Robert S. Ware

Number and Order of Whole Cell Pertussis Vaccines in Infancy and Disease Protection

lowing negative studies. Despite studies showing that echinacea does not treat cold symptoms, it is one of the best selling supplements in the United States with estimated sales exceeding

A systematic review of tests to predict cerebral palsy in young children

300 million per year. Dr Leach claims that I supported my position “through the selective reporting of a few clinical studies.” However, all studies are not equal. The studies I selected regarding gingko, chondroitin sulfate, glucosamine, garlic, St John’s wort, milk thistle, and echinacea were the best controlled, most rigorous, and most internally consistent. Indeed, most of these excellent studies were supported by NCCAM. Briggs and Killen and Leach argue that refraining from studying alternative medicine would deny the public muchneeded clinical data to make informed health care decisions. In a better world, of course, this discussion would not be happening. In a better world, dietary supplements and alternative therapies would be subject to testing before claims were allowed, as is required by the US Food and Drug Administration (FDA) for licensure of drugs, biologicals, and medical devices. Now patients are stuck with a system in which some alternative medicines might be tested after claims have been made and after nutraceutical companies have spent millions of dollars “educating” the public. At best, NCCAM functions as a post-hoc FDA, except without the FDA’s regulatory authority and without the communication skills or dollars to confront a well-heeled nutraceutical industry. Sadly, until the 1994 Dietary Supplement and Health Education Act—which essentially freed the nutraceutical industry from FDA oversight—is repealed, consumers will continue to receive bad information that could lead to bad medical decisions, NCCAM or no NCCAM.

A prospective, randomized trial of rifampicin-minocycline-coated and silver-platinum-carbon-impregnated central venous catheters

This systematic review evaluates the accuracy of predictive assessments and investigations used to assist in the diagnosis of cerebral palsy (CP) in preschool‐age children (<5y).

Long-term azithromycin for Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease (Bronchiectasis Intervention Study): a multicentre, double-blind, randomised controlled trial

Objective:Central venous catheters are the predominant cause of nosocomial bacteremia; however, the effectiveness of different antimicrobial central venous catheters remains uncertain. We compared the infection rate of silver-platinum-carbon (SPC)-impregnated catheters with rifampicin-minocycline (RM)-coated catheters. Design:A large, single-center, prospective randomized study. Setting:Twenty-two-bed adult general intensive care unit in a large tertiary metropolitan hospital in Brisbane, Australia (2000–2001). Patients:Consecutive series of all central venous catheterizations in intensive care unit patients. Interventions:Randomization, concealment, and blinding were carefully performed. Catheter insertion and care were performed according to published guidelines. Blood cultures were taken at central venous catheter removal, and catheter-tip cultures were performed by both roll-plate and sonication techniques. Pulsed field gel electrophoresis was used to establish shared clonal origin for matched isolates. Measurements and Main Results:Central venous catheter colonization and catheter-related bloodstream infection were determined with a blinded technique using the evaluation of the extensive microbiological and clinical data collected and a rigorous classification system. Six hundred forty-six central venous catheters (RM 319, SPC 327) were inserted, and 574 (89%) were microbiologically evaluable. Colonization rates were lower for the RM catheters than SPC catheters (25 of 280, 8.9%; 43 of 294, 14.6%; p = .039). A Kaplan-Meier analysis that included catheter time in situ did not quite achieve statistical significance (p = .055). Catheter-related bloodstream infection was infrequent for both catheter-types (RM 4, 1.4%; SPC 5, 1.7%). Conclusions:The SPC catheter is a clinically effective antimicrobial catheter; however, the RM catheter had a lower colonization rate. Both catheter types had low rates of catheter-related bloodstream infection. These results indicate that future studies will require similar rigorous methodology and thousands of central venous catheters to demonstrate differences in catheter-related bloodstream infection rates.

Oropharyngeal Dysphagia and Gross Motor Skills in Children With Cerebral Palsy

BACKGROUND Indigenous children in high-income countries have a heavy burden of bronchiectasis unrelated to cystic fibrosis. We aimed to establish whether long-term azithromycin reduced pulmonary exacerbations in Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease. METHODS Between Nov 12, 2008, and Dec 23, 2010, we enrolled Indigenous Australian, Maori, and Pacific Island children aged 1-8 years with either bronchiectasis or chronic suppurative lung disease into a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial. Eligible children had had at least one pulmonary exacerbation in the previous 12 months. Children were randomised (1:1 ratio, by computer-generated sequence with permuted block design, stratified by study site and exacerbation frequency [1-2 vs ≥3 episodes in the preceding 12 months]) to receive either azithromycin (30 mg/kg) or placebo once a week for up to 24 months. Allocation concealment was achieved by double-sealed, opaque envelopes; participants, caregivers, and study personnel were masked to assignment until after data analysis. The primary outcome was exacerbation (respiratory episodes treated with antibiotics) rate. Analysis of the primary endpoint was by intention to treat. At enrolment and at their final clinic visits, children had deep nasal swabs collected, which we analysed for antibiotic-resistant bacteria. This study is registered with the Australian New Zealand Clinical Trials Registry; ACTRN12610000383066. FINDINGS 45 children were assigned to azithromycin and 44 to placebo. The study was stopped early for feasibility reasons on Dec 31, 2011, thus children received the intervention for 12-24 months. The mean treatment duration was 20·7 months (SD 5·7), with a total of 902 child-months in the azithromycin group and 875 child-months in the placebo group. Compared with the placebo group, children receiving azithromycin had significantly lower exacerbation rates (incidence rate ratio 0·50; 95% CI 0·35-0·71; p<0·0001). However, children in the azithromycin group developed significantly higher carriage of azithromycin-resistant bacteria (19 of 41, 46%) than those receiving placebo (four of 37, 11%; p=0·002). The most common adverse events were non-pulmonary infections (71 of 112 events in the azithromycin group vs 132 of 209 events in the placebo group) and bronchiectasis-related events (episodes or investigations; 22 of 112 events in the azithromycin group vs 48 of 209 events in the placebo group); however, study drugs were well tolerated with no serious adverse events being attributed to the intervention. INTERPRETATION Once-weekly azithromycin for up to 24 months decreased pulmonary exacerbations in Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease. However, this strategy was also accompanied by increased carriage of azithromycin-resistant bacteria, the clinical consequences of which are uncertain, and will need careful monitoring and further study. FUNDING National Health and Medical Research Council (Australia) and Health Research Council (New Zealand).

Child Protection Outcomes for Infants of Substance-Using Mothers: A Matched-Cohort Study

OBJECTIVES: To determine the prevalence of oropharyngeal dysphagia (OPD) and its subtypes (oral phase, pharyngeal phase, saliva control), and their relationship to gross motor functional skills in preschool children with cerebral palsy (CP). It was hypothesized that OPD would be present across all gross motor severity levels, and children with more severe gross motor function would have increased prevalence and severity of OPD. METHODS: Children with a confirmed diagnosis of CP, 18 to 36 months corrected age, born in Queensland between 2006 and 2009, participated. Children with neurodegenerative conditions were excluded. This was a cross-sectional population-based study. Children were assessed by using 2 direct OPD measures (Schedule for Oral Motor Assessment; Dysphagia Disorders Survey), and observations of signs suggestive of pharyngeal phase impairment and impaired saliva control. Gross motor skills were described by using the Gross Motor Function Measure, Gross Motor Function Classification System (GMFCS), Manual Ability Classification System, and motor type/ distribution. RESULTS: OPD was prevalent in 85% of children with CP, and there was a stepwise relationship between OPD and GMFCS level. There was a significant increase in odds of having OPD, or a subtype, for children who were nonambulant (GMFCS V) compared with those who were ambulant (GMFCS I) (odds ratio = 17.9, P = .036). CONCLUSIONS: OPD was present across all levels of gross motor severity using direct assessments. This highlights the need for proactive screening of all young children with CP, even those with mild impairments, to improve growth and nutritional outcomes and respiratory health.

A new method for objective identification and measurement of airway lumen in paediatric flexible videobronchoscopy

OBJECTIVE: Parental drug use is a critical public health issue; it is estimated to be present in up to 80% of referrals to Australian child protection agencies. However, no data regarding the child protection outcomes of infants of substance-using parents exist in Australia, and no comparisons have been made with infants of non–substance-using parents. We assessed differences in substantiated abuse between 2 groups of mothers in Brisbane to quantify this risk. METHODS: Mothers who disclosed opiate, amphetamine, or methadone use between 2000 and 2003 were identified and compared with non–substance-using mothers who were matched for gender and gestational age. All infants were linked to the Department of Child Safety Child Protection Information System database. Child protection outcomes, such as substantiated notifications and entry into foster care, were compared between groups. RESULTS: We studied 119 infants of substance-using mothers and 238 matched infants. Infants of substance-using mothers were more likely to suffer substantiated harm (hazard ratio 13.3 [95% confidence interval 4.6–38.3]) and to enter foster care (hazard ratio 13.3 [95% confidence interval 5.1–34.3]). Infants of mothers using illicit drugs were more likely to suffer substantiated harm and more likely to enter foster care than infants of mothers who were compliant with a methadone program. CONCLUSIONS: Infants of substance-using mothers have much poorer child protection outcomes than infants of non–substance-using mothers. This study adds substantial evidence toward a real association between maternal drug use and child abuse. Greater interagency collaboration is urgently required to reduce this risk.

Australian Cerebral Palsy Child Study Protocol of a prospective population based study of motor and brain development of preschool aged children with cerebral palsy

Background: Accurate measurements of airway and lesion dimensions are important to the developmental progress of paediatric bronchoscopy. The malacia disorders are an important cause of respiratory morbidity in children, but no methods are currently available to measure these lesions or the airway lumen accurately. A new measurement technique is described here. Methods: The magnification power of a paediatric videobronchoscope was defined and a simple and user friendly computer based program (Image J) was used to develop an objective technique (colour histogram mode technique, CHMT) for measurement of the airway lumen. Results: In vivo intra-observer and inter-observer repeatability coefficients for repeated area measurements from 28 images using the Bland-Altman method were 0.9 mm2 and 1.6 mm2, respectively. The average intraclass correlation coefficient for repeated measurements of area was 0.93. In vitro validation measurements using a 2 mm diameter tube resolved radii measurements to within 0.1 mm (coefficient of variability 8%). An “acceptable result” was defined in 92% of 734 images completed with the CHMT alone and 8% with its modification. The success rate for two of three images being within 10% of each other’s area was 100%. Measurements of cricoid cross sectional areas from 116 patients compared with expected airway areas for age derived from endotracheal tube sizes were comparable. Conclusions: The CHMT method of identifying and measuring airway dimensions is objective, accurate, and versatile and, as such, is important to the future development of flexible videobronchoscopy.

Living with diabetes: rationale, study design and baseline characteristics for an Australian prospective cohort study

BackgroundCerebral palsy (CP) results from a static brain lesion during pregnancy or early life and remains the most common cause of physical disability in children (1 in 500). While the brain lesion is static, the physical manifestations and medical issues may progress resulting in altered motor patterns. To date, there are no prospective longitudinal studies of CP that follow a birth cohort to track early gross and fine motor development and use Magnetic Resonance Imaging (MRI) to determine the anatomical pattern and likely timing of the brain lesion. Existing studies do not consider treatment costs and outcomes. This study aims to determine the pathway(s) to motor outcome from diagnosis at 18 months corrected age (c.a.) to outcome at 5 years in relation to the nature of the brain lesion (using structural MRI).MethodsThis prospective cohort study aims to recruit a total of 240 children diagnosed with CP born in Victoria (birth years 2004 and 2005) and Queensland (birth years 2006–2009). Children can enter the study at any time between 18 months to 5 years of age and will be assessed at 18, 24, 30, 36, 48 and 60 months c.a. Outcomes include gross motor function (GMFM-66 & GMFM-88), Gross Motor Function Classification System (GMFCS); musculoskeletal development (hip displacement, spasticity, muscle contracture), upper limb function (Manual Ability Classification System), communication difficulties using Communication and Symbolic Behaviour Scales-Developmental Profile (CSBS-DP), participation using the Paediatric Evaluation of Disability Inventory (PEDI), parent reported quality of life and classification of medical and allied health resource use and determination of the aetiology of CP using clinical evaluation combined with MRI. The relationship between the pathways to motor outcome and the nature of the brain lesion will be analysed using multiple methods including non-linear modelling, multilevel mixed-effects models and generalised estimating equations.DiscussionThis protocol describes a large population-based study of early motor development and brain structure in a representative sample of preschool aged children with CP, using direct clinical assessment. The results of this study will be published in peer reviewed journals and presented at relevant international conferences.Trial registrationAustralia and New Zealand Clinical Trials Register (ACTRN1261200169820)

Effects of health screening for adults with intellectual disability: a pooled analysis.

BackgroundDiabetes mellitus is a major global public health threat. In Australia, as elsewhere, it is responsible for a sizeable portion of the overall burden of disease, and significant costs. The psychological and social impact of diabetes on individuals with the disease can be severe, and if not adequately addressed, can lead to the worsening of the overall disease picture. The Living With Diabetes Study aims to contribute to a holistic understanding of the psychological and social aspects of diabetes mellitus.Methods/DesignThe Living With Diabetes Study is a 5-year prospective cohort study, based in Queensland, Australia. The first wave of data, which was collected via a mailed self-report survey, was gathered in 2008, with annual collections thereafter. Measurements include: demographic, lifestyle, health and disease characteristics; quality of life (EQ-5D, ADDQoL); emotional well-being (CES-D, LOT-R, ESSI); disease self-management (PAM); and health-care utilisation and patient-assessed quality of care (PACIC). 29% of the 14,439 adults who were invited to participate in the study agreed to do so, yielding a sample size of 3,951 people.DiscussionThe data collected by the Living With Diabetes Study provides a good representation of Australians with diabetes to follow over time in order to better understand the natural course of the illness. The study has potential to further illuminate, and give a comprehensive picture of the psychosocial implications of living with diabetes. Data collection is ongoing.