Purpose To investigate the association between dry eye disease and each of depression and anxiety. Design Retrospective, case-control study. Methods setting : University of North Carolina outpatient ...clinics. study population : All patients over the age of 18 years seen between July 2008 and June 2013 were included in the analysis. observation procedure : Cases were defined according to ICD-9 diagnosis codes for dry eye disease, anxiety, and depression. outcome measure : Separate odds ratios were calculated for dry eye disease and each of anxiety and depression. Similar odds ratios were also calculated between dry eye disease and rheumatoid arthritis, a systemic disease with a known association with dry eye, as a way of validating our approach. Results A total of 460 611 patients were screened; 7207 patients with dry eye were included, while 20 004 patients with anxiety and 30 100 patients with depression were included. The adjusted odds ratio for dry eye disease and anxiety was 2.8 (95% confidence interval CI 2.6–3.0). For dry eye disease and depression, the odds ratio was 2.9 (95% CI 2.7–3.1). Conclusions We identified a statistically significant association between dry eye disease and each of depression and anxiety. Such an association has implications for ophthalmologists in the management and treatment of dry eye disease.
Objective To estimate the frequency with which results of large randomized clinical trials registered with ClinicalTrials.gov are not available to the public.Design Cross sectional analysisSetting ...Trials with at least 500 participants that were prospectively registered with ClinicalTrials.gov and completed prior to January 2009.Data sources PubMed, Google Scholar, and Embase were searched to identify published manuscripts containing trial results. The final literature search occurred in November 2012. Registry entries for unpublished trials were reviewed to determine whether results for these studies were available in the ClinicalTrials.gov results database.Main outcome measures The frequency of non-publication of trial results and, among unpublished studies, the frequency with which results are unavailable in the ClinicalTrials.gov database.Results Of 585 registered trials, 171 (29%) remained unpublished. These 171 unpublished trials had an estimated total enrollment of 299 763 study participants. The median time between study completion and the final literature search was 60 months for unpublished trials. Non-publication was more common among trials that received industry funding (150/468, 32%) than those that did not (21/117, 18%), P=0.003. Of the 171 unpublished trials, 133 (78%) had no results available in ClinicalTrials.gov.Conclusions Among this group of large clinical trials, non-publication of results was common and the availability of results in the ClinicalTrials.gov database was limited. A substantial number of study participants were exposed to the risks of trial participation without the societal benefits that accompany the dissemination of trial results.
Stiffness is a biophysical property of the extracellular matrix that modulates cellular functions, including proliferation, invasion, and differentiation, and it also may affect therapeutic ...responses. Therapeutic durability in cancer treatments remains a problem for both chemotherapies and pathway-targeted drugs, but the reasons for this are not well understood. Tumor progression is accompanied by changes in the biophysical properties of the tissue, and we asked whether matrix rigidity modulated the sensitive versus resistant states in HER2-amplified breast cancer cell responses to the HER2-targeted kinase inhibitor lapatinib. The antiproliferative effect of lapatinib was inversely proportional to the elastic modulus of the adhesive substrata. Down-regulation of the mechanosensitive transcription coactivators YAP and TAZ, either by siRNA or with the small-molecule YAP/TEAD inhibitor verteporfin, eliminated modulus-dependent lapatinib resistance. Reduction of YAP in vivo in mice also slowed the growth of implanted HER2-amplified tumors, showing a trend of increasing sensitivity to lapatinib as YAP decreased. Thus we address the role of stiffness in resistance to and efficacy of a HER2 pathway-targeted therapeutic via the mechanotransduction arm of the Hippo pathway.
To summarize available data on the effectiveness and safety of single-agent misoprostol for medical abortion in the first trimester.
We searched MEDLINE, CABI, Cochrane, EMBASE, LILACS, the Web of ...Science, and ClinicalTrials.gov for English-language studies that evaluated misoprostol alone for abortion of a viable pregnancy in the first trimester.
Our search yielded 1,562 citations, of which 38 included data from 53 trial groups that met our inclusion and exclusion criteria.
We abstracted data about each trial group, including study characteristics, treatment regimen, clinical protocol, number of women treated and followed, and numbers with outcomes of interest. We used meta-analytic methods and logistic regression to examine factors associated with surgical intervention after treatment. Among all 12,829 evaluable women, 2,536 (meta-analytic estimate 22.0%, 95% CI 18.8-25.5%) had surgical uterine evacuation. Multiple factors were significantly associated with this proportion, including misoprostol amount per dose and route of administration, loss to follow-up rate, publication date, geographic region, number of misoprostol doses, duration of dosing, and time between dosing and evaluation. Of 6,359 evaluable women, 384 (meta-analytic estimate 6.8%, 95% CI 5.3-8.5%) had ongoing pregnancies. At most 26 of 12,184 evaluable women (meta-analytic estimate 0.7%, 95% CI 0.4-1.0%) were transfused or hospitalized for abortion-related reasons. In trials that provided satisfaction data, most women were satisfied or very satisfied with the treatment (meta-analytic estimate 78%, 95% CI 71-85%).
Misoprostol alone is effective and safe and is a reasonable option for women seeking abortion in the first trimester. Research is indicated to further refine the regimen and to establish efficacy in the late first trimester.
PROSPERO, CRD42018083589.
A popular pre-harvest strategy to mitigate aflatoxin contamination of corn involves field application of non-aflatoxigenic strains of
. The basis of this biological control may involve multiple ...factors, but competitive displacement of aflatoxigenic strains by the biocontrol strains is a likely mechanism. Three biocontrol strains (NRRL 21882, 18543, and 30797) were applied annually, over a 4-year period, to the same 3.2-ha commercial corn field in the Mississippi Delta, where we monitored their post-release establishment, spread, and persistence. Within 2 months of the first biocontrol application, the percentage of soil-inhabiting aflatoxigenic
strains in some plots was reduced from 48 to 9% of the population. The frequency of aflatoxigenic
strains was also significantly reduced in the rest of field. After 4 years, neighboring plots that had never received a biocontrol treatment, and distanced from our treatment plots by at least 20 meters, had less than 20% aflatoxigenic isolates. This significant halo effect might be attributed to movement of soil through tillage operations, but the aflatoxigenicity shift could be detected in the untreated plots within 2 months of the initial applications, at a time when there was no tillage. The
populations that colonized the grain were also monitored and found to be less than 15% toxigenic in the fourth year for all treatments. Over all treatments and years, less than 2 ppb of aflatoxin was detected, which could be a consequence of the field-wide shift of the inherent
population to predominately non-aflatoxigenic strains. This study supports the efficacy of using non-aflatoxigenic
strains as pre-harvest biocontrol, and shows that most of its effectiveness occurs with the first application.
Abstract Background The dose of mifepristone approved by most government agencies for medical abortion is 600 mg. Our aim was to summarize extant data on the effectiveness and safety of regimens ...using the widely recommended lower mifepristone dose, 200 mg, followed by misoprostol in early pregnancy and to explore potential correlates of abortion failure. Study Design To identify eligible reports, we searched Medline, reviewed reference lists of published reports, and contacted experts to identify all prospective trials of any design of medical abortion using 200 mg mifepristone followed by misoprostol in women with viable pregnancies up to 63 days' gestation. Two authors independently extracted data from each study. We used logistic regression models to explore associations between 15 characteristics of the trial groups and, separately, the rates of medical abortion failure and of ongoing pregnancy. Results We identified 87 trials that collectively included 120 groups of women treated with a regimen of interest. Of the 47,283 treated subjects in these groups, abortion outcome data were reported for 45,528 (96%). Treatment failure occurred in 2,192 (4.8%) of these evaluable subjects. Ongoing pregnancy was reported in 1.1% (499/45,150) of the evaluable subjects in the 117 trial groups reporting this outcome. The risk of medical abortion failure was higher among trial groups in which at least 25% of subjects had gestational age > 8 weeks, the specified interval between mifepristone and misoprostol was less than 24 h, the total misoprostol dose was 400 mcg (rather than higher), or the misoprostol was administered by the oral route (rather than by vaginal, buccal, or sublingual routes). Across all trials, 119 evaluable subjects (0.3%) were hospitalized, and 45 (0.1%) received blood transfusions. Conclusions Early medical abortion with mifepristone 200 mg followed by misoprostol is highly effective and safe.
This study aimed to update our 2019 systematic review of data on the effectiveness and safety of misoprostol-only for first-trimester abortion.
We searched PubMed on December 18, 2022, to find ...published articles describing the outcomes of treatment with misoprostol-only for abortion of viable intrauterine pregnancy at ≤91 days of gestation. From each article identified, two authors independently abstracted relevant data about each group of patients treated with a distinct regimen. We assessed the risk of bias using four defined indicators. We estimated the proportion of patients with treatment failure using meta-analytic methods as well as the proportion hospitalized or transfused after treatment. We examined associations between treatment failure and selected characteristics of the groups.
We identified 49 papers with 66 groups that collectively included 16,354 evaluable patients, of whom 2960 (meta-analytic estimate 15%, 95% CI 12%, 19%) had treatment failures. Of 9228 patients assessed for ongoing pregnancy after treatment, 521 (meta-analytic estimate 6%, 95% CI 5%, 8%) had that condition. Failure risk was significantly associated with misoprostol dose, the total allowed number of doses, the maximum duration of dosing, and certain indicators of risk of bias. Among 11,007 patients allowed to take at least three misoprostol doses, the first consisting of misoprostol 800 mcg administered vaginally, sublingually, or buccally, the meta-analytic estimate of the failure risk was 11% (95% CI 8%, 14%). At most, 0.2% of 15,679 evaluable patients were hospitalized or received transfusions.
Although some studies in this updated review were adjudicated to have a high risk of bias, the results continue to support the key conclusion of our 2019 analysis: misoprostol-only is effective and safe for the termination of first-trimester intrauterine pregnancy.
Misoprostol-only is a safe and effective option for medication abortion in the first trimester if mifepristone is unavailable or inaccessible.
Furazans in Medicinal Chemistry Mancini, Ross S; Barden, Christopher J; Weaver, Donald F ...
Journal of medicinal chemistry,
02/2021, Letnik:
64, Številka:
4
Journal Article
Recenzirano
Incorporation of heterocycles into drug molecules can enhance physical properties and biological activity. A variety of heterocyclic groups is available to medicinal chemists, many of which have been ...reviewed in detail elsewhere. Oxadiazoles are a class of heterocycle containing one oxygen and two nitrogen atoms, available in three isomeric forms. While the 1,2,4- and 1,3,4-oxadiazoles have seen widespread application in medicinal chemistry, 1,2,5-oxadiazoles (furazans) are less common. This Review provides a summary of the application of furazan-containing molecules in medicinal chemistry and drug development programs from analysis of both patent and academic literature. Emphasis is placed on programs that reached clinical or preclinical stages of development. The examples provided herein describe the pharmacology and biological activity of furazan derivatives with comparative data provided where possible for other heterocyclic groups and pharmacophores commonly used in medicinal chemistry.
Severe acute respiratory disease coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19) pandemic. Although a primarily respiratory disease, recent reports indicate that ...it also affects the central nervous system (CNS). Over 25% of COVID-19 patients report neurological symptoms such as memory loss, anosmia, hyposmia, confusion, and headaches. The neurological outcomes may be a result of viral entry into the CNS and/or resulting neuroinflammation, both of which underlie an elevated risk for Alzheimer's disease (AD). Herein, we ask: Is COVID-19 a risk factor for AD? To answer, we identify the literature and review mechanisms by which COVID-19-mediated neuroinflammation can contribute to the development of AD, evaluate the effects of acute versus chronic phases of infection, and lastly, discuss potential therapeutics to address the rising rates of COVID-19 neurological sequelae.
Overweight and obesity (OWOB) is a global epidemic. Adults and adolescents from low-income households are at higher risk to be OWOB. This study examined the relationship between income and OWOB ...prevalence in children and adolescents (518 years) in the United States (US) within and across race/ethnicities, and changes in this relationship from 1971 to 2014.
A meta-analysis of a nationally representative sample (N = 73,891) of US children and adolescents drawn from three datasets (i.e., National Health and Nutrition Examination Survey, National Longitudinal Survey of Youth, & the Early Childhood Longitudinal Program) which included 14 cross-sectional waves spanning 1971-2014 was conducted. The exposure was household income-to-poverty ratio (low income = 0.00-1.00, middle income = 1.01-4.00, high income >4.00) with prevalence of overweight or obesity (body mass index ≥ 85th percentile) as the outcome.
Children and adolescents from middle-income and high-income households were 0.78 (95% CI = 0.72, 0.83) and 0.68 (95% CI = 0.59, 0.77) times as likely to be OWOB compared to children and adolescents in low-income households. Separate analyses restricted to each racial/ethnic group showed children and adolescents from middle- and high-income households were less likely to be OWOB compared to their low-income peers within the White, Hispanic, and Other race/ethnic groups. Children and adolescents from low-income households who were Black were not more likely to be OWOB than their high- and middle-income counterparts. Analyses within each income stratum indicated that race/ethnicity was not related to the prevalence of OWOB in low-income households. However, racial/ethnic differences in OWOB were evident for children and adolescents in middle- and high-income households. Disparities in the prevalence of OWOB between low-income children and adolescents and their middle- and high-income counterparts have increased from 1971 to 2014.
Income and OWOB are related in US children and adolescents. Racial/ethnic differences in the prevalence of OWOB emerge in middle- and high-income households. Disparities in OWOB prevalence are growing.
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