HORYZONS trial: protocol for a randomised controlled trial of a moderated online social therapy to maintain treatment effects from first-episode psychosis services.

INTRODUCTION: Specialised early intervention services have demonstrated improved outcomes in first-episode psychosis (FEP); however, clinical gains may not be sustained after patients are transferred to regular care. Moreover, many patients with FEP remain socially isolated with poor functional outcomes. To address this, our multidisciplinary team has developed a moderated online social media therapy (HORYZONS) designed to enhance social functioning and maintain clinical gains from specialist FEP services. HORYZONS merges: (1) peer-to-peer social networking; (2) tailored therapeutic interventions; (3) expert and peer-moderation; and (4) new models of psychological therapy (strengths and mindfulness-based interventions) targeting social functioning. The aim of this trial is to determine whether following 2 years of specialised support and 18-month online social media-based intervention (HORYZONS) is superior to 18 months of regular care. METHODS AND ANALYSIS: This study is a single-blind randomised controlled trial. The treatment conditions include HORYZONS plus treatment as usual (TAU) or TAU alone. We recruited 170 young people with FEP, aged 16-27 years, in clinical remission and nearing discharge from Early Psychosis Prevention and Intervention Centre, Melbourne. The study includes four assessment time points, namely, baseline, 6-month, 12-month and 18-month follow-up. The study is due for completion in July 2018 and included a 40-month recruitment period and an 18-month treatment phase. The primary outcome is social functioning at 18 months. Secondary outcome measures include rate of hospital admissions, cost-effectiveness, vocational status, depression, social support, loneliness, self-esteem, self-efficacy, anxiety, psychological well-being, satisfaction with life, quality of life, positive and negative psychotic symptoms and substance use. Social functioning will be also assessed in real time through our Smartphone Ecological Momentary Assessment tool. ETHICS AND DISSEMINATION: Melbourne Health Human Research Ethics Committee (2013.146) provided ethics approval for this study. Findings will be made available through scientific journals and forums and to the public via social media and the Orygen website. TRIAL REGISTRATION NUMBER: ACTRN12614000009617; Pre-results.

Insight into the Diversity of Penicillin-Binding Protein 2x Alleles and Mutations in Viridans Streptococci.

The identification of commensal streptococci species is an everlasting problem due to their ability to genetically transform. A new challenge in this respect is the recent description of Streptococcus pseudopneumoniae as a new species, which was distinguished from closely related pathogenic S. pneumoniae and commensal S. mitis by a variety of physiological and molecular biological tests. Forty-one atypical S. pneumoniae isolates have been collected at the German National Reference Center for Streptococci (GNRCS). Multilocus sequence typing (MLST) confirmed 35 isolates as the species S. pseudopneumoniae A comparison with the pbp2x sequences from 120 commensal streptococci isolated from different continents revealed that pbp2x is distinct among penicillin-susceptible S. pseudopneumoniae isolates. Four penicillin-binding protein x (PBPx) alleles of penicillin-sensitive S. mitis account for most of the diverse sequence blocks in resistant S. pseudopneumoniae, S. pneumoniae, and S. mitis, and S. infantis and S. oralis sequences were found in S. pneumoniae from Japan. PBP2x genes of the family of mosaic genes related to pbp2x in the S. pneumoniae clone Spain23F-1 were observed in S. oralis and S. infantis as well, confirming its global distribution. Thirty-eight sites were altered within the PBP2x transpeptidase domains of penicillin-resistant strains, excluding another 37 sites present in the reference genes of sensitive strains. Specific mutational patterns were detected depending on the parental sequence blocks, in agreement with distinct mutational pathways during the development of beta-lactam resistance. The majority of the mutations clustered around the active site, whereas others are likely to affect stability or interactions with the C-terminal domain or partner proteins.

Emergence of invasive pneumococcal disease caused by nonvaccine serotypes in the era of 7-valent conjugate vaccine.

BACKGROUND: Little is known about the epidemiology of invasive pneumococcal disease (IPD) after the introduction of 7-valent pneumococcal conjugate vaccine (PCV7) in Spain and other European countries. METHODS: We performed a 10-year prospective study including all children with culture-proven IPD admitted to Sant Joan de Deu Hospital, a children's center in the southern area of Barcelona, Catalonia, Spain. PCV7 was introduced in June 2001, and the current estimate of PCV7 coverage is 45%-50%. RESULTS: Comparing the prevaccine period (1997-2001) with the vaccine period (2002-2006), among children aged <2 years, the rate of IPD increased from 32.4 episodes per 100,000 population to 51.3 episodes per 100,000 population (an increase of 58%; 95% confidence interval, 2%-145%), and among children aged 2-4 years, the rate increased from 11.3 episodes per 100,000 population to 26.5 episodes per 100,000 population (an increase of 135%; 95% confidence interval, 31%-320%). At clinical presentation, the rate of pneumonia and/or empyema among children aged <5 years increased from 3.6 episodes per 100,000 population to 15.1 episodes per 100,000 population (an increase of 320%; 95% confidence interval, 98%-790%). These increased rates of IPD were caused by non-PCV7 serotypes, which represented 38% and 72% of infecting serotypes in the prevaccine and vaccine periods, respectively (P=.001). Penicillin resistance decreased from 48% in the prevaccine period to 27% in the vaccine period (P=.005). In the vaccine period, there was an emergence of previously established virulent clones of non-PCV7 serotypes 1 and 5. There was also an increase in the prevalence of serotypes 19A and 6A expressed with different clonal types, including Spain(23F)-1 and Spain(6B)-2. CONCLUSIONS: Since the introduction of PCV7 for children, there has been an emergence of IPD caused by virulent clones of non-PCV7 serotypes that has been associated with significant clinical changes and a decrease in antibiotic resistance.

Incidence study of nosocomial infection in pediatric trauma patients.

In this article we intend to describe the epidemiological profile of nosocomial infection in pediatric patients with multiple trauma. We conducted a prospective study from July to November 2003 in a pediatric teaching hospital in Barcelona. We used US Centers for Disease Control and Prevention standard criteria to define nosocomial infection. Of the 121 patients included in the study, 33% had at least one episode of nosocomial infection, with an incidence rate of 9.9 infections per 100 admissions and 1.1 infections per 100 patient-days. The most frequent episode of nosocomial infection was bacteremia. Coagulase-negative staphylococci were the most common pathogens. Nosocomial infection rates per 100 device-days were 3.2 for bacteremia, 1.6 for respiratory infection and 1.0 for urinary tract infection. These findings suggest the need to evaluate infection control measures aimed at reducing the morbidity associated with infections.

Invasive disease caused by Haemophilus influenzae: the sensitivity of statutory reporting.

PURPOSE: The objective of the study was to investigate the sensitivity of the statutory reporting of Haemophilus influenzae invasive disease (HIID) during the period between 1996 and 1997 in Catalonia, Spain. METHODS: The incidence of HIID reported passively by clinicians was compared with the cases detected by a system of microbiological surveillance. In all cases isolated, the age of the patient, the clinical form and the serotype were investigated. RESULTS: Sixty-six cases were passively reported and 111 were detected by microbiological surveillance. Overall sensitivity of reporting was 59.5% (95% CI, 50.7-69.1), with differences being observed according to the variables studied. The highest values were obtained in children under 5 years (87.8%; 95% CI, 73.7-95.9), in cases with meningitis and/or sepsis (64.3%; 95% CI, 50.4-76.6) and in serotype b (73.0%; 95% CI, 60.3-83.4). In the logistical regression analysis, only age under 5 years was associated with greater reporting (OR= 9.8; 95% CI, 2.5-37.8). CONCLUSIONS: Reported morbidity in children under 5 years is a good estimate of the true incidence of HIID in Catalonia (underreporting was 12.2%), but not for those above this age in whom the underreporting was 57.2%.

A prospective incidence study of nosocomial infections in a neonatal care unit.

BACKGROUND: Health care improvements and technical advances for diagnostic and therapeutic management in the neonatal care unit (NCU) have made possible the increasing survival of neonates with severe pathologic conditions. However, nosocomial infections (NI) still represent an important cause of morbidity and mortality in this population. OBJECTIVE: To describe the epidemiologic profile of NI in the NCU. METHODS: A prospective surveillance study was performed in the NCU at a university hospital in Barcelona during 6 months. Two hundred sixty-eight neonates were admitted during the study period. Centers for Disease Control and Prevention criteria were used as standard definitions for NI. Data including risk factors associated with NI were recorded. RESULTS: Sixty-five neonates had a total of 88 NI. The incidence rate of NI was 1.6 per 100 patient-days. The accumulative rate of NI was 32.7 per 100 admissions. Bacteremia (28.4%), conjunctivitis (19.5%), respiratory infection (10.2%), and urinary tract infection (7.9%) were the most common episodes observed. Gram-positive bacteria were the most commonly isolated germs (76.4%), with coagulase-negative Staphylococcus (72.5%) being the main pathogen. Intrinsic risk factors related to NI were low birth weight (<1000 g) and urinary catheter and peripheral venous catheter (P<.01). CONCLUSIONS: NI represent an important and frequent problem in neonates. Knowledge of the incidence of NI allows the targeting and implementation of preventive strategies for reducing morbidity and mortality related to NI in an NCU.

Prospective incidence study of nosocomial infections in a pediatric intensive care unit.

BACKGROUND: Nosocomial infections are important causes of substantial morbidity, mortality and prolonged hospital stay in pediatric intensive care units (PICU). METHODS: A prospective surveillance study was performed in the PICU at a university hospital in Barcelona during the 6 months from May through October 2000 to describe the epidemiologic profile of nosocomial infections. Centers for Disease Control and Prevention criteria were used as standard definitions for nosocomial infections. Data including extrinsic risk factors (invasive devices) associated with nosocomial infections were recorded and device-associated infections were calculated for the specific site. RESULTS: During the study period 257 patients were admitted; 15.1% (39) patients had a total of 58 nosocomial infections. The incidence of nosocomial infection was 1.5 per 100 patient-days. Patients with cardiac surgery had the highest nosocomial infection rate, 2.3 per 100 patient-days. Bacteremia (51.7%), respiratory infection (19.0%) and urinary tract infection (17.2%) were the most frequent nosocomial infections observed, and these were associated with use of invasive device. Coagulase-negative staphylococci (39%) and Pseudomonas aeruginosa (24%) were the most common organisms isolated. Nosocomial infection rates per 1000 device days were 23.9 for respiratory infection, 12.4 for bacteremia and 10.7 for urinary tract infection. The durations of hospitalization for patients with and without infection were 22.5 and 9 days, respectively (P < 0.001). CONCLUSIONS: Performance of surveillance highlights the importance of nosocomial infections and their influence in the hospital stay and can guide selection of prevention and control measures to reduce morbidity and mortality in a PICU.

[Diagnosis of meningococcal disease by polymerase chain reaction]. / Aumento de la rentabilidad diagnóstica en la enfermedad meningocócica mediante la técnica de reacción en cadena de la polimerasa.

BACKGROUND AND OBJECTIVE: The objective of the present study was to evaluate the application of a rapid and simple PCR technique to diagnose meningococcal disease. PATIENTS AND METHOD: A retrospective study was undertaken from January 1999 to June 2002, comprising 110 samples of cerebrospinal fluid (CSF) or plasma from 110 different pediatric patients attending the Hospital Sant Joan de Déu of Barcelona. The selection of patients was based on their diagnosis at discharge: Forty three patients had a discharge diagnose of meningococcal disease (13 meningitis, 12 sepsis and 18 sepsis with meningitis) while 67 had clinical conditions other than meningococcal disease. The samples were processed following standard bacteriological methods (Gram smear and culture) and a PCR technique designed to amplify a segment of the meningococcal insertion sequence IS1106 was performed. RESULTS: Sensitivity of PCR in the group of patients with a clinical diagnosis of meningococcal disease was 93% while sensitivity of the culture was 55.8%. Samples from 19 patients were processed once treatment with -lactam antibiotics had begun (range 8-144 hours), and positive PCR results were seen in 17 cases (sensitivity: 89.4%); a positive culture was observed in two cases of pre-treated patients (sensitivity 10.5%). A false positive result was detected in the group of patients with non-meningococcal disease (specificity 98.5%). CONCLUSIONS: The application of this PCR permits a rapid (roughly 5 hours), specific and sensitive method that increases the microbiologic confirmation of meningococcal disease, mainly in patients who have received previous antibiotic treatment.

[Haemophilus influenzae: phenotype characteristics of strains isolated in 12 Catalan hospitals over one year]. / Haemophilus influenzae: características fenotípicas de las cepas aisladas en 12 hospitales catalanes durante un año.

INTRODUCTION: The purpose of this study was to investigate the antigenic and biochemical characteristics, antibiotic susceptibility, and mechanisms for acquiring resistance of Haemophilus influenzae strains isolated in several Catalan hospitals, to determine the current situation regarding this microorganism in our area. METHODS: Serotype, biotype and betalactamase production, as well as susceptibility to eight antimicrobial agents (ampicillin, cefuroxime, cefotaxime, cefixime, clarithromycin, co-trimoxazole, chloramphenicol and ciprofloxacin) were determined in 497 H. influenzae strains isolated from 1 May 1999 to 30 April 2000 in 12 Catalan hospitals. RESULTS: Among the total, 97.5% of strains were nontypable and 50% of the encapsulated strains were serotype b (all isolated from children under 5 years old). There was a predominance of biotype II, though no age or pathologic tropism was found among any of the biotypes. Our series confirms the previously reported trend to decreasing betalactamase mediated ampicillin resistance in our area, mainly in strains from pediatric patients. More betalactamase negative ampicillin-resistant strains (BLNAR) were isolated in children than in adults. One ciprofloxacin-resistant strain was detected. CONCLUSIONS: Infections caused by encapsulated H. influenzae strains are infrequent in our area and the relative importance of serotype b is decreasing. Mechanisms for acquiring ampicillin resistance other than betalactamase production are emerging. Surveillance of ciprofloxacin susceptibility is required to predict therapeutic failures with this quinolone.

Spontaneous Listeria monocytogenes peritonitis: a population-based study of 13 cases collected in Spain.

OBJECTIVES: We aimed to assess the incidence, demographic data, clinical features, and outcome of peritoneal infections due to Listeria monocytogenes in individuals with cirrhosis. METHODS: During a 10-yr study period, 153 cases of invasive listeriosis were recorded in a prospective population-based surveillance project carried out in Barcelona, Spain. RESULTS: Thirteen cases were of spontaneous bacterial peritonitis by L. monocytogenes. Ages of the patients ranged between 29 and 85 yr. In addition to cirrhosis, underlying conditions included diabetes mellitus in four and malignancy in three. Bacteremia was present in six cases (46%). Only one patient with bacteremia developed meningitis. Analysis of the peritoneal fluid showed a mean (SD) protein content of 21.5 (9.6) g/L and leukocyte count of 7,273 (9,171) cells/ml. L. monocytogenes serotype 4b was the serogroup predominantly isolated (61%). The mortality rate was 30.7%. Eight patients received empirical antibiotic treatment with cephalosporins. CONCLUSIONS: In geographical areas with a high incidence of listeriosis, L. monocytogenes should be suspected as a causative pathogen of spontaneous bacterial peritonitis in cirrhosis. Early adjustment of antibiotic therapy is essential to reduce mortality.

[Prevalence of hepatitis C virus in pregnant women and vertical transmission]. / Prevalencia de la infección por el virus de la hepatitis C en mujeres embarazadas y transmisión vertical de este virus.

BACKGROUND: The objectives of this study were to know the seroprevalence of HCV in pregnant women and to determine its vertical transmission rate as well as the viremia evolution in infected children. PATIENTS AND METHOD: Two different populations were studied: a) all pregnant women (n = 2,615) controlled in our hospital during 1999, and b) newborns (n = 228) to mothers with HCV antibodies (Ab) who were referred to our hospital from January 1995 to September 2000. Eighty of these infants were born to mothers coinfected with HIV-1. HCV Ab were determined by ELISA and RIBA techniques and viral ARN was studied by PCR. Risk factors in infected pregnant women were reviewed. RESULTS: HCV Ab were detected in 37 women using RIBA or PCR, hence meaning a seroprevalence rate of 1.4%. Usual risk factors were not identified in 35% of cases. Median viral load was 3.5 * 105 IU/ml. ARN HCV was detected in 15 infants, 9 out of them being born to mothers coinfected with HIV-1 (vertical transmission rate: 11.25%) and the remaining 6 being born to mothers without HIV-1 coinfection (vertical transmission rate: 4%). The difference in the transmission rate had statistical significance (p < 0.05). CONCLUSIONS: Seroprevalence of HCV infection in our population of pregnant women was relatively high. HCV screening in pregnant women is useful in order to identify this infection not only in this population but also in newborns and, consequently, to follow-up the vertical transmission cases.

[Rapid diagnosis of herpetic meningoencephalitis by PCR]. / Diagnóstico rápido de la meningoencefalitis herpética mediante PCR.

OBJECTIVE: To evaluate the usefulness of a rapid and simple PCR method in the diagnosis of herpetic meningoencephalitis in a pediatric population. PATIENTS AND METHODS: One hundred twenty-three cerebrospinal fluid samples from 114 pediatric patients attending the Hospital Sant Joan de Déu in Barcelona for clinical suspicion of viral meningoencephalitis or to rule out a possible herpetic etiology were evaluated. In addition to classical methods, the diagnostic technique used was PCR amplification of a highly preserved region of the DNA polymerase gene common to herpes virus 1 and 2. All patients were administered acyclovir on admission and until the results of PCR were known. If the result was negative, withdrawal of acyclovir was considered after clinical reexamination. If the result was positive, the therapy was continued for 20 days. RESULTS: Herpes simplex DNA was detected in four patients. In all patients, clinical outcome confirmed the results of PCR, whether positive or negative. PCR results were available within 6.30 and 72 hours (mean: 18 hours). CONCLUSION: This simple and rapid PCR technique can be applied in the daily routine of the microbiology laboratory. It allows early diagnosis of herpetic meningocephalitis or, when lacking, exclusion of Herpes simplex etiology.

Molecular epidemiology of astrovirus infection in Barcelona, Spain.

A 3-year study involving 2,347 gastroenteritis samples was conducted to determine the prevalence, time distribution, and medical significance of human astrovirus infection in Barcelona, Spain. The overall incidence of astrovirus was found to be 4.9%. Mixed infections with other enteric agents were detected in 17.2% of all astrovirus-positive samples. During the 3-year period, the highest astrovirus incidence was reported in the winter months, although infections also occurred in summer. The peak detection rate was observed in children between 2 and 4 years of age. Overall, HAstV-1 was the most prevalent type, followed by HAstV-4, HAstV-3, HAstV-8, and HAstV-2. HAstV-5, HAstV-6, and HAstV-7 were not detected during these 3 years. From our serotype data for each age group, we observed that HAstV-1, HAstV-2, and HAstV-3 affected mostly children younger than 3 years of age, while HAstV-4 and HAstV-8 had a greater impact in older children. Genetic variability was analyzed between astroviruses isolated in Barcelona and strains isolated in other parts of the world. A fourth lineage was described for HAstV-1, most likely due to the large number of assayed samples, which may also explain the high level of genetic variability observed in the astrovirus isolates.