Low-density lipoprotein cholesterol in adolescents and young adults with type 1 diabetes: Data from the Australasian Diabetes Data Network registry.

AIM: To determine low-density lipoprotein cholesterol (LDL-C) screening frequency and levels, and factors associated with elevated LDL-C, in Australasian youth with type 1 diabetes (T1D). METHODS: Data were extracted from the Australasian Diabetes Data Network (ADDN), a prospective clinical quality registry, on all T1D healthcare visits attended by young people aged 16-25 years (with T1D duration of >1 year) between January 2011 and December 2020. The primary outcomes were elevated LDL-C > 2.6 mmol/L (100 mg/dL) and threshold for treatment: >3.4 mmol/L (130 mg/dL), according to consensus guidelines. Multivariable Generalised Estimated Equations (GEE) were used to examine factors associated with elevated LDL-C across all visits. RESULTS: A cohort of 6338 young people (52.6% men) were identified, of whom 1603 (25.3%) had ≥1 LDL-C measurement documented. At last measurement, mean age, age at T1D diagnosis and T1D duration were 18.3 ± 2.4, 8.8 ± 4.5 and 8.9 ± 4.8 years, respectively. LDL-C was elevated in 737 (46.0%) and at the treatment threshold in 250 (15.6%). In multivariable GEE elevated LDL-C continuously was associated with older age (OR = 0.07; 0.01-0.13, p = 0.02), female sex (OR = 0.31; 0.18-0.43; p < 0.001), higher HbA1c (OR = 0.04; 0.01-0.08; p = 0.01) and having an elevated BMI (OR = 0.17, 0.06-0.39, p < 0.001). CONCLUSIONS: LDL-C screening and levels are suboptimal in this cohort, increasing future cardiovascular complication risk. There is an urgent need to understand how healthcare services can support improved screening and management of dyslipidaemia in this population.

A trade-off between plant and soil carbon storage under elevated CO2.

Terrestrial ecosystems remove about 30 per cent of the carbon dioxide (CO2) emitted by human activities each year1, yet the persistence of this carbon sink depends partly on how plant biomass and soil organic carbon (SOC) stocks respond to future increases in atmospheric CO2 (refs. 2,3). Although plant biomass often increases in elevated CO2 (eCO2) experiments4-6, SOC has been observed to increase, remain unchanged or even decline7. The mechanisms that drive this variation across experiments remain poorly understood, creating uncertainty in climate projections8,9. Here we synthesized data from 108 eCO2 experiments and found that the effect of eCO2 on SOC stocks is best explained by a negative relationship with plant biomass: when plant biomass is strongly stimulated by eCO2, SOC storage declines; conversely, when biomass is weakly stimulated, SOC storage increases. This trade-off appears to be related to plant nutrient acquisition, in which plants increase their biomass by mining the soil for nutrients, which decreases SOC storage. We found that, overall, SOC stocks increase with eCO2 in grasslands (8 ± 2 per cent) but not in forests (0 ± 2 per cent), even though plant biomass in grasslands increase less (9 ± 3 per cent) than in forests (23 ± 2 per cent). Ecosystem models do not reproduce this trade-off, which implies that projections of SOC may need to be revised.

Skin autofluorescence in people with type 1 diabetes and people without diabetes: An eight-decade cross-sectional study with evidence of accelerated aging and associations with complications.

AIM: To measure skin autofluorescence in youth (<18 y.o.) and adults (≥18 y.o.) and to assess its relationship with type 1 diabetes, chronic complications and smoking. METHODS: In a cross-sectional study (n = 383) skin autofluorescence was measured in 269 people with type 1 diabetes (67 with vascular complications) and 114 people without diabetes, covering eight decades of age. Associations of skin autofluorescence with demographics and traditional risk factors were assessed. RESULTS: Skin autofluorescence increased with age in people with diabetes: for those with complications it increased by a mean ± se of 0.029 ± 0.003 arbitrary units per year (r = 0.76) and, for those without complications, it increased by 0.028 ± 0.002 arbitrary units (r = 0.77). These increases were higher than for people without diabetes, whose skin autofluorescence increased by 0.022 ± 0.002 arbitrary units (r = 0.78) per year (p = 0.004). Mean ±se age-adjusted skin autofluorescence was higher in people with diabetes complications vs people without diabetes complications (1.85 ± 0.04 vs 1.66 ± 0.02 arbitrary units) and people without diabetes (1.48 ± 0.03 arbitrary units; all P < 0.0001). Age-adjusted skin autofluorescence was higher in current smokers and recent ex-smokers vs non-smokers and longer-term ex-smokers (1.86 ± 0.06 vs 1.63 ± 0.02 arbitrary units; P = 0.0005). Skin autofluorescence area under the receiver-operating characteristic curve was 0.89 (95% CI 0.85-0.94) for retinopathy and 0.56 (95% CI 0.47-0.65) for nephropathy. CONCLUSIONS: Skin autofluorescence increases with age, but faster in people with diabetes, particularly in those with complications and in smokers, consistent with accelerated aging. Skin autofluorescence may facilitate complication screening and prediction. Longitudinal studies are merited.

Early changes of arterial elasticity in Type 1 diabetes with microvascular complications - A cross-sectional study from childhood to adulthood.

AIM: To examine the trajectory of small artery elasticity (SAE) and pulse pressure (PP) in people with Type 1 diabetes and non-diabetic controls across the lifespan, and explore associations with microvascular complications (CX+). METHODS: This cross-sectional study included 477 Type 1 diabetes patients (188 with CX+, 289 without CX-) and 515 controls. Relationships between SAE and PP and age were evaluated using segmented linear regression. Logistic regression was used to assess the associations between microvascular complications (retinopathy and/or nephropathy) and SAE and PP. RESULTS: SAE peaked significantly later among controls than diabetic patients CX- vs. CX+ (21.2 vs. 20.4 vs. 17.6 years respectively, p < 0.001). In adults, mean SAE was significantly lower in CX+ vs. CX- vs. controls (6.8 vs. 7.8 vs. 8.0 ml/mm Hg × 10; p < 0.0001), and mean PP was significantly higher in CX+ vs CX- and controls (60 vs. 55 vs. 53 mm Hg; p < 0.0001). CONCLUSION: Type 1 diabetes CX+ subjects have an earlier peak and decline in SAE relative to CX- and controls, who did not differ. Lower SAE and higher PP were associated with increased odds of Type 1 diabetes complications in adults. These clinically applicable techniques demonstrate an association between accelerated vascular aging and vascular complications in diabetes.

First report on the nationwide incidence and prevalence of Type 1 diabetes among children in Turkey.

AIM: To report, for the first time, the incidence and prevalence of childhood Type 1 diabetes in Turkey using a nationwide registry. METHODS: Information on birth date, city of birth, diagnosis date and gender of all patients with Type 1 diabetes aged < 18 years were obtained from the Turkish Social Security Institute for the period from January 2011 to December 2013. RESULTS: There were 17 175 prevalent cases of Type 1 diabetes over the 3-year period. The prevalence of Type 1 diabetes was 0.75/1 000 (95% CI 0.74-0.76) and was higher in girls than in boys (0.79 vs 0.72 /1 000; P < 0.01). There were 2465 incident cases in 2013. The incidence was slightly higher among girls (50.6%) than boys (49.4%); the girl:boy case ratio was 1.02. The incidence was 10.4/100 000 for boys and 11.3/100 000 for girls. The age-standardized incidence rate was 10.8 per 100 000 (95% CI 10.1-11.5) according to the WHO standard population, estimated using the direct method. The mean patient age at diagnosis was 10.6 ± 4.6 years. The highest proportion of cases (40.6%) was diagnosed in children aged 10-14 years. CONCLUSIONS: This is the first study to report the incidence and prevalence of Type 1 diabetes in children in Turkey. The incidence of Type 1 diabetes reflects the geographical location of Turkey, bridging Asia and Europe, with the incidence being higher than in Asia but lower than in Europe.

Higher skin autofluorescence in young people with Type 1 diabetes and microvascular complications.

AIM: To test the hypothesis that non-invasive skin autofluorescence, a measure of advanced glycation end products, would provide a surrogate measure of long-term glycaemia and be associated with early markers of microvascular complications in adolescents with Type 1 diabetes. METHODS: Forearm skin autofluorescence (arbitrary units) was measured in a cross-sectional study of 135 adolescents with Type 1 diabetes [mean ± sd age 15.6 ± 2.1 years, diabetes duration 8.7 ± 3.5 years, HbA1c 72 ± 16 mmol/mol (8.7 ± 1.5%)]. Retinopathy, assessed using seven-field stereoscopic fundal photography, was defined as ≥1 microaneurysm or haemorrhage. Cardiac autonomic function was measured by standard deviation of consecutive RR intervals on a 10-min continuous electrocardiogram recording, as a measure of heart rate variability. RESULTS: Skin autofluorescence was significantly associated with age (R2 = 0.15; P < 0.001). Age- and gender-adjusted skin autofluorescence was associated with concurrent HbA1c (R2 = 0.32; P < 0.001) and HbA1c over the previous 2.5-10 years (R2 = 0.34-0.43; P < 0.002). Age- and gender-adjusted mean skin autofluorescence was higher in adolescents with retinopathy vs those without retinopathy [mean 1.38 (95% CI 1.29, 1.48) vs 1.22 (95% CI 1.17, 1.26) arbitrary units; P = 0.002]. In multivariable analysis, retinopathy was significantly associated with skin autofluorescence, adjusted for duration (R2 = 0.19; P = 0.03). Cardiac autonomic dysfunction was also independently associated with skin autofluorescence (R2 = 0.11; P = 0.006). CONCLUSIONS: Higher skin autofluorescence is associated with retinopathy and cardiac autonomic dysfunction in adolescents with Type 1 diabetes. The relationship between skin autofluorescence and previous glycaemia may provide insight into metabolic memory. Longitudinal studies will determine the utility of skin autofluorescence as a non-invasive screening tool to predict future microvascular complications.

Healthcare professional requirements for the care of adult diabetes patients managed with insulin pumps in Australia.

BACKGROUND: Healthcare professional (HCP) time supporting insulin pump therapy (IPT) has not been documented, yet it is important in planning and allocating resources for effective care. AIM: This study aims to determine HCP time spent in IPT patient care to inform resource planning for optimal IPT delivery. METHODS: Twenty-four Australian adult IPT-experienced institutions (14 government funded, seven private, three both) collected data between April 2012 and January 2013 prospectively, including: patient demographics, HCP classification, purpose of HCP-patient interaction, interaction mode and HCP time with the patient. A subset of patients was tracked from pre-pump education until stable on IPT. RESULTS: Data on 2577 HCP-adult patient interactions (62% face-to-face, 29% remote, 9% administrative) were collected over 12.2 ± 6.4 weeks for 895 patients; age 35.4 ± 14.2 years; 67% female; 99% type 1 diabetes, representing 25% of all IPT patients of the institutions. Time (hours) spent on IPT interactions per centre per week were: nurses 5.4 ± 2.8, dietitians 0.4 ± 0.2 and doctors 1.0 ± 0.5. IPT starts accounted for 48% of IPT interaction time. The percentage of available diabetes clinic time spent on outpatient IPT interactions was 20.4%, 4.6% and 2.7% for nurses, dietitians and doctors respectively. Fifteen patients tracked from pre-pump to stabilisation over 11.8 ± 4.5 weeks, required a median (range) of 9.2 (3.0-20.9), 2.4 (0.5-6.0) and 1.8 (0.5-5.4) hours per patient from nurses, dietitians and doctors respectively. CONCLUSIONS: IPT patient care represents a substantial investment in HCP time, particularly for nurses. Funding models for IPT care need urgent review to ensure this now mainstream therapy integrates well into healthcare resources.

Plateau of adiposity in Australian children diagnosed with Type 1 diabetes: a 20-year study.

AIMS: To examine temporal trends in anthropometry in children with Type 1 diabetes from Sydney, Australia. METHODS: We conducted a retrospective study in a total of 1975 children with Type 1 diabetes, aged <16 years, between 1990 and 2009. Trends in height, weight and BMI standard deviation score after initial stabilization were examined by age group (<5 years, 5 to <10 years, 10 to 16 years) and time period of diagnosis (T1: 1990-1994, T2: 1995-1999; T3: 2000-2004 and T4: 2005-2009). Factors associated with BMI standard deviation score (time period, age group, gender and socio-economic status) were examined using multivariable linear regression. RESULTS: The mean BMI standard deviation score (±sd) increased between T1 and T2 (0.54 ± 1.14 vs 0.81 ± 1.14, P = 0.002), but remained steady thereafter (T3: 0.85 ± 1.11, T4: 0.87 ± 1.09; T2 to T4: P = 0.40). Similarly, the prevalence of overweight and obesity increased from T1 to T2 (26 to 35%, P = 0.01), but was unchanged thereafter (T3: 34%, T4: 34%; T2 to T4: P = 0.90). On multivariable regression analysis, a higher BMI standard deviation score was associated with younger age (≥5 years vs <5 years, ß=-0.40, 95% CI -0.51 to -0.28, P < 0.001), later time period (T2 to T4 vs T1, ß=0.30, 95% CI 0.16-0.45, P < 0.001) and male gender (ß=0.25, 95% CI 0.15-0.34, P < 0.001). CONCLUSION: The prevalence of overweight and obesity has remained unchanged in children at diagnosis of Type 1 diabetes over 15 years. These findings suggest that higher adiposity alone cannot account for the continued rising incidence of Type 1 diabetes in recent years.

Thyroid autoimmunity in Type 1 diabetes: systematic review and meta-analysis.

AIMS: To review the incidence and evidence for screening for thyroid autoimmunity and thyroid dysfunction in Type 1 diabetes. METHODS: Systematic review and meta-analysis. Inclusion criteria were prospective cohort studies screening for thyroid autoimmunity and/or dysfunction (defined as an abnormal thyroid-stimulating hormone level) in Type 1 diabetes. Exclusion criteria included pregnancy and thyroid dysfunction before diabetes onset. Outcomes examined were: incidence of thyroid autoimmunity and/or dysfunction; association between thyroid autoimmunity and dysfunction; and cost-effectiveness. Data sources were MEDLINE, EMBASE, the Cochrane Library, manual searching and contact with authors, with limitations to English language and human studies. Meta-analysis was performed using random effects models. RESULTS: We identified 14 eligible studies, involving 2972 young people and 789 adults with Type 1 diabetes. Follow-up ranged from 1-18 years. None of the studies were of good methodological quality (Newcastle Ottowa Scale score > 7). The incidence of thyroid dysfunction (11 studies) ranged from 27 (95% CI 15-45) to 246 (95% CI 118-453) per 10 000 patient-years and thyroid autoimmunity (four studies) from 13 (95% CI 0.3-71) to 326 (95% CI 194-510). The risk of thyroid dysfunction was higher in those with thyroid autoimmunity: summary risk ratio 25 (95% CI 9-71) and was higher in children (49, 95% CI 16-150) compared with adults (7, 95% CI 3-13). No studies examined cost-effectiveness of screening. CONCLUSIONS: There is a markedly increased risk of thyroid dysfunction in people with Type 1 diabetes and thyroid autoimmunity. The optimal method or frequency of screening could not be determined from available data. Future studies should examine whether screening improves clinical outcomes in this population.

Blood ß-hydroxybutyrate vs. urine acetoacetate testing for the prevention and management of ketoacidosis in Type 1 diabetes: a systematic review.

AIM: Diabetic ketoacidosis is a life-threatening complication of Type 1 diabetes. Blood ß-hydroxybutyrate testing is now widely available as an alternative to urine acetoacetate testing for detecting ketosis. The aim of this study was to review the effectiveness of capillary or serum ß-hydroxybutyrate compared with urine acetoacetate testing in prevention and management of diabetic ketoacidosis. METHODS: MEDLINE, EMBASE, EBM Reviews, The Cochrane Library and CINAHL (until April 2012, no language restrictions, studies in humans) were searched for experimental and observational studies comparing the effectiveness of blood ß-hydroxybutyrate and urine acetoacetate testing. Outcomes examined were prevention of diabetic ketoacidosis, time to recovery from diabetic ketoacidosis, healthcare costs and patient or caregiver satisfaction. Additional sources included reference lists, conference proceedings and contact with experts in the field. RESULTS: Four studies (two randomized controlled trials and two cohort studies) met eligibility criteria, including 299 participants across 11 centres. Risk of bias was low to moderate. Blood ketone testing compared with urine testing was associated with reduced frequency of hospitalization (one study), reduced time to recovery from diabetic ketoacidosis (three studies), cost benefits (one study) and greater satisfaction (one study, intervention group only). No study assessed prevention of diabetic ketoacidosis. Meta-analysis could not be performed because of heterogeneity in study design and published data. CONCLUSIONS: There is evidence suggesting that blood ß-hydroxybutyrate testing is more effective than urine acetoacetate testing in reducing emergency department assessment, hospitalization and time to recovery from diabetic ketoacidosis, as well as potentially lowering healthcare expenditure. Further research in both young people and adults is needed.

Coeliac disease in Type 1 diabetes from 1990 to 2009: higher incidence in young children after longer diabetes duration.

AIMS: To determine the incidence of coeliac disease in young people with Type 1 diabetes and to examine the effect of age at diabetes onset and disease duration. METHODS: This was a clinic-based observational cohort study of 4379 people aged ≤ 18 years (49% male) between 1990 and 2009 from Sydney, Australia. Screening for coeliac disease was performed at diagnosis and 1-2 yearly using anti-endomysial and/or anti-tissue transglutaminase immunoglobulin A (IgA) antibodies. Coeliac disease was diagnosed by small bowel biopsy based on Marsh score ≥ III. RESULTS: Coeliac disease was confirmed by biopsy in 185; of these, 61 (33%) were endomysial or tissue transglutaminase IgA antibody-positive at diabetes diagnosis. Mean age at diabetes onset was 6.6 ± 4.0 vs. 8.4 ± 4.1 years in those without coeliac disease (P < 0.001). Mean incidence was 7.7 per 1000 person years (95% CI 6.6-8.9) over 20 years. Incidence was higher in children aged < 5 years at diabetes diagnosis (10.4 per 1000 person years) vs. ≥ 5 years (6.4 per 1000), incidence rate ratio 1.6 (95% CI 1.2-2.2, P = 0.002). Coeliac disease was diagnosed after 2, 5 and 10 years of diabetes in 45, 78 and 94% of cases, respectively. Median time to coeliac disease diagnosis was longer in children aged < 5 years at diabetes onset (3.3 years) compared with older children (0.7 years, P < 0.001). CONCLUSIONS: Coeliac disease is common in young people with Type 1 diabetes; the risk is greatest with diabetes onset < 5 years, but after longer diabetes duration. Screening for coeliac disease should be performed at diabetes diagnosis and for at least 10 years in young children.

Australia's national trends in the incidence of Type 1 diabetes in 0-14-year-olds, 2000-2006.

AIMS: To determine the national incidence of Type 1 diabetes in children aged 0-14 years and examine trends in incidence between 2000 and 2006 by age, sex and calendar year. METHODS: Case ascertainment was from the Australian National Diabetes Register, a prospective population-based incidence register established in 1999, with two sources of ascertainment: the National Diabetes Services Scheme and the Australasian Paediatric Endocrine Group's state-based registers. Denominator data were from the Australian Bureau of Statistics. RESULTS: There were 6350 new cases of Type 1 diabetes (3323 boys and 3027 girls). Case ascertainment was 97.1% complete using the capture-recapture method. The mean adjusted incidence rate for 2000-2006 was 21.6 per 100,000 person-years [95% confidence interval (CI) 21.0, 22.1], and increased from 19.8 in 2000 to 23.4 per 100,000 in 2006, an average increase of 2.8% (95% CI 1.5, 4.1) per year. Mean incidence for the 7-year period increased with age, and was significantly higher in boys aged 0-4 years and 10-14 years than in girls of the same age. CONCLUSIONS: The incidence of Type 1 diabetes among 0-14-year-olds in Australia is very high compared with available data from many other countries. The rate of increase observed globally in the last decade has continued well into this decade in Australia. The rising incidence cannot be explained by changes in genetic susceptibility; there is an urgent need to examine the environmental factors that have contributed to this increase. The findings of this study also have important implications for resource planning.

Correlates of placental infection with cytomegalovirus, parvovirus B19 or human herpes virus 7.

Vertical transmission of viruses is an important cause of morbidity in the fetus and neonate. Placental viral infection indicates risk of vertical transmission, but not always transmission to, or disease of the fetus. Specimens from mothers and babies from three groups-two prospective and one retrospective cohort-were tested for pathogens of teratogenic potential using multiplex PCR. Placental infection was present in 13% of the 105 samples collected. Assessment of the prospective cohorts showed cytomegalovirus (CMV) detected in 4% of placentae from unselected women, parvovirus B19 in 1% and Ureaplasma parvum in 1% of placentae. In a retrospective cohort of women at high risk of transmitting congenital infection due to seroconversion during pregnancy, miscarriage or stillbirth, CMV was detected in 64% and human herpes virus type 7 in 9% of placentae. Of 14 PCR-positive placentae, two were associated with the birth of a living symptomatic infant, two with stillbirth, one with miscarriage, and two with elective terminations of pregnancy. Directed laboratory assessment of women at high risk of transmitting congenital infection, on the basis of clinical or laboratory markers, is important for accurate diagnosis of adverse outcomes of pregnancy. However, routine screening for viruses in the placentae from women with a low-risk serological profile for transmitting congenital infection is unlikely to result in significant numbers of additional diagnoses and is confounded by inadequacy of current diagnostic methods. The major pathogen detected in all cases of placental infection associated with fetal death was human CMV.

The re-emerging burden of rickets: a decade of experience from Sydney.

AIM: To define the demographics and clinical characteristics of cases presenting with nutritional rickets to paediatric centres in Sydney, Australia. METHODS: Retrospective descriptive study of 126 cases seen from 1993 to 2003 with a diagnosis of vitamin D deficiency and/or confirmed rickets defined by long bone x ray changes. RESULTS: A steady increase was seen in the number of cases per year, with a doubling of cases from 2002 to 2003. Median age of presentation was 15.1 months, with 25% presenting at less than 6 months of age. The most common presenting features were hypocalcaemic seizures (33%) and bowed legs (22%). Males presented at a younger age, with a lower weight SDS, and more often with seizures. The caseload was almost exclusively from recently immigrated children or first generation offspring of immigrant parents, with the region of origin predominantly the Indian subcontinent (37%), Africa (33%), and the Middle East (11%). Seventy nine per cent of the cases were born in Australia. Eleven cases (all aged <7 months) presented atypically with hyperphosphataemia. CONCLUSIONS: This large case series shows that a significant and increasing caseload of vitamin D deficiency remains, even in a developed country with high sunlight hours. Cases mirror recent immigration trends. Since birth or residence in Australia does not appear to be protective, screening of at risk immigrant families should be implemented through public health policies.

Molecular epidemiology of enterovirus 71 over two decades in an Australian urban community.

Enterovirus 71 (EV71), first isolated in 1969, has been responsible for numerous outbreaks of hand, foot and mouth disease (HFMD) with a small proportion of cases associated with neurological disease. Since 1997 there has been a significant increase in both the prevalence and virulence of EV71 in the Asia-Pacific region. We have examined the genetic diversity of EV71 in a large Australian city (Sydney N.S.W.) over a nineteen-year period. We determined the VP1 gene sequence of forty-eight EV71 strains isolated between 1983 and 2001. Analysis by molecular phylogeny revealed the presence of four subgenogroups B2, B4, C1 and C2. The results indicate that the major lineage circulating in Sydney N.S.W. was subgenogroup C1 with a recent switch in dominance to B4 in 2000 and 2001.

Development of multiplex PCRs for detection of common viral pathogens and agents of congenital infections.

Potential causes of congenital infection include Toxoplasma gondii and viruses such as cytomegalovirus (CMV), enterovirus, hepatitis C virus, herpes simplex virus types 1 and 2 (HSV-1 and -2), human herpesvirus types 6, 7, and 8, lymphocytic choriomeningitis virus, parvovirus, rubella virus, and varicella-zoster virus. Testing for each of these agents using nucleic acid tests is time consuming and the availability of clinical samples such as amniotic fluid or neonatal blood is often limited. The aim of this study was to develop multiplex PCRs (mPCRs) for detection of DNA and RNA agents in the investigation of congenital infection and an mPCR for the viruses most commonly requested in a diagnostic virology laboratory (CMV, Epstein-Barr virus, enterovirus, HSV-1, HSV-2, and varicella-zoster virus). The assays were assessed using known pathogen-positive tissues (cultures, placentae, plasma, and amniotic fluid) and limits of detection were determined for all the agents studied using serial dilutions of plasmid targets. Nested PCR was performed as the most sensitive assay currently available, and detection of the amplicons using hybridization to labeled probes and enzyme-linked immunosorbent assay detection was incorporated into three of the four assays. This allowed detection of 10 to 10(2) copies of each agent in the samples processed. In several patients, an unexpected infection was diagnosed, including a case of encephalitis where HSV was the initial clinical suspicion but CMV was detected. In the majority of these cases the alternative agent could be confirmed using reference culture, serology, or fluorescence methods and was of relevance to clinical care of the patient. The methods described here provide useful techniques for diagnosing congenital infections and a paradigm for assessment of new multiplex PCRs for use in the diagnostic laboratory.

Prevalence of diabetes complications 6 years after diagnosis in an incident cohort of childhood diabetes.

AIMS: To examine the prevalence of early diabetes complications 6 years after diagnosis of diabetes. The hypothesis that initial contact with a multidisciplinary team would be associated with a reduced risk of microvascular complications was tested in this cohort. METHODS: Participants were recruited from an incident cohort of children aged < 15 years diagnosed between 1990 and 1992 in NSW, Australia. Initial management at a teaching hospital was documented at case notification. At 6 years, health care questionnaires and complications were assessed: retinopathy by 7-field stereoscopic retinal photography and elevated albumin excretion rate (AER) defined as the median of three overnight urine collections > or = 7.5 microg/min. Case attainment was 58% (209/361) with participants younger than non-participants and more likely living in an urban than rural location. RESULTS: Retinopathy was present in 24%, median AER > or = 7.5 microg/min in 18%, and median AER > or = 20 microg/min in 2%. In multivariate analysis, initial management at a teaching hospital or consultation with all three allied health professionals combined with pubertal staging and cholesterol or HbA1c were all determinants of risk for retinopathy. CONCLUSIONS: Early retinopathy and elevated AER are common in children 6 years after diagnosis. Initial allied health contact and management at a teaching hospital were associated with a reduced risk of microvascular complications in this cohort.

Survival after pulmonary edema due to enterovirus 71 encephalitis.

BACKGROUND: A distinctive pattern of enterovirus 71 (EV71) infection, characterized by fever, exanthem, acute pulmonary edema (PE), brainstem encephalitis, and flaccid paresis, affects infants and young children. Most die rapidly owing to respiratory failure and fulminant PE. METHOD: The authors report short- and long-term outcome of six survivors of the acute illness. RESULTS: In the context of acute PE and widespread weakness, recognition of the underlying neurologic disorder was facilitated by the distinctive pattern of MRI signal abnormalities in posterior pons and medulla. EV71-specific PCR of clinical samples helped confirm the diagnosis. Acute PE was managed with mechanical ventilation, afterload reduction, and inotrope support, and resolved completely over days. One patient with minimal neurologic recovery died 9 weeks after disease onset. The other patients have residual neurologic dysfunction, varying from subtle monoparesis to severe bulbar dysfunction, central and peripheral respiratory failure, and flaccid quadriparesis. Faster neurologic recovery was associated with less long-term deficit. Long-term outcome was similar in patients treated with and without pleconaril or IV immunoglobulin. Three long-term survivors treated with IV corticosteroids had less severe long-term neurologic disability than two not treated with steroids. CONCLUSION: Acute pulmonary edema and encephalomyelitis occurs with EV71 infection in infants. Long-term neurologic outcome varied from minor, focal weakness to profound, global motor dysfunction with respiratory failure.

Sampling for sand flies (Diptera: Psychodidae) among prairie dog colonies on ranches with histories of vesicular stomatitis in new Mexico and Colorado.

The possible presence of sand flies (Diptera: Psychodidae) among colonies of Gunnison's prairie dogs, Cynomys gunnisoni Baird, was investigated on or near ranches with histories of vesicular stomatitis (VS) in domestic livestock in the mid-Rio Grande River Valley, NM, and west-slope region of Colorado. Sampling was conducted at six locations, three in each region, using three methods: standard down-draft suction/light traps, up-draft suction/light traps (both supplemented with CO2), and burrow-emergence traps. Two male and four female sand flies, Lutzomyia apache, Young and Perkins were recovered from prairie dog colony and sand-sagebrush association habitats on a cattle ranch in Socorro County, NM. Sand flies were captured only in up-draft suction/light traps. This record is of interest for the following reasons: (1) sand flies have not been reported from the Rio Grande River Valley of New Mexico, (2) sand flies are biological vectors of VS viruses in other areas, (3) the mid-Rio Grande River Valley has been a focus of VS virus activity in domestic livestock during recent outbreaks, and (4) the source of vesicular stomatitis viruses that infect livestock in the western United States is unknown, but may involve introductions of virus from Mexico or an endemic cycle maintained by vector insects.