Addressing social determinants of health inequities: what can the state and civil society do?

In this Health Policy article, we selected and reviewed evidence synthesised by nine knowledge networks established by WHO to support the Commission on the Social Determinants of Health. We have indicated the part that national governments and civil society can play in reducing health inequity. Government action can take three forms: (1) as provider or guarantor of human rights and essential services; (2) as facilitator of policy frameworks that provide the basis for equitable health improvement; and (3) as gatherer and monitor of data about their populations in ways that generate health information about mortality and morbidity and data about health equity. We use examples from the knowledge networks to illustrate some of the options governments have in fulfilling this role. Civil society takes many forms: here, we have used examples of community groups and social movements. Governments and civil society can have important positive roles in addressing health inequity if political will exists.     

Can universal access to health care eliminate health inequities between children of poor and nonpoor families?: A case study of childhood asthma in Alberta

STUDY OBJECTIVE: Children from poor families are much more likely to have emergency visits for asthma than those from nonpoor families, which may be related to financial access barriers to good preventive care for the poor. We sought to determine whether in a health-care system that provides free access to outpatient and hospital services, the disparities in the rates of emergency visits for asthma would be less apparent across the income gradient. DESIGN: Longitudinal, population-based study. SETTING: Alberta, Canada. PARTICIPANTS: All children born in Alberta, Canada between 1985 and 1988 (n = 90,845) were classified into three mutually exclusive groups based on the reported annual income of their parents from the previous year: very poor, poor, and nonpoor groups. Measurements and results: We compared the relative risk (RR) of emergency visits for childhood asthma among children of very poor, poor, and nonpoor families using a Cox proportional hazard model during a 10-year follow-up. We found that the very poor children were 23% more likely to have had an emergency visit for asthma than those from nonpoor families (RR, 1.23; 95% confidence interval [CI], 1.14 to 1.33), adjusted for a variety of factors. The poor group, however, had a similar risk of asthma emergency visits as the nonpoor group (RR, 0.97; 95% CI, 0.91 to 1.04). The average number of office visits for asthma was similar between the very poor and nonpoor groups. CONCLUSIONS: In a setting of universal access to health care, children of poor and nonpoor families had similar rates of asthma emergency visits; the very poor children, however, continued to experience an excess risk. These findings suggest that a universal health-care system can reduce, but not fully eliminate, the disparities in emergency utilization of asthma across income categories.     

Which delivery systems reach the poor? A review of equity of coverage of ever-treated nets, never-treated nets, and immunisation to reduce child mortality in Africa

Insecticide-treated nets (ITNs) and childhood vaccination are two of the most powerful interventions available to prevent childhood mortality in Africa, but ITN coverage is still very low. Current debates about how to increase ITN coverage are concerned with the roles of different supply and delivery systems, in particular whether or not commercial net markets have any useful role. Here, we review data available on coverage and equity of coverage of three interventions to prevent childhood mortality. We compiled and analysed data from nationally representative surveys in 26 African countries to compare equity of coverage of (1) the Expanded Programme on Immunisation (EPI), (2) any net, (3) ever-treated nets (ie, ITNs), and (4) never-treated nets (ie, untreated nets; UTNs). We assumed that ever-treated net coverage mostly reflects the activities of public-health programmes and projects, and that never-treated net coverage mostly reflects the activity of local unsubsidised commercial markets. We discuss the validity, limitations, and possible biases of these assumptions. We estimate that 87% of the 8.4 million children protected by nets used UTNs. We used the concentration index (CI) to assess equity of coverage of the interventions. The data shows that never-treated net coverage is surprisingly equitable: overall, and despite substantial regional variations, it is comparable in equity to EPI (median CI(UTN)=0.166, CI(EPI)=0.075; p=0.3). In almost all countries, coverage of ITNs is strongly concentrated in the least poor households, and significantly more inequitable than both UTNs (median CI(ITN)=0.435, mean CI(UTN)=0.158; p<0.001) and EPI (median CI(ITN)=0.435, CI(EPI)=0.075; p<0.001). These results suggest that the public-health value of commercial net markets has been greatly underestimated, and that these markets have so far contributed more to equitable and sustainable coverage of mosquito nets, and hence to the prevention of malaria in Africa, than have the ITNs delivered by public-health systems and projects.     

Transulnar angiography and intervention: The next frontier in vascular access?

• This study demonstrates that in a single center, single operator experience, ulnar artery catheterization is feasible, though even compared to radial access, a significant learning curve remains.
• Although ulnar access is a reasonable alternative approach to catheterization, the true benefits of ulnar access, compared to radial are unclear.
• Further large randomized multicenter, multi‐operator trials are needed to assess the true feasibility and benefit of ulnar artery catheterization.

     

From the Cover: Water access points and hydration pathways in CLC H+/Cl? transporters

CLC transporters catalyze transmembrane exchange of chloride for protons. Although a putative pathway for Cl⁻ has been established, the pathway of H⁺ translocation remains obscure. Through a highly concerted computational and experimental approach, we characterize microscopic details essential to understanding H⁺-translocation. An extended (0.4 µs) equilibrium molecular dynamics simulation of membrane-embedded, dimeric ClC-ec1, a CLC from Escherichia coli, reveals transient but frequent hydration of the central hydrophobic region by water molecules from the intracellular bulk phase via the interface between the two subunits. We characterize a portal region lined by E202, E203, and A404 as the main gateway for hydration. Supporting this mechanism, site-specific mutagenesis experiments show that ClC-ec1 ion transport rates decrease as the size of the portal residue at position 404 is increased. Beyond the portal, water wires form spontaneously and repeatedly to span the 15-Å hydrophobic region between the two known H⁺ transport sites [E148 (Glu_ex) and E203 (Glu_in)]. Our finding that the formation of these water wires requires the presence of Cl⁻ explains the previously mystifying fact that Cl⁻ occupancy correlates with the ability to transport protons. To further validate the idea that these water wires are central to the H⁺ transport mechanism, we identified I109 as the residue that exhibits the greatest conformational coupling to water wire formation and experimentally tested the effects of mutating this residue. The results, by providing a detailed microscopic view of the dynamics of water wire formation and confirming the involvement of specific protein residues, offer a mechanism for the coupled transport of H⁺ and Cl⁻ ions in CLC transporters.The chloride channel (CLC) family (1, 2) includes both passive Cl⁻ channels and secondary active H⁺-coupled Cl⁻ transporters (3–8). The latter, also known as H⁺/Cl⁻ exchangers, drive uphill movement of H⁺ by coupling the process to downhill movement of Cl⁻ or vice versa, thereby exchanging the two types of ions across the membrane at fixed stoichiometry (9). ClC-ec1, a CLC from Escherichia coli, has served as the prototype CLC for biophysical studies because of its known crystal structures (10, 11), its tractable biochemical behavior, and its structural and mechanistic similarities to mammalian CLC transporters (3–8, 12–17). Detailed structural and functional studies of ClC-ec1 (9, 11, 18–27) have shed light on some of its key mechanistic aspects. Most prominently, these studies have characterized the Cl⁻ permeation pathway and its lining residues (10, 18, 25) and established the role of E148, also known as Glu_ex, as the extracellular gate for the Cl⁻ pathway (9, 11).Although much less is known about the H⁺ translocation pathway (and mechanism), experimental studies have provided key information on the involvement of specific residues in H⁺ transport (9, 13, 14, 20, 22, 27, 28). Extensive site-directed mutagenesis studies have zeroed in on two glutamate residues essential for H⁺ transport (Fig. 1A): E148 (Glu_ex), which acts as the main extracellular H⁺ binding site (9, 11, 27), and E203 (Glu_in), which plays a similar role on the cytoplasmic side (20, 22, 28). Neutralization of either glutamate eliminates H⁺ translocation by ClC-ec1 (9, 28). However, the discovery of these H⁺ binding sites also raised a mechanistic puzzle (3, 23): How do protons translocate between the two sites, which are separated by a ∼15-Å-long, largely hydrophobic region within the lumen of the protein?Open in a separate windowFig. 1.Cl⁻ and H⁺ permeation pathways in ClC-ec1. (A) View of the ClC-ec1 structure in a lipid bilayer (the simulation system used here), with the identical subunits shown in yellow and orange. The presumed Cl⁻/H⁺ permeation pathways are indicated by green and red lines, respectively. The dashed segment of the red line denotes the pathway investigated in this study. (B) Close-up of the central hydrophobic region, with the residues forming this region shown as orange sticks and labeled. Also shown are key glutamate residues (E202, E203, and E148) as well as the Cl⁻ at the central anion binding site. (C) Hydration of the central hydrophobic region during the 0.4-µs equilibrium simulation, measured as the number of water molecules in this region for each subunit.Since the report of its first crystal structure, a large number of computational studies have aimed at investigating various molecular details related to the CLC H⁺ transport mechanism (27, 29–34). One model emerging from these studies proposes that water molecules may connect the two H⁺ sites (Glu_ex and Glu_in) and, thereby, facilitate H⁺ transport (29, 30, 34). This idea was initially proposed by Kuang and coworkers (29) on the basis of a hole-searching algorithm applied to static crystal structures of ClC-ec1. In their proposed pathway, water molecules are suggested to form two half-wires that are then connected by the hydroxyl group of Y445 to form a complete path for H⁺ transfer. However, it is known from experiments on the Y445F mutant that this hydroxyl is not required for H⁺ transport (20). Wang and Voth (30) proposed another pathway by combining an improved search algorithm for buried water with short molecular dynamics (MD) simulations, thereby taking into account the dynamic nature of the protein. Their pathway did not rely on Y445 but required reorientation of the side chain of E203 to connect the two H⁺ sites. In another study, these investigators further carried out semiempirical free energy calculations to investigate the Cl⁻/H⁺ coupling mechanism (33).Although the idea of water-mediated H⁺ transport is intriguing and could be key to understanding H⁺ transport in ClC-ec1, several questions relevant to a water wire mechanism remain unanswered: Can the hydrophobic region between the two H⁺ sites actually be hydrated under equilibrium conditions? What is the access/entry point or points for water from the bulk into the hydrophobic region, which is buried inside the protein, approximately at the midpoint of the membrane? Is it possible to observe the spontaneous formation of water wires through MD simulations? If so, how much do the simulated wire structures differ from the ones proposed by the prior studies based on search algorithms? How could the protein affect the dynamics and/or the thermodynamics of water wires?In the current study, we have addressed these questions through a combined computational and experimental approach. An extended 0.4-µs MD simulation of a membrane-embedded model of wild-type (WT) ClC-ec1 reveals that the central hydrophobic region can indeed be hydrated by water molecules mainly from the cytoplasmic bulk phase through pathways near the dimer interface via a portal lined by residues E202, E203, and A404. Water wires connecting the two H⁺ sites form spontaneously and repeatedly during the equilibrium simulation. Formation of wires requires a side-chain conformational change of I109 and the occupancy of the central Cl⁻ binding site, S_cen. These simulation results make two strong and testable predictions: that mutations at A404 and I109 will reduce ClC-ec1 activity and that the reduction in activity occurs via effects on the H⁺ branch of the transport mechanism. Our experimental tests and additional simulations performed on one mutant form of the protein fully support these predictions.     

Recognising and managing dying patients in the acute hospital setting: can we do better?

Healthcare professionals have limited formal end‐of‐life care training despite the large proportion of hospital deaths. A retrospective review of 201 acute hospital deaths revealed 166 (82.6%) had documentation to suggest the patient was dying but this was performed late with a median time between documentation and death of 0.84 days. Furthermore, 132 (66%) patients received an intervention in the final 48 h of life. This highlights the need to improve the recognition and management of dying patients in acute hospitals.