Prediction of protective sensory loss, neuropathy and foot ulceration in type 2 diabetes.

OBJECTIVES: To prospectively determine clinical and biochemical characteristics associated with the development of peripheral neuropathy, loss of protective sensation, and foot ulceration in persons with type 2 diabetes mellitus (DM) over 7 years. RESEARCH DESIGN AND METHODS: Graded monofilament (MF) testing, vibration perception threshold, and neuropathy symptom questionnaires were undertaken in 206 participants with type 2 DM without peripheral vascular disease or history of foot ulceration and 71 healthy participants without DM at baseline and after 7 years. 6 monthly glycosylated hemoglobin (HbA1c) levels and annual serum lipid profiles were measured during follow-up of those with DM. Incident foot ulceration was recorded at follow-up. RESULTS: Taller stature and higher quartiles of serum triglyceride and HbA1c levels were associated with neuropathy at follow-up (p=0.008). Remission of baseline neuropathy was observed in 7 participants at follow-up. 9 participants with type 2 DM developed foot ulcers by the end of the study, only 1 at low risk. Mean HbA1c levels were higher in those who developed foot ulceration (p<0.0001). 1 participant with neuropathy throughout developed a Charcot foot. Failure to perceive 2 or more 2, 4 and 6 g MF stimuli at baseline predicted loss of protective sensation at follow-up. CONCLUSIONS: Tall stature and worse metabolic control were associated with progression to neuropathy. Mean HbA1c levels were higher in those who developed foot ulcers. Graded MF testing may enrich recruitment to clinical trials and assignation of high risk for foot ulceration.

Comparison of the ETDRS logMAR, 'compact reduced logMar' and Snellen charts in routine clinical practice.

AIM: To compare the performance of the ETDRS logMAR, compact reduced logMAR and Snellen charts in an ophthalmic outpatient setting. METHODS: The reliability and reading times of the charts were compared in a stratified sample of 40 eyes of 40 ophthalmic patients with a variety of stable eye diseases. In order to simulate a clinical setting, forced-choice testing was not used. RESULTS: Similar acuity results were recorded from all three charts, suggesting a lack of a systematic bias as regards chart design. A small practice effect was observed for all charts but was greatest for Snellen and least for ETDRS. The test-retest variability of the charts was similar, with the 95% tolerance limit for change being +/-0.14 logMAR for ETDRS, +/-0.16 for reduced logMAR and +/-0.18 for Snellen. The mean reading times for the subjects were 34.65 s for ETDRS, 21.17 s for reduced logMAR and 18.67 s for Snellen. CONCLUSION: The performance of the compact reduced logMAR chart was intermediate between Snellen and ETDRS. The theoretical advantages of the ETDRS design were still measurable in a clinical setting but the magnitude of the advantage in terms of test-retest reliability was fairly small and the time taken to complete the EDTRS was 1.86 times that of the Snellen chart.

Surveillance of cirrhosis for hepatocellular carcinoma: a cost-utility analysis.

Using a decision-analytic model, we evaluated the effectiveness and cost-effectiveness of surveillance for hepatocellular carcinoma (HCC) in individuals with cirrhosis. Separate cohorts with cirrhosis due to alcoholic liver disease, hepatitis B and hepatitis C were simulated. Results were also combined to approximate a mixed aetiology population. Comparisons were made between a variety of surveillance algorithms using alpha-foetoprotein (AFP) assay and/or ultrasound at 6- and 12-monthly intervals. Parameter estimates were obtained from comprehensive literature reviews. Uncertainty was explored using one-way and probabilistic sensitivity analyses. In the mixed aetiology cohort, 6-monthly AFP+ultrasound was predicted to be the most effective strategy. The model estimates that, compared with no surveillance, this strategy may triple the number of people with operable tumours at diagnosis and almost halve the number of people who die from HCC. The cheapest strategy employed triage with annual AFP (incremental cost-effectiveness ratio (ICER): 20,700 pounds per quality-adjusted life-year (QALY) gained). At a willingness-to-pay threshold of 30,000 pounds per QALY the most cost-effective strategy used triage with 6-monthly AFP (ICER: 27,600 pounds per QALY gained). The addition of ultrasound to this strategy increased the ICER to 60,100 pounds per QALY gained. Surveillance appears most cost-effective in individuals with hepatitis B-related cirrhosis, potentially due to younger age at diagnosis of cirrhosis. Our results suggest that, in a UK NHS context, surveillance of individuals with cirrhosis for HCC should be considered effective and cost-effective. The economic efficiency of different surveillance strategies is predicted to vary markedly according to cirrhosis aetiology.

Surveillance of cirrhosis for hepatocellular carcinoma: systematic review and economic analysis.

OBJECTIVES: To evaluate the effectiveness, cost-effectiveness and cost-utility of surveillance of patients with cirrhosis [alcoholic liver disease (ALD)-, hepatitis B (HBV)- and C virus (HCV)-related], using periodic serum alpha-fetoprotein (AFP) testing and/or liver ultrasound examination, to detect hepatocellular carcinoma (HCC), followed by treatment with liver transplantation or resection, where appropriate. DATA SOURCES: Electronic databases were searched up to March 2006. REVIEW METHODS: A systematic review was carried out using standard methodological guidelines. A computerised decision-analytic model was then developed to compare various surveillance strategies. RESULTS: No studies were identified that met the criteria of the systematic review. Based on the assumptions used in the model, the most effective surveillance strategy uses a combination of AFP testing and ultrasound at 6-monthly intervals. Compared with no surveillance, this strategy is estimated to more than triple the number of people with operable HCC tumours at time of diagnosis, and almost halves the number of deaths from HCC. On all effectiveness measures and at both testing frequencies, AFP- and ultrasound-led surveillance strategies are very similar. This may be because test sensitivity was varied according to tumour size, which means that AFP testing is capable of identifying many more small tumours than ultrasound. The best available evidence suggests that AFP tests will detect approximately six times as many small tumours as ultrasound. Increasing the frequency of either test to 6-monthly intervals is more effective than performing combined testing on an annual basis. The undiscounted lifetime cost of the surveillance strategies, including all care and treatment costs, ranges from 40,300 pounds (annual AFP triage) to 42,900 pounds (6-monthly AFP and ultrasound). The equivalent discounted costs are 28,400 pounds and 30,400 pounds. Only a small proportion of these total costs results from the cost of the screening tests. However, screening test costs, and the cost of liver transplants and caring for people post-transplant, accounted for most of the incremental cost differences between alternative surveillance strategies. The results suggest that different surveillance strategies may provide the best value for money in patient groups of different cirrhosis aetiologies. The surveillance of people with HBV-related cirrhosis for HCC provides the best value for money, while surveillance in people with ALD-related cirrhosis provides the poorest value for money. In people with HBV-related cirrhosis, at an assumed maximum willingness to pay (WTP) for a quality-adjusted life-year (QALY) of 30,000 pounds, both the deterministic and probabilistic cost-utility analyses suggest the optimal surveillance strategy would be 6-monthly surveillance with the combination of AFP testing and ultrasound. In contrast, for those with ALD-related cirrhosis, annual screening with AFP as a triage test is the only surveillance strategy that is likely to be considered cost-effective at this WTP. The probabilistic analysis implies that the estimated benefits of a 6-monthly AFP triage strategy will only be worth the cost in those with ALD when society's WTP for a QALY exceeds around 40,000 pounds. For people with HCV-related cirrhosis, the model suggests that the most cost-effective surveillance strategy at a WTP threshold of 30,000 pounds/QALY would be surveillance with a 6-monthly AFP triage strategy. CONCLUSIONS: In a mixed-aetiology cohort, the most effective surveillance strategy is to screen each patient with AFP assay and ultrasound imaging on a 6-monthly basis. However, when costs are taken into account it is doubtful whether ultrasound should be routinely offered to those with blood AFP of less than 20 ng/ml, unless policy-makers are prepared to pay over 60,000 pounds per QALY for the benefits achieved. Furthermore, the cost-effectiveness of surveillance for HCC varies considerably depending on the aetiology of cirrhosis; it is much more likely to be cost-effective in those with HBV-related cirrhosis, and much less likely to be cost-effective in those with ALD-related cirrhosis. Further development of the model would help to enable refinement of an optimal screening strategy. Research into the use of contrast-enhanced ultrasound technology for HCC detection would also be valuable, as would research into the epidemiology and natural history of ALD-related cirrhosis. Studies are also needed to investigate the influence of cirrhosis aetiology on tumour AFP expression.

Childhood autism spectrum disorder in the Barwon region: a community based study.

OBJECTIVE: To establish a community database for children with autism spectrum disorder (ASD) to determine prevalence and identify subgroups based on key intellectual, clinical and family parameters. METHODS: Data were collected for children previously diagnosed with an ASD in the Barwon region using parental interview and review of the child's paediatric and psychological records. Preschool diagnoses were typically made by specialist psychologists and school-age diagnoses made by a multidisciplinary team. RESULTS: One hundred and seventy-seven children in the Barwon region were identified as having ASD (82% response rate). The prevalence of ASD was one per 255 children aged two to 17 years. The prevalence increased 10 fold over a 16-year period and this increase was relatively even across all levels of child intellectual functioning. Forty-two percent of children were intellectually disabled (IQ < 70) and performance IQ was significantly higher than verbal IQ but typical block design-comprehension subtest patterns were not common. Nine sibling pair families were identified, 24% were labelled as having attention deficit hyperactivity disorder (ADHD), 6% had epilepsy, and 18.3% were macrocephalic where data were available. Family difficulty was associated with the degree of obsessions/rituals, frequency and intensity of anger/aggression, and ADHD but overall was not associated with the child's intellectual status. CONCLUSIONS: The relatively rapid increase in prevalence is consistent with overseas studies and suggests significant changes in diagnostic criteria, increasing community awareness and the need for support at all levels of intellectual functioning. Increased occurrence in siblings and relatives gives further evidence for a genetic cause.

The most difficult clinical situations: a survey of Victorian general paediatricians.

OBJECTIVE: To identify which clinical situations are the most difficult to manage for general paediatricians in Victoria, Australia. METHODS: Self-administered questionnaires were sent to general paediatricians in Victoria. They were asked their opinions regarding what were the most difficult and the most dangerous clinical situations with which they deal. RESULTS: The response rate was 64% (63 out of 98 questionnaires sent). The general paediatricians surveyed believed that behavioural, developmental and psychosocial conditions were the most difficult to deal with; conduct disorder was the most nominated clinical category (26% of respondents). The 'dangerous' cases nominated were predominately traditional medical cases. The most commonly nominated category was sepsis and shock (21% of respondents). The most difficult and dangerous clinical situations overall for general paediatricians in Victoria appear to be in the areas of sepsis, child protection, paediatric and neonatal resuscitation, depression and suicide, raised intracranial pressure, intravenous fluid management, and communication with parents and adolescents. CONCLUSIONS: The present survey provides useful information to help with training-programme design and it gives trainee paediatricians an idea of what experienced paediatricians find difficult. Severe behavioural, family and social difficulties, as well as neonatal and childhood resuscitation, severe sepsis, raised intracranial pressure, and intravenous fluid management were the clinical situations most frequently described as difficult.

X-linked myoclonic epilepsy with spasticity and intellectual disability: mutation in the homeobox gene ARX.

OBJECTIVE: To describe a new syndrome of X-linked myoclonic epilepsy with generalized spasticity and intellectual disability (XMESID) and identify the gene defect underlying this disorder. METHODS: The authors studied a family in which six boys over two generations had intractable seizures using a validated seizure questionnaire, clinical examination, and EEG studies. Previous records and investigations were obtained. Information on seizure disorders was obtained on 271 members of the extended family. Molecular genetic analysis included linkage studies and mutational analysis using a positional candidate gene approach. RESULTS: All six affected boys had myoclonic seizures and TCS; two had infantile spasms, but only one had hypsarrhythmia. EEG studies show diffuse background slowing with slow generalized spike wave activity. All affected boys had moderate to profound intellectual disability. Hyperreflexia was observed in obligate carrier women. A late-onset progressive spastic ataxia in the matriarch raises the possibility of late clinical manifestations in obligate carriers. The disorder was mapped to Xp11.2-22.2 with a maximum lod score of 1.8. As recently reported, a missense mutation (1058C>T/P353L) was identified within the homeodomain of the novel human Aristaless related homeobox gene (ARX). CONCLUSIONS: XMESID is a rare X-linked recessive myoclonic epilepsy with spasticity and intellectual disability in boys. Hyperreflexia is found in carrier women. XMESID is associated with a missense mutation in ARX. This disorder is allelic with X-linked infantile spasms (ISSX; MIM 308350) where polyalanine tract expansions are the commonly observed molecular defect. Mutations of ARX are associated with a wide range of phenotypes; functional studies in the future may lend insights to the neurobiology of myoclonic seizures and infantile spasms.

Clinical markers of serious illness in young infants: a multicentre follow-up study.

OBJECTIVE: To perform a multicentre follow-up study to determine if previously identified markers of serious illness in early infancy were robust and statistically reliable. METHODS: Infants aged 1 week to 26 weeks presenting to the Emergency Departments of the Royal Children's Hospital and two Melbourne metropolitan hospitals were seen over a 12-month period. Eleven clinical markers as well as their temperature were documented by nursing staff and resident medical officers. Serious illness was defined if infants had a positive body fluid bacterial culture, a positive chest X-ray or if significant treatment was required in hospital. The predictive values, sensitivity and specificity for the individual and the best combination of clinical markers were determined. RESULTS: Assessments (3806) were performed with 312 infants being assessed as seriously ill (8.2%). The combination of either drowsiness on history or examination, pallor on history or examination, breathing difficulty (chest wall recession), temperature above 38 degrees C and a lump being present, identified 82.5% of all babies deemed subsequently to be seriously ill. The positive predictive value of an infant who was febrile, drowsy and pale on examination was 70.7% (previous study 74%). CONCLUSIONS: This study confirmed the high individual predictive value of arousal variables, pallor, and chest wall recession, especially when associated with fever, reaffirming their utility in the recognition of serious illness in infants under 6 months of age.

Factors associated with recurrent hospitalization in chronically ill children and adolescents.

OBJECTIVES: To determine factors associated with recurrent hospitalization in children with chronic illnesses in the Barwon Region. METHODOLOGY: Patients with four or more admissions to the Geelong Hospital children's ward over a 12-month period were identified. Their records were reviewed and the opinions of involved staff (medical, nursing, psychiatry, psychology, and social work) were sought. Multidisciplinary discussions were held to identify factors precipitating or maintaining the need for hospitalization. The numbers, illnesses and profiles of those admitted recurrently were compared with the data from the Barwon Paediatric Consultation Profile from the same period, and with those patients seen by the local counselling service for young people with chronic illnesses. RESULTS: Twenty-seven children had four or more admissions over the 12 months; these represent 0.05% of the child population regionally, or 2% of those with chronic illness. They account for 8.7% of hospital admissions and 16% of inpatient days. Two-thirds (18/27) had major psychosocial issues largely responsible for their admissions. A checklist was formulated of important medical, family, social, psychological, developmental, and institutional considerations. The most frequently identified psychosocial issues were medical dependency, psychological or medical problems affecting other family members, family and medical disparity regarding the treatment agenda, the lack of more intensive community supports, and medical controversy regarding best management. CONCLUSIONS: Ongoing medicalization and medical dependency, driven both by staff and families, can perpetuate recurrent hospitalization. Further awareness and training in these issues and development of community resources will be necessary if this process is to be changed.

A 12-month profile of community paediatric consultations in the Barwon region.

OBJECTIVE: To determine the profile of all consultations carried out in paediatricians offices in the Barwon region over a 12-month period. METHODOLOGY: The age, sex, category, diagnosis, and outcome of all non-hospital-based paediatric consultations carried out in the Barwon region were documented prospectively on a day by day basis. Relevant demographic data and information on Barwon children treated elsewhere were also collected. The frequency of different categories of illness, systems involved and groups of diagnoses was determined. RESULTS: A total of 14,711 consultations was carried out in the region with 10% of the childhood population having contact with the paediatricians during the year; 3135 new patients or problems were seen with 34.8% of all consultations involving behavioural problems and 76% of these relating to ADHD. The most frequent medical diagnostic group was CNS/disability being 16% of all consultations. At least 50% of the medical consultations involved chronic illness. CONCLUSIONS: Behavioural difficulty, chronic disability, and learning problems represent a significant part of the workload of community-based general paediatricians. Appropriate exposure during paediatric training should be given to these issues along with more sophisticated training in the medical, social and psychological complications of chronic illness and its effect on clients and families.

The evolving role of community-based general paediatricians: the Barwon experience.

OBJECTIVE: To detail the acute and chronic paediatric service and community-orientated activities and responsibilities of community-based general paediatricians. METHODOLOGY: Data were collected over the 12 months July 1996 to June 1997 relevant to (i) acute neonatology and paediatrics, (ii) the different community paediatric service organizations with which the paediatricians were involved, and (iii) the quantification of the amount of time spent in non-consulting paediatric work. RESULTS: Findings revealed decreasing hospital admissions, infrequent severe neonatal resuscitation requirements, extensive involvement in community organizations and a great deal of time spent in non-consulting paediatric work. CONCLUSIONS: Ongoing training and upgrading in acute paediatric diagnostic and procedural skills, rationalization of resuscitation expertise, training in management and administrative skills and models of care for the chronically ill should become part of the training of community-based general paediatricians.

Routine pulmonary function tests in young adolescents with asthma in general practice.

OBJECTIVE: To assess the value of performing routine pulmonary function tests by flow-loop spirometry in young adolescents with asthma. DESIGN: A prospective clinical study comparing clinical assessment and patients' self-reporting of asthma severity with the results of pulmonary function tests. SETTING: General practice in a small rural community of about 30,000 people. PATIENTS: Young adolescents with asthma, aged 10-15 years, were enrolled in the study over a two-year period from July 1993 to June 1995 when they presented for either elective, interval assessments or with an acute exacerbation of asthma. MAIN OUTCOME MEASURES: Discrepancy between (i) the doctor's and the patient's perception of asthma control (six scale measures) and the consequent management plans, and (ii) the results of pulmonary function tests that indicated less than adequate airway function (i.e., forced expiratory volume in one second as a percentage of predicted vital capacity for height and sex [FEV1%] less than 65% or average flow rate over the middle 50% of forced vital capacity as a percentage of predicted normal value [FEF25%-75%] less than 65%). RESULTS: Twenty-seven adolescents with asthma were assessed on a total of 37 occasions. The results of pulmonary function tests did not correlate with asthma symptoms and treatment in 11 of the 37 assessments (30%; 95% confidence interval [CI], 16%-47%). The 11 assessments were performed on eight patients. CONCLUSIONS: This small community-based study of adolescents with asthma supports the view that pulmonary function testing by flow-loop spirometry should be part of the routine assessment of acute and chronic asthmatics. Further study in a larger community is needed to clarify the frequency of over- and underestimation of asthma severity in this difficult age group.

A simple hospital triaging system for infants with acute illness.

OBJECTIVE: To determine the simplest combination of symptoms and signs for use as a triaging procedure in young infants presenting to hospital, and to compare this with the 'Baby Check' system. METHODOLOGY: Six hundred and eighty-two babies were assessed when presenting with acute illness to a children's hospital emergency department. Results of analysis were compared to the results of the Baby Check system, which was derived from the data on the same babies. RESULTS: The presence of at least one of the following markers: drowsiness on examination, significant chest wall recession, generalized pallor, a history of feeding less than 50% or decreased activity, had a sensitivity of 91%, a specificity of 72%, a positive predictive value of 29% and a negative predictive value of 98% when predicting the need for intervention in hospital. The 'Baby Check' system with a score of 13 or more had a sensitivity of 95%, a specificity of 70%, a positive predictive value of 28% and a negative predictive value of 99%. Less common but predictive markers such as bile-stained vomiting, respiratory grunt, apnoea and convulsions add further to the sensitivity. Based on this data set, if historical variables alone (the presence of either drowsiness, difficult breathing, being more pale than usual, feeding less than 50% or decreased activity) were used (as in telephone screening) 92% of babies needing treatment in hospital would be identified. CONCLUSION: A simple five-marker system is almost as powerful as the 19-marker Baby Check system and provides a useful basis for a triaging system and educational guidelines when assessing sick babies.

Axillary and rectal temperature measurements in infants.

Rectal and axillary temperatures were measured during the daytime in 281 infants seen randomly at home and 656 at hospital under 6 months old, using mercury-in-glass thermometers. The normal temperature range derived from the babies at home was 36.7-37.9 degrees C for rectal temperature and 35.6-37.2 degrees C for axillary temperature. Rectal temperature was higher than axillary in 98% of the measurements. The mean (SD) difference between rectal and axillary temperatures was 0.7 (0.5) degrees C, with a range of 3 degrees C. When used in hospital to detect high temperature, axillary temperature had a sensitivity of 73% compared with rectal temperature. This is too insensitive for accurate detection of an infant's high temperature. Rectal temperature measurement is safer than previously suggested: perforation has occurred in less than one in two million measurements. If an infant's temperature needs to be taken, rectal temperature should be used.

Symptoms and signs in infants younger than 6 months of age correlated with the severity of their illness.

Symptoms and signs were recorded for 1007 infants younger than 6 months of age seen at home (298) or hospital (709) and correlated with four grades of illness severity. Most symptoms, present in the preceding 3 days, were associated with all grades of illness. Only four symptoms were not reported in well infants: a fluid intake less than a third of normal, convulsions, frank blood in the stools, and bile-stained vomiting. By comparison, many signs were seen only in ill infants. Those associated only with moderate or serous illness were marked retraction of the lower ribs, high-pitched or moaning cry, expiratory grunt, loss of alertness, central cyanosis, and severe hypotonia. Although these will not identify all seriously ill infants, parents and professionals should be taught to recognize these important symptoms and signs of serious illness.

Baby Check: a scoring system to grade the severity of acute systemic illness in babies under 6 months old.

A scoring system has been developed to grade the severity of acute systemic illness in babies under 6 months of age. Data were collected on 28 symptoms and 47 signs from 1007 babies with a spectrum of illness ranging from well to seriously ill. Ordinal regression analysis identified 19 symptoms and signs which in combination graded the severity of the illness most accurately. The coefficients were converted to scores. The higher the score the more serious the illness. When applied to a theoretical cohort of 10,000 babies at home, a score less than 8 has a specificity of 98%, and a score of 13 or more a sensitivity of 92%. The positive predictive value for serious illness increases from zero at a score of zero to approaching 100% at scores over 30. The scoring system has been developed into score cards for parents and professionals.

Respiratory rate and severity of illness in babies under 6 months old.

This paper defines the normal range of respiratory rate in babies under 6 months of age. It was counted by two observers in 1007 babies of whom 709 were seen when presenting to hospital for assessment of an acute illness, and 298 on a random basis at home. Whether they were asleep, content, or crying was recorded and the severity of their illness graded. The diagnosis was also recorded. The mean (SD) for the respiratory rate in babies seen awake was 61 (18) breaths/minute at hospital and 61 (14) breaths/minute at home. The respiratory rate when awake did not correlate with the severity of a baby's illness or the presence of serious lower respiratory tract infections. Sleeping babies had a significantly lower mean rate than awake babies at 42 (12) breaths/minute. Crying babies had a significantly lower mean rate than awake and content babies: 51 (14) breaths/minute compared with 61 (18) breaths/minute.