Delayed versus Immediate Cord Clamping in Preterm Infants.

BACKGROUND: The preferred timing of umbilical-cord clamping in preterm infants is unclear. METHODS: We randomly assigned fetuses from women who were expected to deliver before 30 weeks of gestation to either immediate clamping of the umbilical cord (≤10 seconds after delivery) or delayed clamping (≥60 seconds after delivery). The primary composite outcome was death or major morbidity (defined as severe brain injury on postnatal ultrasonography, severe retinopathy of prematurity, necrotizing enterocolitis, or late-onset sepsis) by 36 weeks of postmenstrual age. Analyses were performed on an intention-to-treat basis, accounting for multiple births. RESULTS: Of 1634 fetuses that underwent randomization, 1566 were born alive before 30 weeks of gestation; of these, 782 were assigned to immediate cord clamping and 784 to delayed cord clamping. The median time between delivery and cord clamping was 5 seconds and 60 seconds in the respective groups. Complete data on the primary outcome were available for 1497 infants (95.6%). There was no significant difference in the incidence of the primary outcome between infants assigned to delayed clamping (37.0%) and those assigned to immediate clamping (37.2%) (relative risk, 1.00; 95% confidence interval, 0.88 to 1.13; P=0.96). The mortality was 6.4% in the delayed-clamping group and 9.0% in the immediate-clamping group (P=0.03 in unadjusted analyses; P=0.39 after post hoc adjustment for multiple secondary outcomes). There were no significant differences between the two groups in the incidences of chronic lung disease or other major morbidities. CONCLUSIONS: Among preterm infants, delayed cord clamping did not result in a lower incidence of the combined outcome of death or major morbidity at 36 weeks of gestation than immediate cord clamping. (Funded by the Australian National Health and Medical Research Council [NHMRC] and the NHMRC Clinical Trials Centre; APTS Australian and New Zealand Clinical Trials Registry number, ACTRN12610000633088 .).

Predictors of residency status in chronically institutionalized and community dwelling schizophrenia patients.

BACKGROUND: This cross-sectional study contrasted chronically hospitalized schizophrenia (SZ) spectrum disorder inpatients to SZ community dwelling patients on measures of psychopathology, social competence, neuropsychological performance and real-world functioning in order to discern factors predictive of patients' residency status and to characterize the contrasting ends of the SZ outcome continuum. METHOD: Subjects included 26 chronic SZ patients hospitalized continuously on average for 12.8 years, and 26 SZ patients with a history of at least 18 months tenure in community placement. RESULTS: A series of multivariate analyses revealed both chronically hospitalized and community dwelling patients were similar in terms of their real world functioning abilities such as work skills, interpersonal skills, self-care skills and community engagement. Chronic SZ inpatients' manifested more severe functional competency and neurocognitive deficits relative to outpatients. Additionally, chronic inpatients were discriminated from community dwelling outpatients by their symptom severity and commitment of more socially undesirable/antisocial type behaviors. CONCLUSIONS: Factors associated with chronic institutionalization are, in part, related to commission of antisocial type behaviors, as well as poor social and neurocognitive competences, and total symptom severity rather than deficits in everyday functional abilities.

Costs of children with medical complexity in Australian public hospitals.

AIM: To describe the hospital costs, hospital types and differences across states and territories for children with medical complexity cared for in Australian public hospitals. METHODS: Retrospective national administrative database study of 212 Australian public hospitals from six states (excluding Queensland) and two territories that submitted cost data to the National Hospital Costing Data Collection for 2010-2011. Participants included all hospitalised patients with comparisons between adults and children (17 years of age and younger), and adults with chronic diseases and children with medical complexity. Total hospital costs were the main outcome measure. RESULTS: The National Hospital Costing Data Collection contained data from 212 public hospitals; total admissions (adults and children) were 3 519 140 at a total hospital cost of $16 187 400 000. Children accounted for 350 499 (9.9%) of the admissions at a total hospital cost of $1 931 585 123 (11.9%). Of all children, those with medical complexity accounted for 48 758 (13.9%), and their total hospital costs were $620 948 769 (32.1%). Six children's hospitals had 145 213 (41%) of the total children admissions at a total hospital cost of $936 041 843 (48%). Across the states and territories, the number of childhood admissions ranged from 9164 to 146 618 with 4.7-14.8% for children with medical complexity. Total hospital costs ranged from $44 to $592 million with 15.4-39.4% for children with medical complexity. CONCLUSIONS: The national burden of hospitalised children is substantial. Children with medical complexity only account for a small percentage of hospitalisations but almost one third of total hospital costs for children, with children's hospitals bearing the major costs.

Clinician perspectives on rapid transition to telehealth during COVID-19 in Australia - a qualitative study.

Objective The coronavirus disease 2019 (COVID-19) pandemic precipitated a major shift in the use of telehealth in Australia. The changes highlighted gaps in our knowledge regarding the efficacy of, and clinician attitudes to, the use of telehealth. The current study expands and deepens the available evidence as a result of being collected in unique circumstances that removed one of the major barriers (lack of Medicare rebates) and also one major enablers (willingness) of telehealth uptake. Methods Using a semi-structured interview, we invited clinicians (N = 39) to share their perspectives, attitudes and experiences of using telehealth. Topics covered included perceptions of the strengths and challenges of telehealth, and how experience of using telehealth during the COVID-19 pandemic had influenced clinicians' views and intentions regarding their future practice. Participants included clinicians from five disciplines across public and private practice: paediatrics, neurology, immunology, rural general practice, and orthopaedics. Results We found three key dimensions for consideration when assessing the suitability of telehealth for ongoing practice: the attributes of the patient population, the attributes of the clinical context and environment, and the risks and benefits of a telehealth approach. These findings map to the existing literature and allow us to infer that the experiences of clinicians who previously would have chosen telehealth did not differ significantly from those of our 'pandemic-conscripted' clinicians. Conclusions Our findings map clearly to the existing literature and allow us to infer that the experiences of the clinicians who have chosen telehealth (and are already represented in the literature) did not differ significantly from those trying out telehealth under the unique circumstances of the removal of the Medicare Benefits Scheme barrier and external pressure that over-rides the 'willingness' enabling factor in uptake decisions.

Antibiotic prophylaxis and recurrent urinary tract infection in children.

BACKGROUND: Antibiotics are widely administered to children with the intention of preventing urinary tract infection, but adequately powered, placebo-controlled trials regarding efficacy are lacking. This study from four Australian centers examined whether low-dose, continuous oral antibiotic therapy prevents urinary tract infection in predisposed children. METHODS: We randomly assigned children under the age of 18 years who had had one or more microbiologically proven urinary tract infections to receive either daily trimethoprim-sulfamethoxazole suspension (as 2 mg of trimethoprim plus 10 mg of sulfamethoxazole per kilogram of body weight) or placebo for 12 months. The primary outcome was microbiologically confirmed symptomatic urinary tract infection. Intention-to-treat analyses were performed with the use of time-to-event data. RESULTS: From December 1998 to March 2007, a total of 576 children (of 780 planned) underwent randomization. The median age at entry was 14 months; 64% of the patients were girls, 42% had known vesicoureteral reflux (at least grade III in 53% of these patients), and 71% were enrolled after the first diagnosis of urinary tract infection. During the study, urinary tract infection developed in 36 of 288 patients (13%) in the group receiving trimethoprim-sulfamethoxazole (antibiotic group) and in 55 of 288 patients (19%) in the placebo group (hazard ratio in the antibiotic group, 0.61; 95% confidence interval, 0.40 to 0.93; P = 0.02 by the log-rank test). In the antibiotic group, the reduction in the absolute risk of urinary tract infection (6 percentage points) appeared to be consistent across all subgroups of patients (P > or = 0.20 for all interactions). CONCLUSIONS: Long-term, low-dose trimethoprim-sulfamethoxazole was associated with a decreased number of urinary tract infections in predisposed children. The treatment effect appeared to be consistent but modest across subgroups. (Australian New Zealand Clinical Trials Registry number, ACTRN12608000470392.)

Inequality in provider continuity for children by Australian general practitioners.

BACKGROUND: There is little published on provider continuity in Australian general practice and none on its effect on inequality of care for children. METHOD: Questionnaire administered to parents of the ACT Kindergarten Health Screen asking the name of their child's usual GP and practice address between 2001 and 2008. RESULTS: Parents of 30,789 children named 433 GPs and 141 practices. In each year, an average of 77% of parents could name both the GP and the practice, an average of 11% of parents could name only the practice, and an average of 12% of parents could name neither. In each year, 25% of parents could not name a usual GP for children of Aboriginal or Torres Straight Islander descent, or children born outside of Australia, compared to 10% of all other children (p = < 0.0001). The frequency of GPs displaying continuity of care varied over time with 19% of GPs being present in the ACT in only one year and 39% of GPs being present in every year over the eight years of study. GPs displayed two different forms of transience either by working in more than one practice in each year (5% of GPs), or by not being present in the ACT region from one year to the next (15% of GPs). Fewer parents nominated transient GPs as their child's GP compared to choosing GPs who displayed continuity (p < 0.001). CONCLUSIONS: Many GPs (39%) were reported to provide continuity of care for in the ACT region and some GPs (20%) displayed transient care. Indigenous children or children born outside of Australia had less equity of access to a nominated GP than all other children. Such inequity might disappear if voluntary registration of children was adopted in Australian general practice.

A pilot study of the use of oral ivermectin to treat head lice in primary school students in Australia.

Head lice are a common, costly public health problem worldwide. We aimed to determine the feasibility of an ivermectin intervention program. Consenting students in two schools were screened for head lice. Infested students and siblings at one school were offered a head lice fact sheet and two doses of oral ivermectin, 7 days apart. Parents of infested students in the other school were given the same fact sheet and asked to treat the child and siblings using their preferred topical treatment. Seven hundred two of 754 (93.1%) students enrolled in the two schools were screened; 40 (5.3%; 95% CI 3.7-6.9) had head lice; 31 (9.4%; 95% CI 6.1-12.2) in the intervention school and nine (2.5%; 95% CI 1.1-3.8) in the control school. Subsequently 93.6% of children in the intervention school were treated with oral ivermectin. No adverse events were reported. At 6 months the reduction in the head lice infestation rates for the intervention and control schools were 87% and 56%, respectively. This pilot study suggests that school wide screening for head lice and the administration of oral ivermectin is feasible and acceptable. A randomized controlled trial at 20 schools is planned.

Contrasting longitudinal and cross-sectional relationships between insulin resistance and percentage of body fat, fitness, and physical activity in children-the LOOK study.

BACKGROUND: Knowledge of individual changes in insulin resistance (IR) and longitudinal relationships of IR with lifestyle-associated factors are of important practical significance, but little longitudinal data exist in asymptomatic children. We aimed to determine (a) changes in the homeostatic model of insulin resistance (HOMA-IR) over a 2-yr period and (b) comparisons of longitudinal and cross-sectional relationships between HOMA-IR and lifestyle-related risk factors. METHODS: Our subjects, 241 boys and 257 girls, were assessed at age 8.1 yr (SD 0.35) and again 2 yr later for fasting blood glucose and insulin, dual X-ray absorptiometry-assessed percentage of body fat (%BF), pedometer-assessed physical activity (PA), and cardio-respiratory fitness (CRF) by multistage running test. RESULTS: HOMA-IR was initially 9% greater in girls than boys and 27% greater 2 yr later. There was no evidence of longitudinal relationships between HOMA-IR and %BF in boys or girls, despite significant cross-sectional relationships (p < 0.001). In boys, there was evidence of a longitudinal relationship between HOMA-IR and both PA (p < 0.001) and CRF (p = 0.05). In girls, we found a cross-sectional relationship between HOMA-IR and CRF (p < 0.001). CONCLUSIONS: HOMA-IR increases between 8 and 10 yr of age and to a greater extent in girls. Longitudinal, unlike cross-sectional, relationships do not support the premise that body fat has any impact on HOMA-IR during this period or that PA or CRF changes affect HOMA-IR in girls. These data draw attention to difficulties in interpreting observational studies in young children.

The lifestyle of our kids (LOOK) project: outline of methods.

This methods paper outlines the overall design of a community-based multidisciplinary longitudinal study with the intent to stimulate interest and communication from scientists and practitioners studying the role of physical activity in preventive medicine. In adults, lack of regular exercise is a major risk factor in the development of chronic degenerative diseases and is a major contributor to obesity, and now we have evidence that many of our children are not sufficiently active to prevent early symptoms of chronic disease. The lifestyle of our kids (LOOK) study investigates how early physical activity contributes to health and development, utilizing a longitudinal design and a cohort of eight hundred and thirty 7-8-year-old (grade 2) school children followed to age 11-12 years (grade 6), their average family income being very close to that of Australia. We will test two hypotheses, that (a) the quantity and quality of physical activity undertaken by primary school children will influence their psychological and physical health and development; (b) compared with existing practices in primary schools, a physical education program administered by visiting specialists will enhance health and development, and lead to a more positive perception of physical activity. To test the first hypothesis we will monitor all children longitudinally over the 4 years. To test the second we will involve an intervention group of 430 children who receive two 50min physical education classes every week from visiting specialists and a control group of 400 who continue with their usual primary school physical education with their class-room teachers. At the end of grades 2, 4, and 6 we will measure several areas of health and development including blood risk factors for chronic disease, cardiovascular structure and function, physical fitness, psychological characteristics and perceptions of physical activity, bone structure and strength, motor control, body composition, nutritional intake, influence of teachers and family, and academic performance.

Discordance of international adiposity classifications in Australian boys and girls - the LOOK study.

BACKGROUND: Various charts based on body mass index (BMI) and per cent body fat (%BF) are used to classify childhood body composition but outcomes may vary. AIM: The study investigated variation in incidences of childhood obesity as depicted by four classification charts. SUBJECTS AND METHODS: BMI and DXA-derived %BF were assessed in 741 children. Incidences of overweight and obesity were compared between two BMI charts and two bioelectrical impedance (BIA)-based %BF charts. RESULTS: The International Obesity Task Force (IOTF)-adopted BMI chart designated 21%, 6% (boys), and 26%, 9% (girls) as overweight and obese, respectively. Corresponding figures using the USA CDC BMI chart were 27%, 11% (boys) and 27%, 12% (girls). Using a USA-derived %BF chart incidences were 17%, 2% (boys) and 21%, 8% (girls) and using a UK-derived %BF chart 51%, 24% (boys) and 53%, 36% (girls). Sensitivity of BMI varied according to the %BF reference chart. CONCLUSIONS: In contrast to the BMI-based charts, there were considerable variations in depicted incidences of obesity between the %BF-based charts. These discordances were considered to result from previously reported variation within and between BIA and DXA %BF assessments underlying the charts. The present study highlights the need for valid, reliable, unchanging BIA and DXA procedures.

Treatment of pulmonary hypertension with sildenafil in a neonate with spondyloepiphyseal dysplasia congenita.

Persistent pulmonary hypertension of the newborn (PPHN) remains an important cause of mortality and morbidity in the term neonate. Preliminary but limited data suggest that there may be a role for sildenafil in the treatment of PPHN. We report the successful treatment of PPHN caused by pulmonary hypoplasia in a patient with spondyloepiphyseal dysplasia congenita.

Filtration of Glass Delamination Particles with West Pharmaceutical Vial Adapters.

UNLABELLED: One major current challenge facing companies producing injectable drugs contained in glass vials is the phenomenon of delamination that results in drug contamination. Particulate contamination of parenteral fluids is a fact of life. Particulate infusion is unlikely to cause immediate or severe signs and symptoms, but adverse effects, tissue damage, and loss of function are likely in the long term. Since 2010, recalls due to glass delamination have increased, and recently the U.S. Food and Drug Administration exercised temporary regulatory flexibility by allowing filtration as means of removing glass particles. The vial adapter is a needle-free product from West Pharmaceuticals Services that provides a simple and cost-effective solution for the safe and rapid transfer reconstitution of drugs between vials and syringes. One variant of the vial adapter is integrated with a filter to address various types of particles. In the present study, the performance of the filter-integrated vial adapter is evaluated with respect to glass delamination particles. Silica particles of 0.5-10 µm are used to emulate glass delamination particles. High-filtration efficiency is demonstrated according to the severest criteria stated by the British Pharmacopoeia that allows up to 100 particles smaller than 5 µm for every 1 mL liquid of a large-volume parenteral. The study was conducted using environmental scanning electron microscopy and statistical analysis. LAY ABSTRACT: One major current challenge facing companies producing injectable drugs contained in glass vials is the phenomenon of delamination that results in drug contamination. Glass delamination is defined as degradation of surface glass, as from a vial, that produces glass flakes. Contamination of injectable drugs due to glass delamination is a fact of life. Normally, this type of contamination does not involve immediate severe signs, but rather accumulative damage to tissues in the long run. Recently, the U.S. Food and Drug Administration allowed the filtration as means of removing particles. The vial adapter is a needle-free product from West Pharmaceuticals Services that provides a simple and cost-effective solution for the safe and rapid transfer reconstitution of drugs between vials and syringes. One variant of the vial adapter is integrated with a filter to address various types of particles. In the present study, the performance of the filter-integrated vial adapter is evaluated with respect to glass delamination particles. Silica particles of 0.5-10 µm are used to emulate glass delamination particles. High-filtration efficiency is demonstrated according to the severest criteria stated by the British Pharmacopoeia that allows up to 100 particles smaller than 5 µm for every 1 mL liquid of a large-volume parenteral. The study was conducted using environmental scanning electron microscopy and statistical analysis.

Five-year Antibody Persistence and Safety After a Single Dose of Combined Haemophilus influenzae Type B Neisseria meningitidis Serogroup C-Tetanus Toxoid Conjugate Vaccine in Haemophilus influenzae Type B-primed Toddlers.

BACKGROUND: Antibody persistence is evaluated in healthy Australian children 4 and 5 years postvaccination with a single dose of combined Haemophilus influenzae type b-Neisseria meningitidis serogroup C tetanus toxoid conjugate vaccine (Hib-MenC-TT) compared with separately administered Hib-TT and MenC-CRM197 vaccines (Hib + MCC). METHODS: This is another follow-up of a phase III, open, randomized, controlled study (NCT00326118), in which 433 Hib-primed but MenC naïve toddlers aged 12-18 months were randomized 3:1 to receive Hib-MenC-TT or Hib + MCC vaccines. Protection against (1) MenC was measured by serum bactericidal antibody assay using rabbit complement (rSBA) and (2) Hib was measured by enzyme-linked immunosorbent assay of antibodies to polyribosylribitol phosphate (anti-PRP). Study children were assessed for any potentially vaccine-related serious adverse events at each persistence study visit. RESULTS: The according-to-protocol cohorts for persistence at years 4 and 5 included 282 and 263 children, respectively. The percentages of children with rSBA-MenC titers ≥1:8 at years 4 and 5 were 12.5% and 19.0%, respectively, in the Hib-MenC group; and 12.3% and 25.0% in the Hib + MCC group. All children in each group had anti-PRP concentrations ≥0.15 µg/mL at year 5. Exploratory analyses suggested no potential differences between groups in rSBA-MenC or anti-PRP antibody persistence. No vaccine-related serious adverse events were reported. CONCLUSIONS: Antibody persistence was similar for years 4 and 5 after Hib-MenC-TT or Hib + MCC vaccination, with the majority of children retaining anti-PRP antibody concentrations ≥0.15 µg/mL at both timepoints. The percentage of children retaining rSBA-MenC titers ≥1:8 was low (≤25%), suggesting that a MenC booster dose may be warranted before adolescence.

Predictors of disease severity in children hospitalized for pertussis during an epidemic.

BACKGROUND: Australia recently experienced its worst pertussis epidemic since introduction of pertussis vaccine into the National Immunisation Program. This study aimed to determine factors associated with severe pertussis in hospitalized children during an epidemic using a novel pertussis severity scoring (PSS) system. METHODS: This prospective, observational, multicenter study enrolled children hospitalized with laboratory confirmed pertussis from 8 tertiary pediatric hospitals during a 12 month period (May 2009-April 2010). Variables assessed included demographics, clinical symptoms and relevant medical and immunization history. Cases were scored using objective clinical findings with cases classified as either severe (PSS > 5) or not severe (PSS ≤ 5). Logistic regression models were used to predict variables associated with severe disease. RESULTS: One hundred twenty hospitalized children 0-17 years of age were enrolled with a median PSS of 5 (interquartile range 3-7). Most (61.7%) were classified as not severe with 38.3% (46/120) severe. Most severe cases (54.3%) were <2 months of age. Presence of coinfection [odds ratio (OR): 4.82, CI: 1.66-14.00], <2 months old (OR: 4.76, CI: 1.48-15.32), fever >37.5°C (OR: 5.97, CI: 1.19-29.96) and history of prematurity (OR: 5.00, CI: 1.27-19.71) were independently associated with severe disease. A total of 70 cases in children ≥2 months of age, almost a third (n = 23) had not received pertussis vaccine. CONCLUSIONS: Most severe pertussis occurred in young, unimmunized infants, although severe disease was also observed in children >12 months of age and previously vaccinated children. Children admitted with pertussis with evidence of coinfection, history of prematurity or fever on presentation need close monitoring.

Group A Streptococcal Carriage and Seroepidemiology in Children up to 10 Years of Age in Australia.

BACKGROUND: Group A streptococci (GAS) and other ß-hemolytic streptococci (BHS) cause pharyngitis, severe invasive disease and serious nonsuppurative sequelae including rheumatic heart disease and post streptococcal glomerulonephritis. The aim of this study was to assess carriage rates and anti-streptococcal C5a peptidase (anti-SCP) IgG levels and identify epidemiologic factors related to carriage or seropositivity in Australian children. METHODS: A throat swab and blood sample were collected for microbiological and serological analysis (anti-SCP IgG) in 542 healthy children aged 0-10 years. Sequence analysis of the SCP gene was performed. Serological analysis used a competitive Luminex Immunoassay designed to preferentially detect functional antibody. RESULTS: GAS-positive culture prevalence in throat swabs was 5.0% (range 0-10%), with the highest rate in 5 and 9 years old children. The rate of non-GAS BHS carriage was low (<1%). The scp gene was present in all 22 isolates evaluated. As age of child increased, the rate of carriage increased; odds ratio, 1.14 (1.00, 1.29); P = 0.50. Geometric mean anti-SCP titers increased with each age-band from 2 to 7 years, then plateaued. Age, geographic location and number of children within the household were significantly associated with the presence of anti-SCP antibodies. CONCLUSIONS: Children are exposed to GAS and other BHS at a young age, which is important for determining the target age for vaccination to protect before the period of risk.

Anxiety comorbidity in schizophrenia.

Diagnostic and treatment hierarchical reductionisms have led to an oversight of anxiety syndromes in schizophrenia. Nevertheless, recent data have indicated that anxiety can be a significant source of morbidity in this patient group. This paper reviews current knowledge concerning anxiety comorbidity in schizophrenia, its epidemiology, course, and treatment. A computerized search of the literature published from 1966 to July 2012 was conducted on Medline. Comorbid anxiety disorders are present in 38.3% of subjects with schizophrenia spectrum disorders. The most common anxiety disorder is social phobia followed by post-traumatic stress disorder and obsessive compulsive disorder. The presence and severity of symptoms of anxiety are associated with more severe clinical features and poorer outcomes. Available literature on the treatment consists primarily of case reports and open trials. Fragments of data support the notion of treating these anxiety states and syndromes as co-occurring clinical conditions with adjunctive medications and psychosocial interventions. However, additional work remains to be done on this issue before firm conclusions can be drawn.

Three-year antibody persistence and safety after a single dose of combined haemophilus influenzae type b (Hib)-Neisseria meningitidis serogroup C-tetanus toxoid conjugate vaccine in Hib-primed toddlers.

BACKGROUND: Persistence of seroprotective bactericidal antibody titers is important for long-term protection against meningococcal serogroup C disease in young children. Antibody persistence values were determined in children up to 3 years after vaccination with a single dose of the combined Haemophilus influenzae type b (Hib)-Neisseria meningitidis serogroup C (MenC)-tetanus toxoid (TT) conjugate vaccine (Hib-MenC-TT; www.ClinicalTrials.gov: NCT00326118). METHODS: The children had been randomized at ages 12-18 months to receive either 1 dose of Hib-MenC-TT (Hib-MenC group) or separately administered Hib-TT conjugate vaccine and MenC-CRM197 (MCC) vaccine (Hib plus MCC group). All children had been primed in infancy with a Hib vaccine. Antibodies against MenC were measured by a serum bactericidal assay using rabbit complement (rSBA-MenC) and antibodies against Hib polyribosylribitol phosphate were assessed by enzyme-linked immunosorbent assay. RESULTS: The rSBA-MenC titers ≥1:8 were demonstrated 3 years after vaccination in 64.2% and 53.2% of participants in the Hib-MenC group and in the Hib plus MCC group, respectively. Antipolyribosylribitol phosphate concentrations ≥0.15 µg/mL persisted in >98% of participants in both groups. The rSBA-MenC geometric mean titers and antipolyribosylribitol phosphate geometric mean concentrations remained higher 3 years after vaccination than before vaccination. No serious adverse events assessed by the investigator as being related to vaccination were reported. CONCLUSION: In this antibody persistence study of Hib-primed but MenC-naïve toddlers who received a single dose of Hib-MenC-TT, protective antibody levels against Hib and MenC were maintained in the majority of children 3 years after vaccination.

Safety and tolerability of a 2009 trivalent inactivated split-virion influenza vaccine in infants, children and adolescents.

OBJECTIVE: To evaluate the safety of CSL's split-virion inactivated trivalent 2009 Southern Hemisphere formulation influenza vaccine (TIV) in children. METHODS: We enrolled 1992 healthy children into three groups: Cohorts A, ≥ 6 months to <3 years; B, ≥ 3 years to <9 years; and C, ≥ 9 years to <18 years. Children received one or two doses of 0.25 ml (22.5 µg haemagglutinin) or 0.5 ml (45 µg) TIV, depending on age and prior vaccination history. We collected post-vaccination solicited adverse event (AE) data (days 0-6), including fever (temperature: ≥ 37.5°C axilla, ≥ 38.0°C oral), unsolicited AEs (days 0-29) and serious AEs (SAEs) and new-onset chronic illnesses (NOCIs; to day 180 after last vaccination). RESULTS: At least one solicited AE was reported by 80%/78%/78% of children in Cohorts A, B and C, respectively. Systemic AEs were more common among Cohort A (72% of participants), and local AEs were more common among Cohort C (71% of participants). Fever was more common in younger cohorts, in influenza vaccine-naïve children (29% of Cohort A receiving their first dose), and following first compared with second doses. Severe fever following a first dose prevented 20 participants receiving their second scheduled vaccine dose. A 7-month-old participant had a single uncomplicated febrile convulsion on the day of vaccination. CONCLUSIONS: Nearly 80% of subjects reported at least one solicited AE following immunization. Fever prevalence was highest in vaccine-naïve Cohort A participants, similar to other paediatric studies using CSL vaccine. Further research to understand fever-related AEs in children following CSL's TIV is recommended.

A randomized trial to assess safety and immunogenicity of alternative formulations of a quadrivalent meningococcal (A, C, Y, and W-135) tetanus protein conjugate vaccine in toddlers.

BACKGROUND: Neisseria meningitidis is a leading cause of meningitis and septicemia globally. Recent shifts in serogroup dominance in some settings highlight the desirability of polysaccharide-conjugate vaccines with broader meningococcal coverage than serogroup C vaccines in widespread use. METHODS: We assessed the safety and immunogenicity of a single dose of meningococcal quadrivalent (A, C, W-135, Y) tetanus conjugate vaccine (TetraMen-T), administered at 1 year of age. A total of 378 children were randomized to 1 of 6 groups--5 received alternative formulations of TetraMen-T, the sixth licensed adjuvanted serogroup C conjugate vaccine (Neisvac-C). Solicited adverse event reports were collected from day 0 to 7 after vaccination and unsolicited and serious adverse event reports throughout study participation. Immunogenicity was assessed by serum bactericidal assays containing either a human (hSBA) or baby rabbit (rSBA) complement source before and 1 month after immunization. RESULTS: All vaccine formulations were safe and well tolerated. Using the various measures of immunogenicity, no consistent relationships were observed between the dose of either polysaccharide or carrier and serogroup-specific response for any one antigen. The highest-dose vaccine provided optimal coverage for all 4 serogroups, with the percentage of recipients achieving hSBA titers ≥ 8 against each as follows: A, 92%; C, 96%; W-135, 71%; Y, 82% (corresponding proportions with rSBAs titers >8 all exceeded 90%). The investigational vaccines were less immunogenic against the serogroup C capsular polysaccharide than the licensed comparator. CONCLUSIONS: Studies are ongoing that will help to identify optimal scheduling of quadrivalent meningococcal conjugate vaccines, to facilitate their inclusion into national immunization programs seeking extended serogroup coverage against meningococci.