prescribed insomnia medications were associated with increased health care resource utilization and costs across most points of service., Citation: Wickwire EM, Juday TR, Kelkar M, Heo J, Margiotta C, Frech FH. Economic burden of comorbid insomnia in 5 common medical disease subgroups. J Clin Sleep Med . 2023;19(7):1293-1302., (© 2023 American Academy of Sleep Medicine.)

Background: Maternal mental health conditions (MMHCs), which include depression and anxiety disorders during pregnancy and through five years postpartum, are among the most common obstetric complications in the United States overall and in Texas in particular. In the context of potential expansion of postpartum Medicaid coverage from 60 days to one year, we sought to capture the societal, financial burden of untreated MMHCs., Methods: We estimated the economic impact of untreated maternal mental health conditions (MMHCs) among births in Texas in 2019 using a cost-of-illness model., Results: We found that MMHCs affected 13.2% of mothers and, when left untreated, cost $2.2 billion among mothers and children born in Texas in 2019 when following the birth cohort from conception through five years postpartum. We found that MMHCs affected 17.2% of mothers enrolled in Texas' Medicaid for Pregnant Women and cost $962 million. In addition, the prevalence of MMHCs and resulting costs varied considerably among women of different races and ethnicities. Employers and health care payers, including Medicaid, bore most of these costs., Conclusions: The Texas Health and Human Services Commission's (HHSC) efforts to increase awareness about MMHCs and increase access to care represent an important step toward improving maternal and child health and maximizing benefits to Texas HHSC, employers, and insurers., (© 2022. The Author(s).)

Objectives. To estimate the economic burden of untreated perinatal mood and anxiety disorders (PMADs) among 2017 births in the United States. Methods. We developed a mathematical model based on a cost-of-illness approach to estimate the impacts of exposure to untreated PMADs on mothers and children. Our model estimated the costs incurred by mothers and their babies born in 2017, projected from conception through the first 5 years of the birth cohort's lives. We determined model inputs from secondary data sources and a literature review. Results. We estimated PMADs to cost $14 billion for the 2017 birth cohort from conception to 5 years postpartum. The average cost per affected mother-child dyad was about $31 800. Mothers incurred 65% of the costs; children incurred 35%. The largest costs were attributable to reduced economic productivity among affected mothers, more preterm births, and increases in other maternal health expenditures. Conclusions. The US economic burden of PMADs is high. Efforts to lower the prevalence of untreated PMADs could lead to substantial economic savings for employers, insurers, the government, and society.

Background: Trastuzumab may improve disease-free survival after chemotherapy for HER2-positive breast cancer. However, it carries a risk of cardiotoxicity and counseling patients about such risks is part of informed consent. The National Institute for Health and Clinical Excellence has published guidelines for cardiac assessment before and during treatment with trastuzumab in order to minimize the risk of cardiotoxicity. The aim of the present study was to identify risk factors for cardiotoxicity attributed to trastuzumab in a cohort population treated for primary and metastatic breast cancer., Patients and Methods: This study included all women who started a course of trastuzumab from February 2006 - February 2011 at three NHS Trusts in the UK. Their cardiac function during treatment was recorded and cardiotoxicity was defined as a decrease in left ventricular ejection fraction (LVEF) ≥ 10% and a reduction to <50%, or a clinical reduction in cardiac function as defined by the New York Heart Association. An independent samples t-test was used to assess whether patient age predicted cardiotoxicity. Pearson's chi-squared tests of independence were used to investigate the association between cardiotoxicity, the indication for trastuzumab, exposure to anthracycline chemotherapy, and Adult Comorbidity Evaluation-27 index (ACE-27) scores., Results: There were 388 female patients included in this study, with a mean age of 54 (range = 25-100 years). Cardiotoxicity was recorded during 61 (15.72%) courses of trastuzumab treatment. There were no associations between cardiotoxicity and the three factors (indication, exposure to anthracyclines, or ACE-27 score), and no significant difference in age between patients with and those without cardiotoxicity. However, subgroup analysis of patients who experienced cardiotoxicity (n = 61) showed that there was a negative correlation (-0.455; p = 0.001) between time-to-first cardiotoxicity event and age in the group who had received concurrent anthracycline therapy (n=49)., Conclusion: In a real-world 5-year population of patients who received trastuzumab, the incidence of drug-related cardiotoxicity was higher than expected, and the age of the patients appeared to predict the first cardiotoxic event amongst those who experienced cardiotoxicity and had received prior anthracyclines. However, incidence of cardiotoxicity in the whole cohort did not appear to be predicted by age, comorbidity, indication, or exposure to anthracylines. Vigilance, therefore, seems justified when conducting cardiac surveillance for all patients during treatment with trastuzumab, but especially for those who are elderly and receiving concurrent anthracycline therapy.

Background: Bladder cancers have different angiogenic pathways distinguishing not only papillary from solid tumours, but even papillary superficial from papillary invasive ones, thus representing selective targets for antiangiogenic drugs., Methods: The bacterial wall component tecogalan, inhibiting basic fibroblast growth factor (bFGF), the fumagillin derivative TNP-470, inhibiting vascular endothelial growth factor (VEGF), the distamycin A derivative PNU153429, and the tetracycline minocycline were administered to nude mice injected with the human bladder cancer cell lines 639V, causing bFGF-expressing papillary superficial tumours, or T24, causing VEGF-expressing papillary invasive tumours., Results: Tecogalan had no effect even on 639V tumour growth, where bFGF was unaffected. TNP-470 only had an effect on T24 tumours, delaying tumour appearance and growth and lowering VEGF; these effects were augmented by adding minocycline. PNU153429 had no effect on 639V tumours, and a slight effect on T24 tumours., Conclusion: TNP-470 may represent a selective drug for the treatment of VEGF-expressing invasive papillary bladder tumours., (Copyright 2005 S. Karger AG, Basel.)

The region 6q27 from human chromosome 6 has been reported to contain one or more tumor suppressor genes on the basis of cytogenetic, molecular and functional studies. We have recently carried out a detailed analysis of a candidate gene from 6q27 to evaluate its putative role as a tumor suppressor gene involved in ovarian cancer pathogenesis. The RNASET2 gene was shown to behave as a class II tumor suppressor and abolish the tumorigenic potential of an ovarian cancer-derived cell line. In this study, we have started the cellular and biochemical characterization of RNASET2 and showed that it is a secreted glycoprotein. Moreover, we have extended our previous studies by evaluating the effect of RNASET2 on the metastatic behavior of the highly-invasive ovarian cancer cell line HEY3MET2. From such analysis, RNASET2 was found to significantly decrease the metastatic potential of this cell line in vivo. Moreover, RNASET2-mediated suppression of tumorigenesis and metastasis was not affected by a double point mutation targeted to the putative ribonuclease catalytic sites, suggesting that tumor suppression by RNASET2 is not mediated by its ribonuclease activity. The potential biological implications of this unexpected finding are discussed in relation to the current evolutionary models.

Both n-6 and n-3 polyunsaturated fatty acids are dietary fats important for cell function, being involved in several physiologic and pathologic processes, such as tumorigenesis. Linoleic acid and conjugated linoleic acid, its geometrical and positional stereoisomer, were tested on several human tumor cell lines originating from different tissues and with different degrees of malignancy. This was to provide the widest possible view of the impact of dietary lipids on tumor development. While linoleic acid exerted different effects, ranging from inhibitory to neutral, even promoting growth, conjugated linoleic acid inhibited growth in all lines tested and was particularly effective against the more malignant cells, with the exception of mammary tumor cells, in which behavior was the opposite, the more malignant cell line being less affected. The inhibitory effect of conjugated linoleic acid on growth may be accompanied by different contributions from apoptosis and necrosis. The effects of conjugated linoleic acid on growth or death involved positive or negative variations in PPARs. The important observation is that a big increase of PPARalpha protein occurred in cells undergoing strong induction of apoptosis, whereas PPARbeta/delta protein decreased. Although PPARalpha and PPARbeta/delta seem to be correlated to execution of the apoptotic program, the modulation of PPARgamma appears to depend on the type of tumor cell, increasing as protein content, when inhibition of cell proliferation occurred. In conclusion, CLA may be regarded as a component of the diet that exerts antineoplastic activity and its effect may be antiproliferative or pro-apoptotic., ((c) 2004 Wiley-Liss, Inc.)

Peroxisome proliferator-activated receptor gamma (PPAR gamma) immunohistochemical expression was analyzed in 75 human bladder tumor specimens, where the expression of some angiogenic factors, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived endothelial cell growth factor (PDECGF), and tumor progression markers, such as epidermal growth factor receptor (EGFr), p16, mutated p53, and normal pRB, were also analyzed. The results were then compared to the clinical and pathological characteristics of the disease. PPAR gamma was expressed more significantly in papillary tumors than in solid cancers, and its presence was associated with statistical significance to low incidence of tumor recurrence or progression. This significant association was observed also when PPAR gamma was expressed in the presence of PDECGF, which resulted, when considered alone, to an angiogenic factor typical of solid cancers and appeared related to poor prognosis. In the presence of bFGF, on the contrary, PPAR gamma expression no longer resulted to a significant association with low incidence of tumor recurrence or progression, suggesting a possible worsening role of this angiogenic factor, typical of papillary cancers, in its interaction with PPAR gamma.