Sociodemographic differences in symptom severity and duration among women referred to secondary care for menorrhagia in England and Wales: a cohort study from the National Heavy Menstrual Bleeding Audit

Objective: To examine symptom severity and duration at time of referral to secondary care for heavy menstrual bleeding (HMB) by socioeconomic deprivation, age and ethnicity. / Design: Cohort analysis of data from the National HMB Audit linked to Hospital Episode Statistics data. / Setting: English and Welsh National Health Services (secondary care): February 2011 to January 2012. / Participants: 15 325 women aged 18–60 years in England and Wales who had a new referral for HMB to a gynaecology outpatient department. / Methods: Multivariable linear regression to calculate adjusted differences in mean symptom severity and quality of life scores at first outpatient visit. Multivariable logistic regression to calculate adjusted ORs. Adjustment for body mass index, parity and comorbidities. / Primary outcome measures: Mean symptom severity score (0=best, 100=worst), mean condition-specific quality of life score (0=worst, 100=best) and symptom duration (≥1 year). / Results: Women were on average 42 years old and 12% reported minority ethnic backgrounds. Mean symptom severity and condition-specific quality of life scores were 61.8 and 34.7. Almost three-quarters of women (74%) reported having had symptoms for ≥1 year. Women from more deprived areas had more severe symptoms at their first outpatient visit (difference −6.1; 95% CI−7.2 to −4.9, between least and most deprived quintiles) and worse condition-specific quality of life (difference 6.3; 95% CI 5.1 to 7.5). Symptom severity declined with age while quality of life improved. / Conclusions: Women living in more deprived areas reported more severe HMB symptoms and poorer quality of life at the start of treatment in secondary care. Providers should examine referral practices to explore if these differences reflect women’s health-seeking behaviour or how providers decide whether or not to refer

Intestine-Specific, Oral Delivery of Captopril/Montmorillonite: Formulation and Release Kinetics

The intercalation of captopril (CP) into the interlayers of montmorillonite (MMT) affords an intestine-selective drug delivery system that has a captopril-loading capacity of up to ca. 14 %w/w and which exhibits near-zero-order release kinetics

Illuminating the life of GPCRs

The investigation of biological systems highly depends on the possibilities that allow scientists to visualize and quantify biomolecules and their related activities in real-time and non-invasively. G-protein coupled receptors represent a family of very dynamic and highly regulated transmembrane proteins that are involved in various important physiological processes. Since their localization is not confined to the cell surface they have been a very attractive "moving target" and the understanding of their intracellular pathways as well as the identified protein-protein-interactions has had implications for therapeutic interventions. Recent and ongoing advances in both the establishment of a variety of labeling methods and the improvement of measuring and analyzing instrumentation, have made fluorescence techniques to an indispensable tool for GPCR imaging. The illumination of their complex life cycle, which includes receptor biosynthesis, membrane targeting, ligand binding, signaling, internalization, recycling and degradation, will provide new insights into the relationship between spatial receptor distribution and function. This review covers the existing technologies to track GPCRs in living cells. Fluorescent ligands, antibodies, auto-fluorescent proteins as well as the evolving technologies for chemical labeling with peptide- and protein-tags are described and their major applications concerning the GPCR life cycle are presented

Risk factors for failure of the 36 mm metal-on-metal Pinnacle total hip replacement system: a retrospective single-centre cohort study

Aims: To determine 10-year failure rates following 36mm metal-on-metal (MoM) Pinnacle total hip replacement (THR), and identify predictors of failure. Methods: We retrospectively assessed a single-centre cohort of 569 primary 36mm MoM Pinnacle THRs (all Corail stems) followed up since 2012 according to MHRA recommendations. Allcause failure rates (all-cause revision, and non-revised cross-sectional imaging failures) were calculated, with predictors for failure identified using multivariable Cox regression. Results: Failure occurred in 97 hips (17.0%). The 10-year cumulative failure rate was 27.1% (95% CI=21.6%-33.7%). Primary implantation from 2006 onwards (Hazard Ratio (HR)=4.30; CI=1.82-10.1; p=0.001) and bilateral MoM hip arthroplasty (HR=1.59; CI=1.03-2.46; p=0.037) predicted failure. The effect of implantation year on failure varied over time. From 4-years onwards following surgery, hips implanted since 2006 had significantly higher failure rates (8-years=28.3%; CI=23.1%-34.5%) compared to hips implanted before 2006 (8- years=6.3%; CI=2.4%-15.8%) (HR=15.2; CI=2.11-110.4; p=0.007). Conclusion: We observed that 36mm MoM Pinnacle THRs have an unacceptably high 10-year failure rate, especially if implanted from 2006 onwards or in bilateral MoM patients. Our findings regarding implantation year and failure support recent concerns about the device manufacturing process. We recommend all patients undergoing implantation since 2006 and those with bilateral MoM hips undergo regular investigation, regardless of symptoms