Adolescent mental health and behavioural predictors of being NEET: a prospective study of young adults not in employment, education, or training.

BACKGROUND: Young adults who are not in employment, education, or training (NEET) are at risk of long-term economic disadvantage and social exclusion. Knowledge about risk factors for being NEET largely comes from cross-sectional studies of vulnerable individuals. Using data collected over a 10-year period, we examined adolescent predictors of being NEET in young adulthood. METHODS: We used data on 1938 participants from the Victorian Adolescent Health Cohort Study, a community-based longitudinal study of adolescents in Victoria, Australia. Associations between common mental disorders, disruptive behaviour, cannabis use and drinking behaviour in adolescence, and NEET status at two waves of follow-up in young adulthood (mean ages of 20.7 and 24.1 years) were investigated using logistic regression, with generalised estimating equations used to account for the repeated outcome measure. RESULTS: Overall, 8.5% of the participants were NEET at age 20.7 years and 8.2% at 24.1 years. After adjusting for potential confounders, we found evidence of increased risk of being NEET among frequent adolescent cannabis users [adjusted odds ratio (ORadj) = 1.74; 95% confidence interval (CI) 1.10-2.75] and those who reported repeated disruptive behaviours (ORadj = 1.71; 95% CI 1.15-2.55) or persistent common mental disorders in adolescence (ORadj = 1.60; 95% CI 1.07-2.40). Similar associations were present when participants with children were included in the same category as those in employment, education, or training. CONCLUSIONS: Young people with an early onset of mental health and behavioural problems are at risk of failing to make the transition from school to employment. This finding reinforces the importance of integrated employment and mental health support programmes.

Vitamin D insufficiency in the first 6 months of infancy and challenge-proven IgE-mediated food allergy at 1 year of age: a case-cohort study.

BACKGROUND: Ecological evidence suggests vitamin D insufficiency (VDI) due to lower ambient ultraviolet radiation (UVR) exposure may be a risk factor for IgE-mediated food allergy. However, there are no studies relating directly measured VDI during early infancy to subsequent challenge-proven food allergy. OBJECTIVE: To prospectively investigate the association between VDI during infancy and challenge-proven food allergy at 1 year. METHODS: In a birth cohort (n = 1074), we used a case-cohort design to compare 25-hydroxyvitamin D3 (25(OH)D3 ) levels among infants with food allergy vs a random subcohort (n = 274). The primary exposures were VDI (25(OH)D3 <50 nM) at birth and 6 months of age. Ambient UVR and time in the sun were combined to estimate UVR exposure dose. IgE-mediated food allergy status at 1 year was determined by formal challenge. Binomial regression was used to examine associations between VDI, UVR exposure dose and food allergy and investigate potential confounding. RESULTS: Within the random subcohort, VDI was present in 45% (105/233) of newborns and 24% (55/227) of infants at 6 months. Food allergy prevalence at 1 year was 7.7% (61/786), and 6.5% (53/808) were egg-allergic. There was no evidence of an association between VDI at either birth (aRR 1.25, 95% CI 0.70-2.22) or 6 months (aRR 0.93, 95% CI 0.41-2.14) and food allergy at 1 year. CONCLUSIONS: There was no evidence that VDI during the first 6 months of infancy is a risk factor for food allergy at 1 year of age. These findings primarily relate to egg allergy, and larger studies are required.

Morbidity patterns among the underweight, overweight and obese between 2 and 18 years: population-based cross-sectional analyses.

CONTEXT: No study has documented how symptomatic morbidity varies across the body mass index (BMI) spectrum (underweight, normal weight, overweight and obese) or across the entire child and adolescent age range. OBJECTIVE: To (1) quantify physical and psychosocial morbidities experienced by 2-18-year-olds according to BMI status and (2) explore morbidity patterns by age. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional data from two Australian population studies (the Longitudinal Study of Australian Children and the Health of Young Victorians Study) were collected during 2000-2006. Participants were grouped into five age bands: 2-3 (n=4606), 4-5 (n=4983), 6-7 (n=4464), 8-12 (n=1541) and 13-18 (n=928) years. MAIN MEASURES: Outcomes-Parent- and self-reported global health; physical, psychosocial and mental health; special health-care needs; wheeze; asthma and sleep problems. Exposure-measured BMI (kg m(-2)) categorised using standard international cutpoints. ANALYSES: The variation in comorbidities across BMI categories within and between age bands was examined using linear and logistic regression models. RESULTS: Comorbidities varied with BMI category for all except sleep problems, generally showing the highest levels for the obese category. However, patterns differed markedly between age groups. In particular, poorer global health and special health-care needs were associated with underweight in young children, but obesity in older children. Prevalence of poorer physical health varied little by BMI in 2-5-year-olds, but from 6 to 7 years was increasingly associated with obesity. Normal-weight children tended to experience the best psychosocial and mental health, with little evidence that the U-shaped associations of these variables with BMI status varied by age. Wheeze and asthma increased slightly with BMI at all ages. CONCLUSIONS: Deviation from normal weight is associated with health differences in children and adolescents that vary by morbidity and age. As well as lowering risks for later disease, promoting normal body weight appears central to improving the health and well-being of the young.

Lactobacillus GG treatment during pregnancy for the prevention of eczema: a randomized controlled trial.

BACKGROUND: Probiotic supplementation in early life may be effective for preventing eczema. Previous studies have suggested that prenatal administration may be particularly important for beneficial effects. OBJECTIVE: We examined whether prenatal treatment with the probiotic Lactobacillus rhamnosus GG (LGG) can influence the risk of eczema during infancy. METHODS: We recruited 250 pregnant women carrying infants at high risk of allergic disease to a randomized controlled trial of probiotic supplementation (LGG 1.8 × 10(10) cfu/day) from 36 weeks gestation until delivery. Infants were assessed during their first year for eczema or allergic sensitization. Immunological investigations were performed in a subgroup. Umbilical cord blood was examined for dendritic cell and regulatory T cell numbers and production of TGFß, IL-10, IL-12, IL-13, IFN-γ and TNFα. Maternal breast milk was examined for total IgA, soluble CD14 and TGFß. RESULTS: Prenatal probiotic treatment was not associated with reduced risk of eczema (34% probiotic, 39% placebo; RR 0.88; 95% CI 0.63, 1.22) or IgE-associated eczema (18% probiotic, 19% placebo; RR 0.94; 95% CI 0.53, 1.68). Prenatal probiotic treatment was not associated with any change in cord blood immune markers, but was associated with decreased breast milk soluble CD14 and IgA levels. CONCLUSIONS: Prenatal treatment with Lactobacillus rhamnosus GG was not sufficient for preventing eczema. If probiotics are effective for preventing eczema, then a postnatal component to treatment or possibly an alternative probiotic strain is necessary.

Childhood sexual abuse and abnormal personality: a population-based study.

BACKGROUND: Childhood sexual abuse (CSA) has been shown to be a risk factor for personality disorder (PD). However, no previous studies have examined whether associations exist between sexual abuse and abnormal personality as measured both categorically and dimensionally. Such enquiry would more fully illuminate the impact of CSA on adult personality. METHOD: Using a large nationally representative sample, we set out to examine associations between CSA and categorically defined PD. We also examined associations between CSA and the five dimensions of personality (openness to experience, conscientiousness, extraversion, agreeableness and neuroticism). A total of 1520 young adults were interviewed to determine the prevalence of sexual abuse occurring before age 16 years. A dimensional measure of personality was completed by 1469 participants, and 1145 had an informant-based PD assessment. RESULTS: PD was independently associated with repeated CSA [fully adjusted odds ratio (OR) 1.9, 95% confidence interval (CI) 1.1-3.4]. Repeated sexual abuse was also associated with higher neuroticism and lower agreeableness (p values for both <0.001). Adjusting for the effects of potential confounders and mediators, including earlier symptoms of anxiety and depression, had little impact on the strength of associations. CONCLUSIONS: We conclude that repeated CSA is independently associated with categorically defined PD, and also with higher neuroticism and lower agreeableness. Our findings suggest that if a dimensional classification of PDs is adopted in future classification systems, there might be meaningful continuity with previous aetiological research conducted using the current categorical system.

Clinical manifestations and outcome in HIV-infected young infants presenting with acute illness in Durban, South Africa.

OBJECTIVES: In young infants, early development of symptomatic HIV infection increases the risk of morbidity and mortality. A prospective study was conducted over a 1-year period in a region with a high burden of HIV in order to describe the clinical presentation of HIV infection in infants aged between 0 and 59 days on attendance at hospital and the factors associated with the need for urgent hospital management. METHODS: Sick young infants presenting to the King Edward VIII Hospital, Durban between February 2003 and January 2004 were enrolled. After systematic evaluation by a primary health worker, an experienced paediatrician determined the primary diagnosis and need for urgent hospital management. Comparisons of these assessments were stratified by HIV status. Children were classified as HIV-uninfected (HIV ELISA-negative), HIV-exposed-but-uninfected (HIV ELISA-positive and HIV RNA PCR-negative), HIV-infected (HIV ELISA-positive and HIV viral load >400 copies/ml). RESULTS: Of 925 infants enrolled, 652 (70·5%) had their HIV status determined: 70 (10·7%) were HIV-infected, 271 (41·6%) HIV-exposed-but-uninfected, and 311 (47·7%) HIV-uninfected. Factors associated with an increased probability of being HIV-infected included if the mother had children from more than one sexual partner, if the infant had had contact with a tuberculosis-infected person or if the HIV-infected mother and/or her exposed infant failed to receive nevirapine prophylaxis. Signs of severe illness were more frequently encountered in HIV-infected than in HIV-exposed-but-uninfected infants, including the prevalence of chest in-drawing (20·3% vs 8·8%, p = 0·004) and severe skin pustules (18·6% vs 8·6%, p = 0·01). Among infants requiring urgent hospital management, observed or reported feeding difficulties and severe skin pustules were more common in HIV-infected than uninfected infants. More HIV-infected infants (12·9%) required hospitalisation than those who were HIV-exposed-but-uninfected (7·7%) or uninfected (7·4%). Primary diagnoses of pneumonia, sepsis or oral thrush were more frequently seen in HIV-infected than exposed-but-uninfected or HIV-uninfected children. CONCLUSION: Early recognition and triaging of infants suspected of having HIV infection provides an opportunity for early diagnosis and treatment which could prevent the adverse impact of rapidly progressive HIV disease.

Effectiveness of 7-valent pneumococcal conjugate vaccine against radiologically diagnosed pneumonia in indigenous infants in Australia.

OBJECTIVE: To evaluate the effectiveness of the 7-valent pneumococcal conjugate vaccine (PCV7) in preventing pneumonia, diagnosed radiologically according to World Health Organization (WHO) criteria, among indigenous infants in the Northern Territory of Australia. METHODS: We conducted a historical cohort study of consecutive indigenous birth cohorts between 1 April 1998 and 28 February 2005. Children were followed up to 18 months of age. The PCV7 programme commenced on 1 June 2001. All chest X-rays taken within 3 days of any hospitalization were assessed. The primary endpoint was a first episode of WHO-defined pneumonia requiring hospitalization. Cox proportional hazards models were used to compare disease incidence. FINDINGS: There were 526 pneumonia events among 10,600 children - an incidence of 3.3 per 1000 child-months; 183 episodes (34.8%) occurred before 5 months of age and 247 (47.0%) by 7 months. Of the children studied, 27% had received 3 doses of vaccine by 7 months of age. Hazard ratios for endpoint pneumonia were 1.01 for 1 versus 0 doses; 1.03 for 2 versus 0 doses; and 0.84 for 3 versus 0 doses. CONCLUSION: There was limited evidence that PCV7 reduced the incidence of radiologically confirmed pneumonia among Northern Territory indigenous infants, although there was a non-significant trend towards an effect after receipt of the third dose. These findings might be explained by lack of timely vaccination and/or occurrence of disease at an early age. Additionally, the relative contribution of vaccine-type pneumococcus to severe pneumonia in a setting where multiple other pathogens are prevalent may differ with respect to other settings where vaccine efficacy has been clearly established.

Associations between fatty acids in colostrum and breast milk and risk of allergic disease.

BACKGROUND: Exposure to n-3 polyunsaturated fatty acids (PUFA) in early life is hypothesized to offer protection against atopic disease. However, there is controversy in this area, and we have previously observed that high levels of n-3 fatty acid (FA) in colostrum are associated with increased risk of allergic sensitization. OBJECTIVE: The aim of the study was to assess the relationship between FA profile in breast milk and risk of childhood atopic disease. METHODS: A high-risk birth cohort was recruited, and a total of 224 mothers provided a sample of colostrum (n=194) and/or 3-month expressed breast milk (n=118). FA concentrations were determined by gas chromatography. Presence of eczema, asthma and rhinitis were prospectively documented up to 7 years of age. RESULTS: High levels of n-3 22:5 FA (docosapentaenoic acid, DPA) in colostrum were associated with increased risk of infantile atopic eczema [odds ratio (OR)=1.66 per 1 standard deviation increase, 95% confidence interval (CI)=1.11-2.48], while total n-3 concentration in breast milk was associated with increased risk of non-atopic eczema (OR=1.60, 95% CI=1.03-2.50). Higher levels of total n-6 FA in colostrum were associated with increased risk of childhood rhinitis (OR=1.59, 95% CI=1.12-2.25). There was no evidence of associations between FA profile and risk of asthma. CONCLUSION: In this cohort of high-risk children, a number of modest associations were observed between FA concentrations in colostrum and breast milk and allergic disease outcomes. Further research in this area with larger sample sizes is needed.

The association between higher maternal pre-pregnancy body mass index and increased birth weight, adiposity and inflammation in the newborn.

BACKGROUND: Excess adiposity and adiposity-related inflammation are known risk factors for cardiovascular disease in adults; however, little is known regarding the determinants of adiposity-related inflammation at birth. OBJECTIVES: The aim of this study was to investigate the association between maternal pre-pregnancy BMI and newborn adiposity and inflammation. METHODS: Paired maternal (28-week gestation) and infant (umbilical cord) blood samples were collected from a population-derived birth cohort (Barwon Infant Study, n = 1074). Data on maternal comorbidities and infant birth anthropomorphic measures were compiled, and infant aortic intima-media thickness was measured by trans-abdominal ultrasound. In a selected subgroup of term infants (n = 161), matched maternal and cord lipids, high-sensitivity C-reactive protein (hsCRP) and maternal soluble CD14 were measured. Analysis was completed by using pairwise correlation and linear regression. Because of their non-normal distribution, pathology blood measures were log transformed prior to analysis. RESULTS: Maternal pre-pregnancy BMI was positively associated with increased birth weight (mean difference 17.8 g per kg m-2 , 95% CI 6.6 to 28.9; p = 0.002), newborn mean skin-fold thickness (mean difference 0.1 mm per kg m-2 , 95% CI 0.0 to 0.1; p < 0.001) and cord blood hsCRP (mean difference of 4.2% increase in hsCRP per kg m-2 increase in pre-pregnancy BMI, 95% CI 0.6 to 7.7%, p = 0.02), but not cord blood soluble CD14. Inclusion of maternal hsCRP as a covariate attenuated the associations between pre-pregnancy BMI and both newborn skin-fold thickness and cord blood hsCRP. CONCLUSION: Higher maternal pre-pregnancy BMI is associated with increased newborn adiposity and inflammation. These associations may be partially mediated by maternal inflammation during pregnancy.

Randomized, double-blind study comparing the efficacy of moderate-dose metoclopramide and ondansetron for the prophylactic control of postoperative vomiting in children after tonsillectomy.

BACKGROUND: Postoperative vomiting (POV) is a major cause of morbidity after tonsillectomy in children. It has been well established that anti-serotinergic agents are effective for the prophylactic control of POV in this patient group. It has been suggested that at moderate doses (0.5 mg kg(-1)), metoclopramide is also an effective agent. No study has been performed comparing the efficacy of an anti-serotinergic agent and moderate-dose metoclopramide. METHODS: A total of 557 children undergoing tonsillectomy with or without adenoidectomy were randomly allocated to receive either ondansetron 0.1 mg kg(-1) or metoclopramide 0.5 mg kg(-1). All received a standardized muscle-relaxant anaesthetic and dexamethasone 0.1 mg kg(-1). The primary outcome was any vomit in the immediate postoperative period. Comparisons were made of the proportion in each group reaching the primary outcome and the time until their first vomit. The study was designed to detect equivalence. RESULTS: The incidence of vomiting in the group receiving ondansetron (25.3%) was 12% lower (95% CI 4.4-19.7) than those in metoclopramide (37.3%). The time until first vomit was significantly longer in the group receiving ondansetron (hazard ratio 0.61, 95% CI 0.45-0.82). CONCLUSIONS: Although the incidence of vomiting was similar, when these results are compared with a pre-specified zone of equivalence of 0-15%, it cannot be concluded that the effect of metoclopramide is equivalent to ondansetron. Survival analysis indicated that those in the metoclopramide group vomited substantially earlier. It is concluded, therefore, that ondansetron 0.1 mg kg(-1) is a superior drug to metoclopramide 0.5 mg kg(-1) for the prophylactic control of POV in children undergoing tonsillectomy.

Clinico-epidemiological profile and validation of symptoms and signs of severe illness in young infants (< 60 days) reporting to a district hospital.

OBJECTIVES: To describe the clinical and epidemiological profile of infants less than 2 months of age reporting to a district hospital and to assess the ability of simple clinical symptoms and signs used by health workers to detect severe illness warranting hospital admission. METHODS: It was an observational study done at a general district hospital at Chandigarh, North India. Infants less than 2 months of age presenting to this hospital were enrolled. All infants were first evaluated by an auxiliary nurse midwife (ANM) to record a pre-determined set of symptoms and signs. A pediatrician who was blinded to the findings of the ANM did an independent assessment for severe illness needing urgent hospitalization. RESULTS: A total of 1268 infants were enrolled. Of these, 356 (28%) were below 7 days of age. Overall, regurgitation, vomiting and stool problems (25%) were the most common presenting complaints in the first 2 months of life, followed by jaundice (22%) and respiratory symptoms (15%). 112 (8.8%) infants were classified as having "severe illness requiring urgent hospital management" by the pediatrician. Nearly half (46%) of the admissions were because of jaundice while 17% each were due to sepsis and pneumonia / lower respiratory tract infection (LRTI). A history of not feeding well (OR 14.7, 8.0 and 11.3 in 0-6, 7-27 and 28-59 days age groups, respectively) and a respiratory rate >60/min (OR 21.5, 6.2 and 10.5 in 0-6, 7-27 and 28-59 days age groups, respectively) had significant positive predictive value to predict severe illness (except jaundice) in all the 3 age groups studied. In the second month of life, severe chest in-drawing (OR 4.6) was also a significant predictor. CONCLUSIONS: Simple clinical signs are useful in hands of health worker for identifying neonates with serious illness warranting hospital admission. These will be of use in the further development of clinical algorithms for the national integrated management of childhood illnesses.

Clinicoepidemiological profile and predictors of severe illness in young infants (< 60 days) reporting to a hospital in North India.

OBJECTIVES: To describe the clinical and epidemiological profile of young infants reporting to a hospital and assess previously proposed simple clinical signs for their value in enabling health workers to detect young infants with severe illness warranting hospital admission. METHODS: Observational study of infants less than 2 months of age presenting consecutively to a large public hospital in South Delhi who were evaluated by a health worker (nurse), on a standardized list of signs and symptoms, and the ability of these were evaluated against the need for hospital admission which was assessed by an independent pediatrician. RESULTS: Of the 1624 young infants triaged, 878 were enrolled into the study. Of these 100 (11%) were below 7 days of age, for whom the common reasons for seeking care were jaundice (52%), not feeding well (6%) and fever (5%). The remaining 778 (89%) were 7-59 days of age with respiratory symptoms as the main presenting complaints (29.1%). The primary clinical diagnoses in infants with serious illness needing admission to hospital in the age group <7 days (n = 66) were hyperbilirubinemia (56%) and sepsis (21%). In those between 7-27 days of age (n = 60), primary diagnoses were sepsis (27%), pneumonia (13%), diarrhea, dysentery or dehydration (10%), while in the age group 28-59 days of age (n = 47) pneumonia (40%), sepsis (19%) and diarrhea or dehydration (13%) were the common primary diagnoses. Signs that had at least a prevalence of 5% and were strong predictors for all the age categories studied were history of difficult feeding (OR 6.8 for 0-6 days, 15.1 for 2-27 days and 6.2 for 28-59 days age groups), not feeding well on observation (OR 13.7, 27.6 and 20.9 respectively for the 3 age groups), temperature > 37.5C (OR 21.8, 14.6 and 30.0 respectively for the 3 age groups) and respiratory rate > 60 per minute (OR 6.8, 15.1 and 21.0 respectively for the 3 age groups). Additional strong predictors with > 5% prevalence were history of convulsions (OR 7.9, only in 0-6 day age group), lethargy (OR 26.1, only in 7-27 day age group), and history of diarrhea (OR 3.0 for 2-27 days and 2.2 for 28-59 days age groups). CONCLUSIONS: Simple clinical signs are useful in hands of health worker for identifying neonates with serious illness warranting hospital admission. These will be of use in the further development of clinical algorithms for the national integrated management of childhood illnesses.

Age-related pituitary volumes in prepubertal children with normal endocrine function: volumetric magnetic resonance data.

BACKGROUND: Evaluation of the size of the pituitary gland on magnetic resonance imaging (MRI) may be difficult, considering the wide variation in normal gland morphology. Given the paucity of age-related biometric data, our purpose was to obtain standard normal reference values for pituitary volumes in prepubertal children using three-dimensional MRI data. METHODS: Children under the age of 10 yr undergoing brain MRI for seizures or idiopathic developmental delay and who had no endocrine abnormality were recruited prospectively over 2 yr. All MRI studies included a three-dimensional sequence. Only subjects with normal studies were included. One hundred thirty-nine children were eligible (mean age, 5.2 yr). Direct pituitary volumes were measured from contiguous 1-mm thick reconstructed coronal and sagittal images. Estimated pituitary volumes were calculated using pituitary height, width, and length. RESULTS: Volumes obtained from reconstructions in either plane were essentially identical. There was a linear increase in log-transformed pituitary volume with age, but relatively weak correlations with height or body mass index. There was no gender difference and only weak correlations between pituitary height and pituitary volume and between estimated pituitary volume calculation and measured pituitary volume. We provide age-related reference ranges for pituitary volumes in graphical and tabular forms.

Association of body composition and lung function in children with cystic fibrosis.

Survival in cystic fibrosis has improved significantly in the last 30 years, with major therapeutic goals of delaying the progressive loss of pulmonary function and maintaining normal growth. Dual-energy X-ray absorptiometry (DEXA) was performed in children with cystic fibrosis (CF) to assess both bone mineral density and body composition. We hypothesised that there would be an association between body composition and pulmonary function in children with CF. Fifty subjects with CF (28 males), mean age 12.7 years, participated in the study. Body composition was determined by DEXA. Body mass index (BMI) was calculated from the ratio of weight/height2 (kg/m2). Lung function was assessed by spirometry. Most patients (78%) had mild lung disease. The mean forced expired volume in 1 sec percent predicted (FEV1% predicted) for the 50 patients was 79.2% (range, 24-117%). There was a strong association between FEV1% predicted and BMI (R=0.59, P=0.0001). Fat-free mass had positive association with pulmonary function tests (R=0.30, P=0.03). Although fat mass showed a positive correlation with pulmonary function, this association did not reach statistical significance. In our group of children with CF and mild lung disease, pulmonary function was more strongly associated with BMI than with fat and fat-free mass.

The usage and costs of health services for HIV infection in Australia.

OBJECTIVE: To describe patterns of health-service usage and the resulting costs in 1992-1993 for Australian men. DESIGN: A prospective survey, stratified by phase of illness. SETTING: Hospital and community-based care. PATIENTS: A total of 128 homosexual men: 20 in phase 1 (CD4+ count > or = 500 x 10(6)/l), 31 in phase 2 (CD4+ count < 500 and > or = 200 x 10(6)/l), 30 in phase 3 (CD4+ count < 200 x 10(6)/l), and 47 in phase 4 (AIDS). MAIN OUTCOME MEASURES: Mean monthly service usage rates and costs. RESULTS: Health-service utilization increased and became more hospital-based as illness worsened; the main exception was use of antiretroviral drugs, which peaked in phases 2 and 3. Hospital admission was rare before diagnosis of AIDS. Hospital bed-days per patient per month averaged 3.3 for AIDS patients until the final 3 months of life increasing to 15.8 in the 3 months before death. Mean monthly costs (in 1992-1993 Australian dollars) were $331 [95% confidence interval (CI), 218-455] in phase 1, $667 (95% CI, 540-836) in phase 2, $1372 (95% CI, 1044-1776) in phase 3, and $4615 (95% CI, 3456-5985) for AIDS patients until the last 3 months of life and $13,308 (95% CI, 10,538-16,516) in the 3 months before death. Drugs comprised 57% of total costs in phase 1, but only 30% of costs for patients with AIDS, whereas hospital bed-days comprised 10% of phase 1 costs and 60% of AIDS costs. CONCLUSIONS: Health-care utilization and resulting costs increased with severity of illness, and were particularly high for AIDS patients in the 3 months before death. Service-utilization patterns and components of costs varied between each phase.

Predictive value of CD4 lymphocyte numbers for the development of opportunistic infections and malignancies in HIV-infected persons.

Infection with the human immunodeficiency virus (HIV) results in progressive depletion of the CD4 subset T-lymphocytes and the development of opportunistic infections and certain malignancies. Charts were reviewed for 185 HIV-infected individuals with 265 AIDS-defining illnesses (ADIs) who had T-lymphocyte subset analyses performed within 2 months prior to or 1 month following the diagnosis. Also included were 22 HIV-infected patients with oral candidiasis and 20 with asymptomatic infection. Significant differences in CD4 lymphocyte numbers were observed between the 12 ADIs, oral candidiasis, and asymptomatic infection, allowing them to be grouped into five general categories, based on mean CD4 count: (a) asymptomatic infection, CD4 greater than 500/mm3; (b) oral candidiasis and tuberculosis, range 250-500/mm3; (c) Kaposi's sarcoma, lymphoma, and cryptosporidiosis, range 150-200/mm3; (d) Pneumocystis carinii pneumonitis, disseminated Mycobacterium avium complex, herpes simplex ulceration, toxoplasmosis, cryptococcosis, and esophageal candidiasis, range 75-125/mm3; (e) cytomegalovirus retinitis, less than 50/mm3. Our data concur with clinical impressions and provide a basis for interim treatment and prophylaxis recommendations.

Bias, prevalence and kappa.

Since the introduction of Cohen's kappa as a chance-adjusted measure of agreement between two observers, several "paradoxes" in its interpretation have been pointed out. The difficulties occur because kappa not only measures agreement but is also affected in complex ways by the presence of bias between observers and by the distributions of data across the categories that are used ("prevalence"). In this paper, new indices that provide independent measures of bias and prevalence, as well as of observed agreement, are defined and a simple formula is derived that expresses kappa in terms of these three indices. When comparisons are made between agreement studies it can be misleading to report kappa values alone, and it is recommended that researchers also include quantitative indicators of bias and prevalence.

A comparison of patient interview data with pharmacy and medical records for patients with acquired immunodeficiency syndrome or human immunodeficiency virus infection.

To assess the reliability of information reported by patients with AIDS or HIV infection, 123 homosexual men were recruited in Victoria, Australia, in 1992-1993 and interviewed to collect data retrospectively and prospectively on HIV-related illness and treatment. These data were compared with information in medical and pharmacy records. There was no evidence of bias in the patient report of date of diagnosis of HIV infection or date or result of most recent CD4 count, although there was considerable imprecision. Past and current prescription of AZT were recalled accurately by patients compared with medical records (kappa = 0.89 and 0.86, respectively), but previous HIV-related illnesses and enrollment in clinical studies or trials were generally recalled poorly (kappa < 0.4 in some cases). Data collected prospectively on prescription of drugs and use of health care services were reasonably accurately reported by patients. This analysis supports the need for routine assessment of the validity of patient-reported exposure and outcome data in epidemiological studies in order to minimize the possible biases that can result from inaccurate information.

Validation of questionnaire and bronchial hyperresponsiveness against respiratory physician assessment in the diagnosis of asthma.

BACKGROUND: The Tasmanian Asthma survey (TAS) and the International Study of Asthma and Allergies in Childhood (ISAAC) have used questionnaires to measure the prevalence of asthma in adults and children. We have investigated the validity of these questionnaires by comparing response to questionnaire with a physician assessment of asthma status in the past 12 months. METHODS: Ninety-three adults were given the TAS questionnaire to complete and 361 children were given the ISAAC questionnaire. Ninety-one adults and 168 children completed bronchial challenge with hypertonic saline. A consultation with a respiratory physician blinded to the results of the questionnaire and bronchial challenge was given to all subjects. RESULTS: In both adults and children, questionnaires showed high agreement with respiratory physician diagnosis with respect to asthma symptoms in the past 12 months. For the TAS questionnaire the positive and negative predictive values (95% confidence limits) for physician diagnosis for adults were 0.89 (0.68-0.98) and 0.94 (0. 86-0.98) respectively. The instrument was also sensitive 0.80 (0. 58-0.93) and highly specific 0.97 (0.90-0.99). For the ISAAC questionnaire the positive and negative predictive vales for physician diagnosis of asthma in children were 0.61 (0.50-0.71) and 0.94 (0.88-0.98) respectively. Sensitivity and specificity were 0.85 (0.73-0.93) and 0.81 (0.76-0.86) respectively. Compared to the physician diagnosis, the sensitivity of bronchial hyperresponsiveness (BHR) for asthma was low for adults 0.39 (0.21-0. 61) and children 0.54 (0.48-0.67) as were the positive predictive values: 0.55 (0.31-0.79) for adults and 0.64 (0.449-0.77) for children. A definition of asthma requiring both a positive questionnaire response and BHR was highly specific but not sensitive for adults 0.37 (0.20-0.59) or children 0.47 (0.35-0.60). CONCLUSIONS: Both the TAS and ISAAC questionnaires are valid instruments for the determination of asthma symptoms in the past 12 months.

Serum insulin distributions and reproducibility of the relationship between 2-hour insulin and plasma glucose levels in Asian Indian, Creole, and Chinese Mauritians. Mauritius NCD Study Group.

The relationship of 2-hour (post-75 g oral glucose) serum insulin levels with plasma glucose levels was studied in a population-based random sample comprising 2,627 Hindu Indians, 685 Muslim Indians, 1,351 Creoles (African, European, and Indian admixture), and 415 Chinese from the Indian Ocean island of Mauritius. Known diabetic subjects taking oral hypoglycemic drugs or insulin were excluded from these analyses; 64% of all diabetic subjects had usable glucose and insulin data. Both fasting and 2-hour postload insulin levels were significantly higher in women than in men, and levels in both sexes were significantly greater in Hindu and Muslim Indian subjects than in Creoles or Chinese even after controlling for differences in age, body mass index (BMI), waist to hip ratio (WHR), and plasma glucose level. Levels in Muslims were higher than those in Hindus; it was unclear whether these ethnic differences represented hereditary or unmeasured environmental factors closely associated with ethnicity. All four ethnic groups demonstrated similar inverted U- or V-shaped curves when 2-hour insulin was plotted against either basal or 2-hour glucose. Both quadratic (U) and two-piece (V) regression models improved over linear models for 2-hour insulin versus either fasting or 2-hour glucose in all ethnic groups, although in statistical terms they were good models only for the 2-hour glucose comparison. The two-piece models were associated with modest increases in R2 compared with the quadratic models, but it was not possible to precisely determine optimal turning points with either model. However, in all ethnic groups, 2-hour insulin levels decreased above glucose levels of 7.1 to 7.8 (fasting) and 11.3 to 13.5 mmol/L (2-hour) in quadratic models, and 7.5 to 9.5 (fasting) and 8.5 to 10.5 mmol/L (2-hour) in two-piece models. The shape and point of inflection of the quadratic and two-piece curves were influenced little by gender, obesity, fat distribution, and physical activity. These results are in accord with those observed in cross-sectional and longitudinal studies in other ethnic groups, and support the generality of the plasma glucose levels currently used to define diabetes mellitus, which physiologically correspond with a decrease in beta-cell responsiveness to glucose. Asian Indians appear to have an ethnic propensity to hyperinsulinemia that is not explained by obesity or adverse fat distribution.