Twelve-month psychosis-predictive value of the ultra-high risk criteria in children and adolescents

Objective The validity of current ultra-high risk (UHR) criteria is under-examined in help-seeking minors, particularly, in children below the age of 12 years. Thus, the present study investigated predictors of one-year outcome in children and adolescents (CAD) with UHR status. Method Thirty-five children and adolescents (age 9–17 years) meeting UHR criteria according to the Structured Interview for Psychosis-Risk Syndromes were followed-up for 12 months. Regression analyses were employed to detect baseline predictors of conversion to psychosis and of outcome of non-converters (remission and persistence of UHR versus conversion). Results At one-year follow-up, 20% of patients had developed schizophrenia, 25.7% had remitted from their UHR status that, consequently, had persisted in 54.3%. No patient had fully remitted from mental disorders, even if UHR status was not maintained. Conversion was best predicted by any transient psychotic symptom and a disorganized communication score. No prediction model for outcome beyond conversion was identified. Conclusions Our findings provide the first evidence for the predictive utility of UHR criteria in CAD in terms of brief intermittent psychotic symptoms (BIPS) when accompanied by signs of cognitive impairment, i.e. disorganized communication. However, because attenuated psychotic symptoms (APS) related to thought content and perception were indicative of non-conversion at 1-year follow-up, their use in early detection of psychosis in CAD needs further study. Overall, the need for more in-depth studies into developmental peculiarities in the early detection and treatment of psychoses with an onset of illness in childhood and early adolescence was further highlighted

Eligibility criteria for Menopausal Hormone Therapy (MHT): a position statement from a consortium of scientific societies for the use of MHT in women with medical conditions. MHT Eligibility Criteria Group

This project aims to develop eligibility criteria for menopausal hormone therapy (MHT). The tool should be similar to those already established for contraception A consortium of scientific societies coordinated by the Spanish Menopause Society met to formulate recommendations for the use of MHT by women with medical conditions based on the best available evidence. The project was developed in two phases. As a first step, we conducted 14 systematic reviews and 32 metanalyses on the safety of MHT (in nine areas: age, time of menopause onset, treatment duration, women with thrombotic risk, women with a personal history of cardiovascular disease, women with metabolic syndrome, women with gastrointestinal diseases, survivors of breast cancer or of other cancers, and women who smoke) and on the most relevant pharmacological interactions with MHT. These systematic reviews and metanalyses helped inform a structured process in which a panel of experts defined the eligibility criteria according to a specific framework, which facilitated the discussion and development process. To unify the proposal, the following eligibility criteria have been defined in accordance with the WHO international nomenclature for the different alternatives for MHT (category 1, no restriction on the use of MHT; category 2, the benefits outweigh the risks; category 3, the risks generally outweigh the benefits; category 4, MHT should not be used). Quality was classified as high, moderate, low or very low, based on several factors (including risk of bias, inaccuracy, inconsistency, lack of directionality and publication bias). When no direct evidence was identified, but plausibility, clinical experience or indirect evidence were available, "Expert opinion" was categorized. For the first time, a set of eligibility criteria, based on clinical evidence and developed according to the most rigorous methodological tools, has been defined. This will provide health professionals with a powerful decision-making tool that can be used to manage menopausal symptoms

Chinese Enclave Protections Among Married Chinese American Women: Exploratory Secondary Analysis of Colon Cancer Survival

Objective: Like the barrio advantage theory related to Mexican Americans, a theory about the protective effects of Chinese American enclaves is developing. Such protections were examined among socioeconomically vulnerable people with colon cancer. Design: A colon cancer cohort established in California between 1995 and 2000, and followed until the enactment of the Affordable Care Act was utilized in this study. Secondary analysis was conducted on the 5-year survival among 127 Chinese Americans and 4524 other Americans (3810 non-Hispanic white and 714 Hispanic people). A third of the original cohort was selected from high poverty neighborhoods. Chinese American enclaves were neighborhoods where typically 25% or more of the residents were Chinese Americans. Effects were tested with Cox regressions and group differences described with age and stage-standardized survival rate ratios (RR). Results: Though they were less adequately insured, Chinese American women residing in Chinese American enclaves (63%) were more likely to survive than were other Americans (50%, RR = 1.26). The protective effect of being married was also larger for Chinese Americans (RR = 1.31) than for others (RR = 1.17). Chinese American women (61%) were more likely than men (46%) to live in such enclaves and a large enclave survival advantage was observed among Chinese American women only (RR = 1.59). Conclusions: There is consistent evidence of the relatively protected status of Chinese American women, particularly those who were married and resided in Chinese American enclaves. Mechanisms that explain their apparent advantages are not yet well understood, though relatively large, kin-based social networks seem instrumental. Research on the influence of social networks as well as the possible effects of acculturation is needed. This study also exposed structural inequities related to the institutions of marriage, health care and communities that disadvantage others. Policy makers ought to be aware of them as future reforms of American health care are considered

Hormone Replacement Therapy: Would it be Possible to Replicate a Functional Ovary?

Background: Throughout history, menopause has been regarded as a transition in a woman’s life. With the increase in life expectancy, women now spend more than a third of their lives in menopause. During these years, women may experience intolerable symptoms both physically and mentally, leading them to seek clinical advice. It is imperative for healthcare providers to improve the quality of life by reducing bothersome menopausal symptoms and preventing disorders such as osteoporosis and atherosclerosis. The current treatment in the form of hormone replacement therapy (HRT) is sometimes inadequate with several limitations and adverse effects. Objective and rationale: The current review aims to discuss the need, efficacy, and limitations of current HRT; the role of other ovarian hormones, and where we stand in comparison with ovary-in situ; and finally, explore towards the preparation of an HRT model by regeneration of ovaries tissues through stem cells which can replicate a functional ovary. Search methods: Four electronic databases (MEDLINE, Embase, Web of Science and CINAHL) were searched from database inception until 26 April 2018, using a combination of relevant controlled vocabulary terms and free-text terms related to ‘menopause’, ‘hormone replacement therapy’, ‘ovary regeneration’, ‘stem cells’ and ‘ovarian transplantation’. Outcomes: We present a synthesis of the existing data on the efficacy and limitations of HRT. HRT is far from adequate in postmenopausal women with symptoms of hormone deprivation as it fails to deliver all hormones secreted by naïve ovarian tissue. Moreover, the pharmacokinetics of synthetic hormones makes them substantially different from natural ones. Not only does the number and type of hormones given in HRT matter, but the route of delivering and their release in circulation are also imperative. The hormones are delivered either orally or topically in a non-physiological uniform manner, which brings along with it several side effects. These identify the need for a hormone delivery system which replicates, integrates and reacts as per the requirement of the female body. Wider implications: The review outlines the strengths and weaknesses of HRT and highlights the potential areas for future research. There is a tremendous potential for research in this field to understand the collective roles of the various ovarian hormones and to devise an auto-regulated hormone delivery system which replicates the normal physiology. Its clinical applications can prove to be transformative for postmenopausal women helping them to lead a healthy and productive life

Impact of vulvovaginal health on postmenopausal women: A review of surveys on symptoms of vulvovaginal atrophy

Several recent, large-scale studies have provided valuable insights into patient perspectives on postmenopausal vulvovaginal health. Symptoms of vulvovaginal atrophy, which include dryness, irritation, itching, dysuria, and dyspareunia, can adversely affect interpersonal relationships, quality of life, and sexual function. While approximately half of postmenopausal women report these symptoms, far fewer seek treatment, often because they are uninformed about hypoestrogenic postmenopausal vulvovaginal changes and the availability of safe, effective, and well-tolerated treatments, particularly local vaginal estrogen therapy. Because women hesitate to seek help for symptoms, a proactive approach to conversations about vulvovaginal discomfort would improve diagnosis and treatment

An epigenome-wide association study of Alzheimer's disease blood highlights robust DNA hypermethylation in the HOXB6 gene

This is the final version. Available from the publisher via the DOI in this record.A growing number of epigenome-wide association studies have demonstrated a role for DNA methylation in the brain in Alzheimer's disease. With the aim of exploring peripheral biomarker potential, we have examined DNA methylation patterns in whole blood collected from 284 individuals in the AddNeuroMed study, which included 89 nondemented controls, 86 patients with Alzheimer's disease, and 109 individuals with mild cognitive impairment, including 38 individuals who progressed to Alzheimer's disease within 1 year. We identified significant differentially methylated regions, including 12 adjacent hypermethylated probes in the HOXB6 gene in Alzheimer's disease, which we validated using pyrosequencing. Using weighted gene correlation network analysis, we identified comethylated modules of genes that were associated with key variables such as APOE genotype and diagnosis. In summary, this study represents the first large-scale epigenome-wide association study of Alzheimer's disease and mild cognitive impairment using blood. We highlight the differences in various loci and pathways in early disease, suggesting that these patterns relate to cognitive decline at an early stage.Alzheimer's Society, United KingdomMedical Research Council (MRC)NIH, United States, R01 grantAlzheimer's Research U

Pharmacologic intervention for prevention of fractures in osteopenic and osteoporotic postmenopausal women: Systemic review and meta-analysis

Objectives Emerging evidence has indicated a role for pharmacologic agents in the primary prevention of osteoporotic fracture, but have not yet been systematically reviewed for meta-analysis. We conducted a meta-analysis to evaluate the efficacy of pharmacologic interventions in reducing fracture risk and increasing bone mineral density (BMD) in postmenopausal women with osteopenia or osteoporosis but without prevalent fragility fracture. Method The Medline, EMBASE, and CENTRAL databases were searched from inception to September 30, 2019. Only randomized placebo-controlled trials evaluating postmenopausal women with −1.0 > bone mineral density (BMD) T-score > −2.5 (low bone mass) and those with BMD T-score ≤ −2.5 (osteoporosis) but without baseline fractures, who were receiving anti-osteoporotic agents, providing quantitative outcomes data and evaluating risk of vertebral and/or non-vertebral fragility fracture at follow-up. The PRISMA guidelines were followed, applying a random-effects model. The primary endpoint was the effect of anti-osteoporotic regimens in reducing the incidence of vertebral fractures. Secondary endpoints were percentage changes in baseline BMD at the lumbar spine and total hip at 1 and 2 years follow up. Results Full-text review of 144 articles yielded, 20 for meta-analysis. Bisphosphonates reduced the risk of vertebral fracture (pooled OR = 0.50, 95%CIs = 0.36–0.71) and significantly increased lumbar spine BMD after 1 year, by 4.42% vs placebo (95%CIs = 3.70%–5.14%). At the hip, this value was 2.94% (95%CIs = 2.13%–3.75%). Overall results of limited studies for non-bisphosphonate drugs showed increased BMD and raloxifene significantly decreases the risk of subsequent clinical vertebral fractures. Conclusion The bisphosphonates are efficacious and most evident for the primary prevention of osteoporotic vertebral fractures, reducing their incidence and improving BMD in postmenopausal women with osteopenia or osteoporosis

The phenolic complex in flaxseed

Flaxseed is the richest plant source of the lignan secoisolariciresinol diglucoside (SDG). In flaxseed, SDG exists in an oligomeric structure with 3-hydroxy-3-methyl glutaric acid (HMGA) forming a phenolic complex together with p-coumaric acid and ferulic acid glucosides and herbacetin diglucoside (HDG). Epidemiological and animal studies indicate protective effects of flaxseed and SDG towards hormone-dependent cancers and cardiovascular diseases, and reducing effect toward cholesterol levels in blood. Knowledge about the structural features and properties of the phenolic complex are required to further understand bioavailability, bioconversion and bioactivity of flaxseed lignans in humans and animals, the biosynthesis in flaxseed, as well as if it may affect technology and quality of food products containing flaxseed or the phenolic complex. A new fast and simple high-performance liquid chromatographic (HPLC) method was developed for analysing secoisolariciresinol diglucoside (SDG), p-coumaric acid glucoside and ferulic acid glucoside, based on direct hydrolysis of defatted flaxseed flour using alkali. Variations in SDG, p-coumaric acid glucoside and ferulic acid glucoside content were reported in flaxseed samples and bread products containing flaxseed. The composition and properties of flaxseed phenolic complex were studied by reversed-phase liquid chromatography and gel filtration fractionation. Results indicate that the phenolic glucosides exist in oligomers with variable molecular sizes. A complicated linkage pattern and/or possibly interactions with other components may contribute to the observed complexity. SDG and the phenolic complex showed similar hydrogen-donating abilities to ferulic acid but higher than α-tocopherol in the DPPH inhibition metod, suggesting that SDG was the only active antioxidant in the phenolic complex. Contradicting results were obtained on the effect of SDG on levels of Vitamin E and cholesterol in two rat studies

Differences in Atrial Remodeling in Hypertrophic Cardiomyopathy Compared to Hypertensive Heart Disease and Athletes’ Hearts.

BACKGROUND: Hypertrophic cardiomyopathy (HCM), hypertensive heart disease (HHD) and athletes' heart share an increased prevalence of atrial fibrillation. Atrial cardiomyopathy in these patients may have different characteristics and help to distinguish these conditions. METHODS: In this single-center study, we prospectively collected and analyzed electrocardiographic (12-lead ECG, signal-averaged ECG (SAECG), 24 h Holter ECG) and echocardiographic data in patients with HCM and HHD and in endurance athletes. Patients with atrial fibrillation were excluded. RESULTS: We compared data of 27 patients with HCM (70% males, mean age 50 +/- 14 years), 324 patients with HHD (52% males, mean age 75 +/- 5.5 years), and 215 endurance athletes (72% males, mean age 42 +/- 7.5 years). HCM patients had significantly longer filtered P-wave duration (153 +/- 26 ms) and PR interval (191 +/- 48 ms) compared to HHD patients (144 +/- 16 ms, p = 0.012 and 178 +/- 31, p = 0.034, respectively) and athletes (134 +/- 14 ms, p = 0.001 and 165 +/- 26 ms, both p &lt; 0.001, respectively). HCM patients had a mean of 4.9 +/- 16 premature atrial complexes per hour. Premature atrial complexes per hour were significantly more frequent in HHD patients (27 +/- 86, p &lt; 0.001), but not in athletes (2.7 +/- 23, p = 0.639). Left atrial volume index (LAVI) was 43 +/- 14 mL/m(2) in HCM patients and significantly larger than age- and sex-corrected LAVI in HHD patients 30 +/- 10 mL/m(2); p &lt; 0.001) and athletes (31 +/- 9.5 mL/m(2); p &lt; 0.001). A borderline interventricular septum thickness >/=13 mm and </=15 mm was found in 114 (35%) HHD patients, 12 (6%) athletes and 3 (11%) HCM patients. CONCLUSIONS: Structural and electrical atrial remodeling is more advanced in HCM patients compared to HHD patients and athletes