Knowledge and attitudes regarding the personally controlled electronic health record: an Australian national survey.

The personally controlled electronic health record (PCHER) was designed to bring important information together to facilitate effective communication between clinicians and so improve patient care. This national cross-sectional survey of 405 healthcare providers and consumers found that they had relatively low awareness and knowledge about the PCEHR; that 62% of respondents believed that healthcare providers with access to the PCEHR would be able to provide better quality of care but only 50% of respondents would sign up to have a PCEHR.

Drug approval processes in Australian Paediatric Hospitals.

OBJECTIVE: To describe and evaluate the decision-making processes for drug approval in Australian paediatric hospitals. DESIGN: Multicentre descriptive study involving face-to-face interviews of drug and therapeutics committee chairs and secretaries, review of committee documents and drug submissions for all Australian paediatric hospital drug and therapeutics committees over a 1-year period. SETTING: All eight paediatric hospitals in Australia. PARTICIPANTS: Eight committee chairs and seven secretaries or delegates. MAIN OUTCOME MEASURES: Total drug expenditure, number of formulary submissions, individual-patient use approvals and approval rates for each hospital from 1 July 2006 to 30 June 2007, stratified by therapeutic class. Qualitative description of the approval processes. RESULTS: Total drug expenditure varied from $A1.7 million (US$1.5 million) to $A11.1 million (US$9.8 million) per hospital. The number of formulary submissions also varied, from 7 to 21, but approval rate was high (76%-100%) and not significantly different among hospitals (p=0.17). Several committees approved identical submissions for five drugs. The number of individual-patient use applications varied considerably, ranging from 10 to 456 per hospital. Where estimable, individual-patient use approval was 76%-100% and variable (p=0.03). Quality of evidence relating to safety and efficacy of drugs being considered was regarded as the most important factors influencing decision making, with the cost less important. Most committees had poor infrastructural support for approval processes. No committee formally included a pharmaco-economic evaluation. CONCLUSIONS: Most drug submissions in tertiary paediatric hospitals are approved; however, workload, drug expenditure and individual-patient use schemes vary considerably. Duplication of effort occurs, and few committees are resourced sufficiently given their terms of reference.

Long-term results of Dana-Farber Cancer Institute ALL Consortium protocols for children with newly diagnosed acute lymphoblastic leukemia (1985-2000).

The Dana-Farber Cancer Institute (DFCI) acute lymphoblastic leukemia (ALL) Consortium has been conducting multi-institutional clinical trials in childhood ALL since 1981. The treatment backbone has included 20-30 consecutive weeks of asparaginase during intensification and frequent vincristine/corticosteroid pulses during the continuation phase. Between 1985 and 2000, 1457 children aged 0-18 years were treated on four consecutive protocols: 85-01 (1985-1987), 87-01 (1987-1991), 91-01 (1991-1955) and 95-01 (1996-2000). The 10-year event-free survival (EFS)+/-s.e. by protocol was 77.9+/-2.8% (85-01), 74.2+/-2.3% (87-01), 80.8+/-2.1% (91-01) and 80.5+/-1.8% (95-01). Approximately 82% of patients treated in the 1980s and 88% treated in the 1990s were long-term survivors. Both EFS and overall survival (OS) rates were significantly higher for patients treated in the 1990s compared with the 1980s (P=0.05 and 0.01, respectively). On the two protocols conducted in the 1990s, EFS was 79-85% for T-cell ALL patients and 75-78% for adolescents (age 10-18 years). Results of randomized studies revealed that dexrazoxane prevented acute cardiac injury without adversely affecting EFS or OS in high-risk (HR) patients, and frequently dosed intrathecal chemotherapy was an effective substitute for cranial radiation in standard-risk (SR) patients. Current studies continue to focus on improving efficacy while minimizing acute and late toxicities.

Emergency department attendances associated with drug-related problems in paediatrics.

OBJECTIVES: To determine the frequency and characteristics of paediatric emergency department attendances associated with drug-related problems (DRP) at three Victorian hospitals. METHODS: All paediatric medical patients attending the emergency department of the Royal Children's Hospital, Geelong Hospital or Box Hill Hospital were considered for inclusion. The investigator and attending medical practitioners screened eligible patients. A multidisciplinary panel reviewed collated data. Causality, preventability and clinical significance classifications were established by the panel. RESULTS: Combining data from the three hospitals, over 18 weeks of data collection, a total of 8601 patients met the eligibility criteria. Of these, 280 (3.3%, 95% CI 2.9-3.7%) were determined to have emergency department attendances associated with DRP. Of the 187 cases assessed for preventability, 51.3% were judged to be preventable. CONCLUSIONS: Emergency department attendances are associated with DRP in paediatrics. Given that the need to prevent DRP in adults is recognized, it is now time to act to reduce the consequences of DRP in paediatrics.

Second-trimester biochemical screening.

The past years have seen considerable progress in the area of biochemical screening. Increasing data have now clearly shown the advantages of multiple markers, particularly beta-hCG over AFP alone. There continues to be considerable controversy over the best mathematic algorithm and which markers are best (e.g., beta-HCG, uE3, and so forth). There seems to be a plateau of detection frequencies at about 65% to 70% with current methodologies. Further work needs to be done, however, including some new approaches, if there is to be substantial improvement of screening sensitivity. The combination of biochemical with biophysical parameters as discussed elsewhere in this issue represents the next level of sophistication in the attempt to identify the highest proportion of abnormalities with the fewest false-positives.

VAM-1: a new member of the MAGUK family binds to human Veli-1 through a conserved domain.

The MAGUKs (membrane-associated guanylate kinase homologues) constitute a family of peripheral membrane proteins that function in tumor suppression and receptor clustering by forming multiprotein complexes containing distinct sets of transmembrane, cytoskeletal, and cytoplasmic signaling proteins. Here, we report the characterization of the human vam-1 gene that encodes a novel member of the p55 subfamily of MAGUKs. The complete cDNA sequence of VAM-1, tissue distribution of its mRNA, genomic structure, chromosomal localization, and Veli-1 binding properties are presented. The vam-1 gene is composed of 12 exons and spans approx. 115 kb. By fluorescence in situ hybridization the vam-1 gene was localized to 7p15-21, a chromosome region frequently disrupted in some human cancers. VAM-1 mRNA was abundant in human testis, brain, and kidney with lower levels detectable in other tissues. The primary structure of VAM-1, predicted from cDNA sequencing, consists of 540 amino acids including a single PDZ domain near the N-terminus, a central SH3 domain, and a C-terminal GUK (guanylate kinase-like) domain. Sequence alignment, heterologous transfection, GST pull-down experiments, and blot overlay assays revealed a conserved domain in VAM-1 that binds to Veli-1, the human homologue of the LIN-7 adaptor protein in Caenorhabditis. LIN-7 is known to play an essential role in the basolateral localization of the LET-23 tyrosine kinase receptor, by linking the receptor to LIN-2 and LIN-10 proteins. Our results therefore suggest that VAM-1 may function by promoting the assembly of a Veli-1 containing protein complex in neuronal as well as epithelial cells.

Outcome following tricuspid valve detachment for ventricular septal defects closure.

OBJECTIVES: Detachment of the septal leaflet of the tricuspid valve from the annulus (TVD) has been used to improve visualization of ventricular septal defects (VSDs), but may be associated with increased operative time, heart block, and the development of tricuspid regurgitation (TR). METHODS: Patients undergoing VSD closure between 1/1/96 and 31/12/99 were retrospectively reviewed. Follow-up was obtained from the patients' cardiologists. RESULTS: Transatrial VSD closure was performed in 172 patients with TVD in 36 (21%) at the surgeon's discretion. The leaflet incision was repaired with a separate suture (22) or with the VSD patch suture (14). Additional procedures including arch augmentation, closure of atrial septal defects, and closure of additional VSDs were performed in 93 (68%) non-TVD patients and 20 (56%) TVD patients. The median age was 6.2 months (range 1 day to 46 years) and the median weight was 5.9 kg (range 1.5-71.5 kg). Cardiopulmonary bypass (CPB) time was 64+/-24 min and cross-clamp time was 34+/-16 min. One hospital death occurred in an infant with tracheal stenosis. No child in either group developed complete heart block. The median duration of postoperative stay was 4 days (range 2-49 days). There were no differences in CPB time, cross-clamp time or postoperative stay between the TVD and non-TVD groups (P>0.1 for all). At a mean follow-up of 17+/-15 months, there have been two late deaths unrelated to cardiac disease. No child in the TVD group required reoperation for residual VSD, compared to three in the non-TVD group. No child in the TVD group has greater than mild TR, but six in the non-TVD group have greater than mild TR. No child in either group has undergone reoperation for TR. CONCLUSIONS: TVD is a safe, effective technique to improve visualization of VSD and is not associated with heart block, increased operative time, or TR. TVD may result in improved preservation of tricuspid valve architecture and decrease the incidence of significant postoperative TR.

Second-trimester maternal serum marker screening: maternal serum alpha-fetoprotein, beta-human chorionic gonadotropin, estriol, and their various combinations as predictors of pregnancy outcome.

OBJECTIVE: We evaluated the value of all 3 common biochemical serum markers, maternal serum alpha-fetoprotein, beta-human chorionic gonadotropin, and unconjugated estriol, and combinations thereof as predictors of pregnancy outcome. STUDY DESIGN: A total of 60,040 patients underwent maternal serum screening. All patients had maternal serum alpha-fetoprotein measurements; beta-human chorionic gonadotropin was measured in 45,565 patients, and 24,504 patients had determination of all 3 markers, including unconjugated estriol. The incidences of various pregnancy outcomes were evaluated according to the serum marker levels by using clinically applied cutoff points. RESULTS: In confirmation of previous observations, increased maternal serum alpha-fetoprotein levels (>2.5 multiples of the median) were found to be significantly associated with pregnancy-induced hypertension, miscarriage, preterm delivery, intrauterine growth restriction, intrauterine fetal death, oligohydramnios, and abruptio placentae. Increased beta-human chorionic gonadotropin levels (>2.5 multiples of the median [MoM]) were significantly associated with pregnancy-induced hypertension, miscarriage, preterm delivery, and intrauterine fetal death. Finally, decreased unconjugated estriol levels (<0.5 MoM) were found to be significantly associated with pregnancy-induced hypertension, miscarriage, intrauterine growth restriction, and intrauterine fetal death. As with increased second-trimester maternal serum alpha-fetoprotein levels, increased serum beta-human chorionic gonadotropin and low unconjugated estriol levels are significantly associated with adverse pregnancy outcomes. These are most likely attributed to placental dysfunction. CONCLUSION: Multiple-marker screening can be used not only for the detection of fetal anomalies and aneu-ploidy but also for detection of high-risk pregnancies.

Distribution of neural tube defects as a function of maternal weight: no apparent correlation.

OBJECTIVES: Maternal nutritional deficiency is an important predisposing factor to congenital neural tube defects (NTDs). It was hypothesized that obese women may have an increased risk for NTDs. The aim of the present study was to address this question in a large cohort. METHODS: A total of 72,915 consecutive cases of biochemical screening that had documented maternal weights and pregnancy outcomes were identified from the Quest Diagnostic Laboratories database. Patients were divided into five ranges of maternal weights, and the incidence of NTDs was calculated for each group. Based on the different definitions of maternal overweight, the data were also analyzed based on 2 groups only, obese and nonobese, using three cutoff points. RESULTS: Seventy-nine pregnancies were complicated by NTDs (incidence of 1.08 per 1,000 pregnancies). Differences between maternal weights ranges were not found to be statistically significant (chi2 = 5.997, p = 0.19, power = 0.99). Differences between obese and nonobese mothers were not found to be statistically significant for all three analyses as well. CONCLUSIONS: Our present results do not support an association between maternal obesity and NTDs.

Screening for aneuploidy.

Over the past 15 years, biochemical screening for chromosomal abnormalities, particularly Down's syndrome, has advanced from being extremely naive, to now somewhat more sophisticated. Sensitivities have gone from 20% to 60-70%. Considerable work is still required to not only increase the sensitivity, but also the specificity to keep health care costs down.

Variability of adjustments to indices in determining patient risk in biochemical screening.

It has long been appreciated that the measurement of biochemical parameters for prenatal screening for neural tube defects, and later aneuploidy, is not as simple as measuring hemoglobin or hematocrit. Early in the game, it was recognized that there are gestational age curves, and that since alpha-fetoprotein (AFP), for example, is a fetal product, its distribution varies as a function of maternal plasma volume, and therefore the weight of the mother. A number of different adjustment factors have been used for AFP and other parameters for years, with varying degrees of consistency and reliability. Here we review a number of adjustments that have been used, and try to give priority to those that have been most effective. Furthermore, laboratories and programs need to be cognizant that with newer parameters being added, the specifics of requirements will vary on a case-by-case parameter basis, and optimal screening can only be achieved with the appropriate adjustments.

Simple preparation of the major urinary metabolites of flunitrazepam and nitrazepam.

An alarming increase in the misuse/abuse of nitrobenzodiazepine derivatives, especially flunitrazepam, prompted us to establish reliable analytical protocols for their routine detection. Whilst the parent drugs are readily available from a number of commercial sources, it was found difficult to obtain samples of the corresponding amino metabolites which were required as analytical standards. This lead us to develop the straightforward synthetic protocol described here, to convert the readily available parent drugs, namely flunitrazepam and nitrazepam, to their respective 7-amino derivatives. The method requires minimum laboratory facilities. It involves the reduction of the nitro functionality in the parent drug to an amino group using tin (II) chloride under mild conditions, using ultrasonication at room temperature. The method is simple and should give toxicology laboratories better access to these much needed compounds.

Determination of reference values for a novel ketoamine-specific fructosamine assay for assessment of diabetic glycemic control.

BACKGROUND: Intensive monitoring to improve glycemic control is essential for effective management of diabetes and reduction of long-term morbidity and pathology. Measurement of glycated serum proteins (fructosamine) allows more frequent assessment (monthly) of glycemic control than the 2- to 3-month window of the traditional glycated hemoglobin (HbA1c) assay. In response to concerns about assays designed to measure glycated serum proteins based on the nitroblue tetrazolium (NBT) methodology, a novel assay to measure glycated serum proteins has been developed based on the specific oxidation of the ketoamine bonds within the glycated proteins. METHODS: Reference range values for this new, enzymatic glycated-serum-protein assay (GlyPro; Genzyme Corporation, Cambridge, MA) are reported. RESULTS: The GlyPro reference range is lower and shows close correlation with ranges reported for the NBT assay. The 95% overall reference range was 122 to 236 mumol/L. CONCLUSIONS: GlyPro is a reliable, accurate assay and correlates well with the NBT assay for the measurement of glycated serum proteins. The assay may be useful in the short-term assessment of diabetes control, a necessary complement to long-term control as assessed by hemoglobin A1c (HbA1c) assays.

Relationships among liver and kidney volumes, lean body mass and drug clearance.

AIMS: To determine whether lean body mass (LBM), a possible surrogate of liver and kidney volumes, correlates with hepatic and renal drug clearances. METHODS: Twenty-one disease-free patients with a history of cancer and with normal hepatic and renal function were studied. Salivary pharmacokinetics of oral antipyrine (1200 mg) and 24 h creatinine clearance were determined following the determination of LBM by dual energy X-ray absorptiometry and the determination of liver and kidney volumes by helical CT scanning. RESULTS: Liver volume correlated with LBM (r2=0.21, P=0.04), body surface area (BSA) (r2=0.54, P<0.001), and total body weight (TBW) (r2=0.61, P<0.001). Kidney volume correlated with LBM (r2=0.49, P<0.001), BSA (r2=0.43, P=0.002) and TBW (r2=0.24, P=0.03). Stepwise multiple regression analysis, incorporating the independent variables of age, height, weight, sex, BSA, LBM, alcohol consumption, smoking status and liver volume and the dependent variable antipyrine clearance, indicated that LBM was the only independent correlate of antipyrine clearance. A stepwise multiple regression analysis with kidney volume in the independent variables, and creatinine clearance as dependent variable, showed that kidney volume and age were the only independent correlates of creatinine clearance. A nomogram using serum creatinine and LBM was comparable with the Cockcroft and Gault nomogram in calculating creatinine clearance. CONCLUSIONS: Of the anthropometric variables tested, LBM was the only determinant of antipyrine clearance, but this was not due to a relationship between LBM and liver volume. By contrast, the relationship between creatinine clearance and LBM appeared to be due to a relationship between LBM and kidney volume.

The incidence of drug-related problems as a cause of hospital admissions in children.

OBJECTIVES: To determine the incidence of hospital admissions for drug-related problems (DRPs) among children, and to examine cases for causality, preventability and clinical severity. DESIGN: Prospective assessment involving review of case notes and parent interview to determine if an admission was associated with a DRP. PATIENTS AND SETTING: All patients admitted to a large university-affiliated paediatric hospital in Melbourne, Victoria, for medical reasons (i.e., not surgical, trauma or oncology patients) during 56 consecutive days from 24 June to 19 August 1996 for which a DRP could be identified. Patients whose parents or guardians could not communicate adequately in English were excluded. MAIN OUTCOME MEASURES: The incidence, type, causality, preventability and clinical severity of DRPs associated with admission. RESULTS: Of 1682 eligible patients admitted to the Royal Children's Hospital during the study period, 58 admissions (3.4%) were associated with DRPs. Non-compliance was implicated in 50%. Causality was ranked as "definite" (34.5%), "possible" (56.9%) and "doubtful" (8.6). Two-thirds of admissions associated with DRPs were deemed preventable. Although no patients died from DRPs, four were admitted to the intensive care unit. CONCLUSIONS: The incidence of DRPs as a cause of hospital admission in this study falls within the range of incidences published for the Australian adult population (range, 2.4%-22%). In contrast to findings among Australian adults, a high proportion of admissions for DRPs in this study were associated with non-compliance. The high percentage of preventable admissions indicates that further study is necessary to characterise risk factors within this population and to test prevention strategies.

Age-specific variation in aneuploidy incidence among biochemical screening programs.

OBJECTIVE: Our purpose was to compare the observed age-related incidence of Down syndrome in two large screening programs with the commonly quoted incidences used in biochemical screening programs. STUDY DESIGN: Data from two large prenatal screening programs were stratified in 5-year age groups. The age-related incidence of Down syndrome was compared with the commonly used incidence as reported by Cuckle. RESULTS: No significant differences were found in age-related incidences of Down syndrome in any age group between the screening groups or among women ages 15 through 29 in any of the three groups. However, for women 30 to 34 and > or = 40 years old, a trend was noted toward a higher incidence in the screening groups. For women ages 35 to 39, the observed incidence was significantly greater in the screening groups compared with the data of Cuckle. CONCLUSION: Our data suggest an underascertainment in Down syndrome risk built into the Cuckle model, particularly in high-risk patients.

Detection of anomalies: alternatives to ultrasound.

Ultrasound and biochemical screening are complementary screening tests that each have limitations and advantages. The next several years will see variable progress in the evolution of these techniques, which, it is hoped, will result in an appropriate role for each to achieve a cost-effective, highly sensitive and specific screening approach that will allow couples the most comfort in detecting problems during pregnancy, as well as a high degree of confidence that normal results are accurate.