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Adi Cohen Mafo Kamanda-Kosseh David W Dempster Hua Zhou Ralph Müller Elliott Goff Ivelisse Colon Mariana Bucovsky Julie Stubby Thomas L Nickolas Emily M Stein Robert R Recker Joan M Lappe Elizabeth Shane 《Journal of bone and mineral research》2019,34(9):1552-1561
Pregnancy and lactation–associated osteoporosis (PLO) is a rare, severe, early form of osteoporosis in which young women present with fractures, usually multiple vertebral fractures, during late pregnancy or lactation. In studies of idiopathic osteoporosis (IOP) in premenopausal women, we enrolled 78 women with low-trauma fractures and 40 healthy controls, all with normal menses and no secondary cause of bone loss. In 15 of the affected women, the PLO subgroup, fractures had occurred during late pregnancy or lactation. We hypothesized that clinical, bone structural, and metabolic characteristics would differ between women with PLO and those with (non-PLO) IOP and controls. All were evaluated > 12 months postpartum, when structural and remodeling characteristics would be expected to reflect baseline premenopausal status rather than transient postpartum changes. As previously reported, affected subjects (PLO and IOP) had BMD and microarchitectural deficiencies compared to controls. Women with PLO did not differ from those with IOP in terms of age, BMI, body fat, menarcheal age, parity, or age at first pregnancy. However, women with PLO had a more severe clinical presentation than those with IOP: more fractures (5.5 ± 3.3 versus 2.6 ± 2.1; p = 0.005); more vertebral fractures (80% versus 17%; p < 0.001); and higher prevalence of multiple fractures. BMD deficits were more profound and cortical width tended to be lower in PLO. PLO subjects also had significantly lower tissue-level mineral apposition rate and bone formation rates (0.005 ± 0.005 versus 0.011 ± 0.010 mm2/mm/year; p = 0.006), as well as lower serum P1NP (33 ± 12 versus 44 ± 18 µg/L; p = 0.02) and CTX (257 ± 102 versus 355 ± 193 pg/mL; p = 0.01) than IOP. The finding that women with PLO have a low bone remodeling state assessed more than a year postpartum increases our understanding of the pathogenic mechanism of PLO. We conclude that women with PLO may have underlying osteoblast functional deficits which could affect their therapeutic response to osteoanabolic medications. © 2019 American Society for Bone and Mineral Research. 相似文献
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Michael T. Yin Aimee Shu Chiyuan A. Zhang Stephanie Boutroy Donald J. McMahon David C. Ferris Ivelisse Colon Elizabeth Shane 《Calcified tissue international》2013,92(6):557-565
Our objective was to assess the effects of HIV infection and antiretroviral therapy on trabecular and cortical microarchitecture in postmenopausal minority women. A subgroup of 106 (46 HIV-infected, 60 uninfected) postmenopausal Hispanic and African American women from an established cohort had areal bone mineral density (aBMD) measured by dual-energy X-ray absorptiometry and trabecular and cortical volumetric BMD (vBMD) and microarchitecture measured by high-resolution peripheral quantitative computed tomography (HRpQCT) at the radius and tibia. HIV-infected women were slightly younger (58 ± 1 vs. 61 ± 1 years, p = 0.08), and had lower body mass index (BMI; 28 ± 1 vs. 32 ± 1 kg/m2, p < 0.01). BMI-adjusted aBMD Z scores were lower in HIV-infected women at the lumbar spine, total hip, and ultradistal radius. Serum N-telopeptide and C-telopeptide levels were also higher in HIV-infected women. Trabecular and cortical vBMD were similar at the radius, but cortical area (105.5 ± 2.4 vs. 120.6 ± 2.0 mm2, p < 0.01) and thickness (956 ± 33 vs. 1,075 ± 28 μm, p < 0.01) at the tibia were approximately 11–12 % lower in HIV-infected women. Differences remained significant after adjusting for age, BMI, and race/ethnicity. In contrast, cortical porosity was similar in the two groups. Although HIV-infected postmenopausal women had lower aBMD at the spine, total hip, and ultradistal radius and higher levels of bone resorption markers, the only differences detected by HRpQCT were lower cortical thickness and area at the tibia. 相似文献
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Xiaochen Zhao Shahed Iqbal Ivelisse L. Valdes Mark Dresser Sandhya Girish 《CTS Clinical and Translational Science》2022,15(10):2293
Pharmaceutical products in the current accelerated drug development landscape can benefit from tools beyond data generated from randomized control trials. We have seen an abundance of real‐world data (RWD) and real‐world evidence, driven by the digitalization of healthcare systems and an increased awareness that has inspired a heightened interest in their potential use. Literature review suggest leveraging RWD as a promising tool to answer key questions in the areas of clinical pharmacology and translational science. RWD may increase our understanding regarding the impact of intrinsic (e.g., liver, renal impairment, or genetic polymorphisms) and extrinsic (e.g., food consumption or concomitant medications) factors on the clearance of administered drugs. Changes in clearance may lead to clinically relevant changes in drug exposure that may require clinical management strategies, such as change in dose or dosing regimen. RWD can be leveraged to potentially bridge the gaps among research, development, and clinical care. This paper highlights promising areas of how RWD have been used to complement clinical pharmacology throughout various phases of drug development; case examples will include dose/regimen extrapolation, dose adjustments for special populations (organ impairment, pediatrics, etc.), and pharmacokinetic/pharmacodynamic models to assess impact of prognostic factors on outcomes. In addition, this paper will also juxtapose limitations and promises of utilizing RWD to answer key scientific questions in drug development and articulate challenges posed by quality issues, data availability, and integration from various sources as well as the increased need for multidimensional‐omics data that can better guide the development of personalized and predictive medicine. 相似文献
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Julian?Harris Mara?Pillinger Deborah?Fromstein Bayardo?Gomez Ivelisse?Garris Peter?A.?Kanetsky Pablo?Tebas Robert?GrossEmail author 《AIDS and behavior》2011,15(7):1410-1415
High levels of medication adherence are central to HIV treatment success. Barriers to medication adherence may differ by cultural
setting. We aimed to determine risk factors for medication non-adherence in HIV infected individuals in the Dominican Republic.
Adherence was measured in 300 individuals using a visual analog scale assessing the prior month and dichotomized at 95%. High
levels of adherence were reported by 228 (76%). Risk factors for non-adherence included heavy alcohol use: 2.5 times odds
(95% CI: 1.4–4.5), having children: 2.2 times higher odds (95% CI: 1.1–4.9) and perceptions of less social support related
to adherence: 2 times higher odds (95% CI: 1.1–3.6). Culturally appropriate interventions are needed to address alcohol use,
which is common in this setting. Parenting may represent a competing demand on time and resources and be an adherence barrier.
Self-reported perceived lack of adherence support may be a useful marker for need for adherence interventions. 相似文献
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Impact of race and ethnicity on inflammatory bowel disease 总被引:8,自引:0,他引:8
Basu D Lopez I Kulkarni A Sellin JH 《The American journal of gastroenterology》2005,100(10):2254-2261
INTRODUCTION: Inflammatory bowel disease (IBD) is now increasingly recognized in diverse ethnic populations. In the United States, IBD among the minority populations, especially Mexican Americans, has not been extensively studied. Apart from the known genetic influences that differ among the IBD subtypes [ulcerative colitis (UC) vs. Crohn's disease (CD)], serologic markers may differentiate UC and CD, including perinuclear antineutrophilic cytoplasmic antibody (p-ANCA) and anti-Saccharomyces cerevisiae antibody (ASCA) in UC and CD. METHODS: One hundred forty-eight patients with IBD seen in a university gastroenterology practice in Houston, Texas, between June 1999 and November 2003 were analyzed to determine whether there were significant differences among racial/ethnic groups. Whites comprised 40%, African Americans 37%, Mexican Americans 20%, and Asians 3% of the total IBD patients. RESULTS: We found that African Americans and whites predominantly had CD, whereas Mexican Americans predominantly had UC. There was no difference between African Americans and Mexican Americans when separately compared to whites in terms of intestinal manifestations of CD and UC, respectively. However, African Americans with CD had a significantly higher incidence of IBD-associated arthritis (p= 0.004) and ophthalmological manifestations, notably uveitis (p= 0.028), compared to whites with CD. Among UC patients, in comparison to the Mexican Americans, whites had significantly higher incidences of joint symptoms (p < 0.0001) and osteoporosis (p= 0.001). Whites had a stronger family history of IBD and colorectal carcinoma compared to the other ethnic groups. p-ANCA served as a sensitive marker for UC among Mexican Americans. All the Mexican Americans with UC tested had positive p-ANCA compared to only 40% of whites (p= 0.033). CONCLUSION: There are significant differences in IBD subtypes and serologic markers among racial/ ethnic groups with IBD in the United States. 相似文献
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