Raymond K. Neff

Clinical prediction rules: applications and methodological standards

The objective of clinical prediction rules is to reduce the uncertainty inherent in medical practice by defining how to use clinical findings to make predictions. Clinical prediction rules are derived from systematic clinical observations. They can help physicians identify patients who require diagnostic tests, treatment, or hospitalization. Before adopting a prediction rule, clinicians must evaluate its applicability to their patients. We describe methodological standards that can be used to decide whether a prediction rule is suitable for adoption in a clinicians practice. We applied these standards to 33 reports of prediction rules; 42 per cent of the reports contained an adequate description of the prediction rules, the patients, and the clinical setting. The misclassification rate of the rule was measured in only 34 per cent of reports, and the effects of the rule on patient care were described in only 6 per cent of reports. If the objectives of clinical prediction rules are to be fully achieved, authors and readers need to pay close attention to basic principles of study design.

Association between maternal diabetes and the respiratory-distress syndrome in the newborn.

Abstract Perinatal data on 805 infants of diabetic mothers and 10,152 infants of nondiabetic mothers were examined for a relation between maternal diabetes and respiratory-distress syndrome of the newborn. The syndrome occurred in 23.4 per cent of the diabetic vs. 1.3 per cent of the nondiabetic group. The risk of the syndrome in an infant of a diabetic mother was 23.7 times greater than that for an infant of a non diabetic mother (P < 0.00001). Further analysis to control for features associated with diabetes but also in themselves risk factors, such as gestational age and route of delivery, showed that respiratory-distress syndrome in infants of diabetic mothers was 5.6 times as likely to develop as in infants of nondiabetic mothers (P < 0.00001). Thus, maternal diabetes mellitus per se predisposes to newborn respiratory-distress syndrome. (N Engl J Med 294:357–360, 1976)

Coffee and Myocardial Infarction

Abstract A positive association between coffee consumption and acute myocardial infarction was confirmed by analyses of data from a multipurpose survey of 12,759 hospitalized patients, including 440 with a diagnosis of acute myocardial infarction. As compared with those who drink no coffee, the risks of infarction among those drinking one to five and six or more cups of coffee per day are estimated to be increased by 60 and 120 per cent, respectively. This association could not be attributed to confounding by age, sex, past coronary heart disease, hypertension, congestive heart failure, obesity, diabetes, smoking or occupation, nor could it be explained by the use of sugar with coffee. There was no positive association between tea drinking and acute myocardial infarction. (N Engl J Med 289:63–67, 1973)

Prenatal diagnosis of neural tube defects: VIII. The importance of serum alpha-fetoprotein screening in diabetic pregnant women☆

Maternal serum alpha-fetoprotein (AFP) screening of routine pregnancy is a valuable tool for the prenatal detection of neural tube defects (NTDs). Against our background experience with greater than 24,000 screened pregnancies, we have studied 411 pregnant insulin-dependent diabetic women. More than a tenfold increase (19.5/1,000) in the frequency of NTDs was observed in the offspring of these diabetic patients (p less than 0.000001). Serum AFP values were lower in diabetic than in nondiabetic women. Our data indicate that the normal standard of care for diabetic pregnancy should include serum AFP screening.

Prenatal diagnosis of neural tube defects

Abstract Total cholinesterase activity in amniotic fluid obtained from 150 fetuses was measured. Elevated values were found in 94% of samples from fetuses known to have neural tube defects (spina bifida, anencephaly) when compared to nonbloody samples from normal fetuses. Contamination of amniotic fluid with blood was observed to elevate total cholinesterase activity in some, but not all, such specimens. Total cholinesterase activity did not vary gestational age between 15 two 24 weeks. These data were compared to our large alpha-fetoprotein (AFP) assay experience used for the prenatal detection of neural tube defects. We concluded that the assay of total cholinesterase activity in amniotic fluid could be useful adjunct to the AFP assay, especially in those samples contaminated with blood.

Computer diagnosis of depression and anxiety: the Stirling County Study.

A computer programme (DPAX) was constructed for a longitudinal study of psychiatric epidemiology in Stirling County (Canada). It identifies disorders involving the syndromes of depression and anxiety based on responses given in structured questionnaire interviews. The programme follows a diagnostic algorithm that uses criteria for: (1) essential features; (2) number, frequency, and pattern of associated symptoms; (3) impairment; and (4) duration. The programme reproduces case evaluations provided by psychiatrists, as conveyed by a sensitivity of 92% and a specificity of 98%.

Long-term effects of labor and delivery on offspring: A matched-pair analysis☆

An investigation was undertaken in an effort to learn whether the type of delivery or the pattern of labor progression has any lasting effect on the infant. Paired-data design was chosen to ensure that the comparisons between homogeneous groups would be valid. Our objective was to reduce potential bias based on unequal distribution of patient characteristics that might be more or less commonly associated with abnormal labors or with difficult deliveries. Seven-year intelligence quotient data for matched pairs of cases showed significant long-range adverse impact from midforceps operations but not from low-forceps procedures. Comparable paired-data analysis for the effect of labor disorder on the infant verified a similar deleterious influence from both arrest and protraction patterns.

Fetal death in eclampsia: II. The effect of non-therapeutic factors.

The ability of 15 variables to predict fetal death is examined among 173 eclamptic women admitted to the only public maternity hospital in Cali, Colombia, between 1st January 1964 and 31st December 1970. In addition to low gestational age and retarded fetal growth, high systolic pressure and the unmarried status carried excess risk. Primiparae appeared to be of lower risk because their eclampsia tended to occur late in gestation and was characterized by less retarded fetal growth. Older women and women with a history of abortion appeared to be of higher risk because they tended to have higher systolic pressures. A discriminant function risk formula is presented which generated groups with a nine‐fold difference in fetal death rates. This formula could be used to standardize for relevant non‐therapeutic factors which might vary between patient groups who had received different therapeutic regimens.

The Boston Teacher Questionnaire. 2. Assessments of Validity

We assessed the validity of the Boston Teacher Questionnaire in a sample of 3451 9-year-old children. Those identified by the questionnaire as having a learning difficulty syndrome were compared to those without any characteristic of that syndrome. The validity reference measures were individually administered neuropsychological assessments at age 7 years and a group-administered reading achievement test at age 9 years. Girls and boys with the reading syndrome had much lower reading scores at age 9 years than did their peers. Boys, but not girls, with the arithmetic syndrome were much more likely than their peers to have arithmetic scores more than one grade below the expected level at age 7 years. Girls and boys with the tasks syndrome, characterized by impersistence, dependence, and inflexibility, were more likely than those without any features of the syndrome to be classified as having little or no goal orientation by a neuropsychologist who assessed the children in an office setting. Similarly, the neuropsychologist was much more likely than expected to have classified children with the attention syndrome as having a short attention span, and to have classified boys, but not girls, with the hyperactivity syndrome as having an unusual/extreme level and nature of overactivity. Children with any syndrome were more likely than others to have low scores on components of the Wechsler Intelligence Scale for Children, items of the Bender-Gestalt Test that assessed integration and distortion, and measures of reading comprehension. We conclude that the Boston Teacher Questionnaire validly identifies children with learning problems. (J Child Neurol 1993; 8:54-63).

The Boston Teacher Questionnaire. 1. Definition of Syndromes

To obtain information about the academic function of 9-year-old children from their school teachers, we created a short, forced-choice questionnaire that asked about the childs knowledge and use of arithmetic tables, reading, spelling, persistence at tasks, flexibility of approach, ability to function independently, distractibility, daydreaming, impulsivity and overexcitability, hyperactivity, and ability to follow simple and sequential directions. Questionnaires were collected from the teachers of 3451 white children whose mothers had enrolled in the National Collaborative Perinatal Project. Six syndromes in girls and five in boys were identified by both cluster and factor analyses of these data. Common to both sexes were five syndromes we labeled arithmetic, tasks (ie, impersistent/dependent/inflexible), reading, attention, and hyperactive. A syndrome characterized by difficulty following directions was seen in girls only. The prevalence of these syndromes ranged from a low for hyperactivity of 2.3 per 100 girls to a high for the attention syndrome of 27.6 per 100 boys. The congruent results obtained with clustering and factor analysis, and the agreement between the observed prevalence of syndromes and prior expectations suggests that the Boston Teacher Questionnaire, as this instrument is called, identifies learning problems in 9-year-old children. (J Child Neurol 1993;8:43-53).