- Email: [email protected]
Urine testing in young febrile children: a risk-benefit analysis
POSTER ABSTRACTS
performed in nine regional genetic centres and two private laboratories in Ontario. The following methods are in use: Hybritech ERA (6 users), Abbott IMx (4) and Dade STRATUS (1). Three laboratories use a neural tube defect screening cut-off of 2.00 multiples of the median (MoM), and eight use 2.50 MoM; the choice of cut-off reflects local resources for follow-up. The laboratories using the Abbott and Hybritech assays are, by a long-standing consensus among the laboratory directors, using the medians indicated by the reagent manufacturers. Recently, data from the larger volume services was collected for analysis of the Caucasian medians, population standard deviations and initial positive rates. Sources of variance in the "Ontario data" were minimized by selecting only initial samples from the Caucasian population with known singleton pregnancies. There was no selection based on the method of determining gestational age. The Ontario data showed remarkable consistency, not only among centres performing the same assay, but also among the three assays. The Dade STRATUS uses Hybritech antibodies and medians, and therefore the Ontario data from these two reagent sources were combined in subsequent analysis. In contrast to the Ontario data, the Abbott and Hybritech manufacturers' medians differ from each other, and from the Ontario medians. Hybritech's medians are 7-10% lower than the Ontario medians, whereas Abbott's medians range from 3% higher at gestational age 15 weeks, to 9% lower at week 20. All laboratories had population standard deviations (SD) between 0.155 and 0.165 log MSAFP MoM. Those laboratories using the Hybritech method tended to have lower SDs than those using the Abbott method. Adopting the Ontario medians for use in the Ontario screening protocol would significantly decrease the initial-positive rate in all laboratories, and would likely decrease the detection rate. Therefore changing to the Ontario medians would require a reassessment of the screening cut-offs in use.
Pseudo-arylsulfatase-A mutation and pred i s p o s i t i o n to p s y c h i a t r i c d i s o r d e r s Chetty, V?, List, S. b, Molloy, D.W. c and Chang, P.L. d Departments of aMedical Biochemistry, dpaediatrics, bpsychiatry and CMedicine, McMaster University Medical Centre, 1200 Main Street West, Hamilton, Ontario, L8N 3Z5, Canada Metachromatic Leukodystrophy (MLD) is a severe autosomal recessive neurodegenerative disorder due to deficient activity of the lysosomal enzyme arylsulfatase-A. In the adult, behaviour disturbances, bizarre delusions and
CLINICAL BIOCHEMISTRY,VOLUME26, APRIL 1993
dementia are the major presenting signs. Interestingly, some individuals have a similar deficiency but do not demonstrate the classical features of MLD, a condition referred to as pseudo-deficiency (PD). The PD mutation is associated with two A --, G transitions in the arylsulfatase A gene, resulting in the loss of a glycosylation site and polyadenylation signal. Since this enzyme metabolizes a substrate, cerebroside sulfatide, which is an important constituent of the myelin sheath, as well as the serotonin and opiate receptors, we reasoned that the PD mutation may be associated with a predisposition to neuropsychiatric disorders. To date, the literature is unclear about the relationship between neuropsychiatric disorders and the PD mutation. These studies all depended on enzyme activity analysis and predated the recent discovery of the PD molecular mutations. Our objective was to screen Caucasian psychiatric patients, targeting primarily the disorders of schizophrenia and dementia of unknown aetiology for the presence of the PD mutations in the gene coding for arylsulfatase-A. By using a 3' mismatch polymerase chain reaction and confirming with allelespecific oligonucleotide hybridization, we found four patients carrying both A -~ G mutations in one of their two chromosomes and two patients carrying only the first of the two mutations, giving rise to a frequency of the PD mutation of 10%, and a frequency of one of the two PD-related mutations as 5% (our control population frequency being 4% and 7% respectively). testing showed no statistical significance but, because of the small sample size, this must be verified with a larger population study. In conclusion, we have found that the PD and its related mutations seem to occur at a higher frequency among a small sample of psychiatric patients than in the control population. Because these mutations result in an unstable enzyme, they could predispose some individuals to psychiatric disorders through alteration in myelin turnover and neural receptor function.
[I
LABORATORY UTILIZATION
I
Urine testing in young febrile children: a risk-benefit analysis Tange, S., D r u m m o n d , K.N., Mills, E.L. and Kramer, M.S. Departments of Biochemistry and Pediatrics, The Montreal Children's Hospital, and Departments of Epidemiology and Biostatistics, McGill University, Faculty of Medicine, 3655 Drummound Street, Montreal, Quebec, H3G 1Y6, Canada
131
37TH ANNUAL CONFERENCE OF THE CANADIAN SOCIETY OF CLINICAL CHEMISTS
Objective: To assess the relative risks and benefits of 10 potential urine-testing strategies involving urinalysis (UA) and urine culture (UC). Method: Decision analysis based on the published literature and a prospective study of 2,492 children aged 324 months presenting with fever but no focus of bacterial infection. The 10 testing strategies comprise 5 pairs; within each pair of strategies, one calls for a clean-voided (bag) UA and UC (UA + UC), while in the other, UC is sent only if the UA is abnormal (UA first). The 5 pairs differ in selectivity for testing: all children, girls only, temperature (T) >__.39~Conly, fever only (no respiratory or GI symptoms), or T >40°C only. Results are expressed as the preventive fraction (PF) for end-stage renal disease (ESRD) and hypertension and two risk/benefit ratios: the number of children tested per case of ESRD prevented (RB1) and the number of children unnecessarily hospitalized and treated per case of ESRD prevented (RBz). Results: Universal U A + UC testing had the highest PF (0.45), but only at a considerable "price': RB1 = 11,000; RB 2 = 533. Better RBs, but lower PFs, were associated with more selective testing strategies; UA + UC in children with T >39~C (PF = 0.40; RB~ = 6,000; RB2 = 291); UA + UC in girls (PF = 0.30; RB~ = 8,000; RB 2 = 397), and U A first in children with T >39°C (PF = 0.25; RB~ = 10,000; RB2 = 466). Sensitivity analyses revealed that PF and RB1 improve with higher estimates of treatment efficacy in preventing renal scarring, while RBz improves with higher specificity estimates for the urinalysis. Conclusions: Up to half the cases of long-term sequelae of occult UTI in young febrile children appear preventable by urine testing, but even the most favourable strategies require testing thousands of children, and unnecessarily hospitalizing and treating hundreds, for every case prevented.
[•]
Strategies to promote biochemistry test ordering
cost-effective
Lyon, A., Greenway, D.C. and Hindmarsh, J.T. Departments of Pathology and Biochemistry, University of Ottawa; Department of Laboratory Medicine, Ottawa General Hospital, Ottawa, Ontario, K1H 8L6, Canada
The widespread use of sequential multiple analyzers in hospital biochemistry laboratories in the past has promoted a "carpet-bombing" approach to biochemical test ordering: all readily available tests are requested with the hope that abnormalities will be detected. Physicians in our institution have persisted in ordering multitest profiles (eg "SMA 18") even though such groupings do not appear on the
132
laboratory requisitions and education through lectures and newsletters discouraging profiling has been ongoing. To promote a more efficient use of laboratory resources, we first solicited our medical advisory committee to ban the use of multiple test ordering and then undertook to enforce the ban by monitoring physicians' written orders within the inpatient charts and outpatient protocols. This study describes the approach, monitoring methods and impact on laboratory workload that resulted from the ban of panel testing enacted by the laboratory. A biweekly survey of physicians' orders (within patient charts) revealed >90% of physicians no longer wrote names of test panels. Before the ban, 15% of in-patient orders were for large panels (>17 tests/order). This decreased to 6% at one month, and 5% three months after the ban. The corresponding figures for outpatient clinics have been more dramatic: 44% before the ban, 16% at one month, and 5% at three months. A trend towards ordering smaller, more selective profiles has been observed. There has been no change in ordering patterns for small profiles (SMA 6 and 7). To date we feel we have succeeded in educating the medical staff, but impact on workload and cost savings will require further analysis.
~-]
Assessment of acceptance and impact of t h e "Thyroid Testing Guidelines f o r
A l b e r t a P h y s i c i a n s " in c e n t r a l A l b e r t a Carter, ICB. and Wesenberg, J.C. Clinical Laboratory, Red Deer Regional Hospital Centre, P.O. Bag 5030, Red Deer, Alberta, T4N 6R2, Canada The Alberta Medical Association published "Thyroid Testing Guidelines for Alberta Physicians (Guidelines)" in April, 1992. Designed to provide the best quality of care, the Guidelines also recommend progressive testing algorithms and criteria to reduce testing in patients with low probability of thyroid disease which are expected to reduce the number of thyroid tests done in Alberta. Sensitive thyrotropin (TSH) is the single, initial test in all but one algorithm which also suggests either thyroxine, triiodothyronine uptake and free thyroxine index (T4/T3U/FTI) or free T4. The Red Deer Regional Laboratory services the Red Deer Regional Hospital Centre (RDRHC) and the other hospitals and many clinics throughout Central Alberta (Region). This study examined the In-Patient and OutPatient test volumes for T4/T3U/VFI and TSH for R D R H C and the Region over the five years before and in the first six months after the Guidelines. The purpose of the study was to assess the acceptance of the recommendations expected to reduce test volumes and to estimate the impact
CLINICAL BIOCHEMISTRY, VOLUME 26, APRIL 1993
performed in nine regional genetic centres and two private laboratories in Ontario. The following methods are in use: Hybritech ERA (6 users), Abbott IMx (4) and Dade STRATUS (1). Three laboratories use a neural tube defect screening cut-off of 2.00 multiples of the median (MoM), and eight use 2.50 MoM; the choice of cut-off reflects local resources for follow-up. The laboratories using the Abbott and Hybritech assays are, by a long-standing consensus among the laboratory directors, using the medians indicated by the reagent manufacturers. Recently, data from the larger volume services was collected for analysis of the Caucasian medians, population standard deviations and initial positive rates. Sources of variance in the "Ontario data" were minimized by selecting only initial samples from the Caucasian population with known singleton pregnancies. There was no selection based on the method of determining gestational age. The Ontario data showed remarkable consistency, not only among centres performing the same assay, but also among the three assays. The Dade STRATUS uses Hybritech antibodies and medians, and therefore the Ontario data from these two reagent sources were combined in subsequent analysis. In contrast to the Ontario data, the Abbott and Hybritech manufacturers' medians differ from each other, and from the Ontario medians. Hybritech's medians are 7-10% lower than the Ontario medians, whereas Abbott's medians range from 3% higher at gestational age 15 weeks, to 9% lower at week 20. All laboratories had population standard deviations (SD) between 0.155 and 0.165 log MSAFP MoM. Those laboratories using the Hybritech method tended to have lower SDs than those using the Abbott method. Adopting the Ontario medians for use in the Ontario screening protocol would significantly decrease the initial-positive rate in all laboratories, and would likely decrease the detection rate. Therefore changing to the Ontario medians would require a reassessment of the screening cut-offs in use.
Pseudo-arylsulfatase-A mutation and pred i s p o s i t i o n to p s y c h i a t r i c d i s o r d e r s Chetty, V?, List, S. b, Molloy, D.W. c and Chang, P.L. d Departments of aMedical Biochemistry, dpaediatrics, bpsychiatry and CMedicine, McMaster University Medical Centre, 1200 Main Street West, Hamilton, Ontario, L8N 3Z5, Canada Metachromatic Leukodystrophy (MLD) is a severe autosomal recessive neurodegenerative disorder due to deficient activity of the lysosomal enzyme arylsulfatase-A. In the adult, behaviour disturbances, bizarre delusions and
CLINICAL BIOCHEMISTRY,VOLUME26, APRIL 1993
dementia are the major presenting signs. Interestingly, some individuals have a similar deficiency but do not demonstrate the classical features of MLD, a condition referred to as pseudo-deficiency (PD). The PD mutation is associated with two A --, G transitions in the arylsulfatase A gene, resulting in the loss of a glycosylation site and polyadenylation signal. Since this enzyme metabolizes a substrate, cerebroside sulfatide, which is an important constituent of the myelin sheath, as well as the serotonin and opiate receptors, we reasoned that the PD mutation may be associated with a predisposition to neuropsychiatric disorders. To date, the literature is unclear about the relationship between neuropsychiatric disorders and the PD mutation. These studies all depended on enzyme activity analysis and predated the recent discovery of the PD molecular mutations. Our objective was to screen Caucasian psychiatric patients, targeting primarily the disorders of schizophrenia and dementia of unknown aetiology for the presence of the PD mutations in the gene coding for arylsulfatase-A. By using a 3' mismatch polymerase chain reaction and confirming with allelespecific oligonucleotide hybridization, we found four patients carrying both A -~ G mutations in one of their two chromosomes and two patients carrying only the first of the two mutations, giving rise to a frequency of the PD mutation of 10%, and a frequency of one of the two PD-related mutations as 5% (our control population frequency being 4% and 7% respectively). testing showed no statistical significance but, because of the small sample size, this must be verified with a larger population study. In conclusion, we have found that the PD and its related mutations seem to occur at a higher frequency among a small sample of psychiatric patients than in the control population. Because these mutations result in an unstable enzyme, they could predispose some individuals to psychiatric disorders through alteration in myelin turnover and neural receptor function.
[I
LABORATORY UTILIZATION
I
Urine testing in young febrile children: a risk-benefit analysis Tange, S., D r u m m o n d , K.N., Mills, E.L. and Kramer, M.S. Departments of Biochemistry and Pediatrics, The Montreal Children's Hospital, and Departments of Epidemiology and Biostatistics, McGill University, Faculty of Medicine, 3655 Drummound Street, Montreal, Quebec, H3G 1Y6, Canada
131
37TH ANNUAL CONFERENCE OF THE CANADIAN SOCIETY OF CLINICAL CHEMISTS
Objective: To assess the relative risks and benefits of 10 potential urine-testing strategies involving urinalysis (UA) and urine culture (UC). Method: Decision analysis based on the published literature and a prospective study of 2,492 children aged 324 months presenting with fever but no focus of bacterial infection. The 10 testing strategies comprise 5 pairs; within each pair of strategies, one calls for a clean-voided (bag) UA and UC (UA + UC), while in the other, UC is sent only if the UA is abnormal (UA first). The 5 pairs differ in selectivity for testing: all children, girls only, temperature (T) >__.39~Conly, fever only (no respiratory or GI symptoms), or T >40°C only. Results are expressed as the preventive fraction (PF) for end-stage renal disease (ESRD) and hypertension and two risk/benefit ratios: the number of children tested per case of ESRD prevented (RB1) and the number of children unnecessarily hospitalized and treated per case of ESRD prevented (RBz). Results: Universal U A + UC testing had the highest PF (0.45), but only at a considerable "price': RB1 = 11,000; RB 2 = 533. Better RBs, but lower PFs, were associated with more selective testing strategies; UA + UC in children with T >39~C (PF = 0.40; RB~ = 6,000; RB2 = 291); UA + UC in girls (PF = 0.30; RB~ = 8,000; RB 2 = 397), and U A first in children with T >39°C (PF = 0.25; RB~ = 10,000; RB2 = 466). Sensitivity analyses revealed that PF and RB1 improve with higher estimates of treatment efficacy in preventing renal scarring, while RBz improves with higher specificity estimates for the urinalysis. Conclusions: Up to half the cases of long-term sequelae of occult UTI in young febrile children appear preventable by urine testing, but even the most favourable strategies require testing thousands of children, and unnecessarily hospitalizing and treating hundreds, for every case prevented.
[•]
Strategies to promote biochemistry test ordering
cost-effective
Lyon, A., Greenway, D.C. and Hindmarsh, J.T. Departments of Pathology and Biochemistry, University of Ottawa; Department of Laboratory Medicine, Ottawa General Hospital, Ottawa, Ontario, K1H 8L6, Canada
The widespread use of sequential multiple analyzers in hospital biochemistry laboratories in the past has promoted a "carpet-bombing" approach to biochemical test ordering: all readily available tests are requested with the hope that abnormalities will be detected. Physicians in our institution have persisted in ordering multitest profiles (eg "SMA 18") even though such groupings do not appear on the
132
laboratory requisitions and education through lectures and newsletters discouraging profiling has been ongoing. To promote a more efficient use of laboratory resources, we first solicited our medical advisory committee to ban the use of multiple test ordering and then undertook to enforce the ban by monitoring physicians' written orders within the inpatient charts and outpatient protocols. This study describes the approach, monitoring methods and impact on laboratory workload that resulted from the ban of panel testing enacted by the laboratory. A biweekly survey of physicians' orders (within patient charts) revealed >90% of physicians no longer wrote names of test panels. Before the ban, 15% of in-patient orders were for large panels (>17 tests/order). This decreased to 6% at one month, and 5% three months after the ban. The corresponding figures for outpatient clinics have been more dramatic: 44% before the ban, 16% at one month, and 5% at three months. A trend towards ordering smaller, more selective profiles has been observed. There has been no change in ordering patterns for small profiles (SMA 6 and 7). To date we feel we have succeeded in educating the medical staff, but impact on workload and cost savings will require further analysis.
~-]
Assessment of acceptance and impact of t h e "Thyroid Testing Guidelines f o r
A l b e r t a P h y s i c i a n s " in c e n t r a l A l b e r t a Carter, ICB. and Wesenberg, J.C. Clinical Laboratory, Red Deer Regional Hospital Centre, P.O. Bag 5030, Red Deer, Alberta, T4N 6R2, Canada The Alberta Medical Association published "Thyroid Testing Guidelines for Alberta Physicians (Guidelines)" in April, 1992. Designed to provide the best quality of care, the Guidelines also recommend progressive testing algorithms and criteria to reduce testing in patients with low probability of thyroid disease which are expected to reduce the number of thyroid tests done in Alberta. Sensitive thyrotropin (TSH) is the single, initial test in all but one algorithm which also suggests either thyroxine, triiodothyronine uptake and free thyroxine index (T4/T3U/FTI) or free T4. The Red Deer Regional Laboratory services the Red Deer Regional Hospital Centre (RDRHC) and the other hospitals and many clinics throughout Central Alberta (Region). This study examined the In-Patient and OutPatient test volumes for T4/T3U/VFI and TSH for R D R H C and the Region over the five years before and in the first six months after the Guidelines. The purpose of the study was to assess the acceptance of the recommendations expected to reduce test volumes and to estimate the impact
CLINICAL BIOCHEMISTRY, VOLUME 26, APRIL 1993