Nocturnal hypoglycaemias in type 1 diabetic patients: what can we learn with continuous glucose monitoring?

AIM: In type 1 diabetic patients (T1DM), nocturnal hypoglycaemias (NH) are a serious complication of T1DM treatment; self-monitoring of blood glucose (SMBG) is recommended to detect them. However, the majority of NH remains undetected on an occasional SMBG done during the night. An alternative strategy is the Continuous glucose monitoring (CGMS), which retrospectively shows the glycaemic profile. The aims of this retrospective study were to evaluate the true incidence of NH in T1DM, the best SMBG time to predict NH, the relationship between morning hyperglycaemia and NH (Somogyi phenomenon) and the utility of CGMS to reduce NH. METHODS: Eighty-eight T1DM who underwent a CGMS exam were included. Indications for CGMS evaluation, hypoglycaemias and correlation with morning hyperglycaemias were recorded. The efficiency of CGMS to reduce the suspected NH was evaluated after 6-9 months. RESULTS: The prevalence of NH was 67% (32% of them unsuspected). A measured hypoglycaemia at bedtime (22-24 h) had a sensitivity of 37% to detect NH (OR=2.37, P=0.001), while a single measure < or =4 mmol/l at 3-hour had a sensitivity of 43% (OR=4.60, P<0.001). NH were not associated with morning hyperglycaemias but with morning hypoglycaemias (OR=3.95, P<0.001). After 6-9 months, suspicions of NH decreased from 60 to 14% (P<0.001). CONCLUSION: NH were highly prevalent and often undetected. SMBG at bedtime, which detected hypoglycaemia had sensitivity almost equal to that of 3-hour and should be preferred because it is easier to perform. Somogyi phenomenon was not observed. CGMS is useful to reduce the risk of NH in 75% of patients.

Impact of biocontrol strain Pseudomonas fluorescens CHA0 on rhizosphere bacteria isolated from barley (Hordeum vulgare L.) with special reference to Cytophaga-like bacteria.

AIMS: To assess the impact of the biocontrol strain Pseudomonas fluorescens CHA0 on a collection of barley rhizosphere bacteria using an agar plate inhibition assay and a plant microcosm, focusing on a CHA0-sensitive member of the Cytophaga-like bacteria (CLB). METHODS AND RESULTS: The effect of strain CHA0 on a collection of barley rhizosphere bacteria, in particular CLB and fluorescent pseudomonads sampled during a growth season, was assessed by a growth inhibition assay. On average, 85% of the bacteria were sensitive in the May sample, while the effect was reduced to around 68% in the July and August samples. In the May sample, around 95% of the CLB and around 45% of the fluorescent pseudomonads were sensitive to strain CHA0. The proportion of CHA0-sensitive CLB and fluorescent pseudomonad isolates decreased during the plant growth season, i.e. in the July and August samples. A particularly sensitive CLB isolate, CLB23, was selected, exposed to strain CHA0 (wild type) and its genetically modified derivatives in the rhizosphere of barley grown in gnotobiotic soil microcosms. Two dry-stress periods were imposed during the experiment. Derivatives of strain CHA0 included antibiotic or exopolysaccharide (EPS) overproducing strains and a dry-stress-sensitive mutant. Despite their inhibitory activity against CLB23 in vitro, neither wild-type strain CHA0, nor any of its derivatives, had a major effect on culturable and total cell numbers of CLB23 during the 23-day microcosm experiment. Populations of all inoculants declined during the two dry-stress periods, with soil water contents below 5% and plants reaching the wilting point, but they recovered after re-wetting the soil. Survival of the dry-stress-sensitive mutant of CHA0 was most affected by the dry periods; however, this did not result in an increased population density of CLB23. CONCLUSIONS: CLB comprise a large fraction of barley rhizosphere bacteria that are sensitive to the biocontrol pseudomonad CHA0 in vitro. However, in plant microcosm experiments with varying soil humidity conditions, CHA0 or its derivatives had no major impact on the survival of the highly sensitive CLB strain, CLB23, during two dry-stress periods and a re-wetting period; all co-existed well in the rhizosphere of barley plants. SIGNIFICANCE AND IMPACT OF THE STUDY: Results indicate a lack of interaction between the biocontrol pseudomonad CHA0 and a sensitive CLB when the complexity increases from agar plate assays to plant microcosm experiments. This suggests the occurrence of low levels of antibiotic production and/or that the two bacterial genera occupy different niches in the rhizosphere.

The impact of the reference price system on the pharmaceutical market: A theoretical approach

This article analyses the impact of the reference pricesystem on the price-setting strategies of thepharmaceutical firms and on the level of generic usage.This model is the first to take explicitly into accountthe impact of the reference price mechanism on the levelof competition between brand-name and generic drugs andnational pharmaceutical spending. We consider aduopolistic model with one firm producing the brand-namedrug, whose patent has already expired, and the otherproducing the corresponding generic version. We work ina partial equilibrium framework where firms set pricessequentially and consumers face heterogeneous switchingcosts.We show that brand producers compensate thedecline of profits by selling greater quantities insteadof charging higher prices, thus fostering pricecompetition in the pharmaceutical market. This result isa consequence of both the assumption of a verticallydifferentiated model and the introduction of thereference price system.

Intraoperative angiography reloaded: a new hybrid operating theater for combined endovascular and surgical treatment of cerebral arteriovenous malformations: a pilot study on 25 patients.

BACKGROUND: Multimodality treatment suites for patients with cerebral arteriovenous malformations (AVM) have recently become available. This study was designed to evaluate feasibility, safety and impact on treatment of a new intraoperative flat-panel (FP) based integrated surgical and imaging suite for combined endovascular and surgical treatment of cerebral AVM. METHODS: Twenty-five patients with AVMs to treat with combined endovascular and surgical interventions were prospectively enrolled in this consecutive case series. The hybrid suite allows combined endovascular and surgical approaches with intraoperative scanner-like imaging (XperCT®) and intraoperative 3D rotational angiography (3D-RA). The impact of intraoperative multimodal imaging on feasibility, workflow of combined interventions, surgery, and unexpected imaging findings were analyzed. RESULTS: Twenty-five patients (mean age 38 ± 18.6 year) with a median Spetzler-Martin grade 2 AVM (range 1-4) underwent combined endovascular and surgical procedures. Sixteen patients presented with a ruptured AVM and nine with an unruptured AVM. In 16 % (n = 4) of cases, intraoperative imaging visualized AVM remnants ≤3 mm and allowed for completion of the resections in the same sessions. Complete resection was confirmed in all n = 16 patients who had follow-up angiography one year after surgery so far. All diagnostic and therapeutical steps, including angiographic control, were performed without having to move the patients CONCLUSION: The hybrid neurointerventional suite was shown to be a safe and useful setup which allowed for unconstrained combined microsurgical and neuroradiological workflow. It reduces the need for extraoperative angiographic controls and subsequent potential surgical revisions a second time, as small AVM remnants can be detected with high security.

Solving higher-dimensional continuous time stochastic control problems by value function regression

The paper develops a method to solve higher-dimensional stochasticcontrol problems in continuous time. A finite difference typeapproximation scheme is used on a coarse grid of low discrepancypoints, while the value function at intermediate points is obtainedby regression. The stability properties of the method are discussed,and applications are given to test problems of up to 10 dimensions.Accurate solutions to these problems can be obtained on a personalcomputer.

Review of the literature on reference pricing

This paper reviews the literature on reference pricing (RP) in pharmaceutical markets. The RP strategy for cost containment of expenditure on drugs is analyzed as part of the procurement mechanism. We review the existing literature and the state-of-the-art regarding RP by focusing on its economic effects. In particular, we consider: (1) the institutional context and problem-related factors which appear to underline the need to implement an RP strategy; i.e., its nature, characteristics and the sort of health care problems commonly addressed; (2) how RP operates in practice; that is, how third party-payers (the insurers/buyers) have established the RP systems existing on the international scene (i.e., information methods, monitoring procedures and legislative provisions); (3)the range of effects resulting from particular RP strategies (including effects on choice of appropriate pharmaceuticals, insurer savings, total drug expenditures, prices of referenced and non-referenced products and dynamic efficiency; (4) the market failures which an RP policy is supposed to address and the main advantages and drawbacks which emerge from an analysis of its effects. Results suggest that RP systems achieve better their postulated goals (1) if cost inflation in pharmaceuticals is due to high prices rather than to the excess of prescription rates, (2) when the larger is the existing difference in prices among equivalent drugs, and (3) more important is the actual market for generics.

The impact of generic reference pricing interventions in the statin market

The objective of this study was to evaluate the intended and unintended impact on pharmaceutical use and sales of three public financing reforms applied to the prescription of statins: a Spanish generic reference pricing (RP) system for lovastatin and simvastatin, and two competing policies introduced by the Andalusian Public Health Service (APHS) for all statins, first a maximum consumer price (MCP) and then a so called quality prescribing incentive for general practitioners (MCP plus PI).This study is designed as an observational, retrospective, interrupted time series analysis with comparison series (APHS and the rest of Spain) of 46 monthly drug use and sales ratios from January 2001 to October 2004 for each active ingredient in the group of statins.RP has been effective at reducing the volume of sales growth of the off-patent statins, yet its overall impact on sales of all statins has been relatively modest. The quantity and volume of sales impact heavily depends on regulatory RP details such as when the system is introduced, how often it is updated, and how the reference price is calculated.

A theory of reference-dependent behavior

Extensive field and experimental evidence in a variety of environments show that behavior depends on a reference point. This paper provides an axiomatic characterization of this dependence. We proceed by imposing gradually more structure on both choice correspondences and preference relations, requiring increasingly higher levels of rationality, and freeing the decision-maker from certain types of inconsistencies. The appropriate degree of behavioral structure will depend on the phenomenon that is to be modeled. Lastly, we provide two applications of our work: one to model the status-quo bias, and another to model addictive behavior.

Diversity of Calliphoridae and Sarcophagidae (Diptera, Oestroidea) in continuous forest and gaps at different stages of regeneration in the Urucu oilfield in western Brazilian Amazonia

Diversity of Calliphoridae and Sarcophagidae (Diptera, Oestroidea) in continuous forest and gaps at different stages of regeneration in the Urucu oilfield in western Brazilian Amazonia. The diversity of Calliphoridae and Sarcophagidae in continuous forest and gaps at different stages of regeneration was studied in the Urucu river basin, in Coari, state of Amazonas, Brazil. The flies were collected at 16 sampling points, 12 in gaps at different stages of regeneration (early _ C1, mid- C2 and late successional _ C3) and four in continuous forest _ MT. The diversity of blowflies was similar in the two less regenerated habitats (C1 and C2), and lower than that in the late successional (C3) and continuous forests (MT). By contrast, the diversity of flesh flies was much higher in all three types of gaps (C1, C2 and C3) in comparison with continuous forest (MT). Ordination (NMDS) and similarity (ANOSIM) analyses revealed that the blowflies communities were grouped by habitat type, which affected species composition more than diversity. Analysis of the flesh flies revealed two main groupings, gaps (C1, C2 and C3) and continuous forest (MT), with no evidence of any influence of successional stage on the diversity of the community.

Hesperiidae (Lepidoptera, Hesperioidea) from Ponta Grossa, Paraná, Brazil: 70 years of records with special reference to faunal composition of Vila Velha State Park

Hesperiidae (Lepidoptera, Hesperioidea) de Ponta Grossa, Paraná, Brazil: 70 anos de registros com especial referência à composição faunística do Parque Estadual de Vila Velha. O município de Ponta Grossa se destaca por apresentar originalmente uma paisagem peculiar onde capões isolados de Floresta Ombrófila Mista são interligados por grandes extensões de fitofisionomias estépicas, também denominadas campos. No entanto, ambos os ecossistemas atualmente se encontram altamente ameaçados pela ocupação humana, restando na região o Parque Estadual de Vila Velha, cuja composição florística tem sido recentemente relacionada com o bioma Cerrado. Poucos trabalhos são dedicados à caracterização da fauna dos campos e sua relação com outras fitofisionomias estépicas brasileiras, motivo que suscitou a realização deste estudo. Após reunir informações de coletas realizadas por mais de 70 anos, são listadas 225 espécies de Hesperiidae (Lepidoptera, Hesperioidea) presentes no município, entre elas 162 indicadoras de ambientes florestais e 53 de áreas abertas. O Parque Estadual de Vila Velha contribui para a conservação de 65% delas enquanto sua composição se mostra intimamente relacionada tanto aos Pampas como ao Cerrado, em detrimento de hábitats florestais. Tal relação é dada provavelmente pela localização geográfica de Vila Velha, visto que a similaridade da fauna de Hesperiidae se encontrou influenciada pelas distâncias geográficas das amostras no presente estudo. A flora de Vila Velha também deve afetar diretamente a composição observada de Hesperiidae, uma vez que uma grande parte de suas espécies são também encontradas em áreas de Cerrado. No entanto, estudos em ambientes campestres brasileiros ainda se fazem necessários, especialmente em enclaves de Cerrado no Paraná e em São Paulo, para que se adquira um melhor entendimento da dinâmica de suas comunidades.

Variability of resting energy expenditure in healthy volunteers during fasting and continuous enteral feeding.

The magnitude of variability in resting energy expenditure (REE) during the day was assessed in nine healthy young subjects under two nutritional conditions: 1) mixed nutrient (53% carbohydrate, 30% fat, 17% protein) enteral feeding at an energy level corresponding to 1.44 REE; and 2) enteral fasting, with only water allowed. In each subject, six 30-min measurements of REE were performed using indirect calorimetry (hood system) at 90-min intervals from 9 AM to 5 PM. The mean REE and respiratory quotient were significantly (p less than .01) greater during feeding than during fasting (1.08 +/- 0.07 [SEM] vs. 1.00 +/- 0.06 kcal/min and 0.874 +/- 0.007 vs. 0.829 +/- 0.008 kcal/min, respectively). Mean postprandial thermogenesis was 4.9 +/- 0.4% of metabolizable energy administered. The intraindividual variability of REE throughout the day, expressed as the coefficient of variation, ranged from 0.7% to 2.0% in the fasting condition and from 1.2% to 4.1% in the feeding condition. There was no significant difference between the REE measured in the morning and that determined in the afternoon.

Ignoring information in binary choice with continuous variables: When is less 'more'?

When can a single variable be more accurate in binary choice than multiple sources of information? We derive analytically the probability that a single variable (SV) will correctly predict one of two choices when both criterion and predictor are continuous variables. We further provide analogous derivations for multiple regression (MR) and equal weighting (EW) and specify the conditions under which the models differ in expected predictive ability. Key factors include variability in cue validities, intercorrelation between predictors, and the ratio of predictors to observations in MR. Theory and simulations are used to illustrate the differential effects of these factors. Results directly address why and when one-reason decision making can be more effective than analyses that use more information. We thus provide analytical backing to intriguing empirical results that, to date, have lacked theoretical justification. There are predictable conditions for which one should expect less to be more.

Continuous arterial spin labeling of mouse cerebral blood flow using an actively-detuned two-coil system at 9.4T.

Among numerous magnetic resonance imaging (MRI) techniques, perfusion MRI provides insight into the passage of blood through the brain's vascular network non-invasively. Studying disease models and transgenic mice would intrinsically help understanding the underlying brain functions, cerebrovascular disease and brain disorders. This study evaluates the feasibility of performing continuous arterial spin labeling (CASL) on all cranial arteries for mapping murine cerebral blood flow at 9.4 T. We showed that with an active-detuned two-coil system, a labeling efficiency of 0.82 ± 0.03 was achieved with minimal magnetization transfer residuals in brain. The resulting cerebral blood flow of healthy mouse was 99 ± 26 mL/100g/min, in excellent agreement with other techniques. In conclusion, high magnetic fields deliver high sensitivity and allowing not only CASL but also other MR techniques, i.e. (1)H MRS and diffusion MRI etc, in studying murine brains.