Public health investigation and response to a hepatitis A outbreak from imported scallops consumed raw-Hawaii, 2016.

During the summer of 2016, the Hawaii Department of Health responded to the second-largest domestic foodborne hepatitis A virus (HAV) outbreak in the post-vaccine era. The epidemiological investigation included case finding and investigation, sequencing of RNA positive clinical specimens, product trace-back and virologic testing and sequencing of HAV RNA from the product. Additionally, an online survey open to all Hawaii residents was conducted to estimate baseline commercial food consumption. We identified 292 confirmed HAV cases, of whom 11 (4%) were possible secondary cases. Seventy-four (25%) were hospitalised and there were two deaths. Among all cases, 94% reported eating at Oahu or Kauai Island branches of Restaurant Chain A, with 86% of those cases reporting raw scallop consumption. In contrast, a food consumption survey conducted during the outbreak indicated 25% of Oahu residents patronised Restaurant Chain A in the 7 weeks before the survey. Product trace-back revealed a single distributor that supplied scallops imported from the Philippines to Restaurant Chain A. Recovery, amplification and sequence comparison of HAV recovered from scallops revealed viral sequences matching those from case-patients. Removal of product from implicated restaurants and vaccination of those potentially exposed led to the cessation of the outbreak. This outbreak further highlights the need for improved imported food safety.

The Association of Incidental Radiation Dose to the Heart Base with Overall Survival and Cardiac Events after Curative-intent Radiotherapy for Non-small Cell Lung Cancer: Results from the NI-HEART Study.

AIMS: Cardiac disease is a dose-limiting toxicity in non-small cell lung cancer radiotherapy. The dose to the heart base has been associated with poor survival in multiple institutional and clinical trial datasets using unsupervised, voxel-based analysis. Validation has not been undertaken in a cohort with individual patient delineations of the cardiac base or for the endpoint of cardiac events. The purpose of this study was to assess the association of heart base radiation dose with overall survival and the risk of cardiac events with individual heart base contours. MATERIALS AND METHODS: Patients treated between 2015 and 2020 were reviewed for baseline patient, tumour and cardiac details and both cancer and cardiac outcomes as part of the NI-HEART study. Three cardiologists verified cardiac events including atrial fibrillation, heart failure and acute coronary syndrome. Cardiac substructure delineations were completed using a validated deep learning-based autosegmentation tool and a composite cardiac base structure was generated. Cox and Fine-Gray regressions were undertaken for the risk of death and cardiac events. RESULTS: Of 478 eligible patients, most received 55 Gy/20 fractions (96%) without chemotherapy (58%), planned with intensity-modulated radiotherapy (71%). Pre-existing cardiovascular morbidity was common (78% two or more risk factors, 46% one or more established disease). The median follow-up was 21.1 months. Dichotomised at the median, a higher heart base Dmax was associated with poorer survival on Kaplan-Meier analysis (20.2 months versus 28.3 months; hazard ratio 1.40, 95% confidence interval 1.14-1.75, P = 0.0017) and statistical significance was retained in multivariate analyses. Furthermore, heart base Dmax was associated with pooled cardiac events in a multivariate analysis (hazard ratio 1.75, 95% confidence interval 1.03-2.97, P = 0.04). CONCLUSIONS: Heart base Dmax was associated with the rate of death and cardiac events after adjusting for patient, tumour and cardiovascular factors in the NI-HEART study. This validates the findings from previous unsupervised analytical approaches. The heart base could be considered as a potential sub-organ at risk towards reducing radiation cardiotoxicity.

Improvement in metabolic control in diabetic adolescents by the use of increased insulin dose.

Ten diabetic adolescents who had poor blood glucose control during the preceding year were recruited into a crossover insulin dosage study. Diabetic control was assessed on two insulin dosage regimens; either 1.0 U/kg/day ("limited dosage") or 1.4 U/kg/day ("increased dosage"). The study had a 1-mo run-in period followed by two treatment periods each of 3-mo duration. Improvement in control occurred during "increased" insulin dosage with reduction of glycosylated hemoglobin levels (P less than 0.001), self-monitored blood glucose levels (P less than 0.001), and 24-h urine glucose excretion (P less than 0.01). Overnight studies did not reveal hypoglycemia (blood glucose less than 2 mmol/L) in either group, but improved overnight glucose profiles were demonstrated on the "increased" dosage and were associated with higher free insulin levels. The study supports the case for a higher maximal insulin dosage than commonly recommended during adolescence.

A prospective study to evaluate the benefits of long-term self-monitoring of blood glucose in diabetic children.

The benefits of self-monitoring of blood glucose (SMBG) in diabetic children have been assessed in an 18-mo prospective study by comparison of two groups, one receiving intensive education (N = 20) and the other, education combined with SMBG (N = 19). Regular home visits were made with all children during which attempts were made to optimize diabetes control. Mean blood glucose levels in the SMBG group showed a downward trend throughout the study; however, values at baseline (11.7 mmol/L) were not significantly different from those at completion of the study (10.8 mmol/L). Hemoglobin A1c levels showed a seasonal fluctuation, but values at the beginning and end of the study were nearly identical to each other in both groups. The SMBG group showed a reduction in the number of hospital admissions for stabilization of control and for ketoacidosis (P less than 0.04).

A low-cost alternative for nasolaryngoscopy simulation training equipment: a randomised controlled trial.

OBJECTIVES: Flexible nasolaryngoscopy is a key diagnostic procedure used in many specialities. Simulation-based teaching is beneficial for endoscopy training, but it is expensive. This study assessed whether an inexpensive simulation model is an effective training method for flexible nasolaryngoscopy. METHODS: A three-armed, randomised, controlled trial was performed. One group received no simulation training, while two others were trained with either a high-cost or a low-cost model. All candidates then performed flexible nasolaryngoscopy on a volunteer. Their ability to perform this task was assessed by the patient discomfort score and time taken by a blinded expert. RESULTS: Simulation-based teaching reduced patient discomfort and improved candidate skill level. Low-cost model training did not have a negative effect when compared with high-cost model training. CONCLUSION: Simulated flexible nasolaryngoscopy training may be more accessible with the use of an effective low-cost model.

The investigation of neonatal obstructive jaundice using 123I rose bengal.

With the development of new surgical techniques the outlook for infants with biliary atresia has improved significantly. It has therefore become increasingly important to identify these patients quickly in order to allow prompt surgical intervention. Differentiation of biliary atresia from other causes of jaundice, in particular idiopathic neonatal hepatitis, is often difficult as there is considerable clinical and histological overlap of the two conditions. Demonstration of biliary patency using radiopharmaceuticals is a well established technique. 131I rose bengal and the 99Tcm-labelled iminodiacetic acid derivatives have both been used, but are not completely satisfactory, and controversy still exists as to which is the most suitable agent. Nine infants with prolonged jaundice have been studied using 123I-labelled rose bengal. All infants with biliary atresia and neonatal hepatitis were correctly identified. The results indicate that 123I rose bengal provides a reliable tracer for assessing biliary patency and is the agent of choice in the investigation of neonatal obstructive jaundice.

Two or three insulin injections in adolescence?

Morning hyperglycaemia remains a challenge to conventional insulin regimens. Eighteen adolescents participated in a one year crossover study to examine the effect of delaying the evening intermediate acting insulin from before the evening meal to bedtime. This three injection regimen caused slightly higher blood glucose concentrations in the early part of the night, and lower concentrations in the morning, but no overall change in glycosylated haemoglobin concentrations (HbA1c). Seasonal change accounted for substantially more of the variance in HbA1c concentrations than did the regimen change. The three injection regimen did not alter the frequency of hypoglycaemic episodes. Metabolic control on both regimens might have been improved by more intensive monitoring and medical attention. This study suggests that factors beyond medical control, such as seasonal variation, may contribute more to the control of diabetes in adolescents than changes in conventional insulin regimens, particularly when unaccompanied by intensive monitoring.

Total glycosylated haemoglobin (HbA1) levels in diabetic children.

Total glycosylated haemoglobin (HbA1) levels from capillary blood were studied retrospectively during a 1-year period in 148 diabetic children aged between 1.9 and 16.8 years. The clinic range for HbA1 was 6.7 to 22.2% and the results were normally distributed (mean +/- SD 13.2 +/- 2.8%). The normal range in non-diabetics using this method is 4.9 to 8.0%. Results from children who had had diabetes for more than 5 years were higher than those from children with diabetes of 2 to 5 years' duration. Girls had higher average values during the 1-year period than boys. HbA1 measurement serves to identify the deficiencies of current diabetic treatment regimens. It also has more immediate practical benefits in focusing attention on children whose control is deteriorating.

Failure of glucagon release in infants of diabetic mothers.

Two hours after birth 30 normal infants had a fall in blood glucose of 20.6 mg/100 ml and a rise of plasma pancreatic glucagon of 50.7 pg/ml. Fifteen infants of diabetic mothers treated with insulin had a much greater fall in blood glucose of 77.5 mg/100 ml and a smaller rise of glucagon of 20.9 pg/ml. By comparison 14 small-for-dates infants, who are also prone to hypoglycaemia, had a blood glucose fall of 32.8 mg/100 ml and a larger rise of pancreatic glucagon of 96.0 pg/ml. It is suggested that the impaired pancreatic glucagon rise in the infants of diabetic mothers may be a significant factor in their hypoglycaemia.

Bedtime insulin injections: an alternative regimen.

Sixteen children (aged 3 to 12 years) participated in a 12 month crossover study comparing bedtime with teatime insulin injections in an endeavour to reduce morning hyperglycaemia. Blood glucose values were lower at lunch and at teatime on the later injection, but higher at bedtime and midnight. There was no overall change in glycosylated haemoglobin. Despite more frequent mild hypoglycaemic attacks, parents preferred the convenience of the later injection. Analysis of individual children's glycosylated haemoglobin values showed that those whose metabolic control improved on the later injection were younger and went to bed earlier, indicating that this regimen may have a place in the management of younger children with diabetes mellitus.

Spontaneous perforation of common bile duct in infants.

Two infants with spontaneous perforation of the common bile duct are described. One presented with mild jaundice, dark urine, acholic stools, and hydroceles, the other with bilateral inguinal hernia. In both the diagnosis was unsuspected until bile-stained ascites was discovered. Both eventually developed bile-staining of the scrotum. Neither was acutely ill. The 131I-Rose Bengal faecal excretion test showed reduced faecal excretion at 8% and 12% of the injected dose with 16-5 and 17%/dl of the dose being recovered in the ascitic fluid 48 hours after intravenous injection. The ascitic:plasma ratio of isotope at that time was 32:1 and 28:1. Operative cholangiography in both showed a perforation at the junction of the cystic duct and common bile duct with no contrast entering the duodenum. Cholecystenterostomy using a Roux-en-Y loop of jejunum produced a rapid sustained recovery and is suggested as the treatment of choice. This condition should be considered in the differential diagnosis of obstructive jaundice in infancy since early surgical correction is necessary.

Café-au-lait spots in schoolchildren.

This paper reports a study of café-au-lait spots of a minimum diameter of 1 cm in 732 white schoolchildren. Three groups were identified, according to the number of café-au-lait spots on each child: (1) those with none (74%), (2) those with fewer than 5 (25%), and (3) those with at least 5 (5 children, 2 considered to be normal, and 3 siblings each presumed to have neurofibromatosis, one having died from leukaemia). Excluding the last group, the number of café-au-lait spots in the sample was not significantly related to age or sex. Some support is given for using the number of café-au-lait spots as an empirical threshold to diagnose neurofibromatosis.

An investigation of ring and dicentric chromosomes found in three Turner's syndrome patients using DNA analysis and in situ hybridisation with X and Y chromosome specific probes.

We have studied three patients with features of Turner's syndrome, two with a 45,X/46,X,r(?) and the third with a 45,X/46,X,dic?(Y) karyotype. Because Turner's syndrome patients with a mosaic karyotype containing a Y chromosome are known to have a high risk of developing gonadal tumours, we used DNA analysis and in situ hybridisation with X and Y specific probes to identify the chromosomal origin of the rings and dicentric chromosomes in the three index patients. Both ring chromosomes were shown to be of X origin, while the dicentric was composed of Y chromosome material. We discuss the importance of using a combination of molecular and cytogenetic analyses in such cases.

Seasonal variation of haemoglobin A1 in children with insulin-dependent diabetes mellitus.

The results of three controlled trials performed on children with insulin-dependent diabetes mellitus were examined for evidence of seasonal variation in concentrations of glycosylated haemoglobin (HbA1). All three studies showed lower levels during the summer months. Multiple regression analysis showed that the month of sampling accounted for a significant proportion of the total variance in HbA1 levels (P less than 0.001 in all three studies). We suggest that exercise, dietary changes and the frequency of minor illnesses may all contribute to this fluctuation which has important implications for the design of clinical trials in childhood diabetes.

Human insulin and porcine insulin in the treatment of diabetic children: comparison of metabolic control and insulin antibody production.

Semisynthetic human insulin and highly purified porcine insulin were compared in a double blind crossover study in 21 diabetic children. Glycosylated haemoglobin values at the end of four month treatment periods were higher after treatment with human insulin than after treatment with porcine insulin (mean 15.7% (SD 2.3%) v 14.2% (2.3%); p less than 0.01). Higher fasting blood glucose concentrations occurred during treatment with human insulin than with porcine insulin (mean 12.0 (SD 2.1) v 11.0 (2.4) mmol/1; mean 216 (SD 38) v 198 (43) mg/100 ml; p less than 0.05), but there were no significant differences at other time points during the day. The incidence of hypoglycaemia was similar for both treatment groups. Concentrations of antibody reactive with porcine and human insulins were similar for the two treatment groups, although greater fluctuation was observed in the amount of antibody reactive with human insulin. Semisynthetic human insulin is safe and effective in diabetic children, although further work is needed to devise regimens which achieve optimal blood glucose control.

Serum alpha-fetoprotein levels in extrahepatic biliary atresia, idiopathic neonatal hepatitis and alpha-1-antitrypsin deficiency (PiZ).

Serum alpha-fetoprotein levels were measured using a sensitive radioimmunoassay in 77 infants presenting with persistent conjugated hyperbilirubinaemia. A breed range of alpha-fetoprotein concentrations occurred in both the 23 infants with extrahepatic biliary atresia and the 35 with idiopathic neonatal hepatitis but the 13 with alpha-1-antitrypsin deficiency had uniformly low levels. High alpha-fetoprotein concentrations (above 10 000 mug/1) favoured the diagnosis of neonatal hepatitis especially in the first ten weeks of life, but the overlap between neonatal hepatitis and extrahepatic biliary atresia was large and alpha-fetoprotein determination cannot be recommended as a reliable method for distinguishing the two conditions. Serial alpha-fetoprotein values showed no consistent relationship with standard liver function tests and gave no guide to prognosis. There was an association between alpha-fetoprotein production and needle biopsy evidence of hepatic giant cell transformation. The uniformly low alpha-fetoprotein levels in alpha-1-antitrypsin deficient infants with neonatal hepatitis is a new observation and possible mechanisms for disordered glycoprotein release are discussed.