Screening for gestational diabetes : a systematic review and economic evaluation

Background Screening for gestational diabetes mellitus (GDM) has been controversial, with some expert bodies advising universal screening, others selective screening, and yet others advising against screening at all. This has partly been a result of debate about the definition of GDM, and partly because of the profusion of different tests available, both for screening and definite diagnosis. In the UK, there is no national policy on screening, and a variety of practices exist in different parts of the country. There have also been doubts about the treatment of GDM, and particularly about management of minor degrees of glucose elevation, which are better described as glucose intolerance rather than true diabetes. Objectives To provide an updated review of current knowledge, to clarify research needs, and to assist with policy making in the interim, pending future research. Methods A literature review was carried out, with a particular focus on screening methods and costs, and an appraisal of screening for GDM against the criteria for assessing screening programmes used by the UK National Screening Committee (NSC). Results There is still debate about what is meant by GDM – the threshold for diagnosis is not soundly based; the terms GDM and impaired glucose tolerance are not used in a standard fashion in pregnancy; there is almost certainly a continuum of risk to the baby, rather than there being separate normal and abnormal groups; and the key risk factor in most women may be maternal overweight, with glucose intolerance being an associate of that. In addition there are some rare genetic conditions, which affect a few women, such as glucokinase and hepatic nuclear factor disorders. GDM is usually defined according to divergence from normal glucose levels, but glucose levels are usually raised in pregnancy, and so diagnosis by normal levels in non-pregnant women may misclassify many normal pregnant women as abnormal. This may lead to anxiety and the inconvenience of extra investigations and ‘disease’ care. The Caesarean section rate appears to be increased by the diagnosis alone. Ideally, the condition should be defined by the incidence of adverse effects. However, the most common reported complication of GDM is ‘macrosomia’ in the baby. This is usually defined by arbitrary weight cut-offs (usually a birth weight of 4000 g, but sometimes 4500 g), but such neat thresholds fail to distinguish between larger than average healthy babies and those that have the abnormal growth patterns associated with high insulin levels in the womb. Screening for GDM fails to meet some of the NSC criteria. A number of screening tests have been used but some, such as glycosylated haemoglobin and fructosamine, have proved unsatisfactory and can be discarded. Others, such as urine testing or random blood glucose, are far from satisfactory, although they may be cheap to do. There is marked international variation. Risk factors such as weight, age and family history are useful for selective screening but some patients with GDM would be missed. Fasting plasma glucose (FPG) is convenient and reliable, but some pregnant women have normal fasting levels but raised levels of glucose after meals, and would be missed by screening based on FPG alone. Glucose challenge tests (GCTs) are based on glucose levels after a glucose drink, but also have shortcomings. The definitive diagnosis is usually by oral glucose tolerance test (OGTT), but the glucose load and timing vary in different countries; taking a 75 g glucose load is unnatural, makes some women sick, and the reproducibility of the test is poor. More natural methods such as test meals have been used, but not widely. Conclusions Interim conclusions There are clearly some women whose glucose levels rise sufficiently in pregnancy to cause harm to their babies. However, there are also many women with lower levels of glucose intolerance whose babies are not at risk, but who may suffer anxiety and inconvenience as a result of being classed as abnormal. On balance, the present evidence suggests that we should not have universal screening, but a highly selective policy, based on age and overweight. The best test at present, for those deemed to need testing, is probably the GCT, preferably combined with an FPG. The benefits of a follow-up OGTT are doubtful

The Influence and Deception of Twitter: The Authenticity of the Narrative and Slacktivism in the Australian Electoral Process

It is uncertain how many discreet users occupy the social media community. Fake tweets, sock puppets, force‐multipliers and botnets have become embedded within the fabric of new media in sufficient numbers that social media support by means of quantity is no longer a reliable metric for determining authority and influence within openly expressed issues and causes. Election campaigns, and their associated political agendas, can now be influenced by non‐specific virtual presences that cajole and redirect opinions without declaring identity or allegiance. In the lead up to the 2013 Australian Federal Election, the open source Twitter activity for the two major party leaders was examined in order to establish patterns of information diffusion. The results showed fake online personas, fake bots deploying automated Twitter dissemination, and deceptive Twitter strategies. New media tolerates slacktivism, where Twitter users mistake auto‐narrative for genuine political sentiment. This study demonstrates the need to increase legitimacy and validity in micro‐blogging forms of new media

Pennsylvanian Sharon Formation, past and present: sedimentology, hydrogeology, and historical and environmental significance: a field guide to Gorge Metro Park, Virginia Kendall Ledges in the Cuyahoga Valley National Park, and other sites in Northeast Ohio

Prepared for the 2003 Annual Great Lakes Section-SEPM/Northern Ohio Geological Society Field Conference

Quantum Computation with Quantum Dots

We propose a new implementation of a universal set of one- and two-qubit gates for quantum computation using the spin states of coupled single-electron quantum dots. Desired operations are effected by the gating of the tunneling barrier between neighboring dots. Several measures of the gate quality are computed within a newly derived spin master equation incorporating decoherence caused by a prototypical magnetic environment. Dot-array experiments which would provide an initial demonstration of the desired non-equilibrium spin dynamics are proposed.Comment: 12 pages, Latex, 2 ps figures. v2: 20 pages (very minor corrections, substantial expansion), submitted to Phys. Rev.

Respiration by buried echidnas Tachyglossus aculeatus

Short-beaked echidnas have an impressive ability to submerge completely into soil or sand and remain there, cryptic, for long periods. This poses questions about how they manage their respiration, cut off from a free flow of gases. We measured the gradient in oxygen partial pressure (P-O2) away from the snouts of buried echidnas and oxygen consumption (V-O2) in five individuals under similar conditions, in two substrates with different air-filled porosities (f(a)). A theoretical diffusion model indicated that diffusion alone was insufficient to account for the flux of oxygen required to meet measured rates of V-O2. However, it was noticed that echidnas often showed periodic movements of the anterior part of the body, as if such movements were a deliberate effort to flush the tidal air space surrounding their nostrils. These 'flushing movements' were subsequently found to temporarily increase the levels of interstitial oxygen in the soil around the head region. Flushing movements were more frequent while V-O2 was higher during the burrowing process, and also in substrate with lower fa. We conclude that oxygen supply to buried echidnas is maintained by diffusion through the soil augmented by periodic flushing movements, which ventilate the tidal airspace that surrounds the nostrils

Connections Between the Spring Breakup of the Southern Hemisphere Polar Vortex, Stationary Waves, and Air-sea Roughness

A robust connection between the drag on surface-layer winds and the stratospheric circulation is demonstrated in NASA's Goddard Earth Observing System Chemistry-Climate Model (GEOSCCM). Specifically, an updated parameterization of roughness at the air-sea interface, in which surface roughness is increased for moderate wind speeds (4ms to 20ms), leads to a decrease in model biases in Southern Hemispheric ozone, polar cap temperature, stationary wave heat flux, and springtime vortex breakup. A dynamical mechanism is proposed whereby increased surface roughness leads to improved stationary waves. Increased surface roughness leads to anomalous eddy momentum flux convergence primarily in the Indian Ocean sector (where eddies are strongest climatologically) in September and October. The localization of the eddy momentum flux convergence anomaly in the Indian Ocean sector leads to a zonally asymmetric reduction in zonal wind and, by geostrophy, to a wavenumber-1 stationary wave pattern. This tropospheric stationary wave pattern leads to enhanced upwards wave activity entering the stratosphere. The net effect is an improved Southern Hemisphere vortex: the vortex breaks up earlier in spring (i.e., the spring late-breakup bias is partially ameliorated) yet is no weaker in mid-winter. More than half of the stratospheric biases appear to be related to the surface wind speed biases. As many other chemistry climate models use a similar scheme for their surface layer momentum exchange and have similar biases in the stratosphere, we expect that results from GEOSCCM may be relevant for other climate models

Cost-effectiveness of insulin pumps compared with multiple daily injections, both provided with structured education, for adults with type 1 diabetes:a health economic analysis of the Relative Effectiveness of Pumps over Structured Education (REPOSE) randomised controlled trial

Objectives To assess the long-term cost-effectiveness of insulin pumps and Dose Adjustment for Normal Eating (pumps+DAFNE) compared with multiple daily insulin injections and DAFNE (MDI+DAFNE) for adults with type 1 diabetes mellitus (T1DM) in the UK. Methods We undertook a cost–utility analysis using the Sheffield Type 1 Diabetes Policy Model and data from the Relative Effectiveness of Pumps over Structured Education (REPOSE) trial to estimate the lifetime incidence of diabetic complications, intervention-based resource use and associated effects on costs and quality-adjusted life years (QALYs). All economic analyses took a National Health Service and personal social services perspective and discounted costs and QALYs at 3.5% per annum. A probabilistic sensitivity analysis was performed on the base case. Further uncertainties in the cost of pumps and the evidence used to inform the model were explored using scenario analyses. Setting Eight diabetes centres in England and Scotland. Participants Adults with T1DM who were eligible to receive a structured education course and did not have a strong clinical indication or a preference for a pump. Intervention Pumps+DAFNE. Comparator MDI+DAFNE. Main outcome measures Incremental costs, incremental QALYs gained and incremental cost-effectiveness ratios (ICERs). Results Compared with MDI+DAFNE, pumps+DAFNE was associated with an incremental discounted lifetime cost of +£18 853 (95% CI £6175 to £31 645) and a gain in discounted lifetime QALYs of +0.13 (95% CI -0.70 to +0.96). The base case mean ICER was £142 195 per QALY gained. The probability of pump+DAFNE being cost-effective using a cost-effectiveness threshold of £20 000 per QALY gained was 14.0%. All scenario and subgroup analyses examined indicated that the ICER was unlikely to fall below £30 000 per QALY gained. Conclusions Our analysis of the REPOSE data suggests that routine use of pumps in adults without an immediate clinical need for a pump, as identified by National Institute for Health and Care Excellence, would not be cost-effective. Trial registration number ISRCTN61215213

Effects of erythropoietin therapy on the lipid profile in end-stage renal failure

Effects of erythropoietin therapy on the lipid profile in end-stage renal failure. To evaluate the effects of erythropoietin (EPO) therapy on the lipid profile in end-stage renal failure, we undertook a prospective study in patients on both hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD). One hundred and twelve patients (81 HD, 31 CAPD) were enrolled into the study. Lipid parameters [that is, total cholesterol and the LDL and HDL subfractions, triglycerides, lipoprotein (a), apoproteins A and B], full blood count, iron studies, B12, folate, blood urea, aluminium and serum parathyroid hormone were measured prior to commencement of EPO therapy. Ninety-five patients were reassessed 5.2 ± 0.3 (mean ± SEM) months later and 53 patients underwent a further assessment 13.1 ± 0.6 months after the commencement of EPO, giving an overall follow-up of 10.0 ± 0.6 months in 95 patients. As expected, EPO treatment was associated with an increase in hemoglobin (7.7 ± 0.1 vs. 9.9 ± 0.2 g/dl; P < 0.001) and a decrease in ferritin (687 ± 99 vs. 399 ± 69 µg/liter; P < 0.01). A significant fall in total cholesterol occurred (5.8 ± 0.1 vs. 5.4 ± 0.2 mmol/liter; P < 0.05) in association with a fall in apoprotein B (1.15 ± 0.04 vs. 1.04 ± 0.06; P < 0.05) and serum triglycerides (2.26 ± 0.14 vs. 1.99 ± 0.21; P < 0.05) during the course of the study. Other lipid parameters did not change, although there was a trend towards improvement. These changes correlated with the increase in Hb (P < 0.001 in each case), and the reduction in ferritin for total cholesterol (P < 0.02), LDL cholesterol (P < 0.03), and to a lesser extent apoprotein B (P < 0.07). No difference was observed in patients using maintenance HD or CAPD, and similar trends were observed in male and female patients. Improvements in the lipid profile occurred independently of the time on dialysis prior to the commencement of EPO. We conclude that EPO treatment is associated with alterations in the lipid profile which may suggest a long-term improvement in the vascular morbidity of chronic renal failure. The causes of the improved lipids are not addressed by this study and may be equally due to a direct or secondary benefit of EPO therapy

Measurement of Pulmonary Flow Reserve and Pulmonary Index of Microcirculatory Resistance for Detection of Pulmonary Microvascular Obstruction

BACKGROUND: The pulmonary microcirculation is the chief regulatory site for resistance in the pulmonary circuit. Despite pulmonary microvascular dysfunction being implicated in the pathogenesis of several pulmonary vascular conditions, there are currently no techniques for the specific assessment of pulmonary microvascular integrity in humans. Peak hyperemic flow assessment using thermodilution-derived mean transit-time (T(mn)) facilitate accurate coronary microcirculatory evaluation, but remain unvalidated in the lung circulation. Using a high primate model, we aimed to explore the use of T(mn) as a surrogate of pulmonary blood flow for the purpose of measuring the novel indices Pulmonary Flow Reserve [PFR = (maximum hyperemic)/(basal flow)] and Pulmonary Index of Microcirculatory Resistance [PIMR = (maximum hyperemic distal pulmonary artery pressure)x(maximum hyperemic T(mn))]. Ultimately, we aimed to investigate the effect of progressive pulmonary microvascular obstruction on PFR and PIMR. METHODS AND RESULTS: Temperature- and pressure-sensor guidewires (TPSG) were placed in segmental pulmonary arteries (SPA) of 13 baboons and intravascular temperature measured. T(mn) and hemodynamics were recorded at rest and following intra-SPA administration of the vasodilator agents adenosine (10-400 microg/kg/min) and papaverine (3-24 mg). Temperature did not vary with intra-SPA sensor position (0.010+/-0.009 v 0.010+/-0.009 degrees C; distal v proximal; p = 0.1), supporting T(mn) use in lung for the purpose of hemodynamic indices derivation. Adenosine (to 200 microg/kg/min) & papaverine (to 24 mg) induced dose-dependent flow augmentations (40+/-7% & 35+/-13% T(mn) reductions v baseline, respectively; p<0.0001). PFR and PIMR were then calculated before and after progressive administration of ceramic microspheres into the SPA. Cumulative microsphere doses progressively reduced PFR (1.41+/-0.06, 1.26+/-0.19, 1.17+/-0.07 & 1.01+/-0.03; for 0, 10(4), 10(5) & 10(6) microspheres; p = 0.009) and increased PIMR (5.7+/-0.6, 6.3+/-1.0, 6.8+/-0.6 & 7.6+/-0.6 mmHg.sec; p = 0.0048). CONCLUSIONS: Thermodilution-derived mean transit time can be accurately and reproducibly measured in the pulmonary circulation using TPSG. Mean transit time-derived PFR and PIMR can be assessed using a TPSG and adenosine or papaverine as hyperemic agents. These novel indices detect progressive pulmonary microvascular obstruction and thus have with a potential role for pulmonary microcirculatory assessment in humans