Identification of the new progress on Pyrazole Derivatives Molecules as Antimicrobial and Antifungal Agents.

Microbial infections remain a worldwide leading cause of death, despite the evolution of a large number of new antibiotics every year. Currently, several bacteria have developed resistance against antibiotics drugs which remain a major issue in antibiotics drug discovery. This review provides detailed information about antimicrobial and antifungal agent synthesis belonging to the pyrazoles scaffold. We reassemble the results obtained from several studies to characterize the importance of heteroatom nuclei in many synthetic products. Additionally, several compounds based on pyrazole derivatives such as benzimidazole, benzothiazole, indole, acridine, oxadiazole, imidazole, isoxazole, pyrazole, triazole, quinoline and quinazoline including other pyrazole containing drugs such as pyridazine, pyridine and pyrimidine are highlighted. Furthermore, you will find in this review 134 best promise structures collected from recent studies, relating the pyrazoles structures to the relevant biological activities, in particular, antimicrobial and antifungal one.

Les infections microbiennes restent une des principales causes de décès dans le monde, malgré l'évolution d'un grand nombre de nouveaux antibiotiques chaque année. Actuellement, plusieurs bactéries ont développé une résistance aux médicaments antibiotiques, ce qui reste un problème majeur dans la découverte de médicaments antibiotiques. Cette revue fournit des informations détaillées sur la synthèse d'agents antimicrobiens et antifongiques appartenant à l'échafaudage des pyrazoles. Nous rassemblons les résultats obtenus à partir de plusieurs études pour caractériser l'importance des noyaux d'hétéroatomes dans de nombreux produits synthétiques. En outre, plusieurs composés basés sur des dérivés du pyrazole tels que le benzimidazole, le benzothiazole, l'indole, l'acridine, l'oxadiazole, l'imidazole, l'isoxazole, le pyrazole, le triazole, la quinoléine et la quinazoline, ainsi que d'autres médicaments contenant du pyrazole comme la pyridazine, la pyridine et la pyrimidine, sont mis en évidence. En outre, vous trouverez dans cette revue 134 structures les plus prometteuses recueillies dans des études récentes, mettant en relation les structures des pyrazoles avec les activités biologiques pertinentes, en particulier antimicrobiennes et antifongiques. Mots-clés: Dérivés de pyrazoles ; antibiotiques ; activité antifongique; résistance microbienne, azote hétérocyclique.

Identification Des Nouveaux Progrès Sur Les Molécules Dérivées Du Pyrazole Comme AgentsAntimicrobiens Et Antifongiques

Microbial infections remain a worldwide leading cause of death,despite the evolution of a large number of new antibiotics everyyear. Currently, several bacteria have developed resistanceagainst antibiotics drugs which remain a major issue inantibiotics drug discovery. This review provides detailedinformation about antimicrobial and antifungal agent synthesisbelonging to the pyrazoles scaffold. We reassemble the resultsobtained from several studies to characterize the importance ofheteroatom nuclei in many synthetic products. Additionally,several compounds based on pyrazole derivatives such asbenzimidazole, benzothiazole, indole, acridine, oxadiazole,imidazole, isoxazole, pyrazole, triazole, quinoline and quinazolineincluding other pyrazole containing drugs such as pyridazine,pyridine and pyrimidine are highlighted. Furthermore, you willfind in this review 134 best promise structures collected fromrecent studies, relating the pyrazoles structures to the relevantbiological activities, in particular, antimicrobial and antifungalone.

Lung function in Birt-Hogg-Dubé syndrome: a retrospective analysis of 96 patients.

BACKGROUND: Birt-Hogg-Dubé syndrome (BHD) is a rare autosomal dominant disorder caused by mutations in the FLCN gene coding for folliculin. Its clinical expression includes cutaneous fibrofolliculomas, renal tumors, multiple pulmonary cysts, and recurrent spontaneous pneumothoraces. Data on lung function in BHD are scarce and it is not known whether lung function declines over time. We retrospectively assessed lung function at baseline and during follow-up in 96 patients with BHD. RESULTS: Ninety-five percent of BHD patients had multiple pulmonary cysts on computed tomography and 59% had experienced at least one pneumothorax. Mean values of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and total lung capacity were normal at baseline. Mean (standard deviation) residual volume (RV) was moderately increased to 116 (36) %pred at baseline, and RV was elevated > 120%pred in 41% of cases. Mean (standard deviation) carbon monoxide transfer factor (DLco) was moderately decreased to 85 (18) %pred at baseline, and DLco was decreased < 80%pred in 33% of cases. When adjusted for age, gender, smoking and history of pleurodesis, lung function parameters did not significantly decline over a follow-up period of 6 years. CONCLUSIONS: Cystic lung disease in BHD does not affect respiratory function at baseline except for slightly increased RV and reduced DLco. No significant deterioration of lung function occurs in BHD over a follow-up period of 6 years.

New formula for cardiothoracic ratio for the diagnosis of cardiomegaly on post-mortem CT.

The cardiothoracic ratio (CTR) is considered to be a reliable detector of cardiomegaly on computed tomography for livings, with a threshold of 0.5. Our study aimed to establish an adjusted CTR-based score to predict cardiac hypertrophy at PMCT. We selected adult's autopsy cases examined between 2009 and 2016. Two groups were considered, a normal heart weight group and an overweighed heart group. The CTR was measured on axial images. Logistic regression analysis was performed to investigate the discriminating power of the CTR between groups when adjusted to the confounding factors. Sixty-six cases with normal heart weight and 94 cases with overweighed heart were analyzed. The factors associated to the cardiac hypertrophy are CTR (p value 0.003, OR 3.57), BMI (p value 0.055, OR 1.09), age (p value < 0.001, OR 1.67), and gender (p value 0.002, OR 4.85). The area under the ROC curve (receiver operating characteristic curve) was 0.77 when using CTR alone and 0.88 when considering BMI, age, and gender. In conclusion, CTR alone cannot be used to discriminate between normal heart weight and overweighed heart at PMCT. A new formula has been developed, including age, gender, and BMI. Dilatation of the cardiac chambers, which is a subjective evaluation, influences the CTR measure and could be not related to a pre-existing cardiac hypertrophy. This new score formula allows to overpasses this subjective step. We proposed a cut-off value of the score of 32 for the diagnosis of cardiac hypertrophy. The Internet/smartphone application (http://calc.chuv.ch/CTR) facilitates its routine application.

Squamous cell carcinoma of the head and neck - screening in patients who misuse alcohol and tobacco in Switzerland: a prospective pilot study.

Squamous cell carcinoma (SCC) of the head and neck is the sixth most common cancer worldwide. It is preceded by early asymptomatic lesions which, if identified early enough and removed, would prevent malignant transformation or avoid delaying diagnosis to advanced stages. Our aim was to evaluate the feasibility of a screening programme for SCC of the head and neck in a group of high-risk patients, and to investigate their addiction profile. Patients admitted to an inpatient alcohol addiction centre (n=101) were prospectively enrolled and asked to fill in a questionnaire about their use of tobacco and alcohol, and the presence of warning symptoms for SCC of the head and neck from 23 June 2014 to 21 January2016. Participants in the study had a physical examination by an alcohol addiction physician followed by a full examination of the head and neck by an otorhinolaryngologist to rule out premalignant or malignant lesions of the upper aerodigestive tract. Of the 101 patients, 62 (60%) had at least one warning symptom. Alcohol addiction physicians identified leukoplakia in six (6%) and erythroplakia in two. No pre-malignant or malignant lesions were confirmed on examination by the otolaryngologist. We were unable to draw conclusions about the cost-effectiveness or the yield of the screening programme. Despite our negative findings, we may need further investigation to clarify the relevance of such a programme on health-related outcome given the high compliance rate and minimal delay that was achieved by taking advantage of an in-patient alcohol rehabilitation centre.

Level of readiness of chronic pain patients to practise active self-care.

BACKGROUND: Given the limited alleviation of chronic pain with pharmacological treatments, various nonpharmacological and self-care approaches are often proposed that require patients' motivation. OBJECTIVE: To evaluate the level of readiness (LOR) to practise different types of active self-care among chronic pain patients. METHOD: A quantitative cross-sectional survey was conducted among all chronic pain patients seeking care at the Pain Center of an academic hospital from June 2013 to March 2015. Sociodemographic data, pain characteristics, treatments and the LOR to practise active self-care were investigated. RESULTS: Among the 1524 eligible patients, 639 (41.9%) were included. The median pain duration was 8.5 years (interquartile range = 7.5). Two-thirds (63.7%) of the patients reported high pain-related disability, and 64.6% had used opioids during the previous six months. Most patients had a high (44.1%) or moderate (24.6%) LOR to practise active self-care. Multivariable multinomial regression analysis showed that independent factors associated with a high LOR were a higher level of education (relative risk ratio (RRR) = 3.42, 95% confidence interval (CI): 1.90-6.13, p < 0.001), unemployed status due to medical condition (RRR = 2.92, 95% CI: 1.30-6.56, p = 0.009), the use of dietary supplements 'against pain' (RRR = 2.77, 95% CI: 1.52-5.04, p = 0.001) and neuropathic pain characteristics (RRR = 1.80, 95% CI: 1.40-3.12, p = 0.036). Older age was a factor predicting a lower LOR (RRR = 0.97, 95% CI: 0.94-0.99, p = 0.039). Long-term chronic pain, severe pain-related disability and the presence of a mood disorder were not associated with a lower LOR. CONCLUSION: Most chronic pain patients, including those severely affected, indicated their readiness to practise active self-care methods. SIGNIFICANCE: Most chronic pain patients, even those severely affected, appeared to be ready to practise active self-care therapies and we believe that further studies are needed to investigate their impact on pain and quality of life.

Pretherapeutic functional neuroimaging predicts tremor arrest after thalamotomy.

OBJECTIVE: Essential tremor (ET) represents the most common movement disorder. Drug-resistant ET can benefit from standard stereotactic procedures (deep brain stimulation or radiofrequency thalamotomy) or alternatively minimally invasive high-focused ultrasound or radiosurgery. All aim at same target, thalamic ventro-intermediate nucleus (Vim). METHODS: The study included a cohort of 17 consecutive patients, with ET, treated only with left unilateral stereotactic radiosurgical thalamotomy (SRS-T) between September 2014 and August 2015. The mean time to tremor improvement was 3.32 months (SD 2.7, 0.5-10). Neuroimaging data were collected at baseline (n = 17). Standard tremor scores, including activities of daily living (ADL) and tremor score on treated hand (TSTH), were completed pretherapeutically and 1 year later. We further correlate these scores with baseline inter-connectivity in twenty major large-scale brain networks. RESULTS: We report as predictive three networks, with the interconnected statistically significant clusters: primary motor cortex interconnected with inferior olivary nucleus, bilateral thalamus interconnected with motor cerebellum lobule V2 (ADL), and anterior default-mode network interconnected with Brodmann area 103 (TSTH). For all, more positive pretherapeutic interconnectivity correlated with higher drop in points on the respective scores. Age, disease duration, or time-to-response after SRS-T were not statistically correlated with pretherapeutic brain connectivity measures (P > .05). The same applied to pretherapeutic tremor scores, after using the same methodology described above. CONCLUSIONS: Our findings have clinical implications for predicting clinical response after SRS-T. Here, using pretherapeutic magnetic resonance imaging and data processing without prior hypothesis, we show that pretherapeutic network(s) interconnectivity strength predicts tremor arrest in drug-naïve ET, following stereotactic radiosurgical thalamotomy.

Added value of multimodal computed tomography imaging: analysis of 1994 acute ischaemic strokes.

BACKGROUND AND PURPOSE: Multimodal computed tomography (CT) based imaging (MCTI) is widely used in acute ischaemic stroke. It was postulated that the use of MCTI is associated with improved patient outcome without causing harm. METHODS: All patients with an acute ischaemic stroke and CT-based imaging within 24 h from the ASTRAL (Acute Stroke Registry and Analysis of Lausanne) registry were included. Preceding demographic, clinical, biological, radiological and follow-up data were collected. Significant predictors of MCTI use were identified retrospectively to go on to fit a multivariable analysis. Then, patients undergoing additional CT angiography (CTA) or CTA and perfusion CT (CTP) were compared with non-contrast CT only patients with regard to 3-month favourable outcome (modified Rankin Scale score ≤2), 12-month mortality, stroke mechanism, short-term renal failure, use of ancillary diagnostic tests, duration of hospitalization and 12-month stroke recurrence. RESULTS: Of the 1994 included patients, 273 had only non-contrast CT, 411 had both non-contrast CT and CTA and 1310 had all three examinations. Factors independently associated with MCTI were younger age, low pre-stroke modified Rankin Scale score, low creatinine value, known stroke onset, anterior circulation stroke, anticoagulation or antihypertensive therapy (CTA only) and higher National Institutes of Health Stroke Scale scores (CTP only). After adjustment, MCTI was associated with a 50% reduction of 12-month mortality and a lower likelihood of unknown stroke mechanism. No association was found between MCTI and 3-month outcome, contrast-induced nephropathy, hospitalization duration, number of ancillary diagnostic tests or with stroke recurrence. CONCLUSION: Our study shows an association of MCTI use with lower adjusted 12-month mortality, better identification of the stroke mechanism and no signs of harm.

Anticandidal, antibacterial, cytotoxic and antioxidant activities of Calendula arvensis flowers.

Calendula arvensis (CA) is one of the important plants used in traditional medicine in Morocco, due to its interesting chemical composition. The present study aimed to determine the anticandidal, antioxidant and antibacterial activities, and the effects of extracts of CA flowers on the growth of myeloid cancer cells. Also, to characterize the chemical composition of the plant. Flowers of CA were collected based on ethnopharmacological information from the villages around the region Rabat-Khemisset, Moroccco. The hexane and methanol extracts were obtained by soxhlet extraction, while aqueous extracts was obtained by maceration in cold water. CA extracts were assessed for antioxidant activity using four different methods (DPPH, FRAP, TEAC, ß-carotene bleaching test). Furthermore, the phenolic and flavonoid contents were measured, also the antimicrobial activity has been evaluated by the well diffusion method using several bacterial and fungal strains. Finally, extracts cytotoxicity was assessed using MTT test. Phytochemical quantification of the methanolic and aqueous extracts revealed that they were rich with flavonoid and phenolic content and were found to possess considerable antioxidant activities. MIC values of methanolic extracts were 12.5-25µg/mL. While MIC values of hexanolic extracts were between 6.25-12.5µg/mL and were bacteriostatic for all bacteria while methanolic and aqueous extracts were bactericidal. In addition, the extracts exhibited no activity on Candida species except the methanolic extract, which showed antifungal activity onCandida tropicalis 1 and Candida famata 1. The methanolic and aqueous extracts also exhibited antimyeloid cancer activity (IC50 of 31µg/mL). In our study, we conclude that the methanolic and aqueous extracts were a promising source of antioxidant, antimicrobial and cytotoxic agents.

Synthesis, antioxidant and analgesic activities of Schiff bases of 4-amino-1,2,4-triazole derivatives containing a pyrazole moiety.

A series of Schiff bases of 4-amino-1,2,4-triazole derivatives containing pyrazole (5a-h) were synthesized from condensation of 4-amino-5-(5-methyl-1H-pyrazol-3-yl)-4H-1,2,4-triazole-3-thiol (3) derivative with various aromatic aldehydes (4a-h). The structures of the synthesized compounds were elucidated by IR, 1H NMR, 13C NMR, and mass spectrometry. All the synthesized compounds (5a-h) were screened for their in vivo analgesic and in vitro antioxidant activities revealing significant analgesic and antioxidant properties.

The cardiothoracic ratio on post-mortem computer tomography.

In clinical practice, the cardiothoracic ratio (CTR) was first utilized on plain chest radiography, and subsequently with computed tomography (CT) to diagnose cardiomegaly with a threshold of 0.5. Using CTR in forensic practice could help to detect cardiomegaly on post-mortem CT (PMCT) prior to the autopsy. However, an adaption of the threshold could be necessary because of post-mortem changes. Our retrospective study aimed to measure the CTR on PMCT and test the possible influence of variables. We selected 109 autopsy cases in which the heart weight was within normal limits. A forensic pathologist and a radiologist measured separately the CTR on axial and scout views on PMCT. We tested the statistical concordance between the two readers and between the axial and scout view and identified factors that could be associated with a modification of the CTR. The CTR measurements revealed an overestimation of the measurements made on scout compared to axial view. The inter-reader correlation was very high for both views. Among the different variables statistically tested, heart dilatation and body mass index (BMI) were the only two factors statistically associated with an augmentation of the CTR. The CTR can be useful in the diagnosis of cardiomegaly on PMCT. However, dilatation of the cardiac chambers caused by acute heart failure may be misinterpreted radiographically as cardiomegaly. Inter-observer reliability in our study was very high. CTR may be overestimated when measured on the scout view. Further investigations with larger cohorts, including cases with cardiac hypertrophy, are necessary to better understand the relationship between radiological CTR and the morphology of the heart.

Comparison of mortality prediction models and validation of SAPS II in critically ill burns patients.

Specific burn outcome prediction scores such as the Abbreviated Burn Severity Index (ABSI), Ryan, Belgian Outcome of Burn Injury (BOBI) and revised Baux scores have been extensively studied. Validation studies of the critical care score SAPS II (Simplified Acute Physiology Score) have included burns patients but not addressed them as a cohort. The study aimed at comparing their performance in a Swiss burns intensive care unit (ICU) and to observe whether they were affected by a standardized definition of inhalation injury. We conducted a retrospective cohort study, including all consecutive ICU burn admissions (n=492) between 1996 and 2013: 5 epochs were defined by protocol changes. As required for SAPS II calculation, stays <24h were excluded. Data were collected on age, gender, total body surface area burned (TBSA) and inhalation injury (systematic standardized diagnosis since 2006). Study epochs were compared (χ2 test, ANOVA). Score performance was assessed by receiver operating characteristic curve analysis. SAPS II performed well (AUC 0.89), particularly in burns <40% TBSA (AUC 0.93). Revised Baux and ABSI scores were not affected by the standardized diagnosis of inhalation injury and showed the best performance (AUC 0.92 and 0.91 respectively). In contrast, the accuracy of the BOBI and Ryan scores was lower (AUC 0.84 and 0.81) and reduced after 2006. The excellent predictive performance of the classic scores (revised Baux score and ABSI) was confirmed. SAPS II was nearly as accurate, particularly in burns <40% TBSA. Ryan and BOBI scores were least accurate, as they heavily weight inhalation injury.

Les scores prédictifs de mortalité spécifiques aux brûlés comme l'ABSI, le Ryan, le BOBI, ainsi que le Baux révisé ont été très largement étudiés. Les études ayant validé le SAPS II ont certes inclus des brûlés, mais ils n'ont pas été étudiés en tant que sous-population. Cette étude rétrospective, réalisée dans une unité de réanimation de brûlés suisse, avait pour but de comparer les performances de ces scores et d'évaluer l'impact d'une définition standardisée des lésions d'inhalation. Elle a inclus 492 patients hospitalisés entre 1996 et 2013, répartis en 5 périodes définies par des modifications du protocole interne de prise en charge. L'âge, la surface brûlée et l'inhalation (définition standardisée depuis 2006) ont été recueillis. Les périodes ont été comparées par ANOVA et χ2. La performance des scores a été évaluée par analyse des courbes ROC. Le SAPS II a démontré une bonne performance (AUC 0,89), particulièrement en cas de brûlure <40% SCT (AUC 0,93). L'ABSI et le Baux révisé étaient les plus performants (AUC 0,92 et 0,91) et sont avérés peu affectés par le changement de définition de l'inhalation. Le BOBI et le Ryan se sont révélés moins précis (AUC 0,84 et 0,81) avec des performances encore davantage dégradées après le changement de définition de l'inhalation. L'excellente valeur prédictive du Baux révisé et de l'ABSI est ainsi confirmée. Le SAPS II s'est montré presque aussi précis, en particulier pour des surfaces <40%. Les scores Ryan et BOBI ont été les moins précis.

Comparative plasma disposition kinetics of albendazole and its new benzimidazol prodrug in dog.

The comparative pharmacokinetic behavior of albendazole (ABZ) and its new benzimidazol prodrug [1-tert-butyloxycarbonyl-5-propylthio-1-H-benzimidazol-2ylcarbamate of methyl] (ABZBoc), following their oral administration (10mg/kg) to healthy dogs was explored. Blood samples were obtained serially over a 24h period after treatment, then the plasma was analyzed by high-performance liquid chromatography (HPLC) to search the albendazole metabolites (ABZSO and ABZSO2). However, the albendazole parent drug was not detectable at any time after both treatments (ABZ and ABZBoc). By albendazole metabolites (ABZSO and ABZSO2) were the analytes recovered in the plasma after oral administration of ABZ and ABZBoc. Furthermore, some amounts of ABZBoc were also available in the plasma samples treated with this new produg. The plasma profile of each analyte followed a similar pattern after both treatments, the active metabolite (ABZSO) was the major analyte recovered in plasma (between 1 and 24h post-treatment). The pharmacokinetic parameters of both groups were calculated (Cmax, Tmax, t1/2, AUC0->∞), and analyzed using the Student's t-test, P<0.05. Thus,the pharmacokinetic analysis indicated four statistically significant changes in the pharmacokinetic parameters defined above of the albendazole metabolites (ABZSO, ABZSO2) between the group treated with albendazole (group A) and that treated with ABZBoc prodrug (group B). Hence, the levels of the various pharmacokinetics parameters were low in the group treated with prodrug, as well they did not reach equivalent concentrations to that of albendazole. These differences between albendazole and its new prodrug may be explained by the fact that ABZBoc prodrug was not effectively reduced in the intestine of dogs.

Statins are associated with decreased mortality risk after status epilepticus.

BACKGROUND AND PURPOSE: Statins display anti-inflammatory and anti-epileptogenic properties in animal models, and may reduce the epilepsy risk in elderly humans; however, a possible modulating role on outcome in patients with status epilepticus (SE) has not been assessed. METHODS: This cohort study was based on a prospective registry including all consecutive adults with incident SE treated in our center between April 2006 and September 2012. SE outcome was categorized at hospital discharge into 'return to baseline', 'new disability' and 'mortality'. The role of potential predictors, including statins treatment on admission, was evaluated using a multinomial logistic regression model. RESULTS: Amongst 427 patients identified, information on statins was available in 413 (97%). Mean age was 60.9 (±17.8) years; 201 (49%) were women; 211 (51%) had a potentially fatal SE etiology; and 191 (46%) experienced generalized-convulsive or non-convulsive SE in coma. Statins (simvastatin, atorvastatin or pravastatin) were prescribed prior to admission in 76 (18%) subjects, mostly elderly. Whilst 208 (50.4%) patients returned to baseline, 58 (14%) died. After adjustment for established SE outcome predictors (age, etiology, SE severity score), statins correlated significantly with lower mortality (relative risk ratio 0.38, P = 0.046). CONCLUSION: This study suggests for the first time that exposure to statins before an SE episode is related to its outcome, involving a possible anti-epileptogenic role. Other studies are needed to confirm this intriguing finding.

Undernutrition in children with profound intellectual and multiple disabilities (PIMD): its prevalence and influence on quality of life.

BACKGROUND: To estimate the prevalence of undernutrition among children with profound intellectual and multiple disabilities (PIMD) and to explore its influence on quality of life. METHODS: Seventy-two children with PIMD (47 male; 25 female; age range 2 to 15 years 4 months; mean age 8.6, SD 3.6) underwent an anthropometric assessment, including body weight, triceps skinfold thickness, segmental measures and recumbent length. Undernutrition was determined using tricipital skinfold percentile and z-scores of weight-for-height and height-for-age. The quality of life of each child was evaluated using the QUALIN questionnaire adapted for profoundly disabled children. RESULTS: Twenty-five children (34.7%) were undernourished and seven (9.7%) were obese. Among undernourished children only eight (32 %) were receiving food supplements and two (8%) had a gastrostomy, of which one was still on a refeeding programme. On multivariate analysis, undernutrition was one of the independent predictors of lower quality of life. CONCLUSION: Undernutrition remains a matter of concern in children with PIMD. There is a need to better train professionals in systematically assessing the nutritional status of profoundly disabled children in order to start nutritional management when necessary.

[In vitro comparative study of plasma protein binding of 99mTc-DTPA used in renal scintigraphy]. / Étude comparative de l'estimation in vitro de la fixation plasmatique du 99mTc-DTPA utilisé en scintigraphie rénale.

The radiopharmaceutical (99m)Tc-DTPA (diethylene-triamine-pentaacetic acid) is a tracer widely used in renal scintigraphy to assess glomerular filtration rate. The estimation of protein binding is very important due to its impact on clinical parameters biodistribution since only the free fraction is filtered by the kidney. A number of laboratory techniques have been developed to study protein binding. Precipitation and ultrafiltration are the mostly used techniques in pharmacology for studies of the binding between proteins and small molecules. The aim of this work is to apply and compare those two analytical methods in (99m)Tc-DTPA protein binding determination in vitro before in vivo application. The results obtained by precipitation with trichloroacetic acid are not enough reproducible, while those obtained by ultrafiltration seem more consistent and reproducible.

Severe stroke: patient profile and predictors of favorable outcome.

BACKGROUND: Severe stroke carries high rates of mortality and morbidity. The aims of this study were to determine the characteristics of patients who initially presented with severe ischemic stroke, and to identify acute and subacute predictors of favorable clinical outcome in these patients. METHODS: An observational cohort study, Acute Stroke Registry and Analysis of Lausanne (ASTRAL), was analyzed, and all patients presenting with severe stroke - defined as a National Institute of Health Stroke Scale score of ≥ 20 on admission - were compared with all other patients. In a multivariate analysis, associations with demographic, clinical, pathophysiologic, metabolic and neuroimaging factors were determined. Furthermore, we analyzed predictors of favorable outcome (modified Rankin scale score of ≤ 3 at 3 months) in the subgroup of severe stroke patients. RESULTS: Of 1915 consecutive patients, 243 (12.7%) presented with severe stroke. This was significantly associated with cardio-embolic stroke mechanism (odds ratio [OR] 1.74, 95% confidence interval [CI] 1.19-2.54), unknown stroke onset (OR 2.35, 95% CI 1.14-4.83), more neuroimaging signs of early ischemia (mostly computed tomography; OR 2.65, 95% CI 1.79-3.92), arterial occlusions on acute imaging (OR 27.01, 95% CI 11.5-62.9), fewer chronic radiologic infarcts (OR 0.43, 95% CI 0.26-0.72), lower hemoglobin concentration (OR 0.97, 95% CI 0.96-0.99), and higher white cell count (OR 1.05, 95% CI 1.00-1.11). In the 68 (28%) patients with favorable outcomes despite presenting with severe stroke, this was predicted by lower age (OR 0.94, 95% CI 0.92-0.97), preceding cerebrovascular events (OR 3.00, 95% CI 1.01-8.97), hypolipemic pretreatment (OR 3.82, 95% CI 1.34-10.90), lower acute temperature (OR 0.43, 95% CI 0.23-0.78), lower subacute glucose concentration (OR 0.74, 95% CI 0.56-0.97), and spontaneous or treatment-induced recanalization (OR 4.51, 95% CI 1.96-10.41). CONCLUSIONS: Severe stroke presentation is predicted by multiple clinical, radiologic and metabolic variables, several of which are modifiable. Predictors in the 28% of patients with favorable outcome despite presenting with severe stroke include hypolipemic pretreatment, lower acute temperature, lower glucose levels at 24 h, and arterial recanalization.

Correlation of wear in vivo and six laboratory wear methods.

OBJECTIVE: We examined the correlation between clinical wear rates of restorative materials and enamel (TRAC Research Foundation, Provo, USA) and the results of six laboratory test methods (ACTA, Alabama (generalized, localized), Ivoclar (vertical, volumetric), Munich, OHSU (abrasion, attrition), Zurich). METHODS: Individual clinical wear data were available from clinical trials that were conducted by TRAC Research Foundation (formerly CRA) together with general practitioners. For each of the n=28 materials (21 composite resins for intra-coronal restorations [20 direct and 1 indirect], 5 resin materials for crowns, 1 amalgam, enamel) a minimum of 30 restorations had been placed in posterior teeth, mainly molars. The recall intervals were up to 5 years with the majority of materials (n=27) being monitored, however, only for up to 2 years. For the laboratory data, the databases MEDLINE and IADR abstracts were searched for wear data on materials which were also clinically tested by TRAC Research Foundation. Only those data for which the same test parameters (e.g. number of cycles, loading force, type of antagonist) had been published were included in the study. A different quantity of data was available for each laboratory method: Ivoclar (n=22), Zurich (n=20), Alabama (n=17), OHSU and ACTA (n=12), Munich (n=7). The clinical results were summed up in an index and a linear mixed model was fitted to the log wear measurements including the following factors: material, time (0.5, 1, 2 and 3 years), tooth (premolar/molar) and gender (male/female) as fixed effects, and patient as random effect. Relative ranks were created for each material and method; the same was performed with the clinical results. RESULTS: The mean age of the subjects was 40 (±12) years. The materials had been mostly applied in molars (81%) and 95% of the intracoronal restorations were Class II restorations. The mean number of individual wear data per material was 25 (range 14-42). The mean coefficient of variation of clinical wear data was 53%. The only significant correlation was reached by OHSU (abrasion) with a Spearman r of 0.86 (p=0.001). Zurich, ACTA, Alabama generalized wear and Ivoclar (volume) had correlation coefficients between 0.3 and 0.4. For Zurich, Alabama generalized wear and Munich, the correlation coefficient improved if only composites for direct use were taken into consideration. The combination of different laboratory methods did not significantly improve the correlation. SIGNIFICANCE: The clinical wear of composite resins is mainly dependent on differences between patients and less on the differences between materials. Laboratory methods to test conventional resins for wear are therefore less important, especially since most of them do not reflect the clinical wear.

An integer-based score to predict functional outcome in acute ischemic stroke: the ASTRAL score.

OBJECTIVE: To develop and validate a simple, integer-based score to predict functional outcome in acute ischemic stroke (AIS) using variables readily available after emergency room admission. METHODS: Logistic regression was performed in the derivation cohort of previously independent patients with AIS (Acute Stroke Registry and Analysis of Lausanne [ASTRAL]) to identify predictors of unfavorable outcome (3-month modified Rankin Scale score >2). An integer-based point-scoring system for each covariate of the fitted multivariate model was generated by their ß-coefficients; the overall score was calculated as the sum of the weighted scores. The model was validated internally using a 2-fold cross-validation technique and externally in 2 independent cohorts (Athens and Vienna Stroke Registries). RESULTS: Age (A), severity of stroke (S) measured by admission NIH Stroke Scale score, stroke onset to admission time (T), range of visual fields (R), acute glucose (A), and level of consciousness (L) were identified as independent predictors of unfavorable outcome in 1,645 patients in ASTRAL. Their ß-coefficients were multiplied by 4 and rounded to the closest integer to generate the score. The area under the receiver operating characteristic curve (AUC) of the score in the ASTRAL cohort was 0.850. The score was well calibrated in the derivation (p = 0.43) and validation cohorts (0.22 [Athens, n = 1,659] and 0.49 [Vienna, n = 653]). AUCs were 0.937 (Athens), 0.771 (Vienna), and 0.902 (when pooled). An ASTRAL score of 31 indicates a 50% likelihood of unfavorable outcome. CONCLUSIONS: The ASTRAL score is a simple integer-based score to predict functional outcome using 6 readily available items at hospital admission. It performed well in double external validation and may be a useful tool for clinical practice and stroke research.

Streamlining the medication process improves safety in the intensive care unit.

BACKGROUND: Multiple interventions were made to optimize the medication process in our intensive care unit (ICU). 1 Transcriptions from the medical order form to the administration plan were eliminated by merging both into a single document; 2 the new form was built in a logical sequence and was highly structured to promote completeness and standardization of information; 3 frequently used drug names, approved units, and fixed routes were pre-printed; 4 physicians and nurses were trained with regard to the correct use of the new form. This study was aimed at evaluating the impact of these interventions on clinically significant types of medication errors. METHODS: Eight types of medication errors were measured by a prospective chart review before and after the interventions in the ICU of a public tertiary care hospital. We used an interrupted time-series design to control the secular trends. RESULTS: Over 85 days, 9298 lines of drug prescription and/or administration to 294 patients, corresponding to 754 patient-days were collected and analysed for the three series before and three series following the intervention. Global error rate decreased from 4.95 to 2.14% (-56.8%, P < 0.001). CONCLUSIONS: The safety of the medication process in our ICU was improved by simple and inexpensive interventions. In addition to the optimization of the prescription writing process, the documentation of intravenous preparation, and the scheduling of administration, the elimination of the transcription in combination with the training of users contributed to reducing errors and carried an interesting potential to increase safety.