To assess several measures of the long-term outcome of magnetic resonance-guided focused ultrasound surgery for symptomatic uterine leiomyomata.
Data on 359 women completing 24-month follow-up in all ...clinical trials of magnetic resonance-guided focused ultrasound surgery for uterine leiomyomata were analyzed. Quality of life outcomes, measured by the symptom severity score of the Uterine Fibroid Symptoms Quality Of Life Questionnaire were assessed for 24 months after treatment. Clinical endpoints, including uterine shrinkage, the need for additional leiomyoma treatment, and the time to additional leiomyoma treatment, were all assessed. The nonperfused volume ratio after treatment, calculated from the gadolinium-enhanced magnetic resonance imaging after treatment and the best measure of tissue necrosis after treatment, was used to assess outcome based on completeness of leiomyoma ablation.
Women undergoing magnetic resonance-guided focused ultrasound surgery for symptomatic uterine leiomyomata have durable symptom relief, as measured by the symptom severity score at 24 months, with significantly greater improvement with more complete ablation (P<.001). Survival analysis demonstrates a significant reduction in the percentage of women undergoing additional leiomyoma treatment (P=.001) in women in the high nonperfused volume group. The mean shrinkage and mean residual nonperfused volume ratio are both significantly above zero at 6 months in the high nonperfused volume group (P<.001). The incidence of adverse events is low. However, for women with minimal treatment, the risk of additional procedures is high.
Magnetic resonance-guided focused ultrasound surgery is an effective treatment for uterine leiomyomata and results in sustained symptomatic relief.
III.
Geographic regression models of various descriptions are often applied to identify patterns and anomalies in the determinants of spatially distributed observations. These types of analyses focus on ...answering why questions about underlying spatial phenomena, e.g., why is crime higher in this locale, why do children in one school district outperform those in another, etc.? Answers to these questions require explanations of the model structure, the choice of parameters, and contextualization of the findings with respect to their geographic context. This is particularly true for local forms of regression models which are focused on the role of locational context in determining human behavior. In this paper, we present GeoExplainer, a visual analytics framework designed to support analysts in creating explanative documentation that summarizes and contextualizes their spatial analyses. As analysts create their spatial models, our framework flags potential issues with model parameter selections, utilizes template-based text generation to summarize model outputs, and links with external knowledge repositories to provide annotations that help to explain the model results. As analysts explore the model results, all visualizations and annotations can be captured in an interactive report generation widget. We demonstrate our framework using a case study modeling the determinants of voting in the 2016 US Presidential Election.
We compared the relative importance of atypical major depressive disorder (MDD), nonatypical MDD, and dysthymic disorder in predicting 3-year obesity incidence and change in body mass index and ...determined whether race/ethnicity moderated these relationships. We examined data from 17,787 initially nonobese adults in the National Epidemiologic Survey on Alcohol and Related Conditions waves 1 (2001-2002) and 2 (2004-2005) who were representative of the US population. Lifetime subtypes of depressive disorders were determined using a structured interview, and obesity outcomes were computed from self-reported height and weight. Atypical MDD (odds ratio (OR) = 1.68, 95% confidence interval (CI): 1.43, 1.97; P < 0.001) and dysthymic disorder (OR = 1.66, 95% CI: 1.29, 2.12; P < 0.001) were stronger predictors of incident obesity than were nonatypical MDD (OR = 1.11, 95% CI: 1.01, 1.22; P = 0.027) and no history of depressive disorder. Atypical MDD (B = 0.41 (standard error, 0.15); P = 0.007) was a stronger predictor of increases in body mass index than were dysthymic disorder (B = -0.31 (standard error, 0.21); P = 0.142), nonatypical MDD (B = 0.007 (standard error, 0.06); P = 0.911), and no history of depressive disorder. Race/ethnicity was a moderator; atypical MDD was a stronger predictor of incident obesity in Hispanics/Latinos (OR = 1.97, 95% CI: 1.73, 2.24; P < 0.001) than in non-Hispanic whites (OR = 1.54, 95% CI: 1.25, 1.91; P < 0.001) and blacks (OR = 1.72, 95% CI: 1.31, 2.26; P < 0.001). US adults with atypical MDD are at particularly high risk of weight gain and obesity, and Hispanics/Latinos may be especially vulnerable to the obesogenic consequences of depressions.
Familial adenomatous polyposis is an autosomal dominant disorder characterized by the development of hundreds of colorectal adenomas and eventually colorectal cancer. Oral administration of the spice ...curcumin has been followed by regression of polyps in patients with this disorder. We performed a double-blinded randomized trial to determine the safety and efficacy of curcumin in patients with familial adenomatous polyposis.
This study included 44 patients with familial adenomatous polyposis (18–85 years old) who had not undergone colectomy or had undergone colectomy with ileorectal anastomosis or ileal anal pouches, had at least 5 intestinal adenomatous polyps, and had enrolled in Puerto Rico or the United States from September 2011 through November 2016. Patients were randomly assigned (1:1) to groups given 100% pure curcumin (1,500 mg orally, twice per day) or identical-appearing placebo capsules for 12 months. The number and size of lower gastrointestinal tract polyps were evaluated every 4 months for 1 year. The primary outcome was the number of polyps in the curcumin and placebo groups at 12 months or at the time of withdrawal from the study according to the intention-to-treat principle.
After 1 year of treatment, the average rate of compliance was 83% in the curcumin group and 91% in the placebo group. After 12 weeks, there was no significant difference in the mean number of polyps between the placebo group (18.6; 95% CI, 9.3–27.8) and the curcumin group (22.6; 95% CI, 12.1–33.1; P = .58). We found no significant difference in mean polyp size between the curcumin group (2.3 mm; 95% CI, 1.8–2.8) and the placebo group (2.1 mm; 95% CI, 1.5–2.7; P = .76). Adverse events were few, with no significant differences between groups.
In a double-blinded randomized trial of patients with familial adenomatous polyposis, we found no difference in the mean number or size of lower intestinal tract adenomas between patients given curcumin 3,000 mg/day and those given placebo for 12 weeks.
Clinicaltrials.gov ID NCT00641147.
In the LIBERTY Long-Term Extension study, once-daily relugolix combination therapy (40 mg relugolix, estradiol 1 mg, norethindrone acetate 0.5 mg) substantially improved uterine fibroid-associated ...heavy menstrual bleeding throughout the 52-week treatment period in the overall study population.
Black or African American women typically experience a greater extent of disease and symptom burden of uterine fibroids vs other racial groups and have traditionally been underrepresented in clinical trials. This secondary analysis aimed to assess the efficacy and safety of relugolix combination therapy in the subgroup population of Black or African American women with uterine fibroids in the LIBERTY Long-Term Extension study.
Black or African American premenopausal women (aged 18–50 years) with uterine fibroids and heavy menstrual bleeding who completed the 24-week randomized, placebo-controlled, double-blind LIBERTY 1 (identifier: NCT03049735) or LIBERTY 2 (identifier: NCT03103087) trials were eligible to enroll in the 28-week LIBERTY Long-Term Extension study (identifier: NCT03412890), in which all women received once-daily, open-label relugolix combination therapy. The primary endpoint of this subanalysis was the proportion of Black or African American treatment responders: women who achieved a menstrual blood loss volume of <80 mL and at least a 50% reduction in menstrual blood loss volume from the pivotal study baseline to the last 35 days of treatment by pivotal study randomized treatment group. The secondary outcomes included rates of amenorrhea and changes in symptom burden and quality of life.
Overall, 241 of 477 women (50.5%) enrolled in the LIBERTY Long-Term Extension study self-identified as Black or African American. In Black or African American women receiving continuous relugolix combination therapy for up to 52 weeks, 58 of 70 women (82.9%; 95% confidence interval, 72.0%–90.8%) met the treatment responder criteria for reduction in heavy menstrual bleeding (primary endpoint). A substantial reduction in menstrual blood loss volume from the pivotal study baseline to week 52 was demonstrated (least squares mean percentage change: 85.0%); 64.3% of women achieved amenorrhea; 59.1% of women with anemia at the pivotal study baseline achieved a substantial improvement (>2 g/dL) in hemoglobin levels; and decreased symptom severity and distress because of uterine fibroid-associated symptoms and improvements in health-related quality of life through 52 weeks were demonstrated. The most frequently reported adverse events during the cumulative 52-week treatment period were hot flush (12.9%), headache (5.7%), and hypertension (5.7%). Bone mineral density was preserved through 52 weeks.
Once-daily relugolix combination therapy improved uterine fibroid-associated heavy menstrual bleeding in most Black or African American women who participated in the LIBERTY Long-Term Extension study. The safety and efficacy profile of relugolix combination therapy in Black or African American women was consistent with previously published results from the overall study population through 52 weeks. Findings from this subanalysis will assist shared decision-making by helping providers and Black or African American women understand the efficacy and safety of relugolix combination therapy as a pharmacologic option for the management of uterine fibroid-associated symptoms.
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Survey data from the Mayo Clinic Breast Disease Registry were used to assess fertility counseling and fertility preservation strategies in a modern cohort of young women with breast cancer. One ...hundred respondents were identified who were under age 50 at the time of breast cancer diagnosis and who expressed interest in future childbearing near the time of diagnosis and/or 1 year later. Ninety-three percent of the 81 respondents to the year one survey recalled fertility counseling prior to cancer treatment. Most who reported a high level of fertility concern declared that this concern had impacted their treatment decisions, often shortening their planned duration of endocrine therapy. Approximately half had taken steps to preserve future fertility, and a third had used a gonadotropin-releasing hormone agonist either alone or combined with another method (e.g., embryo or oocyte cryopreservation).
To assess outcomes at 6 and 12 months after magnetic resonance–guided focused ultrasound surgery (MRgFUS) for symptomatic uterine leiomyomas.
Multicenter clinical trial.
Academic medical centers.
...Premenopausal women with symptomatic uterine leiomyomas and no plans for future pregnancy (n = 109 at 6 months and n = 82 at 12 months).
A single treatment session of MRgFUS for uterine fibroids.
Reduction in fibroid symptoms as measured by the symptom severity score (SSS) of the Uterine Fibroid Quality-of-Life Instrument (UFS-QOL), the only validated measure of leiomyoma symptomatology. A 10-point reduction in the SSS was selected as the targeted improvement.
Seventy-one percent of women undergoing MRgFUS reached the targeted symptom reduction at 6 months, and 51% reached this at 12 months. The magnitude of improvement in SSS was greater than predicted, with subjects having a mean decrease of 39% and 36% at 6 and 12 months, respectively. This paralleled the improvement seen using the short form-36 instrument. A modest volume reduction similar in magnitude to the treated volume was seen. The incidence of adverse events was low.
MRgFUS treatment results in short-term symptom reduction for women with symptomatic uterine leiomyomas with an excellent safety profile.
Teaching vocabulary and reading comprehension during social studies instruction is critical for reading development and the acquisition of content knowledge. This study systematically investigated ...how elementary teachers integrate vocabulary and reading comprehension instruction during social studies teaching, as well as the extent to which this instruction aligned with evidence-based practices. Thirty-three fourth grade teachers from 12 schools across three school districts recorded their social studies instruction for a total of 2429 min. Findings revealed that two-thirds of social studies instructional time integrated practices for developing vocabulary and reading comprehension. Yet, the approaches for teaching comprehension and methods for instructional delivery (e.g., explicit instruction, high-quality feedback) teachers used infrequently aligned with those identified as effective in previous research. We present opportunities for improving content-area instruction and future research.
To evaluate trends in the incidence of premenopausal unilateral and bilateral oophorectomy between 1950 and 2018.
The Rochester Epidemiology Project medical records-linkage system was used to ...identify all women aged 18-49 years who were residents of Olmsted County, Minnesota, and underwent unilateral or bilateral oophorectomy before spontaneous menopause between January 1, 1950, and December 31, 2018. Population denominators were derived from the U.S. Decennial Censuses for the years 1950-2010, and intercensal year population denominators were linearly interpolated. For 2011-2018, the annual population denominators were obtained from the U.S. Census projections. Where appropriate, overall incidence rates were age-adjusted to the total U.S. female population from the 2010 Census.
There were 5,154 oophorectomies in Olmsted County across the 69-year period between 1950 and 2018, and 2.9% showed malignant disease on pathology. A total of 2,092 (40.6%) women underwent unilateral oophorectomy, and 3,062 (59.4%) women underwent bilateral oophorectomy. More than half (n=1,750, 57.2%) of the bilateral oophorectomies occurred between 1990 and 2009. Until 1975-1979, the incidence of unilateral oophorectomy was mostly higher than bilateral oophorectomy. From 1980-1984 until 2000-2004, the incidence of bilateral oophorectomy more than doubled and the incidence of unilateral oophorectomy declined. After 2005, both procedures declined and converged to a similar incidence in 2015-2018. The decline in premenopausal bilateral oophorectomy over the past 14 years (2005-2018) was most pronounced for women who underwent oophorectomy concurrently with hysterectomy or did not have any ovarian indication.
The incidence rates of unilateral and bilateral oophorectomy have varied greatly across the 69-year period of this study. In the past 14 years, the incidence of premenopausal unilateral and bilateral oophorectomy has decreased. These trends reflect the effects of the initial 2005-2006 publications and the subsequent expanding body of evidence against the practice of oophorectomy for noncancer indications.
Glucocorticoid (GC) excess adversely affects skin integrity, inducing thinning and impaired wound healing. Aged skin, particularly that which has been photo-exposed, shares a similar phenotype. ...Previously, we demonstrated age-induced expression of the GC-activating enzyme 11 beta -hydroxysteroid dehydrogenase type 1 (11 beta -HSD1) in cultured human dermal fibroblasts (HDFs). Here, we determined 11 beta -HSD1 levels in human skin biopsies from young and older volunteers and examined the aged 11 beta -HSD1 KO mouse skin phenotype. 11 beta -HSD1 activity was elevated in aged human and mouse skin and in PE compared with donor-matched photo-protected human biopsies. Age-induced dermal atrophy with deranged collagen structural organization was prevented in 11 beta -HSD1 KO mice, which also exhibited increased collagen density. We found that treatment of HDFs with physiological concentrations of Cortisol inhibited rate-limiting steps in collagen biosynthesis and processing. Furthermore, topical 11 beta -HSD1 inhibitor treatment accelerated healing of full-thickness mouse dorsal wounds, with improved healing also observed in aged 11 beta -HSD1 KO mice. These findings suggest that elevated 11 beta -HSD1 activity in aging skin leads to increased local GC generation, which may account for adverse changes occurring in the elderly, and 11 beta -HSD1 inhibitors maybe useful in the treatment of age-associated impairments in dermal integrity and wound healing.
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