An approach to the diagnosis and management of Rome IV functional disorders of chronic constipation

Introduction: Chronic constipation is highly prevalent, affecting between 10% and 15% of the population. The Rome IV criteria categorizes disorders of chronic constipation into four subtypes: (a) functional constipation, (b) irritable bowel syndrome with constipation, (c) opioid-induced constipation, and (d) functional defecation disorders, including inadequate defecatory propulsion and dyssynergic defecation. The initial management approach for these disorders is similar, focusing on diet, lifestyle and the use of standard over-the-counter laxatives. If unsuccessful, further therapy is tailored according to subtype. Areas covered: This review covers the definition, epidemiology, diagnostic criteria, investigations and management of the Rome IV disorders of chronic constipation. Expert opinion: By adopting a logical step-wise approach toward the diagnosis of chronic constipation and its individual subtypes, clinicians have the opportunity to tailor therapy accordingly and improve symptoms, quality of life, and patient satisfaction

Flux networks in metabolic graphs

A metabolic model can be represented as bipartite graph comprising linked reaction and metabolite nodes. Here it is shown how a network of conserved fluxes can be assigned to the edges of such a graph by combining the reaction fluxes with a conserved metabolite property such as molecular weight. A similar flux network can be constructed by combining the primal and dual solutions to the linear programming problem that typically arises in constraint-based modelling. Such constructions may help with the visualisation of flux distributions in complex metabolic networks. The analysis also explains the strong correlation observed between metabolite shadow prices (the dual linear programming variables) and conserved metabolite properties. The methods were applied to recent metabolic models for Escherichia coli, Saccharomyces cerevisiae, and Methanosarcina barkeri. Detailed results are reported for E. coli; similar results were found for the other organisms.Comment: 9 pages, 4 figures, RevTeX 4.0, supplementary data available (excel

Individualised risk assessment for diabetic retinopathy and optimisation of screening intervals: a scientific approach to reducing healthcare costs.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.To validate a mathematical algorithm that calculates risk of diabetic retinopathy progression in a diabetic population with UK staging (R0-3; M1) of diabetic retinopathy. To establish the utility of the algorithm to reduce screening frequency in this cohort, while maintaining safety standards.The cohort of 9690 diabetic individuals in England, followed for 2 years. The algorithms calculated individual risk for development of preproliferative retinopathy (R2), active proliferative retinopathy (R3A) and diabetic maculopathy (M1) based on clinical data. Screening intervals were determined such that the increase in risk of developing certain stages of retinopathy between screenings was the same for all patients and identical to mean risk in fixed annual screening. Receiver operating characteristic curves were drawn and area under the curve calculated to estimate the prediction capability.The algorithm predicts the occurrence of the given diabetic retinopathy stages with area under the curve =80% for patients with type II diabetes (CI 0.78 to 0.81). Of the cohort 64% is at less than 5% risk of progression to R2, R3A or M1 within 2 years. By applying a 2 year ceiling to the screening interval, patients with type II diabetes are screened on average every 20 months, which is a 40% reduction in frequency compared with annual screening.The algorithm reliably identifies patients at high risk of developing advanced stages of diabetic retinopathy, including preproliferative R2, active proliferative R3A and maculopathy M1. Majority of patients have less than 5% risk of progression between stages within a year and a small high-risk group is identified. Screening visit frequency and presumably costs in a diabetic retinopathy screening system can be reduced by 40% by using a 2 year ceiling. Individualised risk assessment with 2 year ceiling on screening intervals may be a pragmatic next step in diabetic retinopathy screening in UK, in that safety is maximised and cost reduced by about 40%.Icelandic Research Counci

Incidence of and risk factors of chronic kidney disease: Results of a nationwide study in Iceland

Background - Information on the incidence of chronic kidney disease (CKD) in the general population is scarce. This study examined the incidence and risk factors of CKD stages 1–5 in Iceland, based on multiple markers of kidney damage. Methods - All serum creatinine (SCr) values, urine protein measurements and diagnosis codes for kidney diseases and comorbid conditions for people aged ≥18 years were obtained from electronic medical records of all healthcare institutions in Iceland in 2008–2016. CKD was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria as evidence for kidney damage and/or estimated glomerular filtration rate (eGFR) 3 months. Alternatively, CKD was defined using age-adapted eGFR thresholds. Mean annual age-standardized incidence of CKD was calculated for persons without CKD at study entry. Risk factor assessment was based on International Classification of Diseases diagnosis codes. Incidence was reported per 100 000 population. Results - We retrieved 1 820 990 SCr values for 206 727 persons. Median age was 45 years (range, 18–106) and 47% were men. Mean annual age-standardized incidence of CKD per 100 000 was 649 in men and 694 in women, and 480 in men and 522 in women using age-adapted eGFR thresholds. The incidence reached over 3000 in men and women aged >75 years. Traditional CKD risk factors, such as acute kidney injury, diabetes, hypertension and cardiovascular disease, as well as less well characterized risk factors, including chronic lung disease, malignancy and major psychiatric illness were associated with increased risk of CKD, and the same was true for obesity and sleep apnoea in women. Conclusion - The annual incidence of CKD, with strict adherence to the KDIGO criteria, was <0.7% but markedly lower using age-adapted eGFR thresholds. Apart from acute kidney injury, the observed risk factors comprised chronic and potentially modifiable disorders

Association of eGFR and mortality with use of a joint model: results of a nationwide study in Iceland

Objectives. Prior studies on the association of estimated glomerular filtration rate (eGFR) and mortality have failed to include methods to account for repeated eGFR determinations. The aim of this study was to estimate the association between eGFR and mortality in the general population in Iceland employing a joint model. Methods. We obtained all serum creatinine and urine protein measurements from all clinical laboratories in Iceland in the years 2008–16. Clinical data were obtained from nationwide electronic medical records. eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation and categorized as follows: 0–29, 30–44, 45–59, 60–74, 75– 89, 90–104 and >104 mL/min/1.73 m2. A multiple imputation method was used to account for missing urine protein data. A joint model was used to assess risk of all-cause mortality. Results. We obtained 2 120 147 creatinine values for 218 437 individuals, of whom 84 364 (39%) had proteinuria measurements available. Median age was 46 (range 18–106) years and 47% were men. Proteinuria associated with increased risk of death for all eGFR categories in persons of all ages. In persons ≤65 years, the lowest risk was observed for eGFR of 75–89 mL/min/1.73 m2 without proteinuria. For persons aged >65 years, the lowest risk was observed for eGFR of 60–74 mL/min/1.73 m2 without proteinuria. eGFR of 45–59 mL/min/1.73 m2 without proteinuria did not associate with increased mortality risk in this age group. eGFR >104 mL/min/1.73 m2 associated with increased mortality. Conclusions. These results lend further support to the use of age-adapted eGFR thresholds for defining chronic kidney disease. Very high eGFR needs to be studied in more detail with regard to mortalit

Modelling variable glacier lapse rates using ERA-Interim reanalysis climatology: an evaluation at Vestari- Hagafellsjökull, Langjökull, Iceland

The near-surface air temperature lapse rate is an important tool for spatially distributing temperatures in snow- and ice-melt models, but is difficult to parameterize, as it is not simply correlated with boundary-layer meteorological variables, such as temperature itself. This contribution quantifies spring-autumn lapse rate variability over 5 years at Vestari-Hagafellsjökull, a southerly outlet of Langjökull in Iceland. It is observed that summer lapse rates (0.57 °C 100 m) are significantly lower than non-summer rates, and are also lower than the Saturated Adiabatic Lapse Rate (SALR), which is often adopted in melt models. This is consistent with reduced near-surface temperature sensitivity to free-atmosphere temperature change during the occurrence of melting. A Variable Lapse Rate (VLR) regression model is calibrated with standardized, 750 hPa temperature anomalies derived from ERA-Interim climatology, which is shown to be highly significantly correlated with near-surface temperatures. The modelled VLR overestimates cumulative June-September Positive Degree Days (PDDs) by 3% when used to extrapolate temperatures from 1100 to 500 m a.s.l. on the glacier, whereas the SALR overestimates cumulative PDDs by 14%. ERA-Interim data therefore appear to offer a good representation of free-atmosphere temperature variability over Vestari-Hagafellsjökull, and the modelling approach offers a simple means of improving lapse rate parameterizations in melt models. © 2012 Royal Meteorological Society

The simplest demonstrations of quantum nonlocality

We investigate the complexity cost of demonstrating the key types of nonclassical correlations-Bell inequality violation, Einstein, Podolsky, Rosen (EPR)-steering, and entanglement-with independent agents, theoretically and in a photonic experiment. We show that the complexity cost exhibits a hierarchy among these three tasks, mirroring the recently discovered hierarchy for how robust they are to noise. For Bell inequality violations, the simplest test is the well-known Clauser-Horne-Shimony-Holt test, but for EPR-steering and entanglement the tests that involve the fewest number of detection patterns require nonprojective measurements. The simplest EPR-steering test requires a choice of projective measurement for one agent and a single nonprojective measurement for the other, while the simplest entanglement test uses just a single nonprojective measurement for each agent. In both of these cases, we derive our inequalities using the concept of circular two-designs. This leads to the interesting feature that in our photonic demonstrations, the correlation of interest is independent of the angle between the linear polarizers used by the two parties, which thus require no alignment