Managing Water under Uncertainty and Risk: The United Nations World Water Development Report 4

This report introduces new aspects of water issues: 1) it reintroduces the 12 challenge area reports that provided the foundation for the first two World Water Development Reports (WWDR); 2) 4 new reports on water quality, groundwater, gender, and desertification, land degradation and drought; 3) in recognition that the global challenges of water can vary considerably across countries and regions, a series of 5 regional reports have been included; 4) a deeper analysis of the main external forces of freshwater resources and possibilities for their future evolution; 5) managing water under uncertainty and risk

Left ventricular function after valve repair for chronic mitral regurgitation: Predictive value of preoperative assessment of contractile reserve by exercise echocardiography

Objectives.We evaluated the value of preoperative assessment of left ventricular contractile reserve in predicting ventricular function after valve repair for minimally symptomatic mitral regurgitation.Background.The optimal timing for operation in minimally symptomatic patients with significant mitral regurgitation is controversial. Accurate preoperative assessment of left ventricular function is difficult, and the ability to predict postoperative function is limited. Previous studies in patients undergoing mitral valve replacement may not be applicable in the present era of valve repair.Methods.We performed exercise echocardiography in 139 patients with isolated mitral regurgitation and no coronary disease, 74 of whom subsequently underwent uncomplicated valve repair. We measured rest left ventricular end-systolic dimension, end-systolic wall stress and positive first derivative of left ventricular pressure (dP/dt). End-diastolic and end-systolic volumes and ejection fraction were measured preoperatively at rest, immediately after exercise and postoperatively.Results.Ejection fraction decreased postoperatively to 55 ± 10% from a rest preoperative value of 64 ± 9% (p < 0.001). Compared with patients with a postoperative ejection fraction ≥50% (n = 56), patients with postoperative ejection fraction <50% (n = 18) had a significantly lower preoperative exercise ejection fraction (57 ± 11% vs. 73 ± 9%, p < 0.0005), a larger exercise end-systolic volume index (32 ± 8 vs. 18 ± 7 cm3/m2, p < 0.0005) and a lower change in ejection fraction with exercise (−4 ± 8% vs. 9 ± 10%, p < 0.005). Preoperative rest indexes, including dP/dt, end-systolic wall stress and end-systolic volume index were less predictive, whereas exercise capacity, rest ejection fraction and end-systolic dimension were not predictive of postrepair ejection fraction. An exercise end-systolic volume index >25 cm3/m2 was the best predictor of postoperative dysfunction, with a sensitivity and specificity of 83%.Conclusions.In minimally symptomatic patients with mitral regurgitation, latent ventricular dysfunction may be indicated by a limited contractile reserve, manifest at exercise as an inadequate increase in ejection fraction and a larger end-systolic volume. These variables may also be used to predict left ventricular function after repair

Significant regional differences in antibiotic use across 576 US hospitals and 11 701 326 adult admissions, 2016-2017

BACKGROUND: Quantifying the amount and diversity of antibiotic use in United States hospitals assists antibiotic stewardship efforts but is hampered by limited national surveillance. Our study aimed to address this knowledge gap by examining adult antibiotic use across 576 hospitals and nearly 12 million encounters in 2016-2017. METHODS: We conducted a retrospective study of patients aged ≥ 18 years discharged from hospitals in the Premier Healthcare Database between 1 January 2016 and 31 December 2017. Using daily antibiotic charge data, we mapped antibiotics to mutually exclusive classes and to spectrum of activity categories. We evaluated relationships between facility and case-mix characteristics and antibiotic use in negative binomial regression models. RESULTS: The study included 11 701 326 admissions, totaling 64 064 632 patient-days, across 576 hospitals. Overall, patients received antibiotics in 65% of hospitalizations, at a crude rate of 870 days of therapy (DOT) per 1000 patient-days. By class, use was highest among β-lactam/β-lactamase inhibitor combinations, third- and fourth-generation cephalosporins, and glycopeptides. Teaching hospitals averaged lower rates of total antibiotic use than nonteaching hospitals (834 vs 957 DOT per 1000 patient-days; P \u3c .001). In adjusted models, teaching hospitals remained associated with lower use of third- and fourth-generation cephalosporins and antipseudomonal agents (adjusted incidence rate ratio [95% confidence interval], 0.92 [.86-.97] and 0.91 [.85-.98], respectively). Significant regional differences in total and class-specific antibiotic use also persisted in adjusted models. CONCLUSIONS: Adult inpatient antibiotic use remains high, driven predominantly by broad-spectrum agents. Better understanding reasons for interhospital usage differences, including by region and teaching status, may inform efforts to reduce inappropriate antibiotic prescribing

Electronically available patient claims data improve models for comparing antibiotic use across hospitals: Results from 576 US facilities

BACKGROUND: The Centers for Disease Control and Prevention (CDC) uses standardized antimicrobial administration ratios (SAARs)-that is, observed-to-predicted ratios-to compare antibiotic use across facilities. CDC models adjust for facility characteristics when predicting antibiotic use but do not include patient diagnoses and comorbidities that may also affect utilization. This study aimed to identify comorbidities causally related to appropriate antibiotic use and to compare models that include these comorbidities and other patient-level claims variables to a facility model for risk-adjusting inpatient antibiotic utilization. METHODS: The study included adults discharged from Premier Database hospitals in 2016-2017. For each admission, we extracted facility, claims, and antibiotic data. We evaluated 7 models to predict an admission\u27s antibiotic days of therapy (DOTs): a CDC facility model, models that added patient clinical constructs in varying layers of complexity, and an external validation of a published patient-variable model. We calculated hospital-specific SAARs to quantify effects on hospital rankings. Separately, we used Delphi Consensus methodology to identify Elixhauser comorbidities associated with appropriate antibiotic use. RESULTS: The study included 11 701 326 admissions across 576 hospitals. Compared to a CDC-facility model, a model that added Delphi-selected comorbidities and a bacterial infection indicator was more accurate for all antibiotic outcomes. For total antibiotic use, it was 24% more accurate (respective mean absolute errors: 3.11 vs 2.35 DOTs), resulting in 31-33% more hospitals moving into bottom or top usage quartiles postadjustment. CONCLUSIONS: Adding electronically available patient claims data to facility models consistently improved antibiotic utilization predictions and yielded substantial movement in hospitals\u27 utilization rankings

Shifting markers of identity in East London's diasporic religious spaces

This article discusses the historical and geographical contexts of diasporic religious buildings in East London, revealing – contrary both to conventional narratives of immigrant integration, mobility, and succession and to identitarian understandings of belonging – that in such spaces and in the concrete devotional practices enacted in them, markers and boundaries of identity (ritual, spatial, and political) are contested, renegotiated, erased, and rewritten. It draws on a series of case-studies: Fieldgate Street Synagogue in its interrelationship with the East London Mosque; St Antony's Catholic Church in Forest Gate where Hindus and Christians worship together; and the intertwined histories of Methodism and Anglicanism in Bow Road. Exploration of the intersections between ethnicity, religiosity, and class illuminates the ambiguity and instability of identity-formation and expression within East London's diasporic faith spaces

IP-10-Mediated T Cell Homing Promotes Cerebral Inflammation over Splenic Immunity to Malaria Infection

Plasmodium falciparum malaria causes 660 million clinical cases with over 2 million deaths each year. Acquired host immunity limits the clinical impact of malaria infection and provides protection against parasite replication. Experimental evidence indicates that cell-mediated immune responses also result in detrimental inflammation and contribute to severe disease induction. In both humans and mice, the spleen is a crucial organ involved in blood stage malaria clearance, while organ-specific disease appears to be associated with sequestration of parasitized erythrocytes in vascular beds and subsequent recruitment of inflammatory leukocytes. Using a rodent model of cerebral malaria, we have previously found that the majority of T lymphocytes in intravascular infiltrates of cerebral malaria-affected mice express the chemokine receptor CXCR3. Here we investigated the effect of IP-10 blockade in the development of experimental cerebral malaria and the induction of splenic anti-parasite immunity. We found that specific neutralization of IP-10 over the course of infection and genetic deletion of this chemokine in knockout mice reduces cerebral intravascular inflammation and is sufficient to protect P. berghei ANKA-infected mice from fatality. Furthermore, our results demonstrate that lack of IP-10 during infection significantly reduces peripheral parasitemia. The increased resistance to infection observed in the absence of IP-10-mediated cell trafficking was associated with retention and subsequent expansion of parasite-specific T cells in spleens of infected animals, which appears to be advantageous for the control of parasite burden. Thus, our results demonstrate that modulating homing of cellular immune responses to malaria is critical for reaching a balance between protective immunity and immunopathogenesis

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.