Osteosarcoma of the pelvis: experience of the Cooperative Osteosarcoma Study Group.

PURPOSE: To define patients and tumor characteristics as well as therapy results, patients with pelvic osteosarcoma who were registered in the Cooperative Osteosarcoma Study Group (COSS) were analyzed. PATIENTS AND METHODS: Sixty-seven patients with a high-grade pelvic osteosarcoma were eligible for this analysis. Fifteen patients had primary metastases. All patients received chemotherapy according to COSS protocols. Thirty-eight patients underwent limb-sparing surgery, 12 patients underwent hemipelvectomy, and 17 patients did not undergo definitive surgery. Eleven patients received irradiation to the primary tumor site: four postoperatively and seven as the only form of local therapy. RESULTS: Local failure occurred in 47 of all 67 patients (70%) and in 31 of 50 patients (62%) who underwent definitive surgery. Five-year overall survival (OS) and progression-free survival rates were 27% and 19%, respectively. Large tumor size (P =.0137), primary metastases (P =.0001), and no or intralesional surgery (P <.0001) were poor prognostic factors. In 30 patients with no or intralesional surgery, 11 patients with radiotherapy had better OS than 19 patients without radiotherapy (P =.0033). Among the variables, primary metastasis, large tumor, no or intralesional surgery, no radiotherapy, existence of primary metastasis (relative risk [RR] = 3.456; P =.0009), surgical margin (intralesional or no surgical excision; RR = 5.619; P <.0001), and no radiotherapy (RR = 4.196; P =.0059) were independent poor prognostic factors. CONCLUSION: An operative approach with wide or marginal margins improves local control and OS. If the surgical margin is intralesional or excision is impossible, additional radiotherapy has a positive influence on prognosis.     

Impact of pill organizers and blister packs on adherence to pill taking in two vitamin supplementation trials

The impact of pill organizers on pill taking was determined in the Trial of Antioxidant Vitamins C and E (TRACE) Study, a factorial trial of vitamin C and vitamin E supplementation in 184 individuals. Participants were recruited in 1996-1997 and randomized to one of two groups (pill organizer or no organizer) and to one of four supplement groups for 2 months. The pill count (observed/expected X 100%) distribution was similar in the organizer and no organizer group for both vitamins. Mean differences in changes in serum vitamin levels between active and placebo groups did not differ by pill organizer use. The impact of pill organizers and blister packs was compared in another trial, the Vitamins, Teachers, and Longevity (VITAL) Study, in 297 individuals randomized in 1993-1994 to receive study pills either in blister packs or in pill organizers and to take one of two supplements. Among those with lower adherence, the pill count distribution in the blister-pack group exceeded that in the organizer group. Mean differences in serum vitamin E levels between active and placebo groups did not differ by types of pill packaging. In summary, use of blister packs, but not pill organizers, improved adherence as measured by pill counts among those with lower adherence. Neither pill delivery system improved adherence as measured by serum vitamin levels.     

Bisphenol A and Child Vascular Health: A Preview of Future Heart Disease Risk?

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Exposures to phthalates and bisphenols have well-documented adverse effects on reproductive health and human development.¹ These endocrine-disrupting chemicals (EDCs) are also associated with obesity, hypertension, and blood vessel lesions in cross-sectional studies of adolescents and adults.^2–5 It is conceivable that processes leading to such damage start early in life and may be affected by prenatal chemical exposure.^6,7 A study recently published in Environmental Health Perspectives examined this question in children followed from gestation into childhood.⁸The authors measured phthalates and bisphenols in urine samples from 935 pregnant Generation R participants during their first, second, and third trimesters. The Generation R Study, based in Rotterdam, the Netherlands, comprises a population-based prospective cohort.⁹ At approximately 10 years of age, the women’s children underwent ultrasounds for two measurements of the common carotid artery: distensibility (elasticity) and intima-media thickness (the thickness between the intima and media layers of the vessel wall). Both distensibility and intima-media thickness reflect vascular health in the whole body^10–12; thicker vessel walls and reduced elasticity are considered distinct but overlapping risk factors for cardiovascular disease in adulthood, such as atherosclerosis.¹³Open in a separate windowThe intima layer of the artery (shown in black) is composed of endothelial cells, and the media layer (shown in pink) is made of smooth muscle and elastic fibers. Combined expansion (diastole) and contraction (systole) of the media layer pushes blood through the artery and controls blood pressure. In this transmission electron micrograph, the intima has accordioned due to contraction of the media. Image: © Steve Gschmeissner/Science Source.The authors analyzed the children’s vascular measurements in association with their mothers’ prenatal levels of three bisphenols [bisphenol A (BPA), bisphenol S (BPS), and bisphenol F (BPF)], low-molecular-weight phthalates as a group, high-molecular-weight phthalates, and three individual phthalates. They found no associations between any of the chemicals and distensibility. However, higher maternal urine concentrations of total bisphenols and of BPA alone were associated with thinner vessel walls in the children’s carotid artery. No associations were found for BPS, BPF, or any phthalate.The association of higher total bisphenol and BPA exposure with thinner—rather than thicker—vessel walls surprised the team initially but is biologically plausible, says first author Sophia Blaauwendraad. “Associations between higher BPA levels and atherosclerosis in adulthood [demonstrated in earlier studies¹⁴] could be due to oxidative stress that accelerates the formation of atherosclerotic plaques and thickens the vascular wall,” says Blaauwendraad, a physician and graduate student in epidemiology under senior coauthor Vincent Jaddoe at Rotterdam’s Erasmus University Medical Center. Fetal exposures, on the other hand, may be associated with an underdevelopment of the vasculature in childhood, the authors speculate. However, Blaauwendraad says, as yet no prospective studies have tracked intima-media thickness measures from childhood to adulthood.¹⁵Nikki Posnack, an assistant professor of pharmacology, physiology, and pediatrics at Children’s National Hospital in Washington, DC, says the study’s strengths include its large sample size and measurements of several subtypes of phthalates and bisphenols at three different time points during pregnancy. Posnack, who was not involved in the research, says, “This is a compelling study that opens up new opportunities for mechanistic follow-up studies in model systems.” Such studies could examine whether BPA disrupts development of blood vessels and alters their contractile properties,¹⁶ similar to the chemical’s disruption of hormonal regulation.According to Lars Lind, a professor of medicine at Uppsala University in Sweden, who also was not involved in the project, studying the effect of the chemicals on early vascular changes in animal models would be worthwhile and should be accompanied by replication efforts in other human birth cohorts. “Since the findings were unexpected, replication is critical to increase our faith in them,” says Lind. “But it is possible that these chemicals may have different effects at the fetal stage than later in life.”The association with total bisphenols appears to have been driven mainly by BPA; BPS and BPF were below the limit of detection in more than half the samples, possibly because they were collected in 2002–2006, when these chemicals were used less than today. However, human exposure to these BPA replacement chemicals has been increasing.¹⁷ “With that in mind,” Posnack says, “I think the study fills an important knowledge gap by exploring if exposure to any bisphenols in utero may affect subclinical indicators of vascular disease risk later in life.”     

Evaluation of a Wastewater-Based Epidemiological Approach to Estimate the Prevalence of SARS-CoV-2 Infections and the Detection of Viral Variants in Disparate Oregon Communities at City and Neighborhood Scales

Background: Positive correlations have been reported between wastewater SARS-CoV-2 concentrations and a community’s burden of infection, disease or both. However, previous studies mostly compared wastewater to clinical case counts or nonrepresentative convenience samples, limiting their quantitative potential.Objectives: This study examined whether wastewater SARS-CoV-2 concentrations could provide better estimations for SARS-CoV-2 community prevalence than reported cases of COVID-19. In addition, this study tested whether wastewater-based epidemiology methods could identify neighborhood-level COVID-19 hotspots and SARS-CoV-2 variants.Methods: Community SARS-CoV-2 prevalence was estimated from eight randomized door-to-door nasal swab sampling events in six Oregon communities of disparate size, location, and demography over a 10-month period. Simultaneously, wastewater SARS-CoV-2 concentrations were quantified at each community’s wastewater treatment plant and from 22 Newport, Oregon, neighborhoods. SARS-CoV-2 RNA was sequenced from all positive wastewater and nasal swab samples. Clinically reported case counts were obtained from the Oregon Health Authority.Results: Estimated community SARS-CoV-2 prevalence ranged from 8 to 1,687/10,000 persons. Community wastewater SARS-CoV-2 concentrations ranged from 2.9 to 5.1log10 gene copies per liter. Wastewater SARS-CoV-2 concentrations were more highly correlated (Pearson’s r=0.96; R2=0.91) with community prevalence than were clinically reported cases of COVID-19 (Pearson’s r=0.85; R2=0.73). Monte Carlo simulations indicated that wastewater SARS-CoV-2 concentrations were significantly better than clinically reported cases at estimating prevalence (p<0.05). In addition, wastewater analyses determined neighborhood-level COVID-19 hot spots and identified SARS-CoV-2 variants (B.1 and B.1.399) at the neighborhood and city scales.Discussion: The greater reliability of wastewater SARS-CoV-2 concentrations over clinically reported case counts was likely due to systematic biases that affect reported case counts, including variations in access to testing and underreporting of asymptomatic cases. With these advantages, combined with scalability and low costs, wastewater-based epidemiology can be a key component in public health surveillance of COVID-19 and other communicable infections. https://doi.org/10.1289/{"type":"entrez-protein","attrs":{"text":"EHP10289","term_id":"372009674","term_text":"EHP10289"}}EHP10289