Fertility, Living Arrangements, Care and Mobility

There are four main interconnecting themes around which the contributions in this book are based. This introductory chapter aims to establish the broad context for the chapters that follow by discussing each of the themes. It does so by setting these themes within the overarching demographic challenge of the twenty-first century – demographic ageing. Each chapter is introduced in the context of the specific theme to which it primarily relates and there is a summary of the data sets used by the contributors to illustrate the wide range of cross-sectional and longitudinal data analysed

Women’s beliefs about medicines and adherence to pharmacotherapy in pregnancy: Opportunities for community pharmacists?

Background During pregnancy women might weigh benefits of treatment against potential risks to the unborn child. However, non-adherence to necessary treatment can adversely affect both mother and child. To optimize pregnant women’s beliefs and medication adherence, community pharmacists are ideally positioned to play an important role in primary care. Objective This narrative review aimed to summarize the evidence on 1) pregnant women’s beliefs, 2) medication adherence in pregnancy, and 3) community pharmacists’ counselling during pregnancy. Method Three search strategies were used in Medline and Embase to find original studies evaluating women’s beliefs, medication adherence and community pharmacists’ counselling during pregnancy. All original descriptive and analytic epidemiological studies performed in Europe, North America and Australia, written in English and published from 2000 onwards were included. Results We included 14 studies reporting on women’s beliefs, 11 studies on medication adherence and 9 on community pharmacists’ counselling during pregnancy. Women are more reluctant to use medicines during pregnancy and tend to overestimate the teratogenic risk of medicines. Risk perception varies with type of medicine, level of health literacy, education level and occupation. Furthermore, low medication adherence during pregnancy is common. Finally, limited evidence showed current community pharmacists’ counselling is insufficient. Barriers hindering pharmacists are insufficient knowledge and limited access to reliable information. Conclusion Concerns about medication use and non-adherence are widespread among pregnant women. Community pharmacists’ counselling during pregnancy is insufficient. Further education, training and research are required to support community pharmacists in fulfilling all the opportunities they have when counselling pregnant women

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Extension and Compression of Grafted Polymer Layers in Strong Normal Flows

We study the deformation of polymer brushes grafted to porous substrates in strong permeation flows normal to the grafting surface. Our model predicts a strong deformation regime for both compressive and extensive permeation flows of sufficiently high solvent flow rates. These regimes are characterized by non-linear scaling of brush thickness $L$ with molecular weight $N$ and solvent velocity $V$ and by non-linear scaling of solvent velocity $V$ with the pressure drop $\Delta P$ across the brush. For the case of strong brush extension, $L\sim N^3V^2$, as in the case of isolated chains in uniform solvent flows, and $V\sim \Delta P^{1/3}$; while for strong brush compression, $L\sim N^{9/13}V^{-4/13}$ and $V\sim \Delta P^{13/15}$

Shear-Induced Deformation and Desorption of Grafted Polymer Layers

We describe the behaviour of grafted polymer layers in strong solvent shear flows within a model where only a subset of chains are exposed to the flow (hence to the tension arising from hydrodynamic drag forces), leaving the remainder protected. We show that for quite small values of the shear rate, $\dot\gamma$, the system reaches a self-regulating state where the lowest possible fraction of grafted chains is exposed to the flow. This brings quantitative corrections to previous models (all based on the assumption that the chains behave alike) which correspond to a higher susceptibility of the layer to shear fields: the onset of significant swelling occurs at a lower shear rate and at high shear rates the asymptotic value of the relative swelling is somewhat larger. Furthermore we find that the behaviour of the layer strongly depends on both the index of polymerisation of the chains and the grafting density. In particular, for thick brushes, our model predicts a discontinuous (first order) swelling transition at a critical shear rate. The model is used to study the rate of desorption of individual chains grafted via compact end-stickers and insoluble polymer blocks. In both cases, there is a strong increase in desorption at the swelling transition. For the case of end-sticker grafting, we find the desorption rate $\cal{R}$ obeys $\cal{R}$ $\sim \dot \gamma^{3}$ for large shear rates; while in the case of diblock grafting, we find that the barrier height to desorption is a strong function of shear rate, leading to an exponentially enhanced desorption rate for large $\dot\gamma$: $\cal{R}$ $\sim {\rm e}^{\dot\gamma\tau_0}$