An absolute sodium abundance for a cloud-free 'hot Saturn' exoplanet.

Broad absorption signatures from alkali metals, such as the sodium (Na I) and potassium (K I) resonance doublets, have long been predicted in the optical atmospheric spectra of cloud-free irradiated gas giant exoplanets1-3. However, observations have revealed only the narrow cores of these features rather than the full pressure-broadened profiles4-6. Cloud and haze opacity at the day-night planetary terminator are considered to be responsible for obscuring the absorption-line wings, which hinders constraints on absolute atmospheric abundances7-9. Here we report an optical transmission spectrum for the 'hot Saturn' exoplanet WASP-96b obtained with the Very Large Telescope, which exhibits the complete pressure-broadened profile of the sodium absorption feature. The spectrum is in excellent agreement with cloud-free, solar-abundance models assuming chemical equilibrium. We are able to measure a precise, absolute sodium abundance of logεNa = [Formula: see text], and use it as a proxy for the planet's atmospheric metallicity relative to the solar value (Zp/Zʘ = [Formula: see text]). This result is consistent with the mass-metallicity trend observed for Solar System planets and exoplanets10-12.

Gut Dysbiosis With Bacilli Dominance and Accumulation of Fermentation Products Precedes Late-onset Sepsis in Preterm Infants.

BACKGROUND: Gut dysbiosis has been suggested as a major risk factor for the development of late-onset sepsis (LOS), a main cause of mortality and morbidity in preterm infants. We aimed to assess specific signatures of the gut microbiome, including metabolic profiles, in preterm infants <34 weeks of gestation preceding LOS. METHODS: In a single-center cohort, fecal samples from preterm infants were prospectively collected during the period of highest vulnerability for LOS (days 7, 14, and 21 of life). Following 16S rRNA gene profiling, we assessed microbial community function using microbial metabolic network modeling. Data were adjusted for gestational age and use of probiotics. RESULTS: We studied stool samples from 71 preterm infants with LOS and 164 unaffected controls (no LOS/necrotizing enterocolitis). In most cases, the bacteria isolated in diagnostic blood culture corresponded to the genera in the gut microbiome. LOS cases had a decelerated development of microbial diversity. Before onset of disease, LOS cases had specific gut microbiome signatures with higher abundance of Bacilli (specifically coagulase-negative Staphylococci) and a lack of anaerobic bacteria. In silico modeling of bacterial community metabolism suggested accumulation of the fermentation products ethanol and formic acid in LOS cases before the onset of disease. CONCLUSIONS: Intestinal dysbiosis preceding LOS is characterized by an accumulation of Bacilli and their fermentation products and a paucity of anaerobic bacteria. Early microbiome and metabolic patterns may become a valuable biomarker to guide individualized prevention strategies of LOS in highly vulnerable populations.

Combined culture and metagenomic analyses reveal significant shifts in the composition of the cutaneous microbiome in psoriasis.

BACKGROUND: The treatment of psoriasis has been revolutionized by the development of biologic therapies. However, the pathogenesis of psoriasis, in particular the role of the cutaneous microbiome, remains incompletely understood. Moreover, skin microbiome studies have relied heavily on 16S rRNA sequencing data in the absence of bacterial culture. OBJECTIVES: To characterize and compare the cutaneous microbiome in 20 healthy controls and 23 patients with psoriasis using metagenomic analyses and to determine changes in the microbiome during treatment. METHODS: Swabs from lesional and nonlesional skin from patients with psoriasis, and from controls matched for site and skin microenvironment, were analysed using both 16S rRNA sequencing and traditional culture combined with mass spectrometry (MALDI-TOF) in a prospective study. RESULTS: Psoriasis was associated with an increased abundance of Firmicutes and a corresponding reduction in Actinobacteria, most marked in lesional skin, and at least partially reversed during systemic treatment. Shifts in bacterial community composition in lesional sites were reflected in similar changes in culturable bacteria, although changes in the microbiota over repeated swabbing were detectable only with sequencing. The composition of the microbial communities varied by skin site and microenvironment. Prevotella and Staphylococcus were significantly associated with lesional skin, and Anaerococcus and Propionibacterium with nonlesional skin. There were no significant differences in the amount of bacteria cultured from the skin of healthy controls and patients with psoriasis. CONCLUSIONS: Shifts in the cutaneous microbiome in psoriasis, particularly during treatment, may shed new light on the pathogenesis of the disease and may be clinically exploited to predict treatment response. What's already known about this topic? Alterations in the composition of the cutaneous microbiome have been described in psoriasis, although methodological differences in study design prevent direct comparison of results. To date, most cutaneous microbiome studies have focused on 16S rRNA sequencing data, including both living and dead bacteria. What does this study add? This prospective observational study confirms that changes in the composition of the cutaneous microbiome, detected by 16S rRNA sequencing, are consistent with those identified by bacterial culture and mass spectrometry. The changes in the microbiome during antipsoriasis therapy should be further investigated to determine whether these represent potential novel biomarkers of treatment response. What is the translational message? Characterization of cutaneous microbiota may ultimately move into the clinic to help facilitate treatment selection, not only by optimizing currently available treatments, but also by identifying new therapeutic targets.

Understanding Optimum Fluoride Intake from Population-Level Evidence.

Policy on fluoride intake involves balancing caries against dental fluorosis in populations. The origin of this balance lies with Dean's research on fluoride concentration in water supplies, caries, and fluorosis. Dean identified cut points in the Index of Dental Fluorosis of 0.4 and 0.6 as critical. These equate to 1.3 and 1.6 mg fluoride (F)/L. However, 1.0 mg F/L, initially called a permissible level, was adopted for fluoridation programs. McClure, in 1943, derived an "optimum" fluoride intake based on this permissible concentration. It was not until 1944 that Dean referred to this concentration as the "optimal" concentration. These were critical steps that have informed health authorities through to today. Several countries have derived toxicological estimates of an adequate and an upper level of intake of fluoride as an important nutrient. The US Institute of Medicine (IOM) in 1997 estimated an Adequate Intake (AI) of 0.05 mg F/kg bodyweight (bw)/d and a Tolerable Upper Intake Level (UL) of 0.10 mg F/kg bw/d. These have been widely promulgated. However, a conundrum has existed with estimates of actual fluoride intake that exceed the UL without the expected adverse fluorosis effects being observed. Both the AI and UL need review. Fluoride intake at an individual level should be interpreted to inform more nuanced guidelines for individual behavior. An "optimum" intake should be based on community perceptions of caries and fluorosis, while the ultimate test for fluoride intake is monitoring caries and fluorosis in populations.

Exploring the Balance between DNA Pressure and Capsid Stability in Herpesviruses and Phages.

UNLABELLED: We have recently shown in both herpesviruses and phages that packaged viral DNA creates a pressure of tens of atmospheres pushing against the interior capsid wall. For the first time, using differential scanning microcalorimetry, we directly measured the energy powering the release of pressurized DNA from the capsid. Furthermore, using a new calorimetric assay to accurately determine the temperature inducing DNA release, we found a direct influence of internal DNA pressure on the stability of the viral particle. We show that the balance of forces between the DNA pressure and capsid strength, required for DNA retention between rounds of infection, is conserved between evolutionarily diverse bacterial viruses (phages λ and P22), as well as a eukaryotic virus, human herpes simplex 1 (HSV-1). Our data also suggest that the portal vertex in these viruses is the weakest point in the overall capsid structure and presents the Achilles heel of the virus's stability. Comparison between these viral systems shows that viruses with higher DNA packing density (resulting in higher capsid pressure) have inherently stronger capsid structures, preventing spontaneous genome release prior to infection. This force balance is of key importance for viral survival and replication. Investigating the ways to disrupt this balance can lead to development of new mutation-resistant antivirals. IMPORTANCE: A virus can generally be described as a nucleic acid genome contained within a protective protein shell, called the capsid. For many double-stranded DNA viruses, confinement of the large DNA molecule within the small protein capsid results in an energetically stressed DNA state exerting tens of atmospheres of pressures on the inner capsid wall. We show that stability of viral particles (which directly relates to infectivity) is strongly influenced by the state of the packaged genome. Using scanning calorimetry on a bacterial virus (phage λ) as an experimental model system, we investigated the thermodynamics of genome release associated with destabilizing the viral particle. Furthermore, we compare the influence of tight genome confinement on the relative stability for diverse bacterial and eukaryotic viruses. These comparisons reveal an evolutionarily conserved force balance between the capsid stability and the density of the packaged genome.

Functional host-specific adaptation of the intestinal microbiome in hominids.

Fine-scale knowledge of the changes in composition and function of the human gut microbiome compared that of our closest relatives is critical for understanding the evolutionary processes underlying its developmental trajectory. To infer taxonomic and functional changes in the gut microbiome across hominids at different timescales, we perform high-resolution metagenomic-based analyzes of the fecal microbiome from over two hundred samples including diverse human populations, as well as wild-living chimpanzees, bonobos, and gorillas. We find human-associated taxa depleted within non-human apes and patterns of host-specific gut microbiota, suggesting the widespread acquisition of novel microbial clades along the evolutionary divergence of hosts. In contrast, we reveal multiple lines of evidence for a pervasive loss of diversity in human populations in correlation with a high Human Development Index, including evolutionarily conserved clades. Similarly, patterns of co-phylogeny between microbes and hosts are found to be disrupted in humans. Together with identifying individual microbial taxa and functional adaptations that correlate to host phylogeny, these findings offer insights into specific candidates playing a role in the diverging trajectories of the gut microbiome of hominids. We find that repeated horizontal gene transfer and gene loss, as well as the adaptation to transient microaerobic conditions appear to have played a role in the evolution of the human gut microbiome.

High-resolution entry and exit surface dosimetry in a 1.5 T MR-linac.

The magnetic field of a transverse MR-linac alters electron trajectories as the photon beam transits through materials, causing lower doses at flat entry surfaces and increased doses at flat beam-exiting surfaces. This study investigated the response of a MOSFET detector, known as the MOSkin™, for high-resolution surface and near-surface percentage depth dose measurements on an Elekta Unity. Simulations with Geant4 and the Monaco treatment planning system (TPS), and EBT-3 film measurements, were also performed for comparison. Measured MOSkin™ entry surface doses, relative to Dmax, were (9.9 ± 0.2)%, (10.1 ± 0.3)%, (11.3 ± 0.6)%, (12.9 ± 1.0)%, and (13.4 ± 1.0)% for 1 × 1 cm2, 3 × 3 cm2, 5 × 5 cm2, 10 × 10 cm2, and 22 × 22 cm2 fields, respectively. For the investigated fields, the maximum percent differences of Geant4, TPS, and film doses extrapolated and interpolated to a depth suitable for skin dose assessment at the beam entry, relative to MOSkin™ measurements at an equivalent depth were 1.0%, 2.8%, and 14.3%, respectively, and at a WED of 199.67 mm at the beam exit, 3.2%, 3.7% and 5.7%, respectively. The largest measured increase in exit dose, due to the electron return effect, was 15.4% for the 10 × 10 cm2 field size using the MOSkin™ and 17.9% for the 22 × 22 cm2 field size, using Geant4 calculations. The results presented in the study validate the suitability of the MOSkin™ detector for transverse MR-linac surface dosimetry.

[Assessment of a pharmaceutical interventional programme in patients on medications with renal risk]. / Evaluación de un programa de intervención farmacéutica en pacientes con medicamentos de riesgo renal.

OBJECTIVE: To compare the adaptation of medical prescriptions according to the dosage guides in patients with renal disease, before and after applying a pharmaceutical intervention programme. The secondary objectives were to prepare a guide to dosing in renal disease and to measure the prevalence of prescription of drugs with renal risk. METHOD: Non-randomised, experimental interventional study (before/after) conducted in a general hospital with 800 beds, including hospitalised patients, over the age of 18, with kidney disease and drugs with renal risk prescribed in their pharmacotherapeutic profile. The study was designed to be carried out in two descriptive cross-cutting phases (control group) and a prospective interventional cohort study (intervention group). The primary variable was the percentage non-adaptation according to the stage of renal disease. RESULTS: The study included 185 patients, 88 in the control group and 97 in the intervention group. In the intervention group, the prevalence of non-compliance before and after the intervention was 18.7 % and 2.1 %, representing a statistically significant reduction in non-adaptation of the dose. The costs saved with the pharmaceutical intervention programme were 1,939.63 euro over two months, the average saving per medication intervened amounting to 62.57 euro (CI 95 %, 23.99-101.14 euro; p = 0.02). CONCLUSIONS: The results of the study indicate that the application of a pharmaceutical care model based on the prospective validation of drugs with renal risk, very significantly improved the adaptation of dosing regimens in kidney disease.

The effect of sesamoid position on outcome following scarf osteotomy for hallux abducto valgus.

BACKGROUND: Hallux valgus is a common forefoot condition, with numerous operations described to correct the deformity. Debate remains as to the relative importance of correcting the position of the sesamoid apparatus. METHODS: Forty-six cases were reviewed. Preoperative and post-operative X-rays were used to measure forefoot width, inter-metatarsal angle (IM), hallux valgus (HV) angle and sesamoid position (Reynolds stations). Satisfaction was assessed via questionnaire. RESULTS: Significant improvements were seen in all radiological parameters. 37/43 patients were satisfied with the result. Comparison between the satisfied and non-satisfied group revealed significant differences in the IM angle (p<0.05) and HV angle (p<0.05). However, patient satisfaction was not associated with post-op sesamoid position or change in sesamoid position (p>0.05). CONCLUSIONS: This study showed that scarf osteotomy, can successfully correct hallux valgus, with high levels of satisfaction. Satisfaction is associated with a greater correction of deformity. Improvement in sesamoid position was not associated with patient satisfaction.

[Use and cost of biological disease-modifying anti-rheumatic drugs in Spain (PRAXIS study)]. / Utilización y coste de los modificadores biológicos de la artritis reumatoide en España (estudio PRAXIS).

OBJECTIVE: To analyse the use of health care resources and the associated costs in patients with rheumatoid arthritis (RA) treated with three biological disease-modifying anti-rheumatic drugs (bDMARDs): etanercept, infliximab and adalimumab. DESIGN: observational, retrospective, multicentre study. Length of study: 6 months. TARGET POPULATION: patients with RA, who have been undergoing treatment for at least one year. SCOPE: Spanish National Health System hospitals. Use of resources: review of the patient records of all patients included in the study by the Hospital Pharmacy Departments. Health care costs: the unit costs were obtained from Spanish databases; disease costs per patient were estimated from the use of resources results (euro in July 2006). Sensitivity analysis: univariate of base case. Budget impact analysis: replacement of infliximab and adalimumab by etanercept for three hospital populations. RESULTS: 1,111 patient records from 41 Spanish hospitals were reviewed, 432 patients were treated with etanercept, 396 were treated with infliximab and 283 with adalimumab. Mean doses: etanercept: 48.90 mg per week; infliximab: 4.14 mg/kg every 8 weeks; adalimumab: 41.58 mg every two weeks (97.8, 138 and 104% respectively, of recommended doses). Treatment with etanercept led to fewer costs. Compared to infliximab, six-monthly costs per patient were reduced with etanercept as follows: bDMARD treatment (232.23 euro), treatment failure (163.42 euro), consultations (54.88 euro), tests (22.52 euro) and costs associated to bDMARD administration (euro 474.42). The saving per patient treated with etanercept compared to infliximab for six months was 577.94 euro. With respect to adalimumab, the savings with etanercept were mainly related to bDMARDs (1,111.74 euro) and test costs (10.16 euro), obtaining a six-monthly saving of euro 906.68 per patient treated with etanercept. Sensitivity analysis confirmed the robustness of the base case in the majority of cases, with six-monthly savings of 395.79-644.32 euro per patient compared to infliximab and of 672.09-1.159.46 euro compared to adalimumab. Infliximab treatment was less expensive than etanercept and adalimumab treatment when taking into consideration the minimum possible number of doses of infliximab (3 doses for six months). Hospital budget savings could be obtained as a consequence of a reduction in costs due to use of etanercept, ranging from 14,500-231,100 euro when replacing infliximab with etanercept and from 22,600-362,600 euro when replacing adalimumab with etanercept, according to the hospital population included (50 to 200 patients). CONCLUSIONS: Our results showed that in most cases, the treatment of rheumatoid arthritis with etanercept compared to infliximab and adalimumab reduced hospital costs.

Evaluation of certain food additives and contaminants.

This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of various food additives, including flavouring agents, with a view to recommending acceptable daily intakes (ADIs) and to preparing specifications for identity and purity. The Committee also evaluated the risk posed by two food contaminants, with the aim of advising on risk management options for the purpose of public health protection. The first part of the report contains a general discussion of the principles governing the toxicological evaluation and assessment of intake of food additives (in particular flavouring agents) and contaminants. A summary follows of the Committee's evaluations of technical, toxicological and intake data for certain food additives (acidified sodium chlorite, asparaginase from Aspergillus oryzae expressed in Aspergillus oryzae, carrageenan and processed Eucheuma seaweed, cyclotetraglucose and cyclotetraglucose syrup, isoamylase from Pseudomonas amyloderamosa, magnesium sulfate, phospholipase A1 from Fusarium venenatum expressed in Aspergillus oryzae, sodium iron(III) ethylenediaminetetraacetic acid (EDTA) and steviol glycosides); eight groups of related flavouring agents (linear and branched-chain aliphatic, unsaturated, unconjugated alcohols, aldehydes, acids and related esters; aliphatic acyclic and alicyclic terpenoid tertiary alcohols and structurally related substances; simple aliphatic and aromatic sulfides and thiols; aliphatic acyclic dials, trials and related substances; aliphatic acetals; sulfur-containing heterocyclic compounds; aliphatic and aromatic amines and amides; and aliphatic alicyclic linear alpha, beta -unsaturated di- and trienals and related alcohols, acids and esters); and two food contaminants (aflatoxin and ochratoxin A). Specifications for the following food additives were revised: maltol and ethyl maltol, nisin preparation, pectins, polyvinyl alcohol, and sucrose esters of fatty acids. Specifications for the following flavouring agents were revised: maltol and ethyl maltol, maltyl isobutyrate, 3-acetyl-2,5-dimethylfuran and 2,4,5-trimethyl-delta-oxazoline (Nos 1482, 1506 and 1559), and monomenthyl glutarate (No. 1414), as well as the method of assay for the sodium salts of certain flavouring agents. Annexed to the report are tables summarizing the Committee's recommendations for intakes and toxicological evaluations of the food additives and contaminants considered.

Energy expenditure in free-living smokers and nonsmokers: comparison between factorial, intake-balance, and doubly labeled water measures.

Free-living energy expenditure (EE) was measured in 11 smokers (6 females, 5 males) and 10 nonsmokers (6 females, 4 males) by using three methods. Factorial measures (FEE) used measured basal metabolic rate (BMR), records of time spent in six activity categories over 28 d, and average published energy costs of activities. Intake-balance measures (IBEE) used recorded dietary energy intake and changes in energy stores over 28 d. Doubly labeled water measures (DLWEE) used a two-point method over 8-12 d. Level of activity (1.54 +/- 0.07 and 1.55 +/- 0.06 x BMR) and FEE (9573 +/- 1501 and 9540 +/- 1663 kJ/d) were not different between smokers and nonsmokers, respectively. DLWEE was higher than FEE in both smokers (25.9 +/- 13.5%, P < 0.001) and nonsmokers (10.4 +/- 13.8%, P < 0.05), suggesting factorial underestimation in both groups, although the difference between DLWEE and FEE was significantly greater in smokers than in nonsmokers (P < 0.02). IBEE was higher than FEE in smokers (7.5 +/- 10.1%, P < 0.05) but not different from FEE in nonsmokers (2.7 +/- 16.6%), suggesting factorial underestimation in smokers only. DLWEE was higher than IBEE in smokers (13.8 +/- 12.6%, P < 0.01) but not significantly different from IBEE in nonsmokers (6.2 +/- 16.0%). The discrepancies between DLWEE and IBEE in smokers and DLWEE and FEE in nonsmokers preclude conclusion about absolute levels of daily EE. However, both DLWEE-FEE and IBEE-FEE comparisons suggest that our factorial method underestimates free-living EE in smokers relative to nonsmokers, although the effect is larger with the DLWEE-FEE than with the IBEE-FEE comparison.

RNA secondary structure and compensatory evolution.

The classic concept of epistatic fitness interactions between genes has been extended to study interactions within gene regions, especially between nucleotides that are important in maintaining pre-mRNA/mRNA secondary structures. It is shown that the majority of linkage disequilibria found within the Drosophila Adh gene are likely to be caused by epistatic selection operating on RNA secondary structures. A recently proposed method of RNA secondary structure prediction based on DNA sequence comparisons is reviewed and applied to several types of RNAs, including tRNA, rRNA, and mRNA. The patterns of covariation in these RNAs are analyzed based on Kimura's compensatory evolution model. The results suggest that this model describes the substitution process in the pairing regions (helices) of RNA secondary structures well when the helices are evolutionarily conserved and thermodynamically stable, but fails in some other cases. Epistatic selection maintaining pre-mRNA/mRNA secondary structures is compared to weak selective forces that determine features such as base composition and synonymous codon usage. The relationships among these forces and their relative strengths are addressed. Finally, our mutagenesis experiments using the Drosophila Adh locus are reviewed. These experiments analyze long-range compensatory interactions between the 5' and 3' ends of Adh mRNA, the different constraints on secondary structures in introns and exons, and the possible role of secondary structures in RNA splicing.

Bis (2,3-dibromopropyl) phosphate nephrotoxicity: effect of sex and CoCl2 pretreatment.

Bis (2,3-dibromopropyl) phosphate (BIS-BP) is one of two identified metabolites of Tris (2,3-dibromopropyl) phosphate (TRIS-BP). We have previously shown that BIS-BP is more acutely nephrotoxic than TRIS-BP. We now report the effect of sex and inhibition of drug metabolism on BIS-BP toxicity. Compared to male rats, age-matched female rats developed less severe and extensive structural damage after BIS-BP. Renal dysfunction, as indexed by serum creatinine and in vitro renal cortical uptake of para-aminohippurate and N-(14C) methylnicotinamide was similar in males and females. Pretreatment of males with the drug metabolism inhibitor, cobaltous chloride, reduced both functional and structural evidence of BIS-BP toxicity. In separate studies, there was no difference in the distribution of radiolabel in male and female rats three days after administration of 14C-TRIS-BP. These studies showing that female rats are resistant to acute BIS-BP structural damage may explain the previously reported lack of carcinogenicity of TRIS-BP in female rats. The reduction of BIS-BP toxicity by CoCl2 suggests that unidentified, nephrotoxic metabolites exist and are responsible for part of the nephrotoxicity of BIS-BP.

The diversity and unity of Herpesviridae.

The family herpesviridae contains over 100 viruses endogenous to humans and to a wide variety of eukaryotic organisms. Inclusion in the family is based on architecture of the virion. The viruses differ significantly with respect to base composition and sequence arrangements of their DNAs, but share many biologic properties including the ability to remain latent in their hosts. On the basis of their biologic properties the herpesviruses have been classified into three subfamilies, i.e. alphaherpesvirinae, betaherpesvirinae and gammaherpesvirinae. The members of each subfamily share many properties including greater conservation and colinear arrangements of their genes. As a rule, more than one herpesvirus has been isolated from animals of economic importance and both humans have yielded viruses belong to all three subfamilies of the herpesviridae.

Radiological changes five years after unicompartmental knee replacement.

Failure of a unicompartmental knee replacement (UKR) may be caused by progressive osteoarthritis of the knee and/or failure of the prosthesis. Limb alignment can influence both of these factors. We have examined the fate of the other compartments and measured changes in leg alignment after UKR. A total of 50 UKRs was carried out on 45 carefully selected patients between 1989 and 1992. At operation, deliberate attempts were made to avoid overcorrection of the deformity. Four patients died, one patient was lost to follow-up and two knees were revised before review which was at a minimum of five years. Standard long-leg weight-bearing anteroposterior views of the knee and skyline views of the patellofemoral joint were taken before and at eight months and five years after operation. The radiographs of the remaining 43 knees were reviewed twice by blind and randomised assessment to measure the progression of osteoarthritis within the joints. Overcorrection of the deformity in the coronal plane was avoided in all but two knees. Only one showed evidence of progression of osteoarthritis within the patellofemoral joint, and this was only identified in one of the four assessments. Deterioration in the state of the opposite tibiofemoral compartment was not seen. Varus deformity tended to recur. Recurrent varus of 2 degrees was observed between eight months and five years after operation. There was no correlation between the postoperative tibiofemoral angle and the extent of recurrent varus recorded at five years. Changes in alignment may be indicative of minor polyethylene wear or of subsidence of the tibial component. The incidence of progressive osteoarthritis within the knee was very low after UKR. Patients should be carefully selected and overcorrection of the deformity be avoided.

[An analysis of patient information sheets for obtaining informed consent in clinical trials]. / Análisis de las hojas de información al paciente para la obtención de su consentimiento informado en ensayos clínicos.

BACKGROUND: The written information provided to the potential participants in a clinical trial must have certain qualitative and quantitative characteristics to reach the ethical requirements governing the theory of the informed consent. MATERIAL AND METHODS: In a sample of 101 clinical trial protocols approved in two Spanish university general hospitals, the following items were evaluated: a) the amount and quality of the written information given to the patient, in accordance with the established in the Spanish legislation; b) the formal readability of this written forms, by means of the Flesch method, and c) the level of complexity of the vocabulary, by means of the number of non-comprehensible words for two volunteers unaware of the health professions, with high studies. RESULTS: The balance of benefits and risks, the identification and the way of contact with the main investigator, the description of the alternative treatments and the specification of the compensations in case of lesions were the items with highest noncompliance. The mean global readability by means of the index of Flesch was of -12.7 (text with a high level of complexity). The mean percentage of words non-comprehensible for the volunteers that analyzed the texts was 0.3%. CONCLUSIONS: The written form of information provided to the patient in the clinical trials developed in Spain has serious deficiencies, either in their formal readability (complexity of the linguistic structure) or in the amount and quality of the information that provides. These deficiencies could have a wrong influence in the appropriate obtention of the informed consent from the patients.

[The participation of pharmacy services in evaluating parenteral nutrition programs]. / Participación de los Servicios de Farmacia en la valoración de los programas de nutrición parenteral.

The situation of parenteral nutrition practised in our hospital over one year was analyzed from the standpoint of Pharmacy Services, with a random sample of 26 patients with 322 days on parenteral nutrition. The most important results showed that the degree of compliance of the application sheets was 85.3%. The protocolized nutrient units were used in 80.1% of total days on parenteral nutrition, with an average of 0.97 +/- 0.60 modifications per day 855.0% electrolytes and 39.9% insulin). During the follow-up of parenteral nutrition, analytical determinations were performed every 2.3 +/- 1.8 and 4.2 +/- 2.6 days in blood and urine respectively. 30 biochemical alterations were observed, in particular hyperglycaemia (26.7%), hypoglycaemia (10%), hyperpotassemia (13.3%) and hyponatraemia (13.3%). In 70% of cases, corrective action was taken within 24 hours. The average number of multidisciplinary communications was 4.5 per patient. The initiative was taken by the pharmacist in 75.8% of cases, and the most frequent reason for communication was analysis of biochemical situation of patient and proposal for modification in daily intake.

[Pharmacokinetic interaction between valproic acid and carbapenem-like antibiotics: a discussion of three cases]. / Interacción farmacocinética entre ácido valproico y antibióticos carbapenémicos: descripción de tres casos.

A number of literature references suggest that carbapenem-like antibiotics decrease plasma concentrations of valproic acid in epileptic patients. This interaction may result in a recurrence of epileptic seizures in these patients. To clarify the possible mechanism of such carbapenem-valproic acid interaction several experimental studies have been carried out in animals. However, the mechanism of this drug-drug interaction is as yet uncertain. in this article we report three new cases that were observed in our hospital within three months. One of these patients developed seizures. We also review the different mechanisms proposed, as well as cases published to this day. All these data demonstrate that care should be taken in using these potent antibiotics in patients receiving valproic acid.

[Replacement therapy with protein C for meningococcal sepsis and fulminant purpura in pediatric patients]. / Tratamiento sustitutivo con proteína C en sepsis meningocócica y púrpura fulminante en pacientes pediátricos.

Disseminated intravascular coagulation as associated to sepsis contributes to the development of clinical multiple organ failure by extensive thrombosis in microcirculation vessels. This condition commonly manifests itself in severe meningococcal sepsis. On the skin, its clinical manifestation is extensive purpura with necrotic lesions that usually progress to serious distal ischemia and may call for amputation. A common denominator in these events regarding hemostasis is a depletion of so-called natural anticoagulant proteins, particularly protein C. According to clinical observations replacement therapy with human plasma-derived protein C concentrates has been associated with significantly improved clinical outcome in patients with meningococcal sepsis and fulminant purpura. This paper reports a case of acquired protein C deficiency in a girl with meningococcal sepsis, fulminant purpura, disseminated intravascular coagulation, and septic shock. Fresh plasma therapy was intended to increase consumption coagulopathy-depleted coagulation factors and to provide small amounts of protein C. The inability to restore protein C concentrations above 30%, and the presence of severe thrombopenia in the setting of disseminated intravascular coagulation led to the onset of replacement therapy using a human protein C concentrate (Ceprotin), which increased plasma protein C concentrations and contributed to revert the existing hypercoagulability status. Finally, evidence available in the literature regarding fulminant meningococcal sepsis management using human protein C concentrates and recombinant activated protein C is discussed.