Relationship between spatiotemporal parameters and clinical outcomes in children with bilateral spastic cerebral palsy: Clinical interpretation proposal.

BACKGROUND: Understanding the links between gait disorders, impairments, and activity limitations is essential for correctly interpreting the instrumented gait analysis. We aimed to evaluate the relationships between spatiotemporal parameters and clinical outcomes in children with bilateral spastic cerebral palsy, and find out whether spatiotemporal parameters provide clinical information regarding gait pattern and walking. METHODS: Data from 19 children with bilateral spastic cerebral palsy (nine males, ten females, 9.6 ± 2.8 years old) were collected retrospectively. All children underwent an instrumented gait analysis and a standardized clinical assessment. Seven spatiotemporal parameters were calculated: non-dimensional cadence, stride length, step width, gait speed, first double support, single support, and time of toe off. Clinical outcomes included measures of two different components of the International Classification of Functioning, Disability and Health - Children and Youth version: body functions and structures (spasticity, contractures and range of motion, and deformities), and activities and participation (gross motor function, and walking capacity). Pearson correlation, ANOVA, Student's t, Mann-Whitney U, and Kruskal-Wallis tests were used to analyze relationships. Spatiotemporal parameters related to clinical outcomes of body functions and structures were interpreted as outcome measures of gait pattern, while those related to clinical outcomes of activities and participation were interpreted as outcome measures of walking. RESULTS: Non-dimensional cadence, stride length, and gait speed showed relationships (p < 0.05) with hip flexors spasticity and hindfoot deformity, ankle plantar flexors spasticity, and hindfoot deformity, respectively. All spatiotemporal parameters except non-dimensional cadence showed correlation (p < 0.05) with gross motor function and walking capacity. CONCLUSIONS: Spatiotemporal parameters provide clinical information regarding both gait pattern and walking.

Correction: Developing an assistive technology usability questionnaire for people with neurological diseases.

[This corrects the article DOI: 10.1371/journal.pone.0281197.].

Developing an assistive technology usability questionnaire for people with neurological diseases.

PURPOSE: This study describes the development of a questionnaire for assessing the usability of assistive technologies accessible to people with neurological diseases. METHODS: A Delphi study was conducted to identify relevant items for the questionnaire. After that, the content validity was addressed to identify the essential items. Once the questionnaire was designed following the results of the Delphi study and content validity, the reliability, validity, and the Rasch model of the questionnaire were examined. RESULTS: Two rounds of the Delphi study were carried out. A total of 73 participants (42 experts and 31 users) participated in round 1, and 59 people (27 experts and 32 users) in round 2. A total of 53 and 29 items were identified in rounds 1 and 2, respectively. In the content validity, we found nine items above the threshold of 0.58. Finally, ten items were included in the questionnaire. Fifty-one participants participate in the reliability and validity of the questionnaire. The internal consistency reliability of the questionnaire analyzed by Cronbach's Alpha was α = 0,895. There was moderate to considerable concordance among our questionnaire items test-retest in the Kappa coefficient and a strong association between test-retest in the Spearman's coefficient ρ = 0.818 (p<0,001). The intraclass correlation coefficient was 0,869 with a 95% confidence interval (0,781;0,923). There was a strong correlation between the total scores of the new questionnaire and other validated questionnaires analyzed with Spearman's coefficient ρ = 0.756 (p<0,001). The ten items demonstrated a satisfactory fit to the Rasch model. CONCLUSIONS: The present study suggested that the new questionnaire is a reliable 10-item usability questionnaire that allows subjective and quick assessment of the usability of assistive technologies by people with neurological diseases.

Transcutaneous Cervical Spinal Cord Stimulation Combined with Robotic Exoskeleton Rehabilitation for the Upper Limbs in Subjects with Cervical SCI: Clinical Trial.

(1) Background: Restoring arm and hand function is a priority for individuals with cervical spinal cord injury (cSCI) for independence and quality of life. Transcutaneous spinal cord stimulation (tSCS) promotes the upper extremity (UE) motor function when applied at the cervical region. The aim of the study was to determine the effects of cervical tSCS, combined with an exoskeleton, on motor strength and functionality of UE in subjects with cSCI. (2) Methods: twenty-two subjects participated in the randomized mix of parallel-group and crossover clinical trial, consisting of an intervention group (n = 15; tSCS exoskeleton) and a control group (n = 14; exoskeleton). The assessment was carried out at baseline, after the last session, and two weeks after the last session. We assessed graded redefined assessment of strength, sensibility, and prehension (GRASSP), box and block test (BBT), spinal cord independence measure III (SCIM-III), maximal voluntary contraction (MVC), ASIA impairment scale (AIS), and WhoQol-Bref; (3) Results: GRASSP, BBT, SCIM III, cylindrical grip force and AIS motor score showed significant improvement in both groups (p ≤ 0.05), however, it was significantly higher in the intervention group than the control group for GRASSP strength, and GRASSP prehension ability (p ≤ 0.05); (4) Conclusion: our findings show potential advantages of the combination of cervical tSCS with an exoskeleton to optimize the outcome for UE.

To what extent the traffic restriction policies applied in Barcelona city can improve its air quality?

Barcelona city (Spain) is applying a series of traffic restriction measures that aim at renewing and reducing the amount of circulating vehicles to improve air quality. The measures include changes in the built environment to reduce private vehicle space in specific areas through the so-called "superblocks" and tactical urban planning actions, along with the implementation of a city-wide Low Emission Zone (LEZ) that restricts the entry of the most polluting vehicles to the city. Our study quantifies the impact of these measures in the greater area of Barcelona combining a coupled macroscopic traffic and pollutant emission model with a multi-scale air quality model. Our modelling system allows estimating the effect of different traffic restrictions upon traffic and the associated emissions and air quality levels at a very high resolution (20 m). The measures were evaluated both individually and collectively to assess both their relative and overall impact upon emissions and air quality. We show that in the absence of traffic demand reductions, the application of isolated measures that reduce private vehicle space, either through superblocks or tactical urban planning, have no overall emission impacts; only localized street-level NOx positive and negative changes (±17%) are found due to traffic re-routing and the generation of new bottlenecks. It is only when these measures are combined with optimistic fleet renewal as a result of the LEZ implementation and demand reductions, that relevant global emission reductions in NOx are obtained (-13% and -30%, respectively) with estimated NO2 reductions of -36% and -23% at the two traffic air quality monitoring stations. Despite the potential improvements, our simulations suggest that current measures are insufficient to comply with EU air quality standards and that further traffic restriction policies to reduce traffic demand are needed.

Gait event detection using kinematic data in children with bilateral spastic cerebral palsy.

BACKGROUND: Ground reaction forces are the gold standard for detecting gait events, but they are not always applicable in cerebral palsy. Ghoussayni's algorithm is an event detection method based on the sagittal plane velocity of heel and toe markers. We aimed to evaluate whether Ghoussayni's algorithm, using two different thresholds, was a valid event detection method in children with bilateral spastic cerebral palsy. We also aimed to define a new adaptation of Ghoussayni's algorithm for detecting foot strike in cerebral palsy, and study the effect of event detection methods on spatiotemporal parameters. METHODS: Synchronized kinematic and kinetic data were collected retrospectively from 16 children with bilateral spastic cerebral palsy (7 males and 9 females; age 8.9 ± 2.7 years) walking barefoot at self-selected speed. Gait events were detected using methods: 1) ground reaction forces, 2) Ghoussayni's algorithm with a threshold of 0.5 m/s, and 3) Ghoussayni's algorithm with a walking speed dependent threshold. The new adaptation distinguished how foot strikes were performed (heel and/or toe) comparing the timing when the foot markers velocities fell below the threshold. Differences between the three methods, and between spatiotemporal parameters calculated from the two Ghoussayni's thresholds were analyzed. FINDINGS: There were statistically significant (P < 0.05) differences between methods 1 and 3, and between some spatiotemporal parameters calculated from methods 2 and 3. Ghoussayni's algorithm showed better performance for foot strike than for toe off. INTERPRETATION: Ghoussayni's algorithm using 0.5 m/s is valid in children with bilateral spastic cerebral palsy. Event detection methods affect spatiotemporal parameters.

Walking speed as a predictor of community mobility and quality of life after stroke.

Background: Community mobility (CM) is considered a part of community reintegration that enhances Quality of Life (QoL). Achieving an appropriate gait speed is essential in attaining an independent outdoor ambulation and satisfactory CM. Objective: The aim of this study was to identify whether gait speed is a predictor of CM and QoL in patients with stroke following a multimodal rehabilitation program (MRP). Methods: This was a baseline control trial with 6-months follow-up in an outpatient rehabilitation setting at a university hospital. Twenty-six stroke survivors completed the MRP (24 sessions, 2 days/wk, 1 hr/session). The MRP consisted of aerobic exercise, task-oriented exercises, balance exercises and stretching. Participants also performed an ambulation program at home. Outcome variables were: walking speed (10-m walking test) and QoL (physical and psychosocial domains of Euroquol and Sickness Impact Profile). Results: At the end of the intervention, comfortable and fast walking speed increased by an average of 0.16 (SD 0.21) (*p < .05) and 0.40 (SD 0.51) (**p < .001) m/s, respectively. After the intervention, all participants achieved independent outdoor ambulation with an increase of 34.14 of walking minutes/day in the community and a decrease of sitting time of 95.45 minutes/day. Regarding QoL there were increased mean scores on the physical and psychosocial dimensions of Euroquol and the Sickness Impact Profile, respectively (**p < .001). Conclusions: The results suggest that improved walking speed after the MRP is associated with CM and higher scores in QoL. These findings support the need to implement rehabilitation programs to promote increased speed.

Rapid Influenza Testing in Infants and Children Younger than 6 Years in Primary Care: Impact on Antibiotic Treatment and Use of Health Services.

Influenza is often misdiagnosed in children because of the low sensitivity of clinical diagnosis because of nonspecific signs and symptoms. This can be overcome by using digital immunoassays or rapid molecular diagnostic tests with adequate sensitivity and specificity. When using these tests at the patient care site, antibiotic consumption and number of healthcare consultations were reduced.

Optimal design of clinical trials with computer simulation based on results of earlier trials, illustrated with a lipodystrophy trial in HIV patients.

The designer of a clinical trial needs to make many assumptions about real-life practice based on prior knowledge. Simulation allows us to learn from experience by using the information obtained from a trial to improve the original estimators of population parameters. We propose using data from a previous trial to formulate assumptions that can be used to simulate trials and thus improve the design of new trials. To demonstrate our method, we used data from a real clinical trial which had been designed to evaluate cholesterol level changes as a surrogate marker for lipodystrophy in HIV patients. We were able to identify the optimal design that would have minimised the cost of a trial subject to a statistical power constraint which could then be used to design a new trial. In particular, we focused on three factors: the distribution of cholesterol levels in HIV patients, trial recruitment rates and trial dropout rates. We were able to verify our hypothesis that the total cost resulting from carrying out a clinical trial can be minimised by applying simulation models as an alternative to conventional approaches. In our findings the simulation model proved to be very intuitive and a useful method for testing the performance of investigators' assumptions and generating an optimal clinical trial design before being put into practice in the real world. In addition, we concluded that simulation models provide a more accurate determination of power than conventional approaches, thus minimising the total cost of clinical trials.

Clinical trial optimization: Monte Carlo simulation Markov model for planning clinical trials recruitment.

INTRODUCTION: The patient recruitment process of clinical trials is an essential element which needs to be designed properly. METHODS: In this paper we describe different simulation models under continuous and discrete time assumptions for the design of recruitment in clinical trials. RESULTS: The results of hypothetical examples of clinical trial recruitments are presented. The recruitment time is calculated and the number of recruited patients is quantified for a given time and probability of recruitment. The expected delay and the effective recruitment durations are estimated using both continuous and discrete time modeling. CONCLUSION: The proposed type of Monte Carlo simulation Markov models will enable optimization of the recruitment process and the estimation and the calibration of its parameters to aid the proposed clinical trials. A continuous time simulation may minimize the duration of the recruitment and, consequently, the total duration of the trial.

Effectiveness of a multimodal exercise rehabilitation program on walking capacity and functionality after a stroke.

The aim of this study was to determine the effectiveness of a 12-week multimodal exercise rehabilitation program on walking speed, walking ability and activities of daily living (ADLs) among people who had suffered a stroke. Thirty-one stroke survivors who had completed a conventional rehabilitation program voluntarily participated in the study. Twenty-six participants completed the multimodal exercise rehabilitation program (2 days/wk, 1 hr/session). Physical outcome measures were: walking speed (10-m walking test), walking ability (6-min walking test and functional ambulation classification) and ADLs (Barthel Index). The program consisted on: aerobic exercise; task oriented exercises; balance and postural tonic activities; and stretching. Participants also followed a program of progressive ambulation at home. They were evaluated at baseline, postintervention and at the end of a 6-month follow-up period. After the intervention there were significant improvements in all outcomes measures that were maintained 6 months later. Comfortable and fast walking speed increased an average of 0.16 and 0.40 m/sec, respectively. The walking distance in the 6-min walking test increased an average of 59.8 m. At the end of the intervention, participants had achieved independent ambulation both indoors and outdoors. In ADLs, 40% were independent at baseline vs. 64% at the end of the intervention. Our study demonstrates that a multimodal exercise rehabilitation program adapted to stroke survivors has benefits on walking speed, walking ability and independence in ADLs.

Validation by simulation of a clinical trial model using the standardized mean and variance criteria.

OBJECTIVE: To develop and validate a model of a clinical trial that evaluates the changes in cholesterol level as a surrogate marker for lipodystrophy in HIV subjects under alternative antiretroviral regimes, i.e., treatment with Protease Inhibitors vs. a combination of nevirapine and other antiretroviral drugs. METHODS: Five simulation models were developed based on different assumptions, on treatment variability and pattern of cholesterol reduction over time. The last recorded cholesterol level, the difference from the baseline, the average difference from the baseline and level evolution, are the considered endpoints. Specific validation criteria based on a 10% minus or plus standardized distance in means and variances were used to compare the real and the simulated data. RESULTS: The validity criterion was met by all models for considered endpoints. However, only two models met the validity criterion when all endpoints were considered. The model based on the assumption that within-subjects variability of cholesterol levels changes over time is the one that minimizes the validity criterion, standardized distance equal to or less than 1% minus or plus. CONCLUSION: Simulation is a useful technique for calibration, estimation, and evaluation of models, which allows us to relax the often overly restrictive assumptions regarding parameters required by analytical approaches. The validity criterion can also be used to select the preferred model for design optimization, until additional data are obtained allowing an external validation of the model.

Control of serotonergic neurons in the dorsal raphe nucleus by the lateral hypothalamus.

Anatomical evidence indicates the presence of projections from the lateral hypothalamus to serotonergic (5-hydroxytryptamine, 5-HT) neurons of the dorsal raphe nucleus (DR). Using dual probe microdialysis and extracellular recordings in the DR, we show that the application of GABAergic agents in the lateral hypothalamus modulates the activity of 5-HT neurons in the DR. GABA and bicuculline or baclofen, applied in the lateral hypothalamus significantly reduced and increased, respectively, the 5-HT output in the DR. Likewise, the intrahypothalamic application of GABA and bicuculline reduced (14/20 neurons) and increased (8/12 neurons), respectively, the firing rate of 5-HT neurons in the DR. A smaller percentage of neurons, however, were excited by GABA (3/20) and inhibited by bicuculline (1/12). Application of tetrodotoxin in the lateral hypothalamus suppressed the local 5-HT output and reduced that in the DR. The 5-HT output in the DR increased transiently soon after darkness. The hypothalamic application of GABA attenuated and that of bicuculline potentiated this spontaneous change with an efficacy similar to that seen in light conditions. These results indicate that the lateral hypothalamus is involved in the control of 5-HT activity in the DR, possibly through excitatory (major) and inhibitory (minor) inputs.

New biomechanical model for clinical evaluation of the upper extremity motion in subjects with neurological disorders: an application case.

Cervical spinal cord injury and acquired brain injury commonly imply a reduction in the upper extremity function which complicates, or even constrains, the performance of basic activities of daily living. Neurological rehabilitation in specialised hospitals is a common treatment for patients with neurological disorders. This study presents a practical methodology for the objective and quantitative evaluation of the upper extremity motion during an activity of daily living of those subjects. A new biomechanical model (with 10 rigid segments and 20 degrees of freedom) was defined to carry out kinematic, dynamic and energetic analyses of the upper extremity motion during a reaching task through data acquired by an optoelectronic system. In contrast to previous upper extremity models, the present model includes the analysis of the grasp motion, which is considered as crucial by clinicians. In addition to the model, we describe a processing and analysis methodology designed to present relevant summaries of biomechanical information to rehabilitation specialists. As an application case, the method was tested on a total of four subjects: three healthy subjects and one pathological subject suffering from cervical spinal cord injury. The dedicated kinematic, dynamic and energetic analyses for this particular case are presented. The resulting set of biomechanical measurements provides valuable information for clinicians to achieve a thorough understanding of the upper extremity motion, and allows comparing the motion of healthy and pathological cases.

Diagnòstic ràpid de grip en lactants i infants menors de 6 anys a l'atenció primària / Diagnóstico rápido de gripe en lactantes y niños menores de 6 años en atención primaria / Rapid diagnosis of influenza in infants and children younger than 6 years of age in primary care

Fonament: La taxa d'incidència de la grip en l'edat pediàtrica és la més elevada de la població, i el diagnòstic és difícil els primers anys de vida perquè té una simptomatologia inespecífica. Els tests de diagnòstic ràpid (TDR) de grip podrien millorar el maneig dels pacients en atenció primària. Objectiu: Estudiar si el diagnòstic de grip amb un TDR objectiu en lactants i infants menors de 6 anys disminueix el consum d'antibiòtics i el nombre de consultes successives. Mètode: Estudi longitudinal prospectiu descriptiu realitzat durant la temporada epidèmica 2016-2017 en quatre centres d'atenció primària de Barcelona, a lactants i infants fins als 6 anys. Amb una mostra de frotis nasofaringi es van fer dos tipus de TDR i al cap de 10 dies s'efectuava un seguiment telefònic demanant l'evolució de la simptomatologia, l'antibioteràpia rebuda, les consultes fetes i el contagi familiar produït. Resultats: Es van diagnosticar 55 casos de grip A, amb una edat mitjana de 33 mesos. La durada de la febre abans del diagnòstic va ser de 2,1 dies i de 3,2 dies després del diagnòstic, amb una temperatura mitjana de 38,9ºC. La simptomatologia més freqüent va ser la respiratòria, amb una durada mitjana després del diagnòstic de 6-7 dies. Van rebre antibioteràpia dos pacients, es van efectuar 18 reconsultes i es va objectivar un contagi de 50 persones en 29 famílies. Conclusions: La baixa prescripció antibiòtica i de consultes successives semblen confirmar que fer el diagnòstic en la consulta mateix és útil per aconseguir aquest objectiu

Fundamento: La tasa de incidencia de gripe en edad pediátrica es la más elevada de la población y su diagnóstico es difícil en los primeros años de vida por su sintomatología inespecífica. Los tests de diagnóstico rápido (TDR) de gripe podrían mejorar el manejo de los pacientes en atención primaria. Objetivo: Estudiar si el diagnóstico de gripe con un TDR en lactantes y niños menores de 6 años disminuye el consumo de antibióticos y el número de consultas sucesivas. Método: Se realizó un estudio longitudinal prospectivo descriptivo durante la temporada epidémica de 2016-2017 en cuatro centros de atención primaria de Barcelona, a lactantes y niños hasta los 6 años. Con una muestra de frotis nasofaríngeo se realizaron dos tipos de TDR y a los 10 días se efectuaba el seguimiento telefónico, preguntando por la evolución de la sintomatología, la antibioterapia recibida, las consultas realizadas y el contagio familiar producido. Resultados: Se diagnosticaron 55 casos de gripe A, con una edad media de 33 meses. La duración media de la fiebre antes del diagnóstico fue de 2,1 días y de 3,2 días después del diagnóstico, con una temperatura media de 38,9ºC. La sintomatología más frecuente fue la respiratoria, con una duración media tras el diagnóstico de 6-7 días. Recibieron antibioterapia dos pacientes, se efectuaron 18 reconsultas y se objetivó un contagio de 50 pacientes en 29 familias. Conclusiones: La baja prescripción antibiótica y del número de consultas sucesivas parecen confirmar que realizar el diagnóstico en la propia consulta es útil para conseguir este objetivo

Background: The incidence of influenza in children is the highest among all age groups, and its diagnosis may be difficult in the first years of life due to the non-specific symptoms. Rapid diagnostic tests (RDT) of influenza could improve the management of patients in the primary care setting. Objective: To investigate if the diagnosis of influenza using RDT in infants and children under 6 years resulted in a decrease in the prescription of antibiotics and in the number of follow-up medical visits. Method: We conducted a descriptive prospective longitudinal study during the 2016-2017 epidemic season in four primary care centers of Barcelona, with infants and children up to 6 years of age. Two types of RDT using a nasopharyngeal swab sample were performed, with a follow-up telephone call 10 days later to inquire about symptoms, antibiotic treatment received, additional medical visits, and family contagion noted. Results: A total of 55 cases of influenza A were diagnosed, at a median age of 33 months. The median duration of fever before and after the diagnosis was 2.1 and 3.2 days, respectively, with a median temperature of 38.9ºC. The most frequent symptomatology was respiratory, with a median duration after diagnosis of 6-7 days. Two patients received antibiotic therapy, 18 additional medical visits were carried out, and 50 individuals were reported to be infected among 29 families. Conclusions: The low antibiotic prescription and number of following medical visits seem to confirm that a rapid diagnosis performed during the initial consultation is useful for achieving those goals

Efectividad de un programa de rehabilitación basado en ejercicio multimodal de intensidad moderada-baja para supervivientes de ictus / Effectiveness of a multimodal low-moderate intensity exercise rehabilitation program for stroke survivors

Introducción: la cantidad de personas que sobreviven a un accidente cerebrovascular aumenta cada año. Las personas con ictus sufren déficits neurológicos y un desacondicionamiento físico que compromete la capacidad para caminar, las actividades básicas de la vida diaria y la calidad de vida relacionada con la salud (CdVRS). El objetivo de este estudio fue determinar los efectos de un programa de rehabilitación multimodal de 12 semanas de duración, basado en ejercicios de intensidad baja- moderada, en la velocidad de deambulación, la resistencia al caminar y la adherencia a la actividad física. Material y métodos: estudio observacional de medidas repetidas. La intervención consistió en 24 sesiones de 1 hora de duración dos días alternos por semana. Se reclutó un total de 31 participantes que se evaluaron al inicio, después de la intervención y a los seis meses. Resultados: veinticinco participantes completaron el programa de rehabilitación. Al final de la intervención se detectaron mejoras significativas de la velocidad de deambulación (10MWT p≤0.004*), resistencia al caminar (6MWT p≤0.000**) y adherencia (minutos de caminata/día p≤0.000**). Estos resultados se mantuvieron a los seis meses. Los participantes manifestaron una satisfacción general con el programa de rehabilitación del 94% en relación a los siguientes ítems: condición física, capacidad para caminar, equilibrio, expectativas cumplidas, satisfacción con el programa, satisfacción con la autoeficacia, estrategias aprendidas para mejorar la calidad de vida, momento adecuado para participar en el programa y lo recomendarían a terceras personas. Conclusiones: Promover la actividad física de intensidad baja-moderada puede ser una estrategia de rehabilitación interesante para los supervivientes de ictus

Introduction: The amount of people who survive a stroke is increasing annually. Persons with stroke suffer neurological deficits and a physical deconditioning that compromise walking ability, basic activities of daily living and health-related quality of life (HRQoL). The aim of the study was to determine the effects of a 12-week multimodal low-moderate intensity exercise rehabilitation program on walking speed, walking endurance and adherence to physical activity. Material and methods: An observational repeated-measures design was used. The intervention consisted of 24 sessions of 1 hour per session two alternative days a week. A total of 31 participants were recruited and were evaluated at baseline, post-intervention and at six months follow up. Results: Twenty-five participants completed the rehabilitation program. Significant improvements were found at the end of the intervention and those were maintained at six months on walking speed (10MWT *p≤0.004), walking endurance (6MWT **p≤0.000) and adherence (walking min/day **p≤0.000). Participants reported an overall satisfaction with the rehabilitation program of 94%: fitness, walking capacity, balance, accomplished expectations, satisfaction with the rehabilitation program, satisfaction with self-efficacy, learned strategies to improve QoL, adequate timing and would recommend the low-moderate intensity exercise rehabilitation program. Conclusions: Promoting low-moderate intensity physical activity may be an interesting rehabilitation strategy for stroke survivors

Microbiology of bacteria causing recurrent acute otitis media (AOM) and AOM treatment failure in young children in Spain: shifting pathogens in the post-pneumococcal conjugate vaccination era.

OBJECTIVE: To prospectively identify the bacterial aetiology and antimicrobial susceptibility of problematic (recurrent and treatment failure) acute otitis media in Spanish children several years after the introduction of 7-valent pneumococcal conjugate vaccine. METHODS: Tympanocentesis or careful sampling of spontaneous otorrhoea was performed on children aged 3 to <36 months with recurrent acute otitis media, acute otitis media treatment failure or unresolved acute otitis media. RESULTS: 105 acute otitis media episodes (77 sampled by tympanocentesis, 28 otorrhoea samples) were evaluated: 46 recurrent, 35 treatment failures, 24 unresolved acute otitis media. 74 episodes (70.4%) had at least one bacterium identified on culture: Streptococcus pneumoniae was identified in 21 episodes, Haemophilus influenzae (all non-typeable) in 44, Streptococcus pyogenes in 2, Moraxella catarrhalis in 2. No statistically significant difference in bacterial aetiology by episode type was detected. Non-typeable H. influenzae was the most commonly isolated pathogen in all acute otitis media types and in all age sub-groups. Forty percent of S. pneumoniae isolates were multi-drug resistant. Pneumococcal serotype 19A was the most frequently identified serotype (7/21 episodes). Multi-drug resistance was found in 56% of 19A isolates. Of non-typeable H. influenzae isolates, 15% were ampicillin resistant and 13% were amoxicillin/clavulanate resistant. S. pneumoniae and non-typeable H. influenzae DNA were each detected in 57% of samples culture negative for these pathogens, including 12 co-infections. CONCLUSION: Combining culture and polymerase chain reaction results, H. influenzae and S. pneumoniae may be implicated in 70% and 43% of clinically problematic bacterial acute otitis media episodes, respectively. The impact of new vaccines to prevent both S. pneumoniae and non-typeable H. influenzae acute otitis media may be substantial in this population and is worth investigating.

Long-term (5-year) antibody persistence following two- and three-dose regimens of a combined hepatitis A and B vaccine in children aged 1-11 years.

This study compared the long-term persistence of anti-hepatitis A (anti-HAV) and B (anti-HBs) antibodies, 5 years after vaccination of subjects aged 1-11 years with a combined hepatitis A and B vaccine either in a two-dose (0, 6 months, Adult formulation) or a three-dose (0, 1, 6 months, Paediatric formulation) schedule. At the end of the 5 years, all subjects (100%) in both groups continued to have anti-HAV antibodies > or =15mIU/mL, while 94-97% of subjects in both groups had anti-HBs antibody concentrations > or =10mIU/mL. Subjects with anti-HBs antibody concentration < or =10mIU/mL were administered a challenge dose of hepatitis B vaccine. All subjects mounted a vigorous immune response to the challenge indicating the presence of immunological memory to HBV.

Control of the serotonergic system by the medial prefrontal cortex: potential role in the etiology of PTSD and depressive disorders.

The prefrontal cortex is involved in an array of higher brain functions that are altered in psychiatric disorders. Serotonergic neurons of the midbrain rapbe nuclei innervate the prefrontal cortex and are the cellular target for drugs used to treat mood disorders such as the selective serotonin (5-HT) reuptake inhibitors. Anatomical evidence supports the existence of projections from the medial prefrontal cortex (mPFC) to the dorsal raphe nucleus (DR). We report on a functional control of the activity of DR 5-HT neurons by projection neurons in the mPFC. The stimulation of the mPFC elicits two types of responses in DR 5-HT neurons, orthodromic excitations and inhibitions. Excitations are mediated by AMPA/KA and NMDA receptors whereas inhibitions are mediated by GABA(A) and 5-HT(1A) receptors. The activation of a subgroup of 5-HT neurons increases 5-HT release which subsequently activates 5-HT(1A) autoreceptors on other 5-HT neurons. GABA(A)-mediated inhibitions involve GABAergic elements in the DR or adjacent areas. Pyramidal neurons of the mPFC co-express postsynaptic 5-HT(1A) (inhibitory) and 5-HT(2A) (excitatory) receptors. Consistent with the above observations, the selective activation of both receptors in mPFC reduced and increased, respectively, the firing activity of DR 5-HT neurons and the 5-HT release in mPFC. Overall, these data indicate that the activity of the 5-HT system is strongly controlled by the mPFC. Thus, the abnormal prefrontal function in post-traumatic stress disorder and depressive patients may induce a disregulation of 5-HT neurons projecting to other brain areas that can underlie the existing symptomatology in these psychiatric disorders.