Individual patient data systematic review and meta-analysis of optic nerve sheath diameter ultrasonography for detecting raised intracranial pressure: protocol of the ONSD research group.

BACKGROUND: The purpose of the optic nerve sheath diameter (ONSD) research group project is to establish an individual patient-level database from high quality studies of ONSD ultrasonography for the detection of raised intracranial pressure (ICP), and to perform a systematic review and an individual patient data meta-analysis (IPDMA), which will provide a cutoff value to help physicians making decisions and encourage further research. Previous meta-analyses were able to assess the diagnostic accuracy of ONSD ultrasonography in detecting raised ICP but failed to determine a precise cutoff value. Thus, the ONSD research group was founded to synthesize data from several recent studies on the subject and to provide evidence on the diagnostic accuracy of ONSD ultrasonography in detecting raised ICP. METHODS: This IPDMA will be conducted in different phases. First, we will systematically search for eligible studies. To be eligible, studies must have compared ONSD ultrasonography to invasive intracranial devices, the current reference standard for diagnosing raised ICP. Subsequently, we will assess the quality of studies included based on the QUADAS-2 tool, and then collect and validate individual patient data. The objectives of the primary analyses will be to assess the diagnostic accuracy of ONSD ultrasonography and to determine a precise cutoff value for detecting raised ICP. Secondly, we will construct a logistic regression model to assess whether patient and study characteristics influence diagnostic accuracy. DISCUSSION: We believe that this IPD MA will provide the most reliable basis for the assessment of diagnostic accuracy of ONSD ultrasonography for detecting raised ICP and to provide a cutoff value. We also hope that the creation of the ONSD research group will encourage further study. TRIAL REGISTRATION: PROSPERO registration number: CRD42012003072.

Editorial research and the publication process in biomedicine and health: Report from the Esteve Foundation Discussion Group, December 2012.

Despite the fact that there are more than twenty thousand biomedical journals in the world, research into the work of editors and publication process in biomedical and health care journals is rare. In December 2012, the Esteve Foundation, a non-profit scientific institution that fosters progress in pharmacotherapy by means of scientific communication and discussion organized a discussion group of 7 editors and/or experts in peer review biomedical publishing. They presented findings of past editorial research, discussed the lack of competitive funding schemes and specialized journals for dissemination of editorial research, and reported on the great diversity of misconduct and conflict of interest policies, as well as adherence to reporting guidelines. Furthermore, they reported on the reluctance of editors to investigate allegations of misconduct or increase the level of data sharing in health research. In the end, they concluded that if editors are to remain gatekeepers of scientific knowledge they should reaffirm their focus on the integrity of the scientific record and completeness of the data they publish. Additionally, more research should be undertaken to understand why many journals are not adhering to editorial standards, and what obstacles editors face when engaging in editorial research.

Audit report on the Honey Creek Resort Operations Account maintained by Central Group Management, LLC for the year ended June 30, 2010

Audit report on the Honey Creek Resort Operations Account maintained by Central Group Management, LLC for the year ended June 30, 2010

New insights on the crystalline forms in binary systems of n-alkanes: Characterization of the solid ordered phases in the phase diagram tricosane + pentacosane

X-ray diffraction analyses of the pure components n-tricosane and n-pentacosane and of their binary mixed samples have enabled us to characterize the crystalline phases observed at low temperature. On the contrary to what was announced in literature on the structural behavior of mixed samples in odd-odd binary systems with D n = 2, the three domains are not all orthorhombic. This work has enabled us to show that two of the domains are, in fact, monoclinic, (Aa, Z = 4) and the other one is orthorhombic (Pca21, Z = 4). The conclusions drawn in this work can be easily transposed to other binary systems of n-alkanes.

Risperidone versus clozapine in treatment-resistant chronic schizophrenia: a randomized double-blind study. The Risperidone Study Group.

OBJECTIVE: The purpose of this study was to compare the short-term efficacy and safety of risperidone and clozapine in treatment-resistant chronic schizophrenic patients. METHOD: In a controlled double-blind, multicenter study, 86 inpatients with chronic schizophrenia (DSM-III-R), who were resistant to or intolerant of conventional neuroleptics, were randomly assigned to receive risperidone or clozapine for 8 weeks after a 7-day washout period. After a 1-week dose-titration phase, doses were fixed at 6 mg/day of risperidone and 300 mg/day of clozapine for 1 week and then adjusted according to each patient's response. The final mean doses were 6.4 mg/day of risperidone and 291.2 mg/day of clozapine. Treatment efficacy and safety were evaluated with several well-known rating scales. RESULTS: Both risperidone and clozapine significantly reduced the severity of psychotic symptoms (scores on the Positive and Negative Syndrome Scale and the Clinical Global Impression scale) from baseline, with no significant between-group differences. At endpoint, 67% of the risperidone group and 65% of the clozapine group were clinically improved (reduction of 20% or more in total Positive and Negative Syndrome Scale score). Risperidone appeared to have a faster onset of action. In both groups extrapyramidal symptoms and other adverse events were few, and their severity was generally mild. Neither group showed evidence of a relation between drug plasma concentrations and clinical effectiveness. CONCLUSIONS: Risperidone was well tolerated and as effective as medium doses of clozapine in patients with chronic schizophrenia who had been resistant to or intolerant of conventional neuroleptics.

The induced generalized OWA operator

[spa] Se presenta el operador OWA generalizado inducido (IGOWA). Es un nuevo operador de agregación que generaliza al operador OWA a través de utilizar las principales características de dos operadores muy conocidos como son el operador OWA generalizado y el operador OWA inducido. Entonces, este operador utiliza medias generalizadas y variables de ordenación inducidas en el proceso de reordenación. Con esta formulación, se obtiene una amplia gama de operadores de agregación que incluye a todos los casos particulares de los operadores IOWA y GOWA, y otros casos particulares. A continuación, se realiza una generalización mayor al operador IGOWA a través de utilizar medias cuasi-aritméticas. Finalmente, también se desarrolla un ejemplo numérico del nuevo modelo en un problema de toma de decisiones financieras.

The induced 2-tuple linguistic generalized OWA operator and its application in linguistic decision making

[spa] Se presenta el operador de media ponderada ordenada generalizada lingüística de 2 tuplas inducida (2-TILGOWA). Es un nuevo operador de agregación que extiende los anteriores modelos a través de utilizar medias generalizadas, variables de ordenación inducidas e información lingüística representada mediante el modelo de las 2 tuplas lingüísticas. Su principal ventaja se encuentra en la posibilidad de incluir a un gran número de operadores de agregación lingüísticos como casos particulares. Por eso, el análisis puede ser visto desde diferentes perspectivas de forma que se obtiene una visión más completa del problema considerado y seleccionar la alternativa que parece estar en mayor concordancia con nuestros intereses o creencias. A continuación se desarrolla una generalización mayor a través de utilizar medias cuasi-aritméticas, obteniéndose el operador Quasi-2-TILOWA. El trabajo finaliza analizando la aplicabilidad del nuevo modelo en un problema de toma de decisiones sobre gestión de la producción.

The generalized index of maximum and minimum level and its application in decision making

[spa] El índice del máximo y el mínimo nivel es una técnica muy útil, especialmente para toma de decisiones, que usa la distancia de Hamming y el coeficiente de adecuación en el mismo problema. En este trabajo, se propone una generalización a través de utilizar medias generalizadas y cuasi aritméticas. A estos operadores de agregación, se les denominará el índice del máximo y el mínimo nivel medio ponderado ordenado generalizado (GOWAIMAM) y cuasi aritmético (Quasi-OWAIMAM). Estos nuevos operadores generalizan una amplia gama de casos particulares como el índice del máximo y el mínimo nivel generalizado (GIMAM), el OWAIMAM, y otros. También se desarrolla una aplicación en la toma de decisiones sobre selección de productos.

Pulmonary-artery pressure and exhaled nitric oxide in Bolivian and Caucasian high altitude dwellers.

There is evidence that high altitude populations may be better protected from hypoxic pulmonary hypertension than low altitude natives, but the underlying mechanism is incompletely understood. In Tibetans, increased pulmonary respiratory NO synthesis attenuates hypoxic pulmonary hypertension. It has been speculated that this mechanism may represent a generalized high altitude adaptation pattern, but direct evidence for this speculation is lacking. We therefore measured systolic pulmonary-artery pressure (Doppler chocardiography) and exhaled nitric oxide (NO) in 34 healthy, middle-aged Bolivian high altitude natives and in 34 age- and sex-matched, well-acclimatized Caucasian low altitude natives living at high altitude (3600 m). The mean+/-SD systolic right ventricular to right atrial pressure gradient (24.3+/-5.9 vs. 24.7+/-4.9 mmHg) and exhaled NO (19.2+/-7.2 vs. 22.5+/-9.5 ppb) were similar in Bolivians and Caucasians. There was no relationship between pulmonary-artery pressure and respiratory NO in the two groups. These findings provide no evidence that Bolivian high altitude natives are better protected from hypoxic pulmonary hypertension than Caucasian low altitude natives and suggest that attenuation of pulmonary hypertension by increased respiratory NO synthesis may not represent a universal adaptation pattern in highaltitude populations.

Changes in the use of broad-spectrum antibiotics after withdrawal of cefepime from the market: an interrupted time series analysis

Background and objective: Cefepime was one of the most used broad-spectrum antibiotics in Swiss public acute care hospitals. The drug was withdrawn from market in January 2007, and then replaced by a generic since October 2007. The goal of the study was to evaluate changes in the use of broad-spectrum antibiotics after the withdrawal of the cefepime original product. Design: A generalized regression-based interrupted time series model incorporating autocorrelated errors assessed how much the withdrawal changed the monthly use of other broad-spectrum antibiotics (ceftazidime, imipenem/cilastin, meropenem, piperacillin/ tazobactam) in defined daily doses (DDD)/100 bed-days from January 2004 to December 2008 [1, 2]. Setting: 10 Swiss public acute care hospitals (7 with\200 beds, 3 with 200-500 beds). Nine hospitals (group A) had a shortage of cefepime and 1 hospital had no shortage thanks to importation of cefepime from abroad. Main outcome measures: Underlying trend of use before the withdrawal, and changes in the level and in the trend of use after the withdrawal. Results: Before the withdrawal, the average estimated underlying trend (coefficient b1) for cefepime was decreasing by -0.047 (95% CI -0.086, -0.009) DDD/100 bed-days per month and was significant in three hospitals (group A, P\0.01). Cefepime withdrawal was associated with a significant increase in level of use (b2) of piperacillin/tazobactam and imipenem/cilastin in, respectively, one and five hospitals from group A. After the withdrawal, the average estimated trend (b3) was greatest for piperacillin/tazobactam (+0.043 DDD/100 bed-days per month; 95% CI -0.001, 0.089) and was significant in four hospitals from group A (P\0.05). The hospital without drug shortage showed no significant change in the trend and the level of use. The hypothesis of seasonality was rejected in all hospitals. Conclusions: The decreased use of cefepime already observed before its withdrawal from the market could be explained by pre-existing difficulty in drug supply. The withdrawal of cefepime resulted in change in level for piperacillin/tazobactam and imipenem/cilastin. Moreover, an increase in trend was found for piperacillin/tazobactam thereafter. As these changes generally occur at the price of lower bacterial susceptibility, a manufacturers' commitment to avoid shortages in the supply of their products would be important. As perspectives, we will measure the impact of the changes in cost and sensitivity rates of these antibiotics.

Time of ruin in a risk model with generalized Erlang (n) interclaim times and a constant dividend barrier

In this paper we analyze the time of ruin in a risk process with the interclaim times being Erlang(n) distributed and a constant dividend barrier. We obtain an integro-differential equation for the Laplace Transform of the time of ruin. Explicit solutions for the moments of the time of ruin are presented when the individual claim amounts have a distribution with rational Laplace transform. Finally, some numerical results and a compare son with the classical risk model, with interclaim times following an exponential distribution, are given.

Association between white-coat effect and blunted dipping of nocturnal blood pressure.

In this study, we assessed whether the white-coat effect (difference between office and daytime blood pressure (BP)) is associated with nondipping (absence of BP decrease at night). Data were available in 371 individuals of African descent from 74 families selected from a population-based hypertension register in the Seychelles Islands and in 295 Caucasian individuals randomly selected from a population-based study in Switzerland. We used standard multiple linear regression in the Swiss data and generalized estimating equations to account for familial correlations in the Seychelles data. The prevalence of systolic and diastolic nondipping (<10% nocturnal BP decrease) and white-coat hypertension (WCH) was respectively 51, 46, and 4% in blacks and 33, 37, and 7% in whites. When white coat effect and nocturnal dipping were taken as continuous variables (mm Hg), systolic (SBP) and diastolic BP (DBP) dipping were associated inversely and independently with white-coat effect (P < 0.05) in both populations. Analogously, the difference between office and daytime heart rate was inversely associated with the difference between daytime and night-time heart rate in the two populations. These results did not change after adjustment for potential confounders. The white-coat effect is associated with BP nondipping. The similar associations between office-daytime values and daytime-night-time values for both BP and heart rate suggest that the sympathetic nervous system might play a role. Our findings also further stress the interest, for clinicians, of assessing the presence of a white-coat effect as a means to further identify patients at increased cardiovascular risk and guide treatment accordingly.

Serum insulin and inflammatory markers in overweight individuals with and without dyslipidemia.

CONTEXT: The worldwide epidemic of overweight and obesity is setting the scene for a new wave of premature cardiovascular disease. OBJECTIVE: The objective of this study was to define relationships between dyslipidemia and other metabolic abnormalities in overweight subjects. DESIGN: This study included comparison of overweight subjects with and without dyslipidemia. SETTING: The setting was an institutional practice. PATIENTS: Dyslipidemic subjects (n = 715) had plasma triglyceride greater than or equal to the 75th percentile in combination with high-density lipoprotein cholesterol (HDL-C) less than or equal to the 25th percentile. Unrelated, normolipidemic controls (n = 1073) had HDL-C higher than the median and triglyceride lower than the median. It was a requirement for the control subjects to have a body mass index (BMI) greater than 25 kg/m(2). MAIN OUTCOME MEASURES: The main outcome measures included BMI, inflammatory markers, adipokines, blood pressure, and fasting plasma glucose and insulin. RESULTS: The mean BMI in the subjects and controls was 28.7 and 28.2 kg/m(2), respectively. Subjects had higher levels of plasma high-sensitivity C-reactive protein (3.0 vs. 2.0 mg/liter; P < 0.001), lower levels of adiponectin (4.7 vs. 6.6 mg/liter; P < 0.001), and, after adjustment for age, BMI, gender, smoking, statin, and beta-blocker use, higher systolic (P = 0.001) and diastolic (P = 0.05) blood pressures. Fasting plasma glucose, insulin, and homeostasis model of assessment-insulin resistance were all significantly higher in subjects than controls (P < 0.0001). CONCLUSIONS: Identification of people solely on the basis of an elevated plasma triglyceride and a low HDL-C uncovers an overweight group of people who have a generalized metabolic disorder. In contrast, overweight people with normal plasma lipids have normal glucose and insulin metabolism, low levels of inflammatory markers, and normal blood pressure. Such people may thus be at relatively low risk of developing diabetes and cardiovascular disease despite being overweight.