[Interlevel incident management: The experience of a primary care district]. / Gestión de incidencias interniveles. La experiencia de un distrito de atención primaria.

AIM: Determine the prevalence and define the profile of interlevel incidences (ININ) between primary care (PC) and hospital (HC). DESIGN: Multicenter cross-sectional descriptive study. SITE: Primary care. PARTICIPANTS: Professionals from a Health District and its reference hospitals. INTERVENTIONS: ININ are errors in communication between PC and HC professionals derived from administrative, pharmaceutical or clinical procedures not resolved during the formal interlevel communication processes, which requires a coordinated and validated response from the health care directions to not overload the family physician. MAIN MEASUREMENTS: ININ by category, hospital services and health centers, total and validated, relative to the total number of referrals, and the reason for the ININ. RESULTS: We detected 2011 ININs (3.36%) among the 59.859 referrals, although only 1684 were validated (83.7%). Most were administrative (59.5%), followed by pharmaceutical (24.2%), clinical (10.2%) and reverse (6.1%). 41.3% of the clinical ININs were grouped around 5 hospital specialties, and 45.9% in 5 health centers. The main reasons for clinical ININ were non-prescription of the recommended pharmacological treatment in outpatient clinics or on hospital discharge (27.3%), request for referral to another hospital specialist (27.9%), or request to referral in person to patients who had already been referred by teleconsultation (17.8%). CONCLUSIONS: 3.36% of interlevel referrals are accompanied by incidents and 83.7% are validated and processed. It is necessary to develop ININ management tools to guarantee safe healthcare and debureaucratize PC.

Evaluation of hippuric acid content in goat milk as a marker of feeding regimen.

Organic producers, traders, and consumers must address 2 issues related to milk: authentication of the production system and nutritional differentiation. The presence of hippuric acid (HA) in goat milk samples has been proposed as a possible marker to differentiate the feeding regimen of goats. The objective of this work is to check the hypothesis that HA could be a marker for the type of feeding regimen of goats by studying the influence of production system (conventional or organic) and feeding regimen (with or without grazing fodder). With this purpose, commercial cow and goat milk samples (n=27) and raw goat milk samples (n=185; collected from different breeds, localizations, and dates) were analyzed. Samples were grouped according to breed, feeding regimen, production system, and origin to compare HA content by ANOVA and honestly significant difference Tukey test at a confidence level of ≥95%. Hippuric acid content was obtained by analyzing milk samples with capillary electrophoresis. This method was validated by analyzing part of the samples with HPLC as a reference technique. Sixty-nine raw goat milk samples (of the total 158 samples analyzed in this work) were quantified by capillary electrophoresis. In these samples, the lowest average content for HA was 7±3 mg/L. This value corresponds to a group of conventional raw milk samples from goats fed with compound feed. The highest value of this group was 28±10 mg/L, corresponding to goats fed compound feed plus grass. Conversely, for organic raw goat milk samples, the highest concentration was 67±14 mg/L, which corresponds to goats fed grass. By contrast, the lowest value of this organic group was 26±10 mg/L, which belongs to goats fed organic compounds. Notice that the highest HA average content was found in samples from grazing animals corresponding to the organic group. This result suggests that HA is a good marker to determine the type of goats feeding regimen; a high content of HA represents a diet based mainly or exclusively on eating green grass (grazing), independently of the production system. Hence, this marker would not be useful for the actual organic policies to distinguish organic milk under the current regulations, because organic dairy ruminants can be fed organic compound feed and conserved fodder without grazing at all.

Scale-free chaos in the confined Vicsek flocking model.

The Vicsek model encompasses the paradigm of active dry matter. Motivated by collective behavior of insects in swarms, we have studied finite-size effects and criticality in the three-dimensional, harmonically confined Vicsek model. We have discovered a phase transition that exists for appropriate noise and small confinement strength. On the critical line of confinement versus noise, swarms are in a state of scale-free chaos characterized by minimal correlation time, correlation length proportional to swarm size and topological data analysis. The critical line separates dispersed single clusters from confined multicluster swarms. Scale-free chaotic swarms occupy a compact region of space and comprise a recognizable "condensed" nucleus and particles leaving and entering it. Susceptibility, correlation length, dynamic correlation function, and largest Lyapunov exponent obey power laws. The critical line and a narrow criticality region close to it move simultaneously to zero confinement strength for infinitely many particles. At the end of the first chaotic window of confinement, there is another phase transition to infinitely dense clusters of finite size that may be termed flocking black holes.

Communication gaps in knowledge of freshwater fish biodiversity: implications for the management and conservation of Mexican biosphere reserves.

To detect differences in the information available on freshwater fish species found in Mexican biosphere reserves, the number of species considered in three sources of information: management programmes, Global Biodiversity Information Facility (GBIF) and the scientific literature were compared. Additionally, management actions for the reserves were evaluated. More than 55% of freshwater fish species registered for the reserves were found only in one of the three sources of information, while just 12% was shared among all the three. Fifteen threatened species were registered in GBIF and the scientific literature that were not found in management programmes. Although all the management programmes described conservation actions, none of them gave details about how they would be implemented. Lack of communication among the sources studied, unawareness of the existence of threatened species and the absence of detailed management actions hinder the development of adequate conservation strategies.

CT differentiation of fat-poor angiomyolipomas from papillary renal cell carcinomas: development of a predictive model.

PURPOSE: To identify specific contrast-enhanced CT (CECT) findings and develop a predictive model with logistic regression to differentiate fat-poor angiomyolipomas (fpAML) from papillary renal cell carcinomas (pRCC). METHODS: This is a single-institution retrospective study that assess CT features of histologically proven 67 pRCC and 13 fpAML. CECT variables were studied by means of univariate logistic regression. Variables included patients' demographics, tumor attenuation (unenhanced and at arterial, venous and excretory post-contrast phases), type of enhancement, morphological features (axial long and short diameters, long-short axis ratio (LSR) and tumor to kidney angle interface) and presence of visible calcifications or vessels. Those variables with a p ≤ 0.05 underwent standard stepwise logistic regression to find predictive combinations of clinical variables. Best models were evaluated by AUROC curves and were subjected to Leave-one-out cross validation to assess their robustness. RESULTS: Odds ratio (OR) between pRCC and fpAML was statistically significant for patient's gender, tumor attenuation in arterial, venous and excretory phases, tumor's long diameter, short diameter, LSR, type of enhancement, presence of intratumoral vessels and tumor-kidney angle interface. The best predictive model resulted in an area under the curve (AUC) of 0.971 and included gender, tumor-kidney angle interface and venous attenuation with the following equation: Log(p/1 - p) = - 2.834 + 4.052 * gender + - 0.066 * AngleInterface + 0.074 * VenousphaseHU. CONCLUSIONS: The combination of patients' gender, tumor to kidney angle interface and venous enhancement helps to distinguish fpAML from pRCC.

The association of host age and gender with inflammation around neurocysticercosis cysts.

The results of previous investigations indicate that age and gender may influence the strength of the human host's immune response to infection of the central nervous system with the larvae of Taenia solium. Most of the relevant research on such neurocysticercosis (NCC) has, however, been conducted on hospital-based samples in developing countries, where differential access to healthcare may bias the study results. Using data from 171 NCC patients participating in a treatment trial, the associations of patient age and gender with the presence of inflammation around NCC cysts (i.e. cysts in the transitional phase) have recently been explored, after controlling for measures of economic and geographical access to healthcare. Data on cysts were collected from computed-tomography or magnetic-resonance images taken at four time-points, from baseline to 12-months post-treatment. The odds of having transitional cysts were evaluated by logistic regression whereas Poisson regression was used to explore the numbers of transitional cysts, with generalised estimating equations (GEE) used to account for the multiple observations over time. After controlling for healthcare access, the odds of having transitional cysts were found to be 1.5-fold higher for the female patients than for the male, although this association was not statistically significant (P = 0.136). In the Poisson model, however, the number of transitional cysts was found to be 1.8-fold higher in the female patients than in the male, and this gender effect was not only statistically significant (P = 0.002) but also constant over time. The association of host age with transitional cysts was more complicated, with significant interaction between age and time. It therefore appears that there are significant gender and age differences in the local immune response to NCC, even after adjusting for differences in healthcare access.

[Effectiveness of a Decalogue for cardiovascular prevention in diabetics]. / Efectividad del Decálogo de prevención cardiovascular en diabéticos.

INTRODUCTION: To assess the effects of a visual Decalogue aid on the degree of knowledge, control perception and improvement in cardiovascular risk factors (CVRF). MATERIAL AND METHODS: A Primary care randomised non-pharmacological trial of an educational intervention with a parallel control group, and blind evaluation in type 2 diabetic patients. Both groups received an educational intervention on the management of CVRF. The intervention group also received a visual Decalogue aid that showed the level of control patients have over the modifiable CVRF. A total of 50 patients were included in each group in order to identify an improvement of 50% in the multifactorial knowledge of CVRF. All patients received a reminder telephone call at 2 months, with masked evaluation of knowledge and CVRF control perception. In a 6 months visit the level of knowledge and real control of CVRF were re-evaluated. RESULTS: The study included 51 males and 49 females, with mean age of 62.9 years, a mean disease duration of 9.2 years, and low educational level. The level of knowledge, control perception, and real control at baseline was 55%, 80.4%, and 65.9%, respectively. After 2 months the level of knowledge in the Decalogue group increased by 16.5% more than in the conventional education group (73.6% vs. 63.2%; P<.05) and the overestimated control perception improved by 34.5% (P<.001) with no differences between groups, although concordance was better in the Decalogue group. At 6 months there was an overall increase 25.6% (P<.001) in the level of knowledge, with the previous difference between groups levelling off. The final CVRF control improved overall and in the Decalogue group by 6.4% (P<.005) and 9.4% (P<.001), respectively. The SCORE risk significantly decreased overall with no differences between groups. CONCLUSIONS: The educational intervention improves the overall level of knowledge, perception and control of CVRF. The CVRF Decalogue quickly increases the level of knowledge, and decreases the false subjective risk control perception. The benefit, however, becomes equal at 6 months with ongoing education interventions.

Effects of albendazole treatment on neurocysticercosis: a randomised controlled trial.

AIM: The aim of this trial was to evaluate the effects of albendazole (ALB) on cyst disappearance, reduction of the number of cysts and seizure recurrence. METHODS: 178 patients with new onset symptoms due to active or transitional neurocysticercosis were randomly assigned to receive either 800 mg of ALB daily or placebo for 8 days. All patients also received prednisone. Imaging studies were done at baseline and at months 1, 6 and 12 of follow-up. RESULTS: Active cysts were identified in 59 of 88 people randomised to ALB and 57 of the 90 in the placebo arm. By 1 month, 31% were free of active cysts in the treatment group compared with 7% in the placebo group (p = 0.001). In addition, the ALB group had a greater reduction in the number of active cysts compared with the placebo group (p = 0.001). After 1 month following treatment there was no additional gain by treatment group in the disappearance or reduction in the number of active cysts. ALB treatment had little effect on cysts in the transitional or calcification stage. We found no difference between the ALB and placebo groups in symptoms during treatment or in seizure recurrence during the 12 months after treatment. CONCLUSION: Albendazole plus symptomatic treatment leads to the disappearance of active cysts in 31% of patients compared with 7% of those with symptomatic treatment alone. This treatment effect occurs within the first 30 days after treatment. TRIAL REGISTRATION NUMBER: NCT00283699.

[Thyrotropin reference ranges during pregnancy in the province of Huelva, Spain]. / Intervalos de referencia de la tirotropina durante la gestación en la provincia de Huelva.

OBJECTIVE: The correct diagnosis of hypothyroidism during pregnancy requires knowledge of the local trimester-specific thyrotropin (TSH) reference ranges. When these are not available, the guidelines recommend upper limits of 2.5, 3.0, and 3.0µU/ml for the 1st, 2nd, and 3rd trimesters, respectively. The aim is to establish the reference range for our local population. MATERIAL AND METHODS: A population-based observational study was performed on healthy pregnant women from 11 healthcare centres in the province of Huelva. Women were recruited consecutively during 2016 through the pregnancy process. Women were excluded who had a history of thyroid or medical disease, a poor obstetric history, multiple pregnancy, thyroid autoimmunity, and extreme TSH values (<0.4µU/ml or>10µU/ml), as well as women treated with levothyroxine for thyroid dysfunction. RESULTS: The study included a total of 186 pregnant women, with a mean age of 30.7 years (95% CI: 29.8-31.6) and a body mass index (BMI) of 23.6 (95% CI: 23.2-24.0). Most of them had the first laboratory tests performed before week 11 of pregnancy. Valid subjects for analysis were 145, 105, and 67 pregnant women in the 1st, 2nd, and 3rd trimesters, respectively, after excluding those due to abortion (18.9%), autoimmunity (6.5%), hypo/hyperthyroidism (2.2%), and levothyroxine treatment during the 2nd/3rd trimester (18.6%). The 97.5% TSH percentile for the 1st, 2nd, and 3rd trimester was 4.68, 4.83, and 4.57µU/ml, respectively. Thyroid dysfunction was identified in 80 women (55.2%), 33 of whom received treatment with Levothyroxine (22.7%). With the new criteria, thyroid dysfunction prevalence would be reduced to 6.2%, and the need for treatment to 4.1%. CONCLUSION: The reference range for TSH in our population differs from that proposed by the guidelines. Unnecessary treatment was being given to 18.6% of pregnant women.

Development of a QuEChERS-based extraction method for the determination of destruxins in potato plants by UHPLC-MS/MS.

Ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) with electrospray ionization has been proposed for the determination of fifteen natural destruxins (A, B, C, D, E, Ed, Ed1, A2, B2, D2, E2, Cl, DesmA, DesmB, and DH-A), secondary metabolites with insecticidal and phytotoxic activities produced by Metarhizium species fungus, which are being studied as biological agents in pest control. Therefore, procedures to control them in the food chain are required, starting with crops. As a consequence, in this study, a simple QuEChERS-based destruxin (dtx) extraction procedure has been developed and validated in four different parts of potato plant (tuber, root, stem and leaves) for the first time. For dtx A, the limits of detection obtained, ranged between 0.5 and 1.3 µg/kg, and for quantification, ranged between 1.7 and 4.2 µg/kg. Precision values were below 8.5%; and in all cases, recoveries were higher than 91%. Finally, the method has been applied in potato samples inoculated by EAMa 01/58-Su strain, where dtxs A and B were detected and quantified. In all cases, dtx B concentration was higher than dtx A.

Asymptotic construction of pulses in the discrete Hodgkin-Huxley model for myelinated nerves.

A quantitative description of pulses and wave trains in the spatially discrete Hodgkin-Huxley model for myelinated nerves is given. Predictions of the shape and speed of the waves and the thresholds for propagation failure are obtained. Our asymptotic predictions agree quite well with numerical solutions of the model and describe wave patterns generated by repeated firing at a boundary.

Igniting homogeneous nucleation.

Transient homogeneous nucleation is studied in the limit of large critical sizes. Starting from pure monomers, three eras of transient nucleation are characterized in the classic Becker-Döring kinetic equations with two different models of discrete diffusivity: the classic Turnbull-Fisher formula and an expression describing thermally driven growth of the nucleus. The latter diffusivity yields time lags for nucleation which are much closer to values measured in experiments with disilicate glasses. After an initial stage in which the number of monomers decreases, many clusters of small size are produced and a continuous size distribution is created. During the second era, nucleii are increasing steadily in size in such a way that their distribution appears as a wave front advancing towards the critical size for steady nucleation. The nucleation rate at critical size is negligible during this era. After the wave front reaches critical size, it ignites the creation of supercritical clusters at a rate that increases monotonically until its steady value is reached. Analytical formulas for the transient nucleation rate and the time lag are obtained that improve classical ones and compare very well with direct numerical solutions.

Is the course of neurocysticercosis modified by treatment with antihelminthic agents?

BACKGROUND: Neurocysticercosis, occasionally associated with long-term neurologic sequelae such as epilepsy or hydrocephalus, is more often a condition characterized by a benign course and spontaneous remission without permanent neurologic symptoms. This variability in outcome has led to difficulties in the interpretation of studies of the effectiveness of drugs used to treat this condition. OBJECTIVE: To evaluate the relative efficacy of two antihelminthic agents against each other and against symptomatic treatment alone. METHODS: Randomized clinical trial of treatment of patients with newly identified active neurocysticercosis with oral prednisolone alone (27 patients), praziquantel with prednisolone (54 patients), or albendazole with prednisolone (57 patients). RESULTS: At 6 months and at 1 year after treatment, there were no differences in the three treatment groups in terms of the proportion of patients who were free of cysts or the relative reduction of number of cysts. At 2 years, there was no difference in the proportion of patients free of seizures during the entire follow-up period. Early and late sequelae occurred in a higher proportion of patients treated with praziquantel and albendazole, compared with those receiving only prednisolone. CONCLUSIONS: Previous reports of favorable response to treatment of neurocysticercosis with either praziquantel or albendazole are by no means definitive and may be a reflection of the natural history of the condition. The present study, with randomized treatment assignment and including a control group, raises questions as to what extent and in whom treatment with these drugs is effective, and suggests that treatment with antihelminthic agents may be associated with an increased frequency of long-term sequelae.

Theory of force-extension curves for modular proteins and DNA hairpins.

We study a model describing the force-extension curves of modular proteins, nucleic acids, and other biomolecules made out of several single units or modules. At a mesoscopic level of description, the configuration of the system is given by the elongations of each of the units. The system free energy includes a double-well potential for each unit and an elastic nearest-neighbor interaction between them. Minimizing the free energy yields the system equilibrium properties whereas its dynamics is given by (overdamped) Langevin equations for the elongations, in which friction and noise amplitude are related by the fluctuation-dissipation theorem. Our results, both for the equilibrium and the dynamical situations, include analytical and numerical descriptions of the system force-extension curves under force or length control and agree very well with actual experiments in biomolecules. Our conclusions also apply to other physical systems comprising a number of metastable units, such as storage systems or semiconductor superlattices.

Differential growth of wrinkled biofilms.

Biofilms are antibiotic-resistant bacterial aggregates that grow on moist surfaces and can trigger hospital-acquired infections. They provide a classical example in biology where the dynamics of cellular communities may be observed and studied. Gene expression regulates cell division and differentiation, which affect the biofilm architecture. Mechanical and chemical processes shape the resulting structure. We gain insight into the interplay between cellular and mechanical processes during biofilm development on air-agar interfaces by means of a hybrid model. Cellular behavior is governed by stochastic rules informed by a cascade of concentration fields for nutrients, waste, and autoinducers. Cellular differentiation and death alter the structure and the mechanical properties of the biofilm, which is deformed according to Föppl-Von Kármán equations informed by cellular processes and the interaction with the substratum. Stiffness gradients due to growth and swelling produce wrinkle branching. We are able to reproduce wrinkled structures often formed by biofilms on air-agar interfaces, as well as spatial distributions of differentiated cells commonly observed with B. subtilis.

Comparison of intravenous flecainide, propafenone, and amiodarone for conversion of acute atrial fibrillation to sinus rhythm.

In a prospective, single-blind trial, we randomized 150 consecutive symptomatic patients with acute (< or = 48 hours' duration) atrial fibrillation to receive intravenous flecainide, propafenone, or amiodarone. Flecainide and propafenone were administered as a bolus dose of 2 mg/kg in 20 minutes. A second bolus dose of 1 mg/kg in 20 minutes was administered if conversion to sinus rhythm was not achieved after 8 hours. Amiodarone was administered as a bolus of 5 mg/kg in 20 minutes followed by a continuous infusion of 50 mg/hour. By the end of a 12-hour observation period, conversion to sinus rhythm was achieved in 45 patients (90%) in the flecainide group, 36 (72%) in the propafenone group, and 32 (64%) in the amiodarone group (p = 0.008 for the overall comparison, p = 0.002 for flecainide vs amiodarone, p = 0.022 for flecainide vs propafenone, and p = 0.39 for propafenone vs amiodarone). When compared with amiodarone, this higher reversion rate with flecainide was present from the first hour of the study period. However, only after administering the second bolus was there a significant difference between flecainide and propafenone. Median time to conversion to sinus rhythm was different among groups (p < 0.001), and it was lower in the flecainide (25 minutes; range 4 to 660) and propafenone (30 minutes; range 10 to 660) groups than in the amiodarone group (333 minutes; range 15 to 710; p < 0.001 for both comparisons). Flecainide, at the doses administered in this study, is more effective than propafenone and amiodarone for conversion of acute atrial fibrillation to sinus rhythm. Propafenone and amiodarone have similar conversion rates, although propafenone was faster in achieving the conversion to sinus rhythm.

Case-control study of seropositivity for cysticercosis in Cuenca, Ecuador.

The prevalence of neurocysticercosis has been well documented in rural communities in Latin America using the enzyme-linked inmmunoelectrotransfer blot (EITB) assay. We studied the prevalence of neurocysticercosis in an urban, upper-middle class population in Cuenca, Ecuador. Family members of 34 index cases with parenchymal neurocysticercosis on a computed tomography (CT) scan and family members of 14 patients who had normal CT scans after a trauma or migraine were enrolled in the study. Serum was obtained from 226 individuals, 173 (72%) from the case families and 67 (28%) from the control families. Twelve percent of the case family members and 4% of the control family members were seropositive by the EITB assay. This was a statistically significant difference (P < 0.05) when age and education were held constant by logistic regression. Seropositivity was not related to age. No neurologic symptom proved predictive of serostatus and the only demographic variable that correlated with seropositivity was increased crowding. Positive serology in index cases did correlate with CT findings as follows: 86% of patients with active lesions, 67% with transitional lesions, and only 41% of patients with inactive lesions were positive by the EITB assay. Eighteen percent of family members with a positive EITB test result had parenchymal lesions on a subsequent CT scan. This study demonstrates a high rate of seropositivity of cysticercosis among urban, middle to upper-middle class individuals in a region endemic for Taenia solium. Household contacts of patients with neurocysticercosis had a three-fold higher risk of positive serology for cysticercosis, in comparison with controls.

A proposal for classification of neurocysticercosis.

The complicated pathophysiological and immunological changes in the central nervous system of patients with neurocysticercosis produce a variety of signs and symptoms, which complicate the clinical and surgical management of this disease. A complete and objective classification is needed, to improve the medical approach as a whole. We studied 336 patients, in whom we classified neurocysticerosis according to criteria of viability and location of the parasite in the CNS: active form (37.2%) when the cysticercus is alive, transitional form (32.8%) when it is in the degenerative phase, and inactive form (30%) when the parasite is dead. This classification establishes the correlation between the different forms of neurocysticerosis and its clinical manifestations, and can be used for planning therapeutic strategies.

Nonlinear stability of oscillatory wave fronts in chains of coupled oscillators.

We present a stability theory for kink propagation in chains of coupled oscillators and a different algorithm for the numerical study of kink dynamics. The numerical solutions are computed using an equivalent integral equation instead of a system of differential equations. This avoids uncertainty about the impact of artificial boundary conditions and discretization in time. Stability results also follow from the integral version. Stable kinks have a monotone leading edge and move with a velocity larger than a critical value which depends on the damping strength.

Oscillatory wave fronts in chains of coupled nonlinear oscillators.

Wave front pinning and propagation in damped chains of coupled oscillators are studied. There are two important thresholds for an applied constant stress F: for |F|F(cs) (static Peierls stress) there are only stable moving wave fronts. For piecewise linear models, extending an exact method of Atkinson and Cabrera's to chains with damped dynamics corroborates this description. For smooth nonlinearities, an approximate analytical description is found by means of the active point theory. Generically for small or zero damping, stable wave front profiles are nonmonotone and become wavy (oscillatory) in one of their tails.