The impact of COVID-19 on a specialised menopause clinic: Changes in practice and women's experiences.

AIMS: The COVID-19 pandemic necessitated the rapid change in a dedicated multidisciplinary menopause clinic from in-person consultations to telehealth. The aim of this study was to explore the impact of COVID-19 on menopause service delivery and consumer experiences. METHODS: Two-part study involving the following. (i) Clinical audit conducted June-July 2019 (pre-COVID-19) and June-July 2020 (COVID-19) assessing practice and service delivery changes. Assessment outcomes included: patient demographics, cause of menopause, presence of menopause symptoms, appointment attendance, medical history, investigations and menopause treatments. (ii) A post-clinic online survey exploring the acceptability and experience of telehealth, once telehealth models of care had been routinely used in the menopause service (2021). RESULTS: Pre-COVID (n = 156) and COVID-19 (n = 150) clinic consultations were audited. Menopause care delivery changed significantly from 100% face-to-face consultations in 2019 to 95.4% telehealth consultations in 2020. In 2020, fewer women had investigations performed vs 2019 (P < 0.001), although use of menopausal therapies was similar (P < 0.05). Ninety-four women completed the online survey. Most women (70%) were satisfied with their telehealth consultation and perceived that the doctor effectively communicated with them (76%). Women preferred face-to-face consultations for their first menopause clinic visit (69%) and telehealth for review consultations (65%). The majority of women (62%) viewed the continuation of telehealth consultations as 'moderately' to 'extremely useful' post-pandemic. CONCLUSION: The COVID-19 pandemic caused significant changes to menopause service delivery. Telehealth was perceived as feasible and acceptable by women, supporting the continuation of a hybrid service delivery model incorporating telehealth and face-to-face consultation to meet the needs of women.

Optimising Cardiometabolic Risk Factors in Pregnancy: A Review of Risk Prediction Models Targeting Gestational Diabetes and Hypertensive Disorders.

Cardiovascular disease, especially coronary heart disease and cerebrovascular disease, is a leading cause of mortality and morbidity in women globally. The development of cardiometabolic conditions in pregnancy, such as gestational diabetes mellitus and hypertensive disorders of pregnancy, portend an increased risk of future cardiovascular disease in women. Pregnancy therefore represents a unique opportunity to detect and manage risk factors, prior to the development of cardiovascular sequelae. Risk prediction models for gestational diabetes mellitus and hypertensive disorders of pregnancy can help identify at-risk women in early pregnancy, allowing timely intervention to mitigate both short- and long-term adverse outcomes. In this narrative review, we outline the shared pathophysiological pathways for gestational diabetes mellitus and hypertensive disorders of pregnancy, summarise contemporary risk prediction models and candidate predictors for these conditions, and discuss the utility of these models in clinical application.

Ischemic stroke and infection: A brief update on mechanisms and potential therapies.

Ischemic stroke triggers a multifaceted inflammatory response in the brain that contributes to secondary brain injury and infarct expansion. In parallel with brain inflammation, ischemic stroke also leads to post-stroke immunosuppression. Stroke-induced leukopenia then predisposes patients to opportunistic infections potentially leading to pneumonia or unrinary tract infections and a worsened stroke outcome. There is evidence that the hypothalamic-pituitaryadrenal axis plays an important role in the etiology of post-stroke immunosuppression, by which prolonged glucocorticoid signalling leads to changes in immune responses. While opportunistic microbes in hospitals have been thought to be the source of infection, recent studies have reported that gut flora may also be a cause of post-stroke infection as a consequence of compromised integrity of the gut barrier after stroke. While antimicrobial drugs would appear to be a rational form of treatment for bacterial infections in stroke patients, the rise in drug-resistant bacteria and possible adverse effects of disrupting beneficial gut flora represent major challenges with these drugs. Considering the prominent role of gut microbiota in modulating immune responses, protecting and restoring the post-stroke gut bacteriome may provide significant benefit in the context of post-stroke infection. With such broad aspects of post-stroke infection occurring together with an extensive inflammatory response in the brain, a carefully considered administration of therapies for ischemic stroke is warranted.

Mobile Apps for Weight Management: A Review of the Latest Evidence to Inform Practice.

Over the last decade, mobile technology has emerged as a potentially useful platform to facilitate weight management and tackle the current obesity epidemic. Clinicians are being more frequently asked to give advice about the usefulness of mobile apps and many individuals have already integrated apps into their attempts to manage weight. Hence, it is imperative for clinicians involved in weight management to be aware of the latest developments and knowledge about available mobile apps and their usefulness in this field. A number of newly published studies have demonstrated promising results of mobile-based interventions for weight management across different populations, but the extent of their effectiveness remains widely debated. This narrative literature review synthesizes the latest evidence, primarily from randomized controlled trials (RCTs), regarding the clinical use of mobile applications for weight management, as well as highlight key limitations associated with their use and directions for future research and practice. Overall, evidence suggests that mobile applications may be useful as low-intensity approaches or adjuncts to conventional weight management strategies. However, there is insufficient evidence to support their use as stand-alone intensive approaches to weight management. Further research is needed to clarify the extent of utility of these applications, as well as the measures required to maximize their potential both as stand-alone approaches and adjuncts to more intensive programs.

Metabolomic Description of Ivacaftor Elevating Polymyxin B Mediated Antibacterial Activity in Cystic Fibrosis Pseudomonas aeruginosa.

We have demonstrated that ivacaftor displays synergistic antibacterial activity in combination with polymyxin B against polymyxin-resistant Pseudomonas aeruginosa that commonly colonizes the lungs of people with cystic fibrosis (CF). However, the underlying mechanism(s) remain unclear. In the present study, we employed untargeted metabolomics to investigate the synergistic killing mechanism of polymyxin B in combination with ivacaftor against a polymyxin-susceptible P. aeruginosa FADDI-PA111 (polymyxin B MIC = 2 mg/L) and a polymyxin-resistant CF P. aeruginosa FADDI-PA006 (polymyxin B MIC = 8 mg/L). Metabolites were extracted at 3 h after treatments with polymyxin B alone (2 µg/mL for FADDI-PA111 and 4 µg/mL FADDI-PA006 P. aeruginosa), ivacaftor alone (8 µg/mL), and in combination. Polymyxin B monotherapy induced significant perturbations in the glycerophospholipid and fatty acid metabolism pathways against FADDI-PA111 and to a lesser extent in FADDI-PA006. In both strains, treatment with ivacaftor alone induced more pronounced perturbations in glycerophospholipid and fatty acid metabolism pathways than that with polymyxin B alone. This highlights the unique antimicrobial mode of action of ivacaftor. Pathway analysis revealed that in combination treatment, polymyxin B mediated killing is elevated by ivacaftor, largely due to the inhibition of cell envelope biogenesis via suppression of key membrane lipid metabolites (e.g., sn-glycerol 3-phosphate and sn-glycero-3-phosphoethanolamine) as well as perturbations in peptidoglycan and lipopolysaccharide biosynthesis. Furthermore, significant perturbations in the levels of amino sugars and nucleotide sugars, glycolysis, the tricarboxylic acid cycle, and pyrimidine ribonucleotide biogenesis were observed with the combination treatment. These findings provide novel mechanistic information on the synergistic antibacterial activity of polymyxin-ivacaftor combination.

Emerging Cystic Fibrosis Transmembrane Conductance Regulator Modulators as New Drugs for Cystic Fibrosis: A Portrait of in Vitro Pharmacology and Clinical Translation.

Pharmacological correction of the defective ion channel with cystic fibrosis transmembrane conductance regulator (CFTR) has become an attractive approach to therapy directed at the root cause of the life-limiting disease cystic fibrosis (CF). CFTR defects range from absence, misfolding, and resulting degradation to functional defects of the CFTR protein. The discovery and development of the CFTR potentiator ivacaftor was a major break-through in CF therapy and has triggered an enormous incentive for seeking effective modulators such as lumacaftor, tezacaftor or elexacaftor for all patients with CF. A number of emerging CFTR modulators are currently in the development pipeline, and rescue levels of CFTR protein approach a cure for cystic fibrosis. In this review, we identify and characterize all preclinical and clinical emerging CFTR modulators and discuss the in vitro pharmacology, looking at CFTR protein expression and chloride transport and the translation to the clinic. The new emerging CFTR modulators could offer new therapeutic solutions for CF patients.