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Biomedical subjects

John B Carlin

Publications and source records attributed to John B Carlin.

18 recordsLinked to original sources

Prediction of childhood pulmonary function using ulna length.

Pulmonary function is important in neuromuscular weakness. In children, height determines normal values. Height measurement is unreliable when neuromuscular weakness or spinal deformity is present. The aim of this study was to accurately predict pulmonary function from a limb segment measurement that is precise and reproducible. Normal males (n = 1,144) and females (n = 1,199), 5.3 to 19.6 years old, were recruited from Melbourne schools. Height, weight, ulna, forearm, tibia, and lower leg lengths were measured using a Harpenden stadiometer and calipers, and electronic scales. Three maximal expiratory maneuvers were performed. Limb measurements were highly reproducible. Linear regression on log-transformed FEV1 and FVC was used to develop prediction equations from limb measurements and age. In males FEV1 = exp (0.071 x U + 0.046 x A - 1.269), r2 = 0.86; FVC = exp (0.77 x U + 0.041 x A - 1.285), r2 = 0.86 and in females FEV1 = exp (0.072 x U + 0.041 x A - 1.272), r2 = 0.84; FVC = exp (0.078 x U + 0.037 x A - 1.315), r2 = 0.83 (U refers to ulna length and A refers to age). Precision is similar to equations using height. Ulna measurement is accessible in wheelchair-bound children. Using ulna length to predict pulmonary function should facilitate respiratory assessment in children whose height is difficult to measure.

Adolescent↗

The epidemiology of childhood cardiomyopathy in Australia.

BACKGROUND: The incidence and age distribution of primary cardiomyopathy in children are not well defined. We undertook a population-based, retrospective cohort study in Australia to document the epidemiology of childhood cardiomyopathy. METHODS: We analyzed all cases of primary cardiomyopathy in children who presented between 1987 and 1996 and who were younger than 10 years of age. Children were recruited from multiple sources, and cases of cardiomyopathy were classified according to World Health Organization guidelines. RESULTS: Over the 10-year period, 314 new cases of primary cardiomyopathy were identified, for an annual incidence of 1.24 per 100,000 children younger than 10 years of age (95 percent confidence interval, 1.11 to 1.38). Dilated cardiomyopathy made up 58.6 percent of cases, hypertrophic cardiomyopathy 25.5 percent, restrictive cardiomyopathy 2.5 percent, and left ventricular noncompaction 9.2 percent of cases. The incidence of all types of cardiomyopathy except restrictive declined rapidly after infancy. In 11 cases (3.5 percent), sudden death was the first symptom. There was a male predominance among children with hypertrophic and unclassified cardiomyopathy. Indigenous children had a higher incidence of dilated cardiomyopathy than nonindigenous children (relative risk, 2.67; 95 percent confidence interval, 1.42 to 4.63) and a higher rate of death as the presenting symptom (16.7 percent vs. 2.6 percent, P=0.02). Lymphocytic myocarditis was present in 25 of 62 children with dilated cardiomyopathy (40.3 percent) who underwent cardiac histologic examination within two months after presentation. CONCLUSIONS: Lymphocytic myocarditis and left ventricular noncompaction are important causes of childhood cardiomyopathy in Australia. The timing and severity of presentation in children with cardiomyopathy are related to the type of cardiomyopathy, as well as to genetic and ethnic factors.

Age Distribution↗

Transitions in an imperfectly observed binary variable: depressive symptomatology in adolescents.

We describe a methodology for analysing transitions over time in a binary outcome variable that is subject to misclassification (that is, measurement error). Logistic regression models for transition events in the true underlying state are combined with estimates of probabilities of misclassification of the underlying state. The model is based on the Markovian assumption that the probabilities of transition in the underlying state at a given time depend only on the underlying state at the previous time. Hence we estimate odds-ratio effects for transitions that are adjusted for the effect of misclassification. Comparing these adjusted estimates with estimates that are obtained without taking misclassification into account indicates that the latter can be biased either toward or away from the null. For the estimates to exist, certain restrictions on the observed data and misclassification probabilities need to be met. If these restrictions are not satisfied then the conclusion from the analysis is that all observed transition events can be explained solely by the error in outcome assessment, in which case it is likely that an aspect of the model is incorrect. The motivation for this work comes from an analysis of transitions in depression status for a cohort of Australian teenagers participating in a longitudinal study of adolescent health.

Adolescent↗

Repeatability of bronchial responsiveness to mannitol dry powder in children with asthma.

Our objective was to determine the repeatability of bronchial responsiveness to mannitol dry powder (MDP) as an objective marker of asthma in children. MDP challenge was performed in children with stable asthma at the same time of the day on two separate occasions within a week. The test was terminated after a 15% fall of forced expiratory volume in 1 sec (FEV1) and the provocative dose to produce a 15% fall in FEV1 (PD15) were calculated. Seventeen children (aged 9-16 years) on inhaled corticosteroids (200-1,500 mcg) were studied. Mean baseline FEV1 before the challenges were 95% (81-119) and 96% (74-121), respectively, with a standard deviation of differences of 5.2%. PD(15) values ranged from 7-387 mg, with a geometric mean of 38 mg for the first and 49 mg for the second test. Of the 17, all but two pairs of tests achieved a PD15 within one dose of capsules. Four children had a negative challenge on two occasions. A high relative reliability was reflected by a concordance coefficient of 0.86. In conclusion, MDP is a convenient challenge which is easy to administer and is well-tolerated by children. It is a highly reproducible test of airway responsiveness in children with moderate to severe persistent asthma on inhaled corticosteroids within 7 days under laboratory conditions.

Administration, Inhalation↗

A longitudinal study of the effects of adolescent cannabis use on high school completion.

OBJECTIVE: To examine the extent to which weekly cannabis use during mid-adolescence may increase the risk of early school-leaving. SETTING: A prospective study of a general population sample of adolescents studied from ages 15-21 years in Melbourne, Australia. METHOD: Computer-assisted self-completion questionnaires and telephone interviews conducted in six waves at ages 15-18 and again at age 21 in a sample of 1601 male and female school students. RESULTS: Weekly cannabis use, assessed prospectively, was associated with significantly increased risk of early school-leaving. This effect remained after adjustment for a range of prospectively assessed covariates including demographic characteristics, other substance use, psychiatric morbidity and antisocial behavior. There was suggestive evidence of an interaction between weekly cannabis use and age with the effects of weekly cannabis use on early school-leaving being strongest at the youngest ages and diminishing progressively with age. CONCLUSIONS: Early regular cannabis use (weekly use at age 15) is associated with increased risk of early school-leaving. These effects of regular cannabis use may diminish with increasing age and are likely to operate through the social context within which cannabis is used and obtained.

Adolescent↗

Predictors of neonatal sepsis in developing countries.

BACKGROUND: Neonatal infections are a major cause of death worldwide. Simple procedures for identifying infants with infection that need referral for treatment are therefore of major public health importance. METHODS: We investigated 3303 infants <2 months of age presenting with illness to health facilities in Ethiopia, The Gambia, Papua New Guinea and The Philippines, using a standardized approach. Historical factors and clinical signs predicting sepsis, meningitis, hypoxemia, deaths and an ordinal scale indicating severe disease were investigated by logistic regression, and the performance of simple combination rules was explored. RESULTS: In multivariable analysis, reduced feeding ability, no spontaneous movement, temperature >38 degrees C, being drowsy/unconscious, a history of a feeding problem, history of change in activity, being agitated, the presence of lower chest wall indrawing, respiratory rate >60 breaths/min, grunting, cyanosis, a history of convulsions, a bulging fontanel and slow digital capillary refill were independent predictors of severe disease. The presence of any 1 of these 14 signs had a sensitivity for severe disease (defined as sepsis, meningitis, hypoxemia, or radiologically proven pneumonia) of 87% and a specificity of 54%. More stringent combinations, such as demanding 2 signs from the list, resulted in a considerable loss of sensitivity. By contrast only slight loss of sensitivity and considerable gain of specificity resulted from reducing the list to 9 signs. Requiring the presence of fever and any other sign produced a diagnostic rule with extremely low sensitivity (25%). CONCLUSIONS: Physical signs can be used to identify young infants at risk of severe disease, however with limited specificity, resulting in large numbers of unnecessary referrals. Further studies are required to validate and refine the prediction of severe disease, especially in the first week of life, but there appear to be limits on the accuracy of prediction that is achievable.

Bacterial Infections↗

Adolescent precursors of cannabis dependence: findings from the Victorian Adolescent Health Cohort Study.

BACKGROUND: Dependence increases the likelihood of adverse consequences of cannabis use, but its aetiology is poorly understood. AIMS: To examine adolescent precursors of young-adult cannabis dependence. METHOD: Putative risk factors were measured in a representative sample (n=2032) of secondary students in the State of Victoria, Australia, six times between 1992 and 1995. Cannabis dependence was assessed in 1998, at age 20-21 years. RESULTS: Of 1601 young adults, 115 met criteria for cannabis dependence. Male gender (OR=2.6, P < 0.01), regular cannabis use (weekly: OR=4.9; daily: OR=4.6, P=0.02), persistent antisocial behaviour (linear effect P=0.03) and persistent cigarette smoking (linear effect P=0.02) independently predicted cannabis dependence. Neither smoking severity (P=0.83) nor persistent psychiatric morbidity (linear effect P=0.26) independently predicted dependence. Regular cannabis use increased risk only in the absence of persistent problematic alcohol use. CONCLUSIONS: Weekly cannabis use marks a threshold for increased risk of later dependence, with selection of cannabis in preference to alcohol possibly indicating an early addiction process.

Adolescent↗

Studies of twins: can they shed light on the fetal origins of adult disease hypothesis?

There has been much interest in evidence that people with lower birthweight have higher risk of adult cardiovascular disease, but the causal pathways underlying such observations are uncertain. Study of twins offers an opportunity to shed light on these pathways, in three different ways. First, in a twin pregnancy maternal nutritional resources and the "supply line" to the fetuses will be more "stretched". We hypothesise that study of twin pregnancies is a more efficient way to identify modifiable maternal factors that influence later health than studies of singleton pregnancies. Second, twins have lower birthweight than singletons. Comparison of cardiovascular disease risk in twins versus that in singletons will provide insight into whether birthweight per se is in the underlying causal pathway of interest, and whether factors constraining fetal growth of twins (versus singletons) affect later outcome. Third, twin cohorts provide an opportunity to investigate the role of "shared" factors versus factors affecting each individual fetus, by comparing results of within-cohort versus within-pair analyses. Generalisability of findings in twins is debated. We suggest that findings in monochorionic twins (or in the absence of chorionicity data, those from monozygotic twins) need to be interpreted with caution.

Animals↗

Cannabis use and mental health in young people: cohort study.

OBJECTIVE: To determine whether cannabis use in adolescence predisposes to higher rates of depression and anxiety in young adulthood. DESIGN: Seven wave cohort study over six years. SETTING: 44 schools in the Australian state of Victoria. PARTICIPANTS: A statewide secondary school sample of 1601 students aged 14-15 followed for seven years. MAIN OUTCOME MEASURE: Interview measure of depression and anxiety (revised clinical interview schedule) at wave 7. RESULTS: Some 60% of participants had used cannabis by the age of 20; 7% were daily users at that point. Daily use in young women was associated with an over fivefold increase in the odds of reporting a state of depression and anxiety after adjustment for intercurrent use of other substances (odds ratio 5.6, 95% confidence interval 2.6 to 12). Weekly or more frequent cannabis use in teenagers predicted an approximately twofold increase in risk for later depression and anxiety (1.9, 1.1 to 3.3) after adjustment for potential baseline confounders. In contrast, depression and anxiety in teenagers predicted neither later weekly nor daily cannabis use. CONCLUSIONS: Frequent cannabis use in teenage girls predicts later depression and anxiety, with daily users carrying the highest risk. Given recent increasing levels of cannabis use, measures to reduce frequent and heavy recreational use seem warranted.

Adolescent↗

Detection of a widespread clone of Pseudomonas aeruginosa in a pediatric cystic fibrosis clinic.

Cross-infection by Pseudomonas aeruginosa between unrelated patients with cystic fibrosis (CF) is believed to be uncommon. After detecting a genotypically identical strain of P. aeruginosa in five unrelated children with CF dying from severe lung disease, we determined its prevalence within a large CF clinic using pulsed-field gel electrophoresis and random amplified polymorphic DNA assays. The clinical status of P. aeruginosa-infected patients was also determined. Between September and December 1999, 152 patients, aged 3.9-20.7 years, provided sputum for culture. P. aeruginosa was detected in 118 children of mean (SD) age 13.5 (3.8) years. The genotyping techniques were concordant, showing that 65 (55%) infected patients carried an indistinguishable or closely related strain. No distinctive antibiogram or environmental reservoir was found. Patients with the clonal strain were more likely than those with unrelated isolates to have been hospitalized in the preceding 12 months for respiratory exacerbations. This study demonstrates extensive spread of a single, clonal strain of P. aeruginosa in a large pediatric CF clinic. Whether this strain is also more virulent than sporadic isolates remains to be determined. As transmissible strains could emerge elsewhere, other CF clinics may also need to consider molecular methods of surveillance for cross-infection.

Adolescent↗

Early phase II trial of human rotavirus vaccine candidate RV3.

A naturally attenuated, human neonatal strain, rotavirus vaccine candidate RV3, was tested in a limited phase II randomized double-blind controlled trial. Doses of 1 ml, containing placebo or 6.5 x 10(5) fluorescent cell forming units (fcfu) of virus in AGMK cells, were given at 3, 5 and 7 months of age. Limited replication in the small intestine is implied by the lack of virus excretion, and by the occurrence of an immune response in only 46% of the infants. However, those who developed an immune response were partially protected against rotavirus disease during the subsequent winter epidemic (protective efficacy 54%), supporting observations of protection induced by natural infection by this strain. Protection appeared to be heterotypic. Further trials are warranted, employing strategies to increase immunogenicity of this human rotavirus candidate vaccine.

Antibodies, Viral↗

Role of the gubernacular bulb in cremaster muscle development of the rat.

The role of the gubernaculum during the inguino-scrotal phase of testicular descent remains controversial. Some authors propose involution and eversion while others suggest active migration, although the site of growth is unknown. We aimed to determine whether the gubernacular bulb is actively proliferating or regressing during inguino-scrotal testicular descent in the rat. Gubernacula were removed from Sprague-Dawley rats and congenitally-cryptorchid TS mutant rats. Animals (0, 3, 7, 10, and 11 days of age) were treated with bromodeoxyuridine (BUdR) 2 hr before they were killed. BUdR incorporation into newly synthesized DNA served as a marker of cell division. The gubernacula were histologically processed for hematoxylin-eosin (H&E) and immunoperoxidase staining. Four different areas within the gubernaculum were examined for BUdR-positive cells: area 1: plica gubernaculi (cord); area 2: pars infravaginalis gubernaculi (bulb); area 3: distal part of the cremaster muscle; and area 4: proximal part of the cremaster muscle. The rate of cell division for each of these areas was determined by counting the number of BUdR-positive cells per 100 cells. The highest rate of BUdR labeling in both types of rats was in area 2, which is the tip of the gubernacular bulb, and this was significantly greater (P < 0.0001) than in the gubernacular cord or developing cremaster muscle. The mitotic activity was also noted to be significantly greater (P < 0.0001) at the distal end of the cremaster muscle than at the proximal end. The amount of mitosis decreased significantly (P < 0.01) in areas 2 and 4 of the gubernaculum in Sprague-Dawley rats across the period studied. This trend was not observed in TS rats. Our results suggest that the bulb actively proliferates after birth, with possible differentiation into new cremaster muscle cells. We propose that the bulb is the growing end of the elongating gubernaculum, analogous to the growth of a limb bud.

Abdominal Muscles↗

Late reduction in cyclosporine dosage does not improve renal function in pediatric heart transplant recipients.

OBJECTIVE: To determine the relation between cyclosporine (CSA) dosage and late renal function in pediatric heart transplant recipients. METHODS: In this retrospective study, pediatric patients were observed for at least 3 years after transplantation, with serial measurement of renal glomerular filtration rate (GFR). Patient variables examined included pre-existing disease (cardiomyopathy or congenital heart disease), age at transplantation, duration of follow-up, and CSA dosage and trough levels at 3 months after transplantation and yearly until the latest follow-up. For each patient, the least squares regression method was used to estimate the average rate of change per year (slope value) for GFR and CSA dosage during follow-up. RESULTS: Twenty-five patients who met the study criteria underwent transplantation at a median age of 11.7 years (interquartile range [IQR], 6.8-14.5 years) and were observed for a median of 6.0 years (IQR, 4-7). The median GFR at 1 year after transplantation was 73 ml/min/1.73 m(2) (IQR, 50-89) and at latest follow-up was 75 ml/min/1.73 m(2) (IQR, 57-98). The median CSA dosage and trough level at 1 year after transplantation were 6.1 mg/kg/day and 234 ng/ml, and at latest follow-up were 3.45 mg/kg/day and 141 ng/ml, respectively. The median rate of change in GFR was +1.6 ml/year of observation (95% confidence interval, -0.9, 4.7) and was inversely related to measured GFR at 1 year after transplantation. The rate of change of GFR was unrelated to any other patient variables including CSA dosages and levels at the specified time intervals and the rate of change of CSA dosage. CONCLUSIONS: Measured GFR in pediatric cardiac transplant recipients treated with CSA is moderately depressed at 12 months after transplantation and does not change significantly during subsequent years. No evidence suggests that the usual progressive reduction in CSA dosage influences renal function beyond 1 year after transplantation.

Adolescent↗

Cannabis dependence in young adults: an Australian population study.

OBJECTIVES: The symptomatology of cannabis dependence remains ill-defined and its importance controversial. Compared with alcohol dependence, the symptom profile of cannabis dependence has received little attention. We aimed to (a) report cannabis use in a representative population of young adults, (b) examine cannabis dependence symptoms according to frequency in the dependence syndrome and (c) contrast the symptomatology of cannabis and alcohol syndromes. METHODS: 1601 young adults (mean age 20.7 years) from an Australian longitudinal cohort study (N=2032) were surveyed in 1998. Regular substance users were assessed for DSM-IV cannabis and alcohol dependence. Prevalence estimates allowed for sampling variation and attrition. RESULTS: Fifty-nine per cent reported life-time use of cannabis, 17% used at least weekly and 7% (11% males, 4% females) met criteria for cannabis dependence. Symptom prevalence in dependent cannabis users was: persistent desire 91%; unintentional use 84%; withdrawal 74%; excessive time obtaining/using 74%; continued use despite health problems 63%; tolerance 21%; and social consequences 18%. The combination of withdrawal, persistent desire and unintentional use was reported by 57%. Dependent cannabis users reported compulsive and out-of-control use more frequently than dependent alcohol users, withdrawal similarly and tolerance considerably less often. CONCLUSIONS: Cannabis use appears to be normative behaviour in young Australians. Progression beyond weekly use of cannabis carries a significant risk of dependence that should be considered in the public health response. The differing profiles of cannabis and alcohol dependence, particularly with regard to craving, draws attention to the need for further study of cannabis dependence as an important and distinct disorder in young adults.

Adolescent↗

A randomized clinical trial: should the child with transient synovitis of the hip be treated with nonsteroidal anti-inflammatory drugs?

STUDY OBJECTIVES: The diagnosis of transient synovitis of the hip ("irritable hip") is made frequently in the pediatric emergency department. We hypothesized that an anti-inflammatory agent (ibuprofen syrup) would shorten the duration of symptoms. METHODS: Patients who were clinically diagnosed with transient synovitis of the hip in the ED between July 1997 and July 1998 were randomized in a double-blind, placebo-controlled trial to receive either ibuprofen syrup (10 mg/kg 3 times a day for 5 days) or placebo. There were stringent exclusion criteria, and patients were only included if there was a low index of suspicion of more serious pathology. All patients had a hip ultrasonography performed at enrollment and at day 7. Symptoms were monitored by the use of a parental diary and clinical review. RESULTS: Forty patients were initially enrolled, but 4 patients were subsequently excluded, leaving 17 patients in the ibuprofen group and 19 in the placebo group. Although symptoms resolved in more than 80% (30 of 36) of patients in both groups by 7 days, the median duration of symptoms was shorter in the ibuprofen group (2 days compared with 4.5 days in the placebo group; P =.05 on Wilcoxon-Breslow test). The medication was well tolerated, with only minor gastrointestinal side effects being reported by 6 patients (4 ibuprofen and 2 placebo). CONCLUSION: In this small study, ibuprofen shortened the duration of symptoms in children with a clinical diagnosis of transient synovitis of the hip.

Anti-Inflammatory Agents, Non-Steroidal↗

General growth mixture modeling for randomized preventive interventions.

This paper proposes growth mixture modeling to assess intervention effects in longitudinal randomized trials. Growth mixture modeling represents unobserved heterogeneity among the subjects using a finite-mixture random effects model. The methodology allows one to examine the impact of an intervention on subgroups characterized by different types of growth trajectories. Such modeling is informative when examining effects on populations that contain individuals who have normative growth as well as non-normative growth. The analysis identifies subgroup membership and allows theory-based modeling of intervention effects in the different subgroups. An example is presented concerning a randomized intervention in Baltimore public schools aimed at reducing aggressive classroom behavior, where only students who were initially more aggressive showed benefits from the intervention.

Journal Article↗

Increases in vaccination coverage for children in child care, 1997 to 2000: an evaluation of the impact of government incentives and initiatives.

OBJECTIVE: To compare vaccination coverage of children in child care before (1997) and after (2000) implementation of government immunisation strategies including parent/providers incentives and surveillance of vaccination uptake. METHODS: Cross-sectional parent surveys of vaccination coverage for children (<3 years old regularly attending child care) in 47 child care centres and 19 councils operating family day care in metropolitan Melboume. RESULTS: Data were collected for 1,578 (72%) children in 1997 and 1,793 (72%) in 2000. In 2000, 93% were completely immunised, a 9% (95% CI 6%-11%, p<0.001) increase from 1997. Less than 1% of children were unimmunised (0.8% in 1997, 0.5% in 2000). For those >2 years, 94% were completely immunised before their second birthday in 2000 compared with 80% in 1997. Immunisation levels were 10% (95% Cl 6-12) higher in 2000 than in 1997 for those receiving child care benefits compared with a 7% (95% Cl 3-10) increase for families not receiving benefits. In 1997, 8 (17%) child care centres and 4 (21%) councils reported > or = 90% children completely immunised increasing to 33 (70%) and 16 (84%) in 2000 respectively. Fewer families reported delaying immunisations because of minor illness in 2000 (27%) compared to 1997 (44%, p<.001). Updating immunisation data by child care coordinators increased from 51% in 1997 to 98% in 2000. CONCLUSION: A substantial increase in immunisation uptake has been achieved for this population of young children attending child care. This study provides evidence that the increase in vaccination rates is attributable to some extent to increased surveillance of immunisation rates and both parent and provider incentives to immunise.

Australia↗