OBJECTIVES: To analyse the effect of fezolinetant on patient-reported sleep disturbance and impairment in individuals with vasomotor symptoms (VMS) using pooled data from the SKYLIGHT 1 and 2 studies. STUDY DESIGN: The SKYLIGHT studies were phase-3, double-blind investigations. Individuals (≥40-≤65 years) who were assigned female at birth and seeking treatment of/relief from moderate-to-severe VMS were enrolled. Participants were randomised to receive placebo, fezolinetant 30 mg, or fezolinetant 45 mg during a 12-week treatment period. MAIN OUTCOME MEASURES: Sleep assessments: Patient-Reported Outcomes Measurement Information System Sleep Disturbance - Short Form 8b (PROMIS SD SF 8b), PROMIS Sleep-Related Impairment - Short Form 8a (PROMIS SRI SF 8a), and Patient Global Impression of Change/Severity in SD (PGI-C SD and PGI-S SD). Assessments were completed at baseline (except PGI-C SD), weeks 4 and 12. RESULTS: Overall, 1022 individuals were randomised and took ≥1 dose of study drug. PROMIS SD SF 8b results showed that improvements in sleep disturbance were observed for fezolinetant 30 and 45 mg versus placebo (week 12, least squares [LS] mean differences: -0.6 [95 % confidence interval [CI]: -1.7, 0.4] for 30 mg and -1.5 [-2.5, -0.5] for 45 mg). Similar improvements in sleep impairment were reported using the PROMIS SRI SF 8a (week 12, LS mean differences: -1.1 [95 % CI: -2.1, -0.1] for 30 mg and -1.3 [-2.3, -0.3] for 45 mg). For PGI-C SD at week 12, 33.6 % (98/292 participants) of the placebo group felt much/moderately better versus 40.1 % (110/274) and 51.0 % (154/302) of the fezolinetant 30 mg and 45 mg groups, respectively. For PGI-S SD at week 12, 44.0 % (129/293) of the placebo group had severe/moderate problems versus 41.1 % (113/275) and 36.6 % (111/303) of the fezolinetant 30 mg and 45 mg groups, respectively. The 12-week timeframe for this analysis was limited by the length of the placebo-controlled period. CONCLUSIONS: Fezolinetant had a beneficial effect on four measures of sleep disturbance and impairment following treatment for VMS.
OBJECTIVE: Frailty may be increased by menopause. Physical activity has been proposed to reduce frailty, but poor adherence and cost limit effectiveness. We aimed to investigate both the effectiveness against the frailty burden and the adherence rate of a multicomponent physical activity scheme partially managed by the participating women themselves. METHODS: Prospective controlled study consisting of a twice-weekly group physical activity scheme divided into two consecutive periods, one supervised by a health professional (12 wk) and the other supervised by the women themselves (36 wk). Group cohesion and mutual support during the patient-only period were aided by social networking via smartphones. Community-dwelling postmenopausal women were divided into a physical activity group (PAG = 126) and a usual activity control group (UAG = 126), both assessed at baseline and at the end of the study. Participants self-assigned to one of the two study arms. RESULTS: Overall, women in the PAG were more likely to improve their frailty status (60.2% vs 42.6%, P < 0.05). The frailty reversal rate from prefrail to robust was significantly higher in the PAG than in the UAG (34.04 vs 8.00%, P < 0.05). Logistic regression confirmed that women in the PAG were more likely to improve their frailty phenotype (odds ratio [OR], 9.12; 95% confidence interval [CI], 3.45-31.52; P < 0.001). Adherence, defined by participants attending 75% of sessions, was attained by 56.35% of women at 48 wk. CONCLUSION: A physical activity scheme implemented to improve frailty proved effective and attained acceptable adherence. Conditions in the peer-supervised 36-wk phase may increase sustainability.
The presence of melatonin in plants, called phytomelatonin, has gained great interest in recent years. The determination of phytomelatonin levels in plant extracts for both physiological and plant foodstuff studies requires sophisticated techniques due to the low endogenous levels of this indolic compound with hormonal nature. This chapter presents the most common and advanced techniques in the determination of phytomelatonin, with special emphasis on the techniques of extraction, cleaning, separation, detection, identification, and quantification. Multiple examples and recommendations are presented for a clear overview of the pros and cons of phytomelatonin determinations in plant tissues, seeds, and fruits, mainly.
Melatonin , Seeds , Fruit , Indoles
OBJECTIVE: To explore the association between anxiety and frailty in community-dwelling postmenopausal women. METHODS: This was a cross-sectional study in which 390 postmenopausal women (aged 60-83 years) who were attending a comprehensive care program were surveyed between January 2018 and February 2020. Each participant was administered a validated Spanish version of the Hospital Anxiety and Depression Scale (HADS) to assess their anxiety status. Those scoring 8 or higher on the anxiety subscale of the HADS were indicative of anxiety. The assessment of frailty utilized the Fried's phenotype, with a diagnosis of frailty established if the participant met at least three out of the five criteria. Factors associated with frailty were analyzed using multivariate logistic regression. RESULTS: The mean age of participants was 70.08 years, with an average of 12.58 ± 3.19 years since menopause. Frailty was diagnosed in 43.85% of the total series, while anxiety was present in 41.08%, rising to 69.59% in participants with frailty. Neither body mass index, years since menopause, educational level, economic status, nor smoking habit demonstrated significant associations with frailty. Upon multivariate analysis, anxiety (OR 8.56), multimorbidity (OR 2.18), and age (OR 2.73) emerged as independently associated with frailty (p < .001, p = .005, and p < .001, respectively). CONCLUSIONS: Among postmenopausal women with frailty, anxiety was detected in over two thirds of cases and was independently associated with frailty. This underscores the relevance of implementing anxiety screening in comprehensive care programs for postmenopausal women, with the goal of improving frailty through anxiety diagnosis and treatment.
Frailty , Humans , Female , Aged , Frailty/epidemiology , Postmenopause , Cross-Sectional Studies , Menopause , Anxiety/epidemiology
This article reviews and comments on the epidemiological book written by the Spanish physician Benigno Risueño de Amador (1802-1849), initially published in French (1829), and its subsequent translation into Spanish (1831). This retrospective documentary case study of a scientific-medical manual reviews the contents of the book, highlighting its most important aspects. This almost 200-year-old book can be considered a valuable, early contribution to epidemiology, and a sign of the great concern in early 19th Europe about the subject of epidemics. It represents a valuable contribution that shows the enormous efforts made to advance in this medical discipline towards a more scientific position at an incipient microbial time.
En este artículo se revisa y comenta el libro de epidemiología escrito por el médico español Benigno Risueño de Amador (1802-1849), publicado inicialmente en francés (1829) y posteriormente traducido al español (1831). Este estudio documental retrospectivo de un manual científico-médico glosa el contenido del libro, destacando sus aspectos más importantes. El libro de casi doscientos años de antigüedad puede considerarse una valiosa y temprana contribución a la epidemiología, así como una muestra de la gran preocupación existente en la Europa de principios del siglo XIX por el tema de las epidemias. Representa además una valiosa contribución española, que muestra los esfuerzos realizados para avanzar en esta disciplina médica hacia una posición más científica en una época incipientemente microbiana.
Books , Humans , Retrospective Studies , Spain , Europe
OBJECTIVE: To assess the effect of fezolinetant treatment on health-related quality of life using pooled data from SKYLIGHT 1 and 2 studies. DESIGN: Prespecified pooled analysis. SETTING: USA, Canada, Europe; 2019-2021. POPULATION: 1022 women aged ≥40 to ≤65 years with moderate-to-severe vasomotor symptoms (VMS; minimum average seven hot flushes/day), seeking treatment for VMS. METHODS: Women were randomised to 12-week double-blind treatment with once-daily placebo or fezolinetant 30 or 45 mg. Completers entered a 40-week, active extension (those receiving fezolinetant continued that dose; those receiving placebo re-randomised to fezolinetant received 30 or 45 mg). MAIN OUTCOME MEASURES: Mean changes from baseline to weeks 4 and 12 on Menopause-Specific Quality of Life (MENQoL) total and domain scores, Work Productivity and Activity Impairment questionnaire specific to VMS (WPAI-VMS) domain scores, Patient Global Impression of Change in VMS (PGI-C VMS); percentages achieving PGI-C VMS of 'much better' (PGI-C VMS responders). Mean reduction was estimated using mixed model repeated measures analysis of covariance. RESULTS: Fezolinetant 45 mg mean reduction over placebo in MENQoL total score was -0.57 (95% confidence interval [CI] -0.75 to -0.39) at week 4 and -0.47 (95% CI -0.66 to -0.28) at week 12. Reductions were similar for 30 mg. MENQoL domain scores were also reduced and WPAI-VMS scores improved. Twice as many women receiving fezolinetant reported VMS were 'much better' than placebo based on PGI-C VMS assessment. CONCLUSIONS: Fezolinetant treatment was associated with improvement in overall QoL, measured by MENQoL, and work productivity, measured by WPAI-VMS. A high proportion receiving fezolinetant felt VMS were 'much better' based on PGI-C VMS responder analysis.
En este artículo se revisa y comenta el libro de epidemiología escrito por el médico español Benigno Risueño de Amador (1802-1849), publicado inicialmente en francés (1829) y posteriormente traducido al español (1831). Este estudio documental retrospectivo de un manual científico-médico glosa el contenido del libro, destacando sus aspectos más importantes. El libro de casi doscientos años de antigüedad puede considerarse una valiosa y temprana contribución a la epidemio-logía, así como una muestra de la gran preocupación existente en la Europa de principios del siglo XIX por el tema de las epidemias. Representa además una valiosa contribución española, que muestra los esfuerzos realizados para avanzar en esta disciplina médica hacia una posición más científica en una época incipientemente microbiana.(AU)
This article reviews and comments on the epidemiological book written by the Spanish physician Benigno Risueño de Amador (1802-1849), initially published in French (1829), and its subsequent translation into Spanish (1831). This retrospective documentary case study of a scientific-medical manual reviews the contents of the book, highlighting its most important aspects. This almost 200-year-old book can be considered a valuable, early contribution to epidemiology, and a sign of the great concern in early 19th Europe about the subject of epidemics. It represents a valuable contribution that shows the enormous efforts made to advance in this medical discipline towards a more scientific position at an incipient microbial time.(AU)
Humans , Male , Female , History, 19th Century , Epidemics/history , Epidemiology
Adalimumab biosimilar experience is still recent. Interchangeability differences could reduce persistence times. Our goal was to compare biosimilar persistence differences with a reference. A retrospective observational study was performed in three groups divided according to the adalimumab received. The primary outcome measure was persistence, represented with Kaplan-Meier analysis, and we secondarily evaluated security, efficacy, and biomarkers. We obtained approval from the regional ethical committee, and the study was conducted following the Helsinki Declaration as revised in 2013. Data from 104 patients were collected: 50 received the biosimilar, 29 received the reference, and 25 switched from the original to the biosimilar. After a follow-up of 12 months, the biosimilar's persistence was higher, without differences in mild adverse events per group. In contrast, there were differences in severe events, with the switched group's frequency being higher. Biomarkers were reduced at similar proportions in all groups, and 43% had a clinical response at week 20 without differences. Adalimumab biosimilars are a valuable option for IBD based on clinical equivalence that are less expensive than the original drug. Their use does not have a detrimental influence on disease, although there are a few nuances in terms of interchangeability. These results support increasing confidence in using biosimilars, thus promoting the better sustainability of health systems.
PURPOSE: Ovarian decortication may affect ovarian function. We investigated the status of ovarian reserve after ovarian decortication plus chemotherapy at a stage of presumed stabilized recovery in women surviving cancer. METHODS: We searched our database for cancer survivors subjected to ovarian decortication and chemotherapy at least 3 years previously. Ovarian function was explored for levels of anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), and estradiol (E2), and menstrual pattern. RESULTS: Forty women (mean age 29.6 (SD, 6.1) years) were assessed at a mean of 4.7 (1.5) years after surgery. The predecortication levels of AMH and FSH changed at post-treatment from 2.2 (1.4) to 0.5 (1.3) ng/mL for AMH (p < 0.001) and from 4.7 (2.1) to 16.7 (21. 6) IU/L for FSH (p < 0.001). Amenorrhea consistent with primary ovarian insufficiency (POI) was diagnosed in 11 women, and normal ovarian reserve (AMH ≥ 1.0 ng/mL) was found in 4 of the 21 women who recovered regular cycles. Logistic regression confirmed AMH as an independent predictor of diminished ovarian reserve (OR = 0.24, 95% CI: 0.04-0.63, p = 0.025) and POI (OR = 0.11, 95% CI: 0.01-0.52, p = 0.027), and age was predictive of POI (OR = 1.36, 95% CI: 1.08-1.96, p = 0.035) and of irregular menstrual cycle (OR = 1.20, 95% CI: 1.03-1.46, p = 0.034). CONCLUSION: Ovarian decortication plus chemotherapy had a deleterious effect when assessed at a stage of stabilized ovarian recovery, but whether ovarian decortication had a specific impact cannot be revealed from our data.
Neoplasms , Ovarian Reserve , Female , Humans , Adult , Prospective Studies , Ovary/surgery , Estradiol/pharmacology , Follicle Stimulating Hormone/pharmacology , Amenorrhea , Follicle Stimulating Hormone, Human/pharmacology , Anti-Mullerian Hormone/pharmacology
Increased life expectancy means that women are now in a hypoestrogenic state for approximately one-third of their lives. Overall health and specifically bone health during this period evolves in accordance with aging and successive exposure to various risk factors. In this review, we provide a summary of the approaches to the sequential management of osteoporosis within an integrative model of care to offer physicians a useful tool to facilitate therapeutic decision-making. Current evidence suggests that pharmacologic agents should be selected based on the risk of fractures, which does not always correlate with age. Due to their effect on bone turnover and on other hormone-regulated phenomena, such as hot flushes or breast cancer risk, we position hormone therapy and selective estrogen receptor modulators as an early postmenopause intervention for the management of postmenopausal osteoporosis. When the use of these agents is not possible, compelling evidence supports antiresorptive agents as first-line treatment of postmenopausal osteoporosis in many clinical scenarios, with digestive conditions, kidney function, readiness for compliance, or patient preferences playing a role in choosing between bisphosphonates or denosumab during this period. For patients at high risk of osteoporotic fracture, the "anabolic first" approach reduces that risk. The effect on bone health with these bone-forming agents or with denosumab should be consolidated with the subsequent use of antiresorptive agents. Regardless of the strategy, follow-up and treatment should be maintained indefinitely to help prevent fractures.
Cancer is one of the main noncommunicable diseases in terms of health impact. Factors such as a progressively aging population point to future increases in the incidence of cancer on a global level. The elevated number of affected individuals, together with continuous improvements in cancer prevention and therapy, is creating a growing population of cancer survivors, with often inadequately met needs. Lifestyle is a key modulator of cancer risk and of associated morbidity and mortality, and is included in all approaches to the long-term management of cancer. Diet is a principal component of lifestyle, and most of the available evidence is centered on the Mediterranean diet. Our objective was to provide a narrative review of the evidence on the effect of the Mediterranean diet on cancer risk and health threats related to cancer survivorship. For this purpose, we searched the PubMed database for articles published between January 1, 2000, and June 12, 2023. Current data show that the Mediterranean diet is inversely associated with risk, or is risk neutral, for most types of cancer. Tumors of the digestive system have received preferential interest, but studies have also been published on tumors in other organs. The evidence, however, is meager due to the observational nature of most studies, although it is reassuring that benefit is reproduced in studies performed in different populations and environments. Evidence related to cancer survivors is limited by the paucity of studies, yet several findings regarding survival, recurrence, and short- and long-term morbidity suggest a potential role for the Mediterranean diet that warrants further research.
Cancer Survivors , Diet, Mediterranean , Neoplasms , Humans , Aged , Survivorship , Neoplasms/etiology , Neoplasms/prevention & control , Risk
Background and study aims Effective bowel cleansing is critical for detecting lesions during colonoscopy, highlighting the importance of bowel preparations. 1L polyethylene glycol (PEG) + ascorbate (Asc) is the only recommended 1L PEG product in Europe and the United States. Its efficacy was demonstrated in large-scale controlled trials and confirmed in smaller-scale real-world studies. However, no large-scale real-world data exist. Patients and methods This observational, retrospective, multicenter study, used outpatient follow-up data from medical records from 10 centers in Spain and two in Portugal. Outpatients aged ≥18 years using 1L PEG + Asc as bowel preparation were included. The main outcome measures were overall adequate colon cleansing (Boston Bowel Preparation Scale [BBPS] score ≥6 with BBPS score ≥2 in each segment) and high-quality cleansing of the right colon (BBPS score=3). Results Data from 13169 eligible patients were included. Overall cleansing success was achieved in 89.3% (95%CI 88.7%-89.8%) and high-quality cleansing in the right colon in 49.3% (95%CI 48.4%-50.2%) of patients. For the overnight split-dose and same-day regimens, overall adequate quality cleansing success rate was 94.7% and 86.7% ( P <0.0001) and high-quality cleansing of the right colon rate was 65.4% and 41.4% ( P <0.0001), respectively. Colonoscopy was completed in 97.3% of patients, with non-completion due to poor preparation in only 0.8%; 2.3% of patients experienced at least one adverse event (AE). Conclusions This large-scale, real-world study demonstrates the effectiveness of 1L PEG + Asc in the total and right colon, with a low percentage of patients with AEs in routine clinical practice.
BACKGROUND: Once a mate choice decision has been made, couples that fail to reach a live birth in natural and/or intrauterine insemination (IUI) cycles will likely visit fertility clinics seeking assisted reproductive technology (ART) treatment. During the more or less prolonged period of infertility experienced, those couples with mild/moderate reproductive anomalies would have advantage over couples displaying more severe reproductive alterations in achieving a natural or IUI conception. Thus, we can expect to find a progressive increase in the proportion of couples with more severe reproductive anomalies as duration of infertility rises. In this study, we aim to ascertain whether there is an association between male and female infertility diagnoses and duration of infertility in couples seeking ART treatment for the first time. METHODS: A cross-sectional analysis of 1383 infertile couples that sought ART treatment for the first time. Forward-stepwise binary logistic regression analyses were applied to calculate exponentiated regression coefficients. RESULTS: Men suffering from any combination of oligo-, astheno-, and teratozoospermia (ACOAT) exhibited higher odds of having a duration of infertility > 2 years compared with non-ACOAT men [odds ratio (95% confidence interval): 1.340 (1.030-1.744)]. Women from ACOAT couples displaying a duration of infertility > 2 years presented shorter menstrual cycles (P ≤ 0.047) and lower antral follicular count (AFC) values (P ≤ 0.008) and serum anti-Müllerian hormone (AMH) levels (P ≤ 0.007) than women from non-ACOAT couples exhibiting > 2 years of infertility. Likewise, AFC values (P ≤ 0.013) and serum AMH levels (P ≤ 0.001) were decreased when compared with women from ACOAT couples displaying ≤ 2 years of infertility. A relative low but significant percentage of ACOAT couples displaying > 2 years of infertility stood out for their smoking habits. CONCLUSIONS: Couples consisting of ACOAT men and women with a relative low ovarian reserve are overrepresented in couples seeking ART treatment for the first time after experiencing > 2 years of infertility. This outcome leads us to develop a general hypothesis proposing that the origin of couple's infertility is a consequence of a process of positive assortative mating shaped by sexual selection forces.
Infertility, Female , Ovarian Reserve , Pregnancy , Female , Male , Humans , Cross-Sectional Studies , Semen , Reproductive Techniques, Assisted , Infertility, Female/therapy , Live Birth
INTRODUCTION: Around 80% of women suffer menopause-related symptoms that affect their daily activities and quality of life. Menopausal hormone therapy (MHT) has proven to be beneficial in relieving these symptoms. Nevertheless, only 20/30% of symptomatic women seek treatment. This has resulted in neglect of a generation of healthcare professionals' (HCPs) education in menopausal medicine and a reduction in the prescription of MHT in menopausal women for over two decades. AREAS COVERED: The aim of this article was to identify the main barriers that HCPs face for prescribing MHT and menopausal women for using it. Six European experts in menopause agreed on the profiles of women that benefit from MHT and proposed strategies to break down these barriers. EXPERT OPINION: The most important barrier for HCPs was deficient knowledge of the true evidence-based information, with inadequate training regarding the efficacy and safety of personalized MHT and the real benefit/risk ratio in the treatment of symptomatic women. For patients, fear of developing breast cancer was identified as the single most important barrier. Breaking down barriers is possible, by providing appropriate training and education to HCPs and women. This should result in fully informed, evidence based, shared treatment decisions by women and their physicians.
Estrogen Replacement Therapy , Quality of Life , Female , Humans , Estrogen Replacement Therapy/adverse effects , Menopause , Hormone Replacement Therapy/adverse effects , Hormones
INTRODUCTION: Preventative surgical procedures for patients who are breast cancer (BRCA) positive-namely, bilateral salpingo-oophorectomy and mastectomy-have been linked to changes in sexual function, including surgically induced menopause. A patient's decision to undergo preventive surgery as opposed to high-risk screening is heavily reliant on advice received from one's health care provider. Quality of life should be considered when shared decision making is conducted with patients. OBJECTIVES: To assemble and analyze findings related to patient-reported sexual function after these surgical procedures, to see if and how either procedure affects sexual function from patient baseline, and to determine whether the effects can be mitigated with menopausal hormone therapy. METHODS: A literature review based on the PubMed, Embase, and MEDLINE databases was conducted from inception through January 25, 2022. To be included, studies had to meet an a priori list of Medical Subject Headings: "BRCA" AND "sexual dysfunction" OR "dyspareunia." GRADE criteria were used to determine the quality of studies relating to menopause hormone therapy. RESULTS: The search yielded 14 results, and 11 reported sufficient data for systematic review. Sexual function was measured via validated and investigator-generated surveys. All studies, no matter the survey metric, found significant reduction in sexual function with bilateral salpingo-oophorectomy; no studies revealed sexual function changes associated with mastectomy postsurgery. Few studies indicated that menopause hormone therapy resulted in significant improvement in sexual function, and all studies reported that postoperative sexual function could not reach baseline levels with therapy. No studies were high quality by GRADE metrics. CONCLUSION: Prophylactic mastectomies and bilateral salpingo-oophorectomies among patients who are BRCA positive cause SF changes postprocedure. Menopausal hormone therapy offers little help in mediating symptoms. Significantly more research is needed to explore potential changes in sexual function, as it is an important aspect of quality of life for patients with BRCA positivity.
Breast Neoplasms , Prophylactic Mastectomy , Female , Humans , Salpingo-oophorectomy , Breast Neoplasms/surgery , Breast Neoplasms/prevention & control , Mastectomy , Quality of Life , Genes, BRCA2 , Hormone Replacement Therapy , Menopause
The purpose of this work was to investigate, for the first time to our knowledge, the chemical composition and bioactivity of methanolic extracts (roots, stems, leaves, and flowers) from Cladanthus mixtus (L.) Chevall. that grows wild in northern Morocco (the Tangier-Tetouan-Al Hoceima region). The phenolic and flavonoid contents were determined by spectrophotometer methods, and the composition of derivatized methanolic extracts from C. mixtus using N-O-bis(trimethylsilyl) trifluoroacetamide (BSTFA) was analyzed by gas chromatography-mass spectrometry (GC-MS). The antioxidant activity was carried out by applying the 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and DPPH (2,2-diphenyl-1-picrylhydrazyl) tests. The micro-dilution technique was chosen to investigate the antimicrobial activity of methanolic extracts against two bacterial strains and three fungal species. The results showed that the values of total phenolic and flavonoid contents were found to be higher in flower extracts (30.55 ± 0.85 mg of gallic acid equivalents (GAE)/g of dried weight (DW) and 26.00 ±1.34 mg of quercetin equivalents (QE)/g DW, respectively). Other groups of chemical compounds were revealed by GC-MS, such as carbohydrates (27.25-64.87%), fatty acids (1.58-9.08%), organic acids (11.81-18.82%), and amino acids (1.26-7.10%). Root and flower methanolic extracts showed the highest antioxidant activity using ABTS (39.49 mg of Trolox equivalents (TE)/g DW) and DPPH (36.23 mg TE/g DW), respectively. A positive correlation between antioxidant activity and polyphenol and flavonoid amounts was found. Antibacterial tests showed that the best activity was presented by the leaf extract against Staphylococcus aureus (minimum inhibitory concentration (MIC) = minimum bactericidal concentration (MBC) = 20 mg/mL) and Escherichia coli (MIC of 30 mg/mL and MBC of 35 mg/mL). S. aureus was more sensitive to the extracts compared to E. coli. All extracts showed antifungal activity against Trichophyton rubrum, with the best efficacy reported by the flower and leaf extracts (MIC = 1.25 mg/mL and minimum fungicidal concentration (MFC) = 2.5 mg/mL). In general, extracts of C. mixtus appeared less effective against Candida albicans and Aspergillus fumigatus.
Antioxidants , Plant Extracts , Plant Extracts/pharmacology , Plant Extracts/chemistry , Antioxidants/pharmacology , Antioxidants/chemistry , Staphylococcus aureus , Escherichia coli , Morocco , Flavonoids/pharmacology , Flavonoids/analysis , Phenols/pharmacology , Phenols/analysis , Methanol/pharmacology
BACKGROUND: Dynapenia increases with age and in the case of women is possibly influenced by menopause, yet whether vitamin D affects this increase remains controversial. The influence of genetic variants (single nucleotide polymorphisms) of the vitamin D receptor on dynapenia is an understudied area. AIM: To analyze the association between genetic variants of the vitamin D receptor gene and dynapenia in a cohort of community-dwelling postmenopausal women. METHODS: We performed a cross-sectional study of 463 women in a university hospital. Grip strength was used as an indicator of dynapenia. Differences in grip strength among single nucleotide polymorphisms rs11568820 and rs2228570 genotypes of the vitamin D receptor gene were assessed after adjusting for confounding variables, and the percentage of phenotypic variance was estimated by linear regression. RESULTS: Dynapenia (grip strength <20 kg) was diagnosed in 178 of the women (38.45 %). A difference in grip strength, corresponding to variants of the vitamin D receptor gene single nucleotide polymorphism rs11568820, was found when using an additive model of inheritance, with lower grip strength for the TT genotype (ANOVA, p = 0.030, close to the 0.025 significance level determined by Bonferroni correction). Assuming a recessive inheritance model for allele T, the between-group difference in grip strength was significant (TT = 19.79 ± 3.10 kg vs. CC/CT = 21.58 ± 3.49 kg, p = 0.008) after adjusting for age, body mass index, comorbidities, and sociodemographic variables. More women with dynapenia had the TT genotype (60.71 %) than the CC or CT genotype (37.01 %) (p = 0.012). CONCLUSION: This study demonstrates that the TT genotype of the rs11568820 SNP of the vitamin D receptor gene was associated with decreased grip strength in community-dwelling postmenopausal women.
Postmenopause , Receptors, Calcitriol , Humans , Female , Receptors, Calcitriol/genetics , Postmenopause/genetics , Cross-Sectional Studies , Vitamin D , Polymorphism, Single Nucleotide , Genotype
BACKGROUND: Neurokinin 3 receptor antagonists are potential non-hormonal therapies for the treatment of vasomotor symptoms in menopausal women as options are scarce for those who cannot or do not want to take hormone therapy. Fezolinetant is one of the first non-hormonal neurokinin 3 receptor antagonists in development for the treatment of vasomotor symptoms due to menopause. This study investigated the safety and efficacy of fezolinetant for the treatment of moderate-to-severe vasomotor symptoms associated with menopause. METHODS: SKYLIGHT 1 is a randomised, double-blind, placebo-controlled, 12-week, phase 3 trial with a 40-week active treatment extension. This trial was done at 97 facilities across the USA, Canada, Czech Republic, Hungary, Poland, Spain, and the UK. Women aged 40-65 years with an average of seven or more moderate-to-severe hot flashes per day were randomly assigned (1:1:1) to once-daily exact-matched placebo, fezolinetant 30 mg, or fezolinetant 45 mg. Randomisation was done using a web-based interactive response system and investigators, project team members, clinical staff, and participants were masked to treatment assignment. Coprimary endpoints were mean change in frequency and severity of vasomotor symptoms from baseline to weeks 4 and 12. The efficacy and safety analyses comprised all randomly assigned participants who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov (NCT04003155) and is completed. FINDINGS: Between July 11, 2019, and Aug 11, 2021, 2205 women were recruited of whom 175 were assigned to placebo, 176 to fezolinetant 30 mg, and 176 to fezolinetant 45 mg (175 in the placebo group, 174 in the fezolinetant 30 mg group, and 173 in the fezolinetant 45 mg received at least one dose [safety analysis set]). One participant randomly assigned to fezolinetant 45 mg received fezolinetant 30 mg in error, so the efficacy analysis set (full analysis set) consisted of 173 in the fezolinetant 30 mg group and 174 in the fezolinetant 45 mg group. 23 participants in the placebo group, 31 in the fezolinetant 30 mg group, and 13 in the fezolinetant 45 mg group discontinued treatment before week 12, mostly due to adverse events or participant withdrawal. Compared with placebo, fezolinetant 30 mg and fezolinetant 45 mg significantly reduced the frequency of vasomotor symptoms at week 4 (difference in change in least squares mean -1·87 [SE 0·42; p<0·001], -2·07 [SE 0·42; p<0·001]) and week 12 (-2·39 [SE 0·44; p<0·001], -2·55 [SE 0·43; p<0·001]). Compared with placebo, fezolinetant 30 mg and 45 mg significantly reduced the severity of vasomotor symptoms at week 4 (-0·15 [0·06; p=0·012], -0·19 [0·06; p=0·002]) and week 12 (-0·24 [0·08; p=0·002], -0·20 [0·08; p=0·007]). Improvements in frequency and severity of vasomotor symptoms were observed after 1 week and maintained over 52 weeks. During the first 12 weeks, treatment-emergent adverse events occurred in 65 (37%) of 174 women in the fezolinetant 30 mg group, 75 (43%) of 173 in the fezolinetant 45 mg group, and 78 (45%) of 175 in the placebo group. The incidence of liver enzyme elevations was low (placebo n=1; fezolinetant 30 mg n=2; fezolinetant 45 mg n=0) and these events were generally asymptomatic, transient, and resolved while on treatment or after treatment discontinuation. INTERPRETATION: Data support the clinical use of fezolinetant as a non-hormonal treatment for vasomotor symptoms associated with menopause. The study was placebo-controlled for 12 weeks followed by a 40-week blinded extension to assess the maintenance of effect. Furthermore, the population studied was diverse and representative of the potential target population for fezolinetant therapy. Further characterisation of the benefit of fezolinetant on quality of life, including on symptoms of mood and sexual wellbeing, merits investigation. FUNDING: Astellas Pharma.
Quality of Life , Receptors, Neurokinin-3 , Humans , Female , Treatment Outcome , Menopause , Double-Blind Method
