Disparities in preconception health indicators in U.S. women: a cross-sectional analysis of the behavioral risk factor surveillance system 2019.

OBJECTIVES: Optimized preconception care improves birth outcomes and women's health. Yet, little research exists identifying inequities impacting preconception health. This study identifies age, race/ethnicity, education, urbanicity, and income inequities in preconception health. METHODS: We performed a cross-sectional analysis of the Center for Disease Control and Prevention's (CDC) 2019 Behavioral Risk Factor Surveillance System (BRFSS). This study included women aged 18-49 years who (1) reported they were not using any type of contraceptive measure during their last sexual encounter (usage of condoms, birth control, etc.) and (2) reported wanting to become pregnant from the BRFSS Family Planning module. Sociodemographic variables included age, race/ethnicity, education, urbanicity, and annual household income. Preconception health indicators were subdivided into three categories of Physical/Mental Health, Healthcare Access, and Behavioral Health. Chi-squared statistical analysis was utilized to identify sociodemographic inequities in preconception health indicators. RESULTS: Within the Physical/Mental Health category, we found statistically significant differences among depressive disorder, obesity, high blood pressure, and diabetes. In the Healthcare Access category, we found statistically significant differences in health insurance status, having a primary care doctor, and being able to afford a medical visit. Within the Behavioral Health category, we found statistically significant differences in smoking tobacco, consuming alcohol, exercising in the past 30 days, and fruit and vegetable consumption. CONCLUSIONS: Maternal mortality and poor maternal health outcomes are influenced by many factors. Further research efforts to identify contributing factors will improve the implementation of targeted preventative measures in directly affected populations to alleviate the current maternal health crisis.

Tolerating Subretinal Fluid in Neovascular Age-Related Macular Degeneration Treated with Ranibizumab Using a Treat-and-Extend Regimen: FLUID Study 24-Month Results.

PURPOSE: To test the hypothesis that tolerating some subretinal fluid (SRF) in patients with neovascular age-related macular degeneration (nAMD) treated with ranibizumab using a treat-and-extend (T&E) regimen can achieve similar visual acuity (VA) outcomes as treatment aimed at resolving all SRF. DESIGN: Multicenter, randomized, 24-month, phase 4, single-masked, noninferiority clinical trial. PARTICIPANTS: Participants with treatment-naïve active subfoveal choroidal neovascularization (CNV). METHODS: Participants were randomized to receive ranibizumab 0.5 mg monthly until either complete resolution of SRF and intraretinal fluid (IRF; intensive arm: SRF intolerant) or resolution of all IRF only (relaxed arm: SRF tolerant except for SRF >200 µm at the foveal center) before extending treatment intervals. A 5-letter noninferiority margin was applied to the primary outcome. MAIN OUTCOME MEASURES: Mean change in best-corrected VA (BCVA), and central subfield thickness and number of injections from baseline to month 24. RESULTS: Of the 349 participants randomized (intensive arm, n = 174; relaxed arm, n = 175), 279 (79.9%) completed the month 24. The mean change in BCVA from baseline to month 24 was 3.0 letters (standard deviation, 16.3 letters) in the intensive group and 2.6 letters (standard deviation, 16.3 letters) in the relaxed group, demonstrating noninferiority of the relaxed compared with the intensive treatment (P = 0.99). Similar proportions of both groups achieved 20/40 or better VA (53.5% and 56.6%, respectively; P = 0.92) and 20/200 or worse VA (8.7% and 8.1%, respectively; P = 0.52). Participants in the relaxed group received fewer ranibizumab injections over 24 months (mean, 15.8 [standard deviation, 5.9]) than those in the intensive group (mean, 17 [standard deviation, 6.5]; P = 0.001). Significantly more participants in the intensive group never extended beyond 4-week treatment intervals (13.5%) than in the relaxed group (2.8%; P = 0.003), and significantly more participants in the relaxed group extended to and maintained 12-week treatment intervals (29.6%) than the intensive group (15.0%; P = 0.005). CONCLUSIONS: Patients treated with a ranibizumab T&E protocol who tolerated some SRF achieved VA that is comparable, with fewer injections, with that achieved when treatment aimed to resolve all SRF completely.

The role of sub-retinal fluid in determining treatment outcomes in patients with neovascular age-related macular degeneration--a phase IV randomised clinical trial with ranibizumab: the FLUID study.

BACKGROUND: With increasing experience using anti-VEGF therapy for the treatment of neovascular age-related macular degeneration (nAMD), ophthalmologists have shifted away from a "one size fits all" to an "individualised" approach based on disease activity with the aim of achieving a fluid-free retina. The FLUID study investigates the non-inferiority of a Treat and Extend (T&E) protocol of 0.5 mg ranibizumab, which allows treatment extension in the presence of incomplete resolution of sub-retinal fluid (SRF) ≤200 µm at the foveal centre relative to a T&E protocol that requires complete resolution of all retinal fluid (i.e., both SRF and intra-retinal fluid [IRF]) in patients with nAMD. METHODS/DESIGN: This 24 month, randomised, phase IV trial has completed recruitment of treatment-naïve patients randomised 1:1 to ranibizumab "intensive" treatment (complete resolution of IRF and SRF) or ranibizumab "relaxed" treatment (resolution of IRF or >200 µm SRF only at foveal centre). Patients in both arms follow a T&E regimen where extension decisions are based upon assessment of lesion activity: loss of ≥5 letters of visual acuity, new haemorrhage, presence of IRF and SRF on an optical coherence tomography (OCT) scan. The determination of SRF is conducted at a reading centre while the assessment of IRF is physician-determined. The primary endpoint is the mean change in best-corrected visual acuity (BCVA) from baseline to 24 months. Secondary endpoints include the mean change in central retinal thickness (CRT) from baseline to 12 and 24 months, the number of ranibizumab injections administered at 12 and 24 months, and the pharmacogenomic assessment of AMD Gene Consortium-identified single-nucleotide polymorphisms (SNPs) and their association with treatment response. Three hundred and forty seven (347) patients have been recruited by 16 Australian sites within approximately 16 months. A protocol to adjudicate on SRF has been established by the central reading centre and is demonstrating good concordance with investigator assessment. DISCUSSION: This study will provide important insights into retreatment criteria for managing nAMD using a T&E regimen. The current paper describes the clinical rationale for using a less intensive treatment approach using ranibizumab and details of the treatment protocol. TRIAL REGISTRATION NUMBER: NCT01972789. Date of registration: 24th October 2013.

Photodynamic therapy with verteporfin for choroidal neovascularization due to age-related macular degeneration and other causes: a New Zealand outcomes study.

PURPOSE: To assess the efficacy and safety of photodynamic therapy (PDT) for choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) and other conditions by analysing visual acuity changes. METHODS: A retrospective review of patients treated with PDT was conducted. CNV was confirmed on fluorescein angiography. Visual acuity outcomes were recorded at 3-monthly intervals to a maximum of 48 months. The primary outcome measure was the proportion of patients avoiding moderate visual loss (losing less than three lines of visual acuity relative to baseline) at 12 months. RESULTS: A total of 343 patients receiving PDT were followed up for a mean of 14.9 months. Two hundred and eighty-five (83%) patients presented with CNV due to AMD and 58 patients (17%) due to other causes. Seventy per cent of patients with CNV secondary to AMD avoided moderate visual loss at both 12 and 24 months. Secondary outcomes (including mean change in visual acuity, proportion of patients with stable or improved vision and proportion of patients with severe vision loss) also compared favourably with the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Investigation. Of patients with CNV secondary to causes other than AMD, 76% avoided moderate visual loss at both 12 and 24 months. The safety profile identified one severe adverse reaction, with development of a serous pigment epithelial detachment and subsequent rip. CONCLUSION: The results of this present retrospective, open-label, clinical practice study in New Zealand are consistent with the findings of multicentre randomized, placebo-controlled trials and confirm the treatment benefit of PDT in a clinical setting.

Timing of dose relative to sexual intercourse attempt in previous sildenafil citrate users treated with tadalafil.

OBJECTIVES: Tadalafil, a phosphodiesterase type 5 inhibitor, has an extended period of effectiveness, up to 36 hours, for the treatment of erectile dysfunction (ED). Changes in behavior of long-term sildenafil users were evaluated by assessing time of dose relative to sexual intercourse attempts during treatment with sildenafil and tadalafil. MATERIALS AND METHODS: This open-label study was conducted in men with ED and a history of >or=6-week prior sildenafil use in Australia, New Zealand, Asia, Central and Eastern Europe, the Middle East, and Latin America. Patients continued sildenafil treatment for 4 weeks, then switched to tadalafil for 8 weeks. Timing of sexual intercourse attempt relative to dose was assessed through patient diaries for the final 4 weeks of each treatment period. Patients continued their treatment of choice in an extension period. RESULTS: A total of 2,760 men (mean age 54.4 years) with a median duration of prior sildenafil use of 474 days were enrolled. Significant increases in median time from dose to intercourse attempt were observed when changing treatment from sildenafil citrate (1.21 hours) to tadalafil (3.25 hours; P < 0.001). Fifty-nine percent of intercourse attempts were within 4 hours of dosing when patients were treated with tadalafil (88% with sildenafil). The proportion of intercourse attempts per patient made >4 hours after dose was considerably higher during the tadalafil than during the sildenafil assessment period. Similar daily cycles of frequency of dosing and intercourse attempts were observed in all study periods and were characterized by a small peak in the morning and a large peak in the evening. When changing treatment to tadalafil, patients administered the drug earlier in the day and over a broader period of time. CONCLUSION: Following the dosing instructions reflecting tadalafil's extended period of effectiveness, men with a history of established sildenafil use changed their dose-attempt behavior when treated with tadalafil.

Perinatal exposure to bisphenol-A alters peripubertal mammary gland development in mice.

Developmental exposure to estrogenic chemicals induces morphological, functional, and behavioral anomalies associated with reproduction. Humans are exposed to bisphenol-A (BPA), an estrogenic compound that leaches from dental materials and plastic food and beverage containers. The aim of the present study was to determine the effects of perinatal exposure to low, environmentally relevant doses of BPA [25 and 250 ng BPA/kg body weight (bw).d] on the peripubertal development of the mammary gland. BPA exposure enhanced the mammary glands' sensitivity to estradiol in ovariectomized CD-1 mice. In their intact 30-d-old littermates, the area and numbers of terminal end buds relative to the gland ductal area increased whereas their apoptotic activity decreased. There was a positive correlation between ductal length and the age at first proestrus; that was reduced as the BPA dose increased, suggesting that BPA exposure slows down ductal invasion of the stroma. There was also a significant increase of progesterone receptor-positive ductal epithelial cells that were localized in clusters, suggesting future branching points. Indeed, lateral branching was significantly enhanced at 4 months of age in mice exposed to 25 ng BPA /kg bw.d. In conclusion, perinatal exposure to environmentally relevant BPA doses results in persistent alterations in mammary gland morphogenesis. Of special concern is the increased terminal end bud density at puberty as well as the increased number of terminal ends reported previously in adult animals, as these two structures are the sites at which cancer arises in humans and rodents.

Long-term effects of fetal exposure to low doses of the xenoestrogen bisphenol-A in the female mouse genital tract.

Developmental exposure to estrogenic chemicals induces morphological, functional, and behavioral anomalies associated with reproduction. Humans are routinely exposed to bisphenol-A (BPA), an estrogenic compound that leaches from dental materials and plastic food and beverage containers. The aim of the present study was to determine the effects of in utero exposure to low, environmentally relevant doses of BPA on the development of female reproductive tissues in CD-1 mice. In previous publications, we have shown that this treatment alters the morphology of the mammary gland and affects estrous cyclicity. Here we report that in utero exposure to 25 and 250 ng BPA/ kg of body weight per day via osmotic pumps implanted into pregnant dams at Gestational Day 9 induces alterations in the genital tract of female offspring that are revealed during adulthood. They include decreased wet weight of the vagina, decreased volume of the endometrial lamina propria, increased incorporation of bromodeoxyuridine into the DNA of endometrial gland epithelial cells, and increased expression of estrogen receptor-alpha (ERalpha) and progesterone receptor in the luminal epithelium of the endometrium and subepithelial stroma. Because ERalpha is known to be expressed in these estrogen-target organs at the time of BPA exposure, it is plausible that BPA may directly affect the expression of ER-controlled genes involved in the morphogenesis of these organs. In addition, BPA-induced alterations that specifically affect hypothalamic-pituitary-gonadal axis function may further contribute to the anomalies observed at 3 mo of age, long after the cessation of BPA exposure.

Mammalian development in a changing environment: exposure to endocrine disruptors reveals the developmental plasticity of steroid-hormone target organs.

Recent findings in the field of environmental endocrine disruption have revealed that developmental exposure to estrogenic chemicals induces morphological, functional, and behavioral anomalies associated with reproduction. The aim of the present study was to determine the effects of in utero exposure to low doses of the estrogenic chemical bisphenol A (BPA) on the development of the female reproductive tissues and mammary glands in CD-1 mice. Humans are exposed to BPA, which leaches from dental materials and plastic food and beverage containers. Here we report that prenatal exposure to BPA induces alterations in tissue organization within the ovaries and mammary glands and disrupts estrous cyclicity in adulthood. Because estrogen receptors are expressed developmentally in these estrogen-target organs, we propose that BPA may directly affect the expression of genes involved in their morphogenesis. In addition, alterations in the sexual differentiation of the brain, and thus the hypothalamic-pituitary-gonadal axis, may further contribute to the observed phenotype. The emerging field of endocrine disruptors promises to provide new insights into the mechanisms underlying the development of hormone-target organs and demonstrates that the environment plays important roles in the making of phenotypes.

Endocrine disruptors: from Wingspread to environmental developmental biology.

The production and release of synthetic chemicals into the environment has been a hallmark of the "Second Industrial Revolution" and the "Green Revolution." Soon after the inception of these chemicals, anecdotal evidence began to emerge linking environmental contamination of rivers and lakes with a variety of developmental and reproductive abnormalities in wildlife species. The accumulation of evidence suggesting that these synthetic chemicals were detrimental to wildlife, and potentially humans, as a result of their hormonal activity, led to the proposal of the endocrine disruptor hypothesis at the 1991 Wingspread Conference. Since that time, experimental and epidemiological data have shown that exposure of the developing fetus or neonate to environmentally-relevant concentrations of certain synthetic chemicals causes morphological, biochemical, physiological and behavioral anomalies in both vertebrate and invertebrate species. The ubiquitous use, and subsequent human exposure, of one particular chemical, the estrogen mimic bisphenol A (BPA), is the subject of this present review. We have highlighted this chemical since it provides an arresting model of how chemical exposure impacts developmental processes involved in the morphogenesis of tissues and organs, including those of the male and female reproductive systems, the mammary glands and the brain.